Chloroquine and hydroxychloroquine inhibit bladder cancer cell growth by targeting basal autophagy and enhancing apoptosis.

PubMed

Lin, Yi-Chia; Lin, Ji-Fan; Wen, Sheng-I; Yang, Shan-Che; Tsai, Te-Fu; Chen, Hung-En; Chou, Kuang-Yu; Hwang, Thomas I-Sheng

2017-05-01

Chloroquine (CQ) and hydroxychloroquine (HCQ), two antimalarial drugs, are suggested to have potential anticancer properties. in the present study, we investigated the effects of CQ and HCQ on cell growth of bladder cancer with emphasis on autophagy inhibition and apoptosis induction in vitro. The results showed that CQ and HCQ inhibited the proliferation of multiple human bladder cell lines (including RT4, 5637, and T24) in a time- and dose-dependent fashion, especially in advanced bladder cancer cell lines (5637 and T24) compared to immortalized uroepithelial cells (SV-Huc-1) or other reference cancer cell lines (PC3 and MCF-7). We found that 24-hour treatment of CQ or HCQ significantly decreased the clonogenic formation in 5637 and T24 cells compared to SV-Huc-1. As human bladder cancer tumor exhibits high basal level of autophagic activities, we detected the autophagic flux in cells treated with CQ and HCQ, showing an alternation in LC3 flux in CQ- or HCQ-treated cells. Moreover, bladder cancer cells treated with CQ and HCQ underwent apoptosis, resulting in increased caspase 3/7 activities, increased level of cleaved poly(ADP-ribose) polymerase (PARP), caspase 3, and DNA fragmentation. Given these results, targeting autophagy with CQ and HCQ represents an effective cancer therapeutic strategy against human bladder cancer. Copyright © 2017. Published by Elsevier Taiwan.

Natalizumab Modifies Catecholamines Levels Present in Patients with Relapsing- Remitting Multiple Sclerosis.

PubMed

Escribano, Begona M; Aguilar-Luque, Macarena; Bahamonde, Carmen; Conde, Cristina; Lillo, Rafael; Sanchez-Lopez, Fernando; Giraldo, Ana I; Cruz, Antonio H; Luque, Evelio; Gascon, Felix; Aguera, Eduardo; Tunez, Isaac

2016-01-01

The main aim of this study was to verify the effect of natalizumab on the levels of circulating catecholamines and indolamine and their possible relation with MS. For this purpose, 12 healthy individuals (control group) and 12 relapsing-remitting multiple sclerosis patients (RR-MS) were selected. The patients were treated with 300 mg of natalizumab during 56 weeks (1 dose/4 weeks) (MS-56). This selection was based on the McDonalds revision criterion and scheduled to star treatment with natalizumab. Blood samples were taken before treatment (basal level) and after 56 weeks of using natalizumab. Melatonin was measured in serum and in plasma, catecholamines (dopamine, epinephrine, and norepinephrine), carbonylated proteins, 8-hydroxy-2'deoxyguanosine (8OH-dG) and the ratio reduced glutathione/oxidised glutathione (GSH/GSSG). The epinephrine and dopamine levels diminished in the basal group with respect to the control and did not recover normal levels with the treatment. The melatonin was decreased in RR-MS patients and went back to its normal levels with natalizumab. Norepinephrine was increased in RR-MS and decreased in MS-56 until it equalled the control group. Natalizumab normalizes altered melatonin and norepinephrine levels in MS.

In-situ analysis of the slip activity during tensile deformation of cast and extruded Mg-10Gd-3Y-0.5Zr (wt.%) at 250 °C

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, H.; The State Key Laboratory of Metal Matrix Composites, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240; Department of Chemical Engineering and Materials Science, Michigan State University, East Lansing, MI 48824

The slip activity and slip interaction in tensile deformation of peak-aged cast and extruded Mg-10Gd-3Y-0.5Zr (wt.%) at 250 °C was investigated using in-situ scanning electron microscopy. Basal slip was the most likely system to be activated during the tensile deformation, while prismatic < a > and pyramidal < c + a > slip also contributed to the deformation. No twinning was observed. The number of non-basal slip systems accounted for ~ 36% of the total active slip systems for the cast alloy, while non-basal slip accounted for 12–17% of the total deformation observations in the extruded alloy. Multiple-slip was observedmore » within grains, and the basal/prismatic pairing type dominated the multiple-slip observations. Slip transfer occurred across grain boundaries and most of the slip transfer observations showed basal-basal type. The involved slip systems of slip transfer pairs were always associated with the same < a > direction. The slip transfer occurred more easily at low angle boundaries (LABs) and boundaries with misorientations greater than 75°. - Highlights: • Slip deformation of a Mg-RE alloy at 250 °C was investigated using in-situ SEM. • The extruded-T5 GW103 alloy did not exhibit a high anisotropic behavior. • Multiple-slip was observed within grains, and basal/prismatic type dominated. • Slip transfer occurred and most of the observations showed basal-basal type. • Slip transfer occurred more easily at LABs and boundaries with misorientations > 75°.« less

980nm laser for difficult-to-treat basal cell carcinoma

NASA Astrophysics Data System (ADS)

Derjabo, A. D.; Cema, I.; Lihacova, I.; Derjabo, L.

2013-06-01

Begin basal cell carcinoma (BCC) is most common skin cancer over the world. There are around 20 modalities for BCC treatment. Laser surgery is uncommon option. We demonstrate our long term follow up results. Aim: To evaluate long term efficacy of a 980nm diode laser for the difficult-to-treat basal cell carcinoma. Materials and Methods: 167 patients with 173 basal cell carcinoma on the nose were treated with a 980 nm diode laser from May 1999 till May 2005 at Latvian Oncology center. All tumors were morphologically confirmed. 156 patients were followed for more than 5 years. Results: The lowest recurrence rate was observed in cases of superficial BCC, diameter<6mm bet the highest recurrence rate was in cases of infiltrative BCC and nodular recurrent BCC. Conclusions: 980 nm diode laser is useful tool in dermatology with high long term efficacy, good acceptance by the patients and good cosmetics results.

Effect of partial supplementation of sun-dried Azolla as a protein source on the immunity and antioxidant status of commercial broilers.

PubMed

Chichilichi, Biswal; Mohanty, G P; Mishra, S K; Pradhan, C R; Behura, N C; Das, A; Behera, K

2015-09-01

The present study was conducted to evaluate the effect of partial supplementation of sun-dried Azolla as a protein source on the immunity of commercial broilers in coastal Odisha. A 180 day-old broiler chicks were distributed in six dietary treatments viz. C1: Basal diet, C2: Basal diet + enzyme, T1: Basal diet +5% protein from Azolla, T2: Basal diet + 5% protein from Azolla + enzyme, T3: Basal diet +10% protein from Azolla, and T4: Basal diet + 10% protein from Azolla + enzyme. Cutaneous basophilc hypersensitivity (CBH) and humoral immunity response were determined at the 38(th) day of age. At 42(nd) day, the weight of lymphoid organs, an antioxidant enzyme, and lipid peroxidation activity were determined. The CBH response did not differ significantly among the treated groups, but the sheep red blood cells response was significantly higher in T4. The weight of lymphoid organs or immune organs of all the treated groups did not differ significantly (p>0.05). The erythrocyte catalase level of T4 group was found to be significantly higher than rest of the treated groups except T3. It may be concluded that supplementation of Azolla at 10% of dietary protein requirement along with enzyme supplementation in an isonitrogenous diet showed a better immune response in broilers.

Effect of partial supplementation of sun-dried Azolla as a protein source on the immunity and antioxidant status of commercial broilers

PubMed Central

Chichilichi, Biswal; Mohanty, G. P.; Mishra, S. K.; Pradhan, C. R.; Behura, N. C.; Das, A.; Behera, K.

2015-01-01

Aim: The present study was conducted to evaluate the effect of partial supplementation of sun-dried Azolla as a protein source on the immunity of commercial broilers in coastal Odisha. Materials and Methods: A 180 day-old broiler chicks were distributed in six dietary treatments viz. C1: Basal diet, C2: Basal diet + enzyme, T1: Basal diet +5% protein from Azolla, T2: Basal diet + 5% protein from Azolla + enzyme, T3: Basal diet +10% protein from Azolla, and T4: Basal diet + 10% protein from Azolla + enzyme. Cutaneous basophilc hypersensitivity (CBH) and humoral immunity response were determined at the 38th day of age. At 42nd day, the weight of lymphoid organs, an antioxidant enzyme, and lipid peroxidation activity were determined. Results: The CBH response did not differ significantly among the treated groups, but the sheep red blood cells response was significantly higher in T4. The weight of lymphoid organs or immune organs of all the treated groups did not differ significantly (p>0.05). The erythrocyte catalase level of T4 group was found to be significantly higher than rest of the treated groups except T3. Conclusion: It may be concluded that supplementation of Azolla at 10% of dietary protein requirement along with enzyme supplementation in an isonitrogenous diet showed a better immune response in broilers. PMID:27047208

Metastatic Basal cell carcinoma accompanying gorlin syndrome.

PubMed

Bilir, Yeliz; Gokce, Erkan; Ozturk, Banu; Deresoy, Faik Alev; Yuksekkaya, Ruken; Yaman, Emel

2014-01-01

Gorlin-Goltz syndrome or basal cell nevus syndrome is an autosomal dominant syndrome characterized by skeletal anomalies, numerous cysts observed in the jaw, and multiple basal cell carcinoma of the skin, which may be accompanied by falx cerebri calcification. Basal cell carcinoma is the most commonly skin tumor with slow clinical course and low metastatic potential. Its concomitance with Gorlin syndrome, resulting from a mutation in a tumor suppressor gene, may substantially change morbidity and mortality. A 66-year-old male patient with a history of recurrent basal cell carcinoma was presented with exophthalmus in the left eye and the lesions localized in the left lateral orbita and left zygomatic area. His physical examination revealed hearing loss, gapped teeth, highly arched palate, and frontal prominence. Left orbital mass, cystic masses at frontal and ethmoidal sinuses, and multiple pulmonary nodules were detected at CT scans. Basal cell carcinoma was diagnosed from biopsy of ethmoid sinus. Based on the clinical and typical radiological characteristics (falx cerebri calcification, bifid costa, and odontogenic cysts), the patient was diagnosed with metastatic skin basal cell carcinoma accompanied by Gorlin syndrome. Our case is a basal cell carcinoma with aggressive course accompanying a rarely seen syndrome.

Metastatic Basal Cell Carcinoma Accompanying Gorlin Syndrome

PubMed Central

Bilir, Yeliz; Gokce, Erkan; Ozturk, Banu; Deresoy, Faik Alev; Yuksekkaya, Ruken; Yaman, Emel

2014-01-01

Gorlin-Goltz syndrome or basal cell nevus syndrome is an autosomal dominant syndrome characterized by skeletal anomalies, numerous cysts observed in the jaw, and multiple basal cell carcinoma of the skin, which may be accompanied by falx cerebri calcification. Basal cell carcinoma is the most commonly skin tumor with slow clinical course and low metastatic potential. Its concomitance with Gorlin syndrome, resulting from a mutation in a tumor suppressor gene, may substantially change morbidity and mortality. A 66-year-old male patient with a history of recurrent basal cell carcinoma was presented with exophthalmus in the left eye and the lesions localized in the left lateral orbita and left zygomatic area. His physical examination revealed hearing loss, gapped teeth, highly arched palate, and frontal prominence. Left orbital mass, cystic masses at frontal and ethmoidal sinuses, and multiple pulmonary nodules were detected at CT scans. Basal cell carcinoma was diagnosed from biopsy of ethmoid sinus. Based on the clinical and typical radiological characteristics (falx cerebri calcification, bifid costa, and odontogenic cysts), the patient was diagnosed with metastatic skin basal cell carcinoma accompanied by Gorlin syndrome. Our case is a basal cell carcinoma with aggressive course accompanying a rarely seen syndrome. PMID:25506011

O6-methylguanine-DNA methyltransferase as a prognostic and predictive marker for basal-like breast cancer treated with cyclophosphamide-based chemotherapy

PubMed Central

ISONO, SAYURI; FUJISHIMA, MAKOTO; AZUMI, TATSUYA; HASHIMOTO, YUKIHIKO; KOMOIKE, YOSHIFUMI; YUKAWA, MASAO; WATATANI, MASAHIRO

2014-01-01

The O6-methylguanine-DNA methyltransferase (MGMT) protein protects cells from alkylating agents by removing alkyl groups from the O6-position of guanine. However, its effect on DNA damage induced by cyclophosphamide (CPM) is unclear. The present study investigated whether MGMT expression was correlated with prognosis in patients with breast cancer that was managed according to a common therapeutic protocol or treated with CPM-based chemotherapy. The intrinsic subtypes and MGMT protein expression levels were assessed in 635 consecutive patients with breast cancer using immunohistochemistry. In total, 425 (67%) luminal A, 95 (15%) luminal B, 47 (7%) human epidermal growth factor receptor-2+/estrogen receptor− (HER2+/ER−) and 48 (8%) basal-like subtypes were identified. Of these, MGMT positivity was identified in 398 (63%) of 635 breast cancers; 68% of luminal A, 67% of luminal B, 30% of HER2+/ER− and 46% of basal-like subtypes were positive. The overall survival (OS) and disease-free survival (DFS) rates did not significantly differ according to the MGMT status among patients with luminal A, luminal B or HER2+/ER− subtypes, and patients with MGMT-negative basal-like cancers tended to have a longer DFS, but not a significantly longer OS time. CPM-containing chemotherapy was administered to 26%, 40%, 47% and 31% of patients with luminal A, luminal B, HER2+/ER− and basal-like tumors, respectively. Although the MGMT status and clinical outcomes of patients with the luminal A, luminal B or HER2+/ER− subtypes treated with CPM were not significantly correlated, the patients with MGMT-negative basal-like tumors who received CPM exhibited significantly improved DFS and OS compared with the CPM-treated patients with MGMT-positive tumors. MGMT may be a useful prognostic and predictive marker for CPM-containing chemotherapy in basal-like breast cancer. PMID:24932232

O6-methylguanine-DNA methyltransferase as a prognostic and predictive marker for basal-like breast cancer treated with cyclophosphamide-based chemotherapy.

PubMed

Isono, Sayuri; Fujishima, Makoto; Azumi, Tatsuya; Hashimoto, Yukihiko; Komoike, Yoshifumi; Yukawa, Masao; Watatani, Masahiro

2014-06-01

The O 6 -methylguanine-DNA methyltransferase (MGMT) protein protects cells from alkylating agents by removing alkyl groups from the O 6 -position of guanine. However, its effect on DNA damage induced by cyclophosphamide (CPM) is unclear. The present study investigated whether MGMT expression was correlated with prognosis in patients with breast cancer that was managed according to a common therapeutic protocol or treated with CPM-based chemotherapy. The intrinsic subtypes and MGMT protein expression levels were assessed in 635 consecutive patients with breast cancer using immunohistochemistry. In total, 425 (67%) luminal A, 95 (15%) luminal B, 47 (7%) human epidermal growth factor receptor-2 + /estrogen receptor - (HER2 + /ER - ) and 48 (8%) basal-like subtypes were identified. Of these, MGMT positivity was identified in 398 (63%) of 635 breast cancers; 68% of luminal A, 67% of luminal B, 30% of HER2 + /ER - and 46% of basal-like subtypes were positive. The overall survival (OS) and disease-free survival (DFS) rates did not significantly differ according to the MGMT status among patients with luminal A, luminal B or HER2 + /ER - subtypes, and patients with MGMT-negative basal-like cancers tended to have a longer DFS, but not a significantly longer OS time. CPM-containing chemotherapy was administered to 26%, 40%, 47% and 31% of patients with luminal A, luminal B, HER2 + /ER - and basal-like tumors, respectively. Although the MGMT status and clinical outcomes of patients with the luminal A, luminal B or HER2 + /ER - subtypes treated with CPM were not significantly correlated, the patients with MGMT-negative basal-like tumors who received CPM exhibited significantly improved DFS and OS compared with the CPM-treated patients with MGMT-positive tumors. MGMT may be a useful prognostic and predictive marker for CPM-containing chemotherapy in basal-like breast cancer.

Treatment of hidradenitis suppurativa with intralesional photodynamic therapy with 5-aminolevulinic acid and 630nm laser beam.

PubMed

Suárez Valladares, María Jesús; Eiris Salvado, Noemi; Rodríguez Prieto, Manuel Angel

2017-03-01

Hidradenitis suppurativa (HS) is a chronic relapsing inflammatory skin disease with multiple treatment options that have been used with mixed results. To evaluate the effectiveness, safety and tolerability of intralesional photodynamic therapy (I-PDT) in the management of HS. Also, to assess the effect of this technique on the different areas treated. Case series of 38 HS patients treated with I-PDT between 2011-2015 following a standardized protocol to assess response at the treated areas RESULTS: 29 patients achieved a complete response, while persistence was noted on 8 cases and only 1 suffered a recurrence. Difference between basal (median 28.5) and final (0) Hidradenitis Severity Score showed a significant reduction of 24.5 points (p<0.001, 95% OR 19.5-31). Basal (median 10) and final (1) Dermatology Life Quality Index scores reached a reduction of 10 points (p<0.001, 95%OR 8-12). Complete response was achieved in 68.2% of armpits, 88.5% of groins, 88.9% of buttocks and 100% of other locations. 18 out of 38 patients needed only a session to achieve a complete response, while maintaining a good tolerability. We believe that I-PDT might be an alternative treatment option for localized HS lesions, achieving a high rate of remission with an adequate maintenance of response i and few complications. Copyright © 2016 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.

A feasibility study of a 3-day basal-bolus insulin delivery device in individuals with type 2 diabetes.

PubMed

Mader, Julia K; Lilly, Leslie C; Aberer, Felix; Korsatko, Stefan; Strock, Ellie; Mazze, Roger S; Damsbo, Peter; Pieber, Thomas R

2014-05-01

This study tested the feasibility of transition from multiple daily injections (MDI) to a 3-day, basal-bolus insulin delivery device (PaQ) for type 2 diabetes (T2D). Twenty MDI-treated individuals with T2D with HbA(1c) ≤9% (75 mmol/mol) were enrolled in a single-center, single-arm pilot study, lasting three 2-week periods: baseline (MDI), transition to PaQ, and PaQ therapy. Feasibility of use, glycemic control, safety, and patient satisfaction were assessed. Nineteen participants transitioned to PaQ treatment and demonstrated competency in assembling, placing, and using the device. Self-monitored blood glucose and blinded continuous glucose-monitoring data showed glycemic control similar to MDI. Study participants reported high satisfaction and device acceptance. PaQ treatment is both feasible and acceptable in individuals with T2D. Transition from MDI is easy and safe. PaQ treatment might lead to better therapy adherence and improvements in glycemic control and clinical outcomes.

Deep-Brain Stimulation for Basal Ganglia Disorders.

PubMed

Wichmann, Thomas; Delong, Mahlon R

2011-07-01

The realization that medications used to treat movement disorders and psychiatric conditions of basal ganglia origin have significant shortcomings, as well as advances in the understanding of the functional organization of the brain, has led to a renaissance in functional neurosurgery, and particularly the use of deep brain stimulation (DBS). Movement disorders are now routinely being treated with DBS of 'motor' portions of the basal ganglia output nuclei, specifically the subthalamic nucleus and the internal pallidal segment. These procedures are highly effective and generally safe. Use of DBS is also being explored in the treatment of neuropsychiatric disorders, with targeting of the 'limbic' basal ganglia-thalamocortical circuitry. The results of these procedures are also encouraging, but many unanswered questions remain in this emerging field. This review summarizes the scientific rationale and practical aspects of using DBS for neurologic and neuropsychiatric disorders.

Tazarotene-induced gene 3 is suppressed in basal cell carcinomas and reversed in vivo by tazarotene application.

PubMed

Duvic, Madeleine; Ni, Xiao; Talpur, Rakhashandra; Herne, Kelly; Schulz, Claudia; Sui, Dawen; Ward, Staci; Joseph, Aaron; Hazarika, Parul

2003-10-01

Basal cell carcinomas are the most common form of skin cancer. Tazarotene is a retinoic acid receptor selective retinoid that upregulates a tumor suppressor, tazarotene-induced gene 3 (TIG-3), in keratinocytes and psoriasis. Expression of TIG-3 in basal cell carcinomas was studied in an opened-label pilot biomarker study of 22 patients with basal cell carcinomas who applied tazarotene 0.1% gel for up to 12 wk prior to excision. Nineteen paired baseline and treated specimens were compared using immunohistochemistry and in situ hybridization. Compared to overlying normal epidermis, TIG-3 protein and mRNA were decreased in 14 and 18 of 19 basal cell carcinomas (74% and 95%), respectively (p < 0.001). Tazarotene treatment was associated with increased TIG-3 protein and mRNA expression in basal cell carcinomas compared to baseline levels (p < or = 0.001 and p = 0.028, respectively). Sixty percent of basal cell carcinomas treated with tazarotene decreased in size by at least 25%. Ten of 19 lesions improved histologically, including three complete responses. There was a correlation between the increased expression of TIG-3 protein and histologic improvement (p = 0.020), suggesting that suppression of TIG-3 may underlie the development of basal cell carcinomas. This association suggests that reversal of TIG-3 expression may help to explain the mechanism of retinoid action in epidermal differentiation and chemoprevention.

Efficacy of basal soil injection at different water volumes and landscape settings for Asian longhorn beetle control

Treesearch

Phillip A. Lewis

2007-01-01

The Asian longhorn beetle eradication program currently treats at-risk trees by soil injection with a high volume solution of pesticide placed in concentric rings expanding out from the trunk to the dripline of the tree. Using this method in wooded habitats has previously resulted in no detectable residue in treated trees. Basal soil injection (BSI) uses a high...

Basal Cell Carcinoma of the Dorsal Hand: An Update and Comprehensive Review of the Literature.

PubMed

Loh, Tiffany Y; Rubin, Ashley G; Brian Jiang, Shang I

2016-04-01

Excessive ultraviolet radiation (UVR) exposure is the primary predisposing factor for basal cell carcinoma (BCC). However, surprisingly, BCCs occur very rarely on the dorsal hand, which is subject to intense sun exposure, and their infrequent presentation in this location suggests that other factors besides UVR may play a role in BCC pathogenesis. Because dorsal hand BCCs are uncommon, knowledge of their characteristics is limited, and more data are needed to describe their clinical presentation and treatment. To perform an updated review of the literature on the management of dorsal hand BCCs. The authors conducted a comprehensive literature review by searching the PubMed database with the key phrases "basal cell carcinoma dorsal hand," "basal cell carcinoma hand," and "basal cell carcinoma finger," and "basal cell carcinoma thumb." The authors identified 176 cases of dorsal hand BCCs in the literature, 120 of which had sufficient data for analysis. Only 4 cases were treated with Mohs micrographic surgery (MMS). The authors present 14 additional cases of dorsal hand BCCs treated with MMS. Basal cell carcinomas on the dorsal hand occur infrequently, and potential risk factors include being a male of white descent and personal history of skin cancer. Mohs micrographic surgery seems to be an effective treatment method.

Simultaneous adenomatoid odontogenic and keratocystic odontogenic tumours in a patient with Gorlin-Goltz syndrome.

PubMed

Shephard, M; Shepard, M; Coleman, H

2014-03-01

Gorlin and Goltz described a syndrome in which multiple basal cell carcinomas, odontogenic keratocysts and bifid ribs occurred in combination. The jaw keratocysts are a consistent feature of 'Gorlin-Goltz' or naevoid basal cell carcinoma syndrome. Central nervous system and ocular involvement occurred together with the fairly typical facial features of frontal bossing and hypertelorism. This case report documents the pathology associated with an impacted maxillary canine tooth in a boy with Gorlin-Goltz syndrome. The patient presented for investigation of the failure of eruption of the right permanent maxillary canine tooth. Radiographic investigation showed the presence of a well circumscribed radiolucency located around the crown of an impacted right maxillary canine tooth. The patient's medical history revealed a medulloblastoma that was treated 13 years ago. The right maxillary canine tooth and associated peri-coronal tissue were removed under general anaesthetic. A diagnosis of a keratocystic odontogenic tumour with an associated adenomatoid odontogenic tumour was made. The common differential diagnoses for a peri-coronal radiolucency in the maxilla that need to be considered by dentists include a dentigerous cyst, follicular keratocystic odontogenic tumour and adenomatoid odontogenic tumour. A rare case of both keratocystic odontogenic tumour and associated follicular adenomatoid odontogenic tumour is described in a patient with naevoid basal cell carcinoma syndrome. © 2014 Australian Dental Association.

Steroids alter ion transport and absorptive capacity in proximal and distal colon.

PubMed

Sellin, J H; DeSoignie, R C

1985-07-01

Steroids are potent absorbagogues, increasing Na and fluid absorption in a variety of epithelia. This study characterizes the in vitro effects of pharmacological doses of gluco- and mineralocorticoids on transport parameters of rabbit proximal and distal colon. Treatment with methylprednisolone (MP, 40 mg im for 2 days) and desoxycortone acetate (DOCA, 12.5 mg im for 3 days) resulted in a significant increase in short-circuit current (Isc) in distal colon, suggesting an increase in basal Na absorption. Amiloride (10(-4) M) caused a significantly negative Isc in MP-treated tissue, demonstrating a steroid-induced, amiloride-insensitive electrogenic ion transport in distal colon. The effect of two absorbagogues, impermeant anions (SO4-Ringer) and amphotericin, were compared in control and steroid-treated distal colon. In controls, both absorbagogues increased Isc. Impermeant anions caused a rise in Isc in both MP and DOCA tissues, suggesting that the high rate of basal Na absorption had not caused a saturation of the Na pump. The steroid-treated colons, however, did not consistently respond to amphotericin. Amiloride inhibited the entire Isc in MP-treated distal colon that had been exposed to amphotericin; this suggested that amphotericin had not exerted its characteristic effect on the apical membrane of steroid-treated colon. In proximal colon, steroids did not alter basal rates of transport; however, epinephrine-induced Na-Cl absorption was significantly greater in MP-treated vs control (P less than 0.005). Steroids increase the absorptive capacity of both proximal and distal colon for Na, while increasing basal Na absorption only in the distal colon.(ABSTRACT TRUNCATED AT 250 WORDS)

Altered frontocortical, cerebellar, and basal ganglia activity in adjuvant-treated breast cancer survivors 5-10 years after chemotherapy.

PubMed

Silverman, Daniel H S; Dy, Christine J; Castellon, Steven A; Lai, Jasmine; Pio, Betty S; Abraham, Laura; Waddell, Kari; Petersen, Laura; Phelps, Michael E; Ganz, Patricia A

2007-07-01

To explore the relationship of regional cerebral blood flow and metabolism with cognitive function and past exposure to chemotherapy for breast cancer. Subjects treated for breast cancer with adjuvant chemotherapy remotely (5-10 years previously) were studied with neuropsychologic testing and positron emission tomography (PET), and were compared with control subjects who had never received chemotherapy. [O-15] water PET scans was acquired during performance of control and memory-related tasks to evaluate cognition-related cerebral blood flow, and [F-18] fluorodeoxyglucose (FDG) PET scans were acquired to evaluate resting cerebral metabolism. PET scans were analyzed by statistical parametric mapping and region of interest methods of analysis. During performance of a short-term recall task, modulation of cerebral blood flow in specific regions of frontal cortex and cerebellum was significantly altered in chemotherapy-treated subjects. Cerebral activation in chemotherapy-treated subjects differed most significantly from untreated subjects in inferior frontal gyrus, and resting metabolism in this area correlated with performance on a short-term memory task previously found to be particularly impaired in chemotherapy-treated subjects. In examining drug-class specific effects, metabolism of the basal ganglia was significantly decreased in tamoxifen + chemotherapy-treated patients compared with chemotherapy-only breast cancer subjects or with subjects who had not received chemotherapy, while chemotherapy alone was not associated with decreased basal ganglia activity relative to untreated subjects. Specific alterations in activity of frontal cortex, cerebellum, and basal ganglia in breast cancer survivors were documented by functional neuroimaging 5-10 years after completion of chemotherapy.

Deep-Brain Stimulation for Basal Ganglia Disorders

PubMed Central

Wichmann, Thomas; DeLong, Mahlon R.

2011-01-01

The realization that medications used to treat movement disorders and psychiatric conditions of basal ganglia origin have significant shortcomings, as well as advances in the understanding of the functional organization of the brain, has led to a renaissance in functional neurosurgery, and particularly the use of deep brain stimulation (DBS). Movement disorders are now routinely being treated with DBS of ‘motor’ portions of the basal ganglia output nuclei, specifically the subthalamic nucleus and the internal pallidal segment. These procedures are highly effective and generally safe. Use of DBS is also being explored in the treatment of neuropsychiatric disorders, with targeting of the ‘limbic’ basal ganglia-thalamocortical circuitry. The results of these procedures are also encouraging, but many unanswered questions remain in this emerging field. This review summarizes the scientific rationale and practical aspects of using DBS for neurologic and neuropsychiatric disorders. PMID:21804953

Primary Cutaneous Carcinosarcoma of the Basal Cell Subtype Should Be Treated as a High-Risk Basal Cell Carcinoma.

PubMed

Bourgeault, Emilie; Alain, Jimmy; Gagné, Eric

2015-01-01

Cutaneous carcinosarcoma is a rare primary tumor of the skin, characterized by biphasic epithelial and mesenchymal differentiation. Due to the limited number of cases reported, there is no consensus regarding treatment and prognosis. Some authors suggest that cutaneous carcinosarcomas should be viewed as aggressive tumors, with ancillary imaging used to evaluate potential metastatic disease. Other reports demonstrate an indolent disease course, especially with epidermal-type cutaneous carcinosarcomas. We report a case of cutaneous carcinosarcoma, which we treated with electrodessication and curettage following a shave biopsy. The tumor had an epithelial component resembling a basal cell carcinoma and a fibrosarcomatous stroma. At 1-year follow-up, our patient did not show evidence of recurrence or metastasis. Our case suggests that a cutaneous carcinosarcoma with an epithelial component composed of basal cell carcinoma can be regarded as a high-risk nonmelanoma skin cancer. © The Author(s) 2015.

Chemoprevention of Basal and Squamous Cell Carcinoma With a Single Course of Fluorouracil, 5%, Cream: A Randomized Clinical Trial.

PubMed

Weinstock, Martin A; Thwin, Soe Soe; Siegel, Julia A; Marcolivio, Kimberly; Means, Alexander D; Leader, Nicholas F; Shaw, Fiona M; Hogan, Daniel; Eilers, David; Swetter, Susan M; Chen, Suephy C; Jacob, Sharon E; Warshaw, Erin M; Stricklin, George P; Dellavalle, Robert P; Sidhu-Malik, Navjeet; Konnikov, Nellie; Werth, Victoria P; Keri, Jonette E; Robinson-Bostom, Leslie; Ringer, Robert J; Lew, Robert A; Ferguson, Ryan; DiGiovanna, John J; Huang, Grant D

2018-02-01

Keratinocyte carcinoma (ie, cutaneous basal and squamous cell carcinoma) is the most common cancer in the United States. To determine whether topical fluorouracil could prevent surgically treated keratinocyte carcinoma. The Veterans Affairs Keratinocyte Carcinoma Chemoprevention Trial was a randomized, double-blind, placebo-controlled trial of topical fluorouracil for chemoprevention of keratinocyte carcinoma. Participants were recruited from May 2009 to September 2011 from 12 Veterans Affairs medical centers and followed until June 30, 2013. Participants were veterans (n = 932) with a history of at least 2 keratinocyte carcinomas in the past 5 years; almost all were white males and the median age was 70 years. Application of fluorouracil, 5%, (n = 468) or vehicle control cream (n = 464) to the face and ears twice daily for 2 to 4 weeks upon randomization. Surgically treated keratinocyte, basal cell, and squamous cell carcinoma risk on the face and ears in the first year after enrollment; and time to first surgically treated keratinocyte, basal cell, and squamous cell carcinoma. The a priori hypothesis was that fluorouracil would be effective in preventing these cancers. Of 932 participants (916 men [98%]; 926 white [99%]; median age, 70 years), 299 developed a basal cell carcinoma end point (95 in year 1) and 108 developed a squamous cell carcinoma end point (25 in year 1) over 4 years (median follow-up, 2.8 years). Over the entire study, there was no difference between treatment groups in time to first keratinocyte, basal cell, or squamous cell carcinoma. During the first year, however, 5 participants (1%) in the fluorouracil group developed a squamous cell carcinoma vs 20 (4%) in the control group, a 75% (95% CI, 35%-91%) risk reduction (P = .002). The 11% reduction in basal cell carcinoma risk during year 1 (45 [10%] in the fluorouracil group vs 50 [11%] in the control group) was not statistically significant (95% CI, 39% reduction to 31% increase), nor was there a significant effect on keratinocyte carcinoma risk. However, a reduction in keratinocyte carcinomas treated with Mohs surgery was observed. A conventional course of fluorouracil to the face and ears substantially reduces surgery for squamous cell carcinoma for 1 year without significantly affecting the corresponding risk for basal cell carcinoma. clinicaltrials.gov Identifier: NCT00847912.

Vismodegib hedgehog-signaling inhibition and treatment of basal cell carcinomas as well as keratocystic odontogenic tumors in Gorlin syndrome.

PubMed

Booms, Patrick; Harth, Marc; Sader, Robert; Ghanaati, Shahram

2015-01-01

Vismodegib hedgehog signaling inhibition treatment has potential for reducing the burden of multiple skin basal cell carcinomas and jaw keratocystic odontogenic tumors. They are major criteria for the diagnosis of Gorlin syndrome, also called nevoid basal cell carcinoma syndrome. Clinical features of Gorlin syndrome are reported, and the relevance of hedgehog signaling pathway inhibition by oral vismodegib for maxillofacial surgeons is highlighted. In summary, progressed basal cell carcinoma lesions are virtually inoperable. Keratocystic odontogenic tumors have an aggressive behavior including rapid growth and extension into adjacent tissues. Interestingly, nearly complete regression of multiple Gorlin syndrome-associated keratocystic odontogenic tumors following treatment with vismodegib. Due to radio-hypersensitivity in Gorlin syndrome, avoidance of treatment by radiotherapy is strongly recommended for all affected individuals. Vismodegib can help in those instances where radiation is contra-indicated, or the lesions are inoperable. The effect of vismodegib on basal cell carcinomas was associated with a significant decrease in hedgehog-signaling and tumor proliferation. Vismodegib, a new and approved drug for the treatment of advanced basal cell carcinoma, is a specific oncogene inhibitor. It also seems to be effective for treatment of keratocystic odontogenic tumors and basal cell carcinomas in Gorlin syndrome, rendering the surgical resections less challenging.

Gorlin-goltz syndrome: a rare case.

PubMed

Ganguly, Satyaki; Jaykar, Kranti C; Kumar, Rajesh; Jha, Abhijeet Kumar; Banerjee, P K

2015-01-01

Gorlin-Goltz syndrome or nevoid basal cell carcinoma syndrome is characterized by multiple basocellular epitheliomas, keratocysts in the jaws, bifid ribs, palmar and/or plantar pits and ectopic calcifications of the falx cerebri. We describe a case of Gorlin-Goltz syndrome illustrating the importance of a thorough examination including the examination of palms and soles and detailed investigations in a patient having lesions suggestive of basal cell carcinoma and multiple naevi.

Gorlin-Goltz Syndrome: A Rare Case

PubMed Central

Ganguly, Satyaki; Jaykar, Kranti C; Kumar, Rajesh; Jha, Abhijeet Kumar; Banerjee, PK

2015-01-01

Gorlin-Goltz syndrome or nevoid basal cell carcinoma syndrome is characterized by multiple basocellular epitheliomas, keratocysts in the jaws, bifid ribs, palmar and/or plantar pits and ectopic calcifications of the falx cerebri. We describe a case of Gorlin-Goltz syndrome illustrating the importance of a thorough examination including the examination of palms and soles and detailed investigations in a patient having lesions suggestive of basal cell carcinoma and multiple naevi. PMID:25814758

Institution of basal-bolus therapy at diagnosis for children with type 1 diabetes mellitus.

PubMed

Adhikari, Soumya; Adams-Huet, Beverley; Wang, Yu-Chi A; Marks, James F; White, Perrin C

2009-04-01

We studied whether the institution of basal-bolus therapy immediately after diagnosis improved glycemic control in the first year after diagnosis for children with newly diagnosed type 1 diabetes mellitus. We reviewed the charts of 459 children > or =6 years of age who were diagnosed as having type 1 diabetes between July 1, 2002, and June 30, 2006 (212 treated with basal-bolus therapy and 247 treated with a more-conventional neutral protamine Hagedorn regimen). We abstracted data obtained at diagnosis and at quarterly clinic visits and compared groups by using repeated-measures, mixed-linear model analysis. We also reviewed the records of 198 children with preexisting type 1 diabetes mellitus of >1-year duration who changed from the neutral protamine Hagedorn regimen to a basal-bolus regimen during the review period. Glargine-treated subjects with newly diagnosed diabetes had lower hemoglobin A1c levels at 3, 6, 9, and 12 months after diagnosis than did neutral protamine Hagedorn-treated subjects (average hemoglobin A1c levels of 7.05% with glargine and 7.63% with neutral protamine Hagedorn, estimated across months 3, 6, 9, and 12, according to repeated-measures models adjusted for age at diagnosis and baseline hemoglobin A1c levels; treatment difference: 0.58%). Children with long-standing diabetes had no clinically important changes in their hemoglobin A1c levels in the first year after changing regimens. The institution of basal-bolus therapy with insulin glargine at the time of diagnosis of type 1 diabetes was associated with improved glycemic control, in comparison with more-conventional neutral protamine Hagedorn regimens, during the first year after diagnosis.

Management of Mucosal Basal Cell Carcinoma of the Lip: An Update and Comprehensive Review of the Literature.

PubMed

Loh, Tiffany; Rubin, Ashley G; Brian Jiang, Shang I

2016-12-01

Basal cell carcinoma (BCC) is the most common malignancy in the United States. Most BCCs occur on cutaneous surfaces, but rare cases on the mucosal lip have also been documented. Because only a small number of mucosal BCC (mBCC) cases have been reported, data on their clinical characteristics and management are limited. To perform an updated literature review of the management of mBCCs on the lip. A comprehensive literature review was conducted through a search of the PubMed database with the key phrases "mucosal basal cell carcinoma," "basal cell carcinoma mucosa," and "basal cell carcinoma lip mucosa." Forty-eight cases of mBCCs have been reported, and 35 had sufficient data for analysis. The average age at presentation was 66.8 years, and 57% (n = 20) had a history of skin cancer. Most cases were treated with surgical excision or Mohs micrographic surgery (MMS), with only 1 recurrence in the literature. Furthermore, the authors present 8 additional cases of mBCCs successfully treated with MMS. Mucosal basal cell carcinomas are rare, and skin cancer history may be a risk factor. Because the lip is a cosmetically and functionally important area, MMS may be the preferred treatment method for mBCCs in this location.

Basal Cell Carcinoma of the Dorsal Foot: An Update and Comprehensive Review of the Literature.

PubMed

Loh, Tiffany Y; Rubin, Ashley G; Jiang, Shang I Brian

2017-01-01

Ultraviolet radiation is a well-known risk factor for basal cell carcinoma (BCC). Therefore, the high incidence of BCCs in sun-exposed areas such as the head and neck is unsurprising. However, unexpectedly, BCCs on the sun-protected dorsal foot have also been reported, and tumor occurrence here suggests that other factors besides ultraviolet radiation may play a role in BCC pathogenesis. Because only few dorsal foot BCCs have been reported, data on their clinical features and management are limited. To perform an updated review of the literature on clinical characteristics and treatment of dorsal foot BCCs. We conducted a comprehensive literature review by searching the PubMed database with the key phrases "basal cell carcinoma dorsal foot," "basal cell carcinoma foot," and "basal cell carcinoma toe." We identified 20 cases of dorsal foot BCCs in the literature, 17 of which had sufficient data for analysis. Only 1 case was treated with Mohs micrographic surgery. We present 8 additional cases of dorsal foot BCCs treated with Mohs micrographic surgery. Basal cell carcinomas on the dorsal foot are rare, and potential risk factors include Caucasian descent and personal history of skin cancer. Mohs micrographic surgery seems to be an effective treatment option.

Intensification of insulin therapy in patients with type 2 diabetes mellitus: An algorithm for basal-bolus therapy

PubMed Central

2012-01-01

The incidence of diabetes mellitus is projected to continue to increase worldwide over the next 20 years leading to increased costs in the management of the disease and its associated co-morbidities. Insulin replacement is one of many treatment options that can help to bring about near normoglycemia in the patient with type 2 diabetes mellitus (T2DM). Glycemic control as close to normoglycemia as possible can help to reduce the risk of microvascular and macrovascular complications, yet less than one-half of patients with T2DM achieve glycemic targets as recommended by practice guidelines. The purpose of this review is to provide guidance to primary care physicians for the initiation and intensification of basal-bolus insulin therapy in patients with T2DM. Two treatment algorithms that can be both patient- and physician-driven are proposed: a stepwise approach and a multiple daily injections approach. Evidence shaping the two approaches will be discussed alongside management issues that surround the patient treated with insulin: hypoglycemia, weight gain, patient education, and quality of life. PMID:22822902

Pathogenesis of human papillomavirus-associated mucosal disease.

PubMed

Groves, Ian J; Coleman, Nicholas

2015-03-01

Human papillomaviruses (HPVs) are a necessary cause of carcinoma of the cervix and other mucosal epithelia. Key events in high-risk HPV (HRHPV)-associated neoplastic progression include persistent infection, deregulated expression of virus early genes in basal epithelial cells and genomic instability causing secondary host genomic imbalances. There are multiple mechanisms by which deregulated virus early gene expression may be achieved. Integration of virus DNA into host chromosomes is observed in the majority of cervical squamous cell carcinomas (SCCs), although in ∼15% of cases the virus remains extrachromosomal (episomal). Interestingly, not all integration events provide a growth advantage to basal cervical epithelial cells or lead to increased levels of the virus oncogenes E6 and E7, when compared with episome-containing basal cells. The factors that provide a competitive advantage to some integrants, but not others, are complex and include virus and host contributions. Gene expression from integrated and episomal HRHPV is regulated through host epigenetic mechanisms affecting the virus long control region (LCR), which appear to be of functional importance. New approaches to treating HRHPV-associated mucosal neoplasia include knockout of integrated HRHPV DNA, depletion of virus transcripts and inhibition of virus early gene transcription through targeting or use of epigenetic modifiers. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Basal thumb arthritis

PubMed Central

Dias, Richard; Chandrasenan, Jeevan; Rajaratnam, Vaikunthan; Burke, Frank D

2007-01-01

Basal thumb arthritis is a common condition seen in hand clinics across the United Kingdom and is often associated with other pathological conditions such as carpal tunnel syndrome and scaphotrapezial arthritis. Typically, patients complain of pain localised to the base of the thumb. This pain is often activity related, particularly after excessive use involving forceful pinch. A detailed history and examination is normally all that is needed to make the diagnosis. Provocative manoeuvres may be helpful in localising symptoms to the basal joint with degenerative changes or synovitis. Radiographs are useful for confirming the diagnosis and staging the disease in order to plan for surgery. The mainstay of initial treatment of basal thumb arthritis of any stage is activity modifications, rest, nonsteroidal anti‐inflammatory drugs, exercises and splinting. A variety of surgical procedures are available to treat the condition when conservative measures have failed, in order to control symptoms and improve function. We review the current literature and discuss the clinical aspects of this condition, staging, and treatment options available, and the difficulties treating this group of patients. PMID:17267677

Transdifferentiation between Luminal- and Basal-Type Cancer Cells

DTIC Science & Technology

2013-04-01

cancer patients have few choices of therapeutic agents. The MB231 cell line is a basal type cell line and is resistant to EGFR inhibitor erlotinib...mitotic inhibitor paclitaxel and DNA damaging agent cisplatin. However, over- expression of PKD1 makes the cell line sensitive to erlotinib and...approach will help to understand how PKD1 acts in basal-type cancer cells; (3) using existing small molecule inhibitors for PKD1 to treat breast cancer

Effects of chronic lithium administration on renal acid excretion in humans and rats

PubMed Central

Weiner, I. David; Leader, John P.; Bedford, Jennifer J.; Verlander, Jill W.; Ellis, Gaye; Kalita, Priyakshi; Vos, Frederiek; de Jong, Sylvia; Walker, Robert J.

2014-01-01

Abstract Lithium therapy's most common side effects affecting the kidney are nephrogenic diabetes insipidus (NDI) and chronic kidney disease. Lithium may also induce a distal renal tubular acidosis. This study investigated the effect of chronic lithium exposure on renal acid–base homeostasis, with emphasis on ammonia and citrate excretion. We compared 11 individuals on long‐term lithium therapy with six healthy individuals. Under basal conditions, lithium‐treated individuals excreted significantly more urinary ammonia than did control subjects. Following an acute acid load, urinary ammonia excretion increased approximately twofold above basal rates in both lithium‐treated and control humans. There were no significant differences between lithium‐treated and control subjects in urinary pH or urinary citrate excretion. To elucidate possible mechanisms, rats were randomized to diets containing lithium or regular diet for 6 months. Similar to humans, basal ammonia excretion was significantly higher in lithium‐treated rats; in addition, urinary citrate excretion was also significantly greater. There were no differences in urinary pH. Expression of the critical ammonia transporter, Rhesus C Glycoprotein (Rhcg), was substantially greater in lithium‐treated rats than in control rats. We conclude that chronic lithium exposure increases renal ammonia excretion through mechanisms independent of urinary pH and likely to involve increased collecting duct ammonia secretion via the ammonia transporter, Rhcg. PMID:25501430

Multiple odontogenic keratocysts associated with Gorlin-Goltz syndrome.

PubMed

Dixit, S; Acharya, S; Dixit, P B

2009-01-01

Gorlin-Goltz syndrome or Nevoid basal cell carcinoma syndrome is an autosomal dominant disorder with a predisposition to cancer. Features like basal cell carcinoma, odontogenic keratocysts, calcification of falx cerebri, bifid ribs, pits on palms and soles and hypertelorism are evident. A case of this rare disease seen on a 13 year old female patient is presented here, where multiple odontogenic keratocysts were causing disfigurement of the lower jaw as well as displacement and malocclusion of the lower teeth.

High-frequency stimulation of the subthalamic nucleus restores neural and behavioral functions during reaction time task in a rat model of Parkinson's disease.

PubMed

Li, Xiang-Hong; Wang, Jin-Yan; Gao, Ge; Chang, Jing-Yu; Woodward, Donald J; Luo, Fei

2010-05-15

Deep brain stimulation (DBS) has been used in the clinic to treat Parkinson's disease (PD) and other neuropsychiatric disorders. Our previous work has shown that DBS in the subthalamic nucleus (STN) can improve major motor deficits, and induce a variety of neural responses in rats with unilateral dopamine (DA) lesions. In the present study, we examined the effect of STN DBS on reaction time (RT) performance and parallel changes in neural activity in the cortico-basal ganglia regions of partially bilateral DA- lesioned rats. We recorded neural activity with a multiple-channel single-unit electrode system in the primary motor cortex (MI), the STN, and the substantia nigra pars reticulata (SNr) during RT test. RT performance was severely impaired following bilateral injection of 6-OHDA into the dorsolateral part of the striatum. In parallel with such behavioral impairments, the number of responsive neurons to different behavioral events was remarkably decreased after DA lesion. Bilateral STN DBS improved RT performance in 6-OHDA lesioned rats, and restored operational behavior-related neural responses in cortico-basal ganglia regions. These behavioral and electrophysiological effects of DBS lasted nearly an hour after DBS termination. These results demonstrate that a partial DA lesion-induced impairment of RT performance is associated with changes in neural activity in the cortico-basal ganglia circuit. Furthermore, STN DBS can reverse changes in behavior and neural activity caused by partial DA depletion. The observed long-lasting beneficial effect of STN DBS suggests the involvement of the mechanism of neural plasticity in modulating cortico-basal ganglia circuits. (c) 2009 Wiley-Liss, Inc.

Gorlin-Goltz syndrome: A series of three cases.

PubMed

Patankar, Amod P; Kshirsagar, Rajesh A; Dugal, Arun; Mishra, Akshay; Ram, Hari

2014-01-01

The Gorlin-Goltz syndrome (GGS) is also known as nevoid basal cell carcinoma syndrome. It is characterized by multiple keratocystic odontogenic tumors (KCOTs) in the jaw, multiple basal cell nevi carcinomas and skeletal abnormities. The syndrome may be diagnosed early by a dentist during the routine radiographic exams in the first decade of life, since the KCOTs are usually one of the first manifestations of the syndrome. This article reports the series of 3 cases, emphasizing its clinical and radiographic manifestations of GGS.

Gorlin-Goltz syndrome: A series of three cases

PubMed Central

Patankar, Amod P.; Kshirsagar, Rajesh A.; Dugal, Arun; Mishra, Akshay; Ram, Hari

2014-01-01

The Gorlin-Goltz syndrome (GGS) is also known as nevoid basal cell carcinoma syndrome. It is characterized by multiple keratocystic odontogenic tumors (KCOTs) in the jaw, multiple basal cell nevi carcinomas and skeletal abnormities. The syndrome may be diagnosed early by a dentist during the routine radiographic exams in the first decade of life, since the KCOTs are usually one of the first manifestations of the syndrome. This article reports the series of 3 cases, emphasizing its clinical and radiographic manifestations of GGS. PMID:25937738

Basal cell carcinoma arising in association with a maxillary keratocyst in a patient with Gorlin-Goltz syndrome. Report of a case.

PubMed

Lazaridou, Maria Nikolaou; Dimitrakopoulos, Ioannis; Tilaveridis, Ioannis; Iliopoulos, Christos; Heva, Antigoni

2012-03-01

Gorlin-Goltz syndrome, also known as nevoid basal cell carcinoma syndrome, is an autosomal dominant inherited disorder which is characterized by the presence of multiple basal cell carcinomas, maxillary keratocysts, and musculoskeletal anomalies. We present a case of a patient suffering from Gorlin-Goltz syndrome who developed an intraosseous basal cell carcinoma associated with a recurrent maxillary keratocyst. To our knowledge, this is the first case of malignant transformation of a keratocyst into a basal cell carcinoma described in the literature. This case highlights the importance of careful histologic examination of keratocysts excised in patients suffering from Gorlin-Goltz syndrome.

[Basal cell carcinoma among the cases of Dermatology Clinic I of the Silesian Medical Academy in Katowice].

PubMed

Bogdanowski, T; Rubisz-Brzezińska, J; Sleczka, A

1988-01-01

The authors present their own experiences in the treatment of 24 patients with the nevoid basal-cell carcinoma syndrome. All the patients underwent surgical treatment, in 12 of them some of the tumours were treated with X-rays. Two patients were found to have 32 and 26 nevoid basal-cell carcinoma respectively. In none of the 24 patients recurrence was noted. However in many of them the new foci of carcinoma required systemic treatment.

Basal cell carcinomas in elderly patients treated by cryotherapy

PubMed Central

Chiriac, Anca; Mihaila, Doina; Foia, Liliana; Solovan, Caius

2013-01-01

Basal cell carcinoma is a malignant skin tumor with high incidence in our country, especially in rural areas, on sun-exposed skin (particularly on the face) in elderly patients. We present three cases of basal cell carcinoma with good results with cryotherapy. This report aims to outline and to prove that in some difficult situations, a simple, inexpensive, easy-to-perform procedure with no contraindications and with minimal side effects (erythema, mild pain) can be applied and resolve such cases. PMID:23569366

Testosterone-induced increase of insulin-like growth factor I levels depends upon normal levels of growth hormone.

PubMed

Saggese, G; Cesaretti, G; Franchi, G; Startari, L

1996-08-01

Pubertal development is associated with a rise in plasma insulin-like growth factor I (IGF-I) levels that is related both to the increase in sex steroids and/or to the sex steroid-induced augmentation in endogenous growth hormone (GH) secretion. In order to investigate the relationship between IGF-I, GH and testosterone, we examined 42 male subjects with various clinical conditions (classical GH deficiency (CGHD, N = 5), non-classical GH deficiency (NCGHD, N = 7), short idiopathic stature (N = 6), nutritional obesity (N = 8), GH-treated CGHD (N = 4), GH-treated NCGHD (N = 5) and normal stature (N = 7)) in which , for evaluation of hypogonadism (i.e. the absence of one or both testes from the scrotal sac), human chorionic gonadotropin (hCG) tests were performed. We measured IGF-I, total and free testosterone and dehydroepiandrosterone sulfate (DHEAS) by radioimmunoassays before and 48 and 96 h after the start of the test. The values of IGF-I were lower (0.001 < p < 0.005) in CGHD and NCGHD than in the other groups. In comparison to basal levels, IGF-I values increased (0.005 < p < 0.05) both 48 and 96 h after the start of the hCG test in short idiopathic and normal stature children and in GH-treated subjects with NCGHD, but only 96 h in subjects with untreated NCGHD and GH-treated CGHD. No difference was demonstrated in basal values of total testosterone among any of the groups, while basal free testosterone levels were higher (0.001 < p < 0.05) in GH-treated subjects with NCGHD than in all the other groups except nutritional obesity; furthermore, free testosterone was higher (p < 0.05) in nutritional obesity than in CGHD. The values of total and free testosterone obtained both 48 and 96 h after the start of the hCG test were higher (0.001 < p < 0.05) than basal values in all groups. The DHEAS values did not show any significant change during the hCG test. Basal values were higher (0.01 < p < 0.05) in nutritional obesity than in the other groups. Considering all groups, chronological age, bone age and bone age/chronological age ratio were correlated with basal free testosterone, IGF-I and DHEAS levels (0.001 < p < 0.05), while basal free testosterone and IGF-I values were correlated with DHEAS levels (p < 0.005 and < 0.01, respectively). In conclusion, our study during the hCG test in boys with various clinical conditions demonstrated an increase in IGF-I concentrations only in those boys with sufficient GH secretion or GH replacement therapy. These findings indicate that both sex steroids and GH are necessary to allow for the pubertal increase in IGF-I levels.

Enhanced systemic immune reactivity to a Basal cell carcinoma associated antigen following photodynamic therapy.

PubMed

Kabingu, Edith; Oseroff, Allan R; Wilding, Gregory E; Gollnick, Sandra O

2009-07-01

Numerous preclinical studies have shown that local photodynamic therapy (PDT) of tumors enhances systemic antitumor immunity. However, other than single-case and anecdotal reports, this phenomenon has not been examined following clinical PDT. To determine whether PDT in a clinical setting enhances systemic recognition of tumor cells, we examined whether PDT of basal cell carcinoma resulted in an increased systemic immune response to Hip1, a tumor antigen associated with basal cell carcinoma. Basal cell carcinoma lesions were either treated with PDT or surgically removed. Blood was collected from patients immediately before or 7 to 10 days following treatment. Peripheral blood leukocytes were isolated from HLA-A2-expressing patients and reactivity to a HLA-A2-restricted Hip1 peptide was measured by INF-gamma ELISpot assay. Immune recognition of Hip1 increased in patients whose basal cell carcinoma lesions were treated with PDT. This increase in reactivity was significantly greater than reactivity observed in patients whose lesions were surgically removed. Patients with superficial lesions exhibited greater enhancement of reactivity compared with patients with nodular lesions. Immune reactivity following PDT was inversely correlated with treatment area and light dose. These findings show for the first time that local tumor PDT can enhance systemic immune responses to tumors in patients, and validate previous preclinical findings.

Lesion of the Centromedian Thalamic Nucleus in MPTP-Treated Monkeys

PubMed Central

Lanciego, Jose L.; Rodríguez-Oroz, Maria C.; Blesa, Francisco J.; Alvarez-Erviti, Lydia; Guridi, Jorge; Barroso-Chinea, Pedro; Smith, Yoland; Obeso, Jose A.

2015-01-01

The caudal intralaminar nuclei are a major source of glutamatergic afferents to the basal ganglia. Experiments in the 6-hydroxydopamine rat model have shown that the parafascicular nucleus is overactive and its lesion alleviates basal ganglia neurochemical abnormalities associated with dopamine depletion. Accordingly, removal of this excitatory innervation of the basal ganglia could have a beneficial value in the parkinsonian state. To test this hypothesis, unilateral kainate-induced chemical ablation of the centromedian thalamic nucleus (CM) has been performed in MPTP-treated monkeys. Successful lesions restricted to the CM boundaries (n = 2) without spreading over other neighboring thalamic nuclei showed an initial, short-lasting, and mild change in the parkinsonian motor scale but no effect against levodopa-induced dyskinesias. The lack of significant and persistent motor improvement leads us to conclude that unilateral selective lesion of the CM alone cannot be considered as a suitable surgical approach for the treatment of PD or levo-dopa-induced dyskinesias. The role of the caudal intralaminar nuclei in the pathophysiology of movement disorders of basal ganglia origin remains to be clarified. PMID:18175345

Reliability of basal plasma vasopressin concentrations in healthy male adults.

PubMed

Quintana, Daniel S; Westlye, Lars T; Smerud, Knut T; Mahmoud, Ramy A; Djupesland, Per G; Andreassen, Ole A

2017-10-01

The neuropeptides oxytocin (OT) and arginine vasopressin (AVP) play important and interrelated roles in modulating mammalian social behaviour. While the OT system has received considerable research attention for its potential to treat psychiatric symptoms, comparatively little is known about the role of the AVP system in human social behaviour. To better understand the intraindividual stability of basal AVP, the present study assessed the reproducibility of basal plasma AVP concentrations. Basal plasma AVP was assessed at four sampling points separated by 8 days, on average, in 16 healthy adult males. Only one out of six comparisons revealed strong evidence for reproducibility of basal AVP concentrations (visit 2 vs. visit 4: r=0.8, p0.1). The concordance correlation coefficient [0.15, 95% CI (-0.55, 0.73)] also revealed poor overall reproducibility. Poor reliability of basal AVP concentrations suggests future work covarying AVP with trait markers should proceed with careful consideration of intraindividual fluctuations.

Metastatic spinal cord compression from basal cell carcinoma of the skin treated with surgical decompression and vismodegib: case report and review of Hedgehog signalling pathway inhibition in advanced basal cell carcinoma.

PubMed

McGrane, J; Carswell, S; Talbot, T

2017-01-01

We report a case of a 66-year-old man with locally advanced and metastatic basal cell carcinoma (BCC) causing spinal cord compression, which was treated with spinal surgery and subsequent vismodegib. The patient presented with a large fungating chest wall lesion and a metastasis in T8 that was causing cord compression. He had neurosurgical decompression of the T8 lesion and fixation of the spine. Punch biopsy from the fungating chest wall lesion showed a BCC with some malignant squamous differentiation (basosquamous). Histopathological examination of the metastatic lesion in T8 at the time of surgical decompression identified features identical to the punch biopsy. The patient was referred to the oncology clinic for adjuvant treatment. In light of his metastatic disease and the large area over his chest wall that could not fully be covered by radiotherapy, he was treated with the novel oral Hedgehog signalling pathway (HHSP) inhibitor vismodegib, which led to marked improvement. © 2016 British Association of Dermatologists.

The efficacy of facial skin cancer treatment with high-energy pulsed neodymium and Nd:YAG lasers.

PubMed

Moskalik, Konstantin; Kozlov, Alexander; Demin, Eugeny; Boiko, Ernest

2009-04-01

The aim of this study was to assess the curative and cosmetic efficacy of treatment for facial skin cancer using neodymium laser irradiation. Due to the complex anatomy of the area, therapy for facial skin cancer is difficult. Laser irradiation was used for the treatment of 3461 patients with 3624 facial skin cancer lesions of stages T(1-2)N(0)M(0:) 3346 basal cell skin cancers, 188 limited basal cell skin cancer recurrences, and 90 squamous cell skin cancers. Pulsed neodymium (Nd) and Nd:YAG lasers were used as the energy sources. The patients were followed-up from 3 mo to 5 y or more. Patients with basal cell skin cancer treated by irradiation with the Nd laser developed recurrences in 1.8% of cases, and patients treated with the Nd:YAG laser had a recurrence rate of 2.5%. Recurrences following treatment for basal cell skin cancer, and those of squamous cell skin cancer, after irradiation with the Nd laser appeared in 3.7% and 4.4% of patients, respectively. Overall, the frequency of facial skin cancer recurrences after treatment with laser irradiation was 2.1% of all the irradiated tumors. Neodymium laser irradiation is an effective method to treat facial skin cancer of stages T(1-2)N(0)M(0), and results in acceptable cosmetic results.

[Gorlin-Goltz syndrome: review of the neuroradiological and maxillofacial features illustrated with two clinical cases].

PubMed

Safronova, Marta Maia; Arantes, Mavilde; Lima, Iva; Domingues, Sara; Almeida, Marta; Moniz, Pedro

2010-01-01

Gorlin-Goltz syndrome or nevoid basal cell carcinoma syndrome is a rare hereditary autosomal-dominant disorder characterized by multiple basal cell carcinomas in young patients, odontogenic keratocysts, palmar or plantar pits, calcification of the falx cerebri and skeletal malformations. This syndrome is due to mutations in PTCH1 (patched homolog 1 da Drosophila), a tumor suppressor gene. Diagnostic criteria were defined by Evans, revised by Kimonis and include major and minor criteria. The authors review in particular the neuroradiological and maxillofacial characteristics of the syndrome. The authors describe the clinical presentation of two children with Gorlin-Goltz syndrome without affected first degree relatives. In both the clinical suspicion of the syndrome is raised by the presence of multiple odontogenic cysts surgically removed. Histopathological exam revealed keratocysts. None of the patients has basal cell carcinomas but both present with skeletal anomalies, namely marked pectus deformity. The absence of major diagnostic criteria like basal cell carcinomas or palmar or plantar pits in young patients delay the early diagnosis and the correct screening for medulloblastoma, basal cell carcinomas and cardiac fibromas. Odontogenic keratocysts are the most consistent clinical finding in Gorlin-Goltz syndrome in the first one or two decades of life. These patients are very sensitive to ionizing radiation, being able to develop basal cell carcinomas and meningiomas. Treatment should accomplish the complete resection of the tumors.

[Total brain T2-hyperintense lesion-volume and the axonal damage in the normal-appearing white matter of brainstem in early lapsing-remitting multiple sclerosis].

PubMed

Pascual-Lozano, A M; Martínez-Bisbal, M C; Boscá-Blasco, I; Valero-Merino, C; Coret-Ferrer, F; Martí-Bonmatí, L; Martínez-Granados, B; Celda, B; Casanova-Estruch, B

To evaluate the relationship between the total brain T2-hyperintense lesion volume (TBT2LV) and the axonal damage in the normal-appearing white matter of brainstem measured by 1H-MRS in a group of early relapsing-remitting multiple sclerosis patients. 40 relapsing-remitting multiple sclerosis patients and ten sex- and age-matched healthy subjects were prospectively studied for two years. T2-weighted MR and 1H-MRS imaging were acquired at time of recruitment and at year two. The TBT2LV was calculated with a semiautomatic program; N-acetylaspartate (NAA), creatine (Cr) and choline (Cho) resonances areas were integrated with jMRUI program and the ratios were calculated for four volume elements that represented the brainstem. At basal study we obtained an axonal loss (as a decrement of NAA/ Cho ratio) in the group of patients compared with controls (p = 0.017); this axonal loss increased at the second year of the follow-up for patients (NAA/Cho decrease, p = 0.004, and NAA/Cr decrease, p = 0.002) meanwhile control subjects had no significant metabolic changes. Higher lesion load was correlated with a poor clinical outcome, being the correlation between the basal TBT2LV and the Expanded Disability Status Scale at second year (r = 0.299; p = 0.05). Besides, axonal loss was not homogeneous for all multiple sclerosis patients, being stronger in the subgroup of patients with high basal TBT2LV (p = 0.043; ANOVA). Our data suggest that axonal damage is early in multiple sclerosis and higher in patients high basal TBT2LV, suggesting a possible relationship between these two phenomena.

Comparative study between cold air analgesia and supraorbital and supratrochlear nerve block for the management of pain during photodynamic therapy for actinic keratoses of the frontotemporal zone.

PubMed

Serra-Guillen, C; Hueso, L; Nagore, E; Vila, M; Llombart, B; Requena Caballero, C; Botella-Estrada, R; Sanmartin, O; Alfaro-Rubio, A; Guillen, C

2009-08-01

Photodynamic therapy (PDT) is an effective treatment for actinic keratoses, Bowen's disease and basal cell carcinoma. The main drawback of PDT is pain during application. To compare the efficacy of supratrochlear and supraorbital nerve block with cold air analgesia to control the pain experienced during PDT. A controlled open clinical trial was conducted in 34 patients having multiple actinic keratoses in the frontal region treated with PDT. On one side of the frontal region the supratrochlear and supraorbital nerves were blocked, while on the other side cold air was used as the method of analgesia. Pain was recorded on a visual analogue scale after treatment. Thirty-one of 34 patients reported less pain in the zone treated with nerve block. This difference was statistically significant. Nerve block is superior to cold air and is an easy, safe, effective means of controlling the pain associated with PDT.

Treatment of Bowen Disease With Photodynamic Therapy and the Advantages of Sequential Topical Imiquimod.

PubMed

Victoria-Martínez, A M; Martínez-Leborans, L; Ortiz-Salvador, J M; Pérez-Ferriols, A

2017-03-01

Photodynamic therapy (PDT) has been shown to be useful and effective in the treatment of actinic keratosis, Bowen disease, and basal cell carcinoma. We present a series of 13 Bowen disease lesions treated using PDT. Complete responses were achieved in 11 (84%) of the lesions after 3 months of treatment; at 18 months, complete responses were seen in 9 (70%) of the lesions. Patients who presented a partial response or recurrence were treated with topical 5% imiquimod and achieved complete responses. The lesions that presented partial response or recurrence were the largest lesions, between 3 and 5cm in diameter. PDT in monotherapy or combined sequentially with imiquimod is an excellent and well-tolerated therapeutic option for Bowen disease. The treatment has few adverse effects and shows satisfactory results, particularly in multiple large lesions in areas of difficult surgical reconstruction or in elderly patients with a high surgical risk. Copyright © 2016 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

Basal cortisol's relation to testosterone changes may not be driven by social challenges.

PubMed

Welker, Keith M; Prasad, Smrithi; Srivastava, Sanjay; Mehta, Pranjal H

2017-11-01

Multiple studies show a negative correlation between basal cortisol and testosterone changes in the presence of competition and social-evaluative stressors. These negative associations are proposed to be derived from psychological responses to competition and social-evaluative stress. However, we argue that the association between basal cortisol and testosterone change may instead be a statistical consequence of positively associated variables. In this paper, we present a mathematical rationale for this alternative explanation and examples from two studies that are consistent with this alternative explanation. Both studies show that the associations between basal cortisol and testosterone change have covariance patterns consistent with this alternative possibility. We conclude that the often-found positive association between basal cortisol and basal testosterone opens the door for alternative explanations of the basal cortisol-testosterone change association rooted in the patterns of associations between hormones measured over time. We also suggest future research directions and methods for testing alternative explanations. Copyright © 2017 Elsevier Ltd. All rights reserved.

Evidence for constitutional mutations in patients with multiple BCCs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bonifas, J.M.; Leyden, W.A.; Epstein, E.H. Jr.

Basal cell nevus syndrome (BCNS) is an autosomal dominant disease, one of whose prominent phenotypic features is a large number of cutaneous basal cell carcinomas. The gene whose mutation underlies this disease has been mapped to chromosome 9q22.3-q31, and basal cell carcinomas frequently have allelic losses at this area. We have reported recently that the chromosome 9q22.3-q31 alleles lost in 57% (24/42) of basal cell carcinomas from BCNS patients were those alleles predicted by linkage to contain the wild type gene, as is expected for a tumor suppressor gene. We have extended this work to patients with multiple basal cellmore » carcinomas with no other phenotypic manifestations of BCNS. We found in two individuals that 88% (30 out of 34) had loss of heterozygosity (LOH) in this region. Surprisingly, in both patients the allele lost in tumors was not random; it was the same in 29/30 tumors (19 form one patient and 10 from the other). This suggests that constitutional mutations in the BCNS gene region may underlie skin carcinomas in patients without BCNS. The mutations may have been somatic, because neither of one patient`s two adult sons have BCCs even though they have inherited different copies of his 9q.« less

Differential expression of c-fos following administration of two tremorgenic agents: harmaline and oxotremorine.

PubMed

Miwa, H; Nishi, K; Fuwa, T; Mizuno, Y

2000-08-03

The regional distribution of c-Fos expression in the brain after the administration of two tremorgenic agents was studied. In both the harmaline- and oxotremorin-treated rats, c-Fos-positive neurons were extensively distributed in the basal ganglia nuclei and the cerebellum. Additionally, in the harmaline-treated rats, numerous c-Fos-positive neurons were also distributed throughout the inferior olivary nucleus. In the oxotremorine-treated rats, while the inferior olive was not involved, c-Fos was strongly expressed in the neurons of the reticular thalamic nucleus, possibly due to the muscarinic effects of oxotremorine. The present study revealed that the inferior olive is selectively activated in the harmaline-administered animals and that the basal ganglia are involved in both harmaline- and oxotremorine-induced tremors.

Squamous cell and basal cell carcinoma of the skin in relation to radiation therapy and potential modification of risk by sun exposure.

PubMed

Karagas, Margaret R; Nelson, Heather H; Zens, Michael S; Linet, Martha; Stukel, Therese A; Spencer, Steve; Applebaum, Katie M; Mott, Leila; Mabuchi, Kiyohiko

2007-11-01

Epidemiologic studies consistently find enhanced risk of basal cell carcinoma of the skin among individuals exposed to ionizing radiation, but it is unclear whether the radiation effect occurs for squamous cell carcinoma. It is also not known whether subgroups of individuals are at greater risk, eg, those with radiation sensitivity or high ultraviolet radiation exposure. We analyzed data from a case-control study of keratinocyte cancers in New Hampshire. Incident cases diagnosed in 1993-1995 and 1997-2000 were identified through a state-wide skin cancer surveillance system, and controls were identified through the Department of Transportation and Center for Medicare and Medicaid Service Files (n = 1121 basal cell carcinoma cases, 854 squamous cell carcinoma cases, and 1049 controls). We found an association between history of radiation treatment and basal cell carcinoma. The association was especially strong for basal cell carcinomas arising within the radiation treatment field (odds ratio = 2.6; 95% confidence interval = 1.5-4.3), and among those treated with radiation therapy before age 20 (3.4; 1.8-6.4), those whose basal cell carcinomas occurred 40 or more years after radiation treatment (3.2; 1.8-5.8), and those treated with radiation for acne (11; 2.7-49). Similar age and time patterns of risk were observed for squamous cell carcinoma, although generally with smaller odds ratios. For basal cell carcinoma, early exposure to radiation treatment was a risk factor largely among those without a history of severe sunburns, whereas for squamous cell carcinoma, radiation treatment was a risk factor primarily among those with a sun-sensitive skin type (ie, a tendency to sunburn). Radiation treatment, particularly if experienced before age 20, seems to increase the long-term risk of both basal and squamous cell carcinomas of the skin. These risks may differ by sun exposure or host response to sunlight exposure.

Social context differentially modulates activity of two interneuron populations in an avian basal ganglia nucleus

PubMed Central

2016-01-01

Basal ganglia circuits are critical for the modulation of motor performance across behavioral states. In zebra finches, a cortical-basal ganglia circuit dedicated to singing is necessary for males to adjust their song performance and transition between spontaneous singing, when they are alone (“undirected” song), and a performance state, when they sing to a female (“female-directed” song). However, we know little about the role of different basal ganglia cell types in this behavioral transition or the degree to which behavioral context modulates the activity of different neuron classes. To investigate whether interneurons in the songbird basal ganglia encode information about behavioral state, I recorded from two interneuron types, fast-spiking interneurons (FSI) and external pallidal (GPe) neurons, in the songbird basal ganglia nucleus area X during both female-directed and undirected singing. Both cell types exhibited higher firing rates, more frequent bursting, and greater trial-by-trial variability in firing when male zebra finches produced undirected songs compared with when they produced female-directed songs. However, the magnitude and direction of changes to the firing rate, bursting, and variability of spiking between when birds sat silently and when they sang undirected and female-directed song varied between FSI and GPe neurons. These data indicate that social modulation of activity important for eliciting changes in behavioral state is present in multiple cell types within area X and suggests that social interactions may adjust circuit dynamics during singing at multiple points within the circuit. PMID:27628208

[The effect of neonatal administration of monosodium glutamate on behavior and blood corticosterone level].

PubMed

Kuznetsova, E G; Amstislavskaia, T G; Bulygina, V V; Il'nitskaia, S I; Tibeĭkina, M A; Skrinskaia, Iu A

2006-06-01

DBA/2 male mice were treated with monosodium glutamate (MSG) in a dose of 4 mg/g on 1, 3, 5, 7, 9 days after birth. Saline treated and intact males were used as control groups. MSG treated males displayed decreased number of crossed squares, rearings, entries in the centre and time in the centre of open field in comparison with saline-treated but not intact animals. Time in the light compartment of the light-dark box was increased in MSG-treated mice versus both saline treated and intact animals. MSG administration reduced acoustic startle response but did not affect the magnitude of prepulse inhibition of the startle reflex. Sexual motivation in male mice was reduced by MSG, the same trend was observed after saline treatment. MSG administration increased corticosterone basal level 4-fold while saline treatment did not affect it. These data suggest that neonatal administration of MSG decreases locomotion, exploratory activity, anxiety in male mice, while corticosterone level is increased. Saline treatment increases these parameters (except sexual motivation), and this augmentation is not connected to changes in corticosterone basal level.

Alcohol Intoxication Impact on Outcome from Traumatic Injury

DTIC Science & Technology

2008-05-01

emergency department. Previously we have demonstrated that ICV choline increased basal MABP (+17%) and produced a similar increase in basal MABP in...alcohol intoxicated. However, ICV choline did not alter the initial % decrease in blood pressure nor did it improve MABP throughout hemorrhagic...shock or fluid resuscitation in alcohol-treated animals. These studies showed that intracerebroventricular (ICV) choline (acetylcholine precursor

Estimation of crown cover in interior ponderosa pine stands: Effects of thinning and prescribed fire

Treesearch

Nicholas Vaughn; Martin W. Ritchie

2005-01-01

We evaluated the relationship between crown cover measured with a vertical sight tube and stand basal area per acre in treated (thinned, burned, and thinned and burned) and untreated interior ponderosa pine (Pinus ponderosa P. & C. Lawson) stands in northeastern California. Crown cover was significantly related to basal area at the plot level and...

The Influence of Stand Density and Structure on Growth of Northern Hardwoods in New England

Treesearch

Dale S. Solomon

1977-01-01

Growth of northern hardwoods over a 10-year period was studied in plots that were treated to produce residual densities of 40, 60, 80, and 100 square feet of basal area per acre with stand structures of 30, 45 and 60 percent sawtimber. Both diameter and basal area growth are tabulated by treatment and species.

Endoscopic Evacuation of Basal Ganglia Hemorrhage via Keyhole Approach Using an Adjustable Cannula in Comparison with Craniotomy

PubMed Central

Zhang, Heng-Zhu; Li, Yu-Ping; Yan, Zheng-cun; Wang, Xing-dong; She, Lei; Wang, Xiao-dong; Dong, Lun

2014-01-01

Neuroendoscopic (NE) surgery as a minimal invasive treatment for basal ganglia hemorrhage is a promising approach. The present study aims to evaluate the efficacy and safety of NE approach using an adjustable cannula to treat basal ganglia hemorrhage. In this study, we analysed the clinical and radiographic outcomes between NE group (21 cases) and craniotomy group (30 cases). The results indicated that NE surgery might be an effective and safe approach for basal ganglia haemorrhage, and it is also suggested that NE approach may improve good functional recovery. However, NE approach only suits the selected patient, and the usefulness of NE approach needs further randomized controlled trials (RCTs) to evaluate. PMID:24949476

House dust mite-specific immunotherapy alters the basal expression of T regulatory and FcεRI pathway genes.

PubMed

Pevec, Branko; Radulovic Pevec, Mira; Stipic Markovic, Asja; Batista, Irena; Rijavec, Matija; Silar, Mira; Kosnik, Mitja; Korosec, Peter

2012-01-01

Regulatory T (Treg) cells and IgE-mediated signaling pathways could play important roles in the induction of allergen tolerance during house dust mite-specific subcutaneous immunotherapy (HDM-SCIT). Our aim was to compare the basal expression levels of Treg, T helper 1 (Th1) and Th2 transcription factors and components involved in IgE-mediated signaling in healthy subjects with those in HDM-allergic patients both untreated and successfully treated with HDM-SCIT. Thirty-nine HDM-allergic patients who completed a 3- to 5-year course of mite extract SCIT, 20 mite-allergic controls and 25 healthy controls participated in this study. The efficacy of SCIT was monitored using skin-prick tests (SPTs), total immunoglobulin E (tIgE), specific IgE (sIgE), sIgG(4), nasal challenge and visual analog scale (VAS) scores at several time points. The mRNA levels of forkhead box protein 3 (FOXP3), T-BET, GATA-3, FcεRI, spleen tyrosine kinase (Syk), phosphatidylinositol 3 kinase (PI3K) and SH2 domain-containing inositol phosphatase (SHIP) were quantified by real-time RT-PCR using nonstimulated whole blood samples. Decreased wheal sizes and VAS scores, negative challenges and increased sIgG(4) levels indicated that SCIT was effective in the treated patients. Basal expression levels of FOXP3 and GATA-3 decreased and T-BET levels increased in both treated patients and in healthy controls compared to untreated patients. The IgE-mediated pathway kinases Syk and PI3K exhibited reduced expression, whereas SHIP phosphatase levels were elevated in both treated patients and healthy controls relative to untreated patients. The expression levels of FcεRI were not significantly altered. Immunotherapy using HDM extracts results in a modification of the basal expression levels of several IgE-related signaling factors and induces a highly significant upregulation of Th1-response and downregulation of Th2-response transcription factors. Interestingly, this therapy also appears to reduce the basal expression of FOXP3. Copyright © 2012 S. Karger AG, Basel.

Manifestations, Treatment Implications and Speech-Language Consideration in Gorlin Syndrome: A Case Study.

ERIC Educational Resources Information Center

Andrews, Alice E.; Stonestreet, Ruth H.

This paper presents a case study of Gorlin Syndrome, also known as Basal Cell Nevus Syndrome, a rare genetic disorder characterized by widespread developmental defects. Criteria for diagnosis are listed, noting the presence of frequent basal cell carcinomas at a relatively young age and multiple cysts of the jaw. Speech and/or language impairments…

Endothelial MMP14 is required for endothelial-dependent growth support of human airway basal cells

PubMed Central

Ding, Bi-Sen; Gomi, Kazunori; Rafii, Shahin; Crystal, Ronald G.; Walters, Matthew S.

2015-01-01

ABSTRACT Human airway basal cells are the stem (or progenitor) population of the airway epithelium, and play a central role in anchoring the epithelium to the basement membrane. The anatomic position of basal cells allows for potential paracrine signaling between them and the underlying non-epithelial stromal cells. In support of this, we have previously demonstrated that endothelial cells support growth of basal cells during co-culture through vascular endothelial growth factor A (VEGFA)-mediated signaling. Building on these findings, we found, by RNA sequencing analysis, that basal cells expressed multiple fibroblast growth factor (FGF) ligands (FGF2, FGF5, FGF11 and FGF13) and that only FGF2 and FGF5 were capable of functioning in a paracrine manner to activate classical FGF receptor (FGFR) signaling. Antibody-mediated blocking of FGFR1 during basal-cell–endothelial-cell co-culture significantly reduced the endothelial-cell-dependent basal cell growth. Stimulation of endothelial cells with basal-cell-derived growth factors induced endothelial cell expression of matrix metallopeptidase 14 (MMP14), and short hairpin RNA (shRNA)-mediated knockdown of endothelial cell MMP14 significantly reduced the endothelial-cell-dependent growth of basal cells. Overall, these data characterize a new growth-factor-mediated reciprocal ‘crosstalk’ between human airway basal cells and endothelial cells that regulates proliferation of basal cells. PMID:26116571

RB1 status in triple negative breast cancer cells dictates response to radiation treatment and selective therapeutic drugs.

PubMed

Robinson, Tyler J W; Liu, Jeff C; Vizeacoumar, Frederick; Sun, Thomas; Maclean, Neil; Egan, Sean E; Schimmer, Aaron D; Datti, Alessandro; Zacksenhaus, Eldad

2013-01-01

Triple negative breast cancer (TNBC) includes basal-like and claudin-low subtypes for which only chemotherapy and radiation therapy are currently available. The retinoblastoma (RB1) tumor suppressor is frequently lost in human TNBC. Knockdown of RB1 in luminal BC cells was shown to affect response to endocrine, radiation and several antineoplastic drugs. However, the effect of RB1 status on radiation and chemo-sensitivity in TNBC cells and whether RB1 status affects response to divergent or specific treatment are unknown. Using multiple basal-like and claudin-low cell lines, we hereby demonstrate that RB-negative TNBC cell lines are highly sensitive to gamma-irradiation, and moderately more sensitive to doxorubicin and methotrexate compared to RB-positive TNBC cell lines. In contrast, RB1 status did not affect sensitivity of TNBC cells to multiple other drugs including cisplatin (CDDP), 5-fluorouracil, idarubicin, epirubicin, PRIMA-1(met), fludarabine and PD-0332991, some of which are used to treat TNBC patients. Moreover, a non-biased screen of ∼3400 compounds, including FDA-approved drugs, revealed similar sensitivity of RB-proficient and -deficient TNBC cells. Finally, ESA(+)/CD24(-/low)/CD44(+) cancer stem cells from RB-negative TNBC lines were consistently more sensitive to gamma-irradiation than RB-positive lines, whereas the effect of chemotherapy on the cancer stem cell fraction varied irrespective of RB1 expression. Our results suggest that patients carrying RB-deficient TNBCs would benefit from gamma-irradiation as well as doxorubicin and methotrexate therapy, but not necessarily from many other anti-neoplastic drugs.

Knockdown of CAVEOLIN-1 Sensitizes Human Basal-Like Triple-Negative Breast Cancer Cells to Radiation.

PubMed

Zou, Man; Li, Yanhui; Xia, Shu; Chu, Qian; Xiao, Xiaoguang; Qiu, Hong; Chen, Yu; Zheng, Zu'an; Liu, Fei; Zhuang, Liang; Yu, Shiying

2017-01-01

Triple-negative breast cancer (TNBC) is a high-risk breast cancer phenotype without specific targeted therapy options and is significantly associated with increased local recurrence in patients treated with radiotherapy. CAVEOLIN-1 (CAV-1)-mediated epidermal growth factor receptor (EGFR) nuclear translocation following irradiation promotes DNA repair and thus induces radiation resistance. In this study, we aimed to determine whether knockdown of CAV-1 enhances the radiosensitivity of basal-like TNBC cell lines and to explore the possible mechanisms. Western blotting was used to compare protein expression in a panel of breast cancer cell lines. Nuclear accumulation of EGFR as well as DNA repair and damage at multiple time points following irradiation with or without CAV-1 siRNA pretreatment were investigated using western blotting and confocal microscopy. The radiosensitizing effect of CAV-1 siRNA was evaluated using a clonogenic assay. Flowcytometry was performed to analyse cell apoptosis and cell cycle alteration. We found that CAV-1 is over-expressed in basal-like TNBC cell lines and barely expressed in HER-2-positive cells; additionally, we observed that HER-2-positive cell lines are more sensitive to irradiation than basal-like TNBC cells. Our findings revealed that radiation-induced EGFR nuclear translocation was impaired by knockdown of CAV-1. In parallel, radiation-induced elevation of DNA repair proteins was also hampered by pretreatment with CAV-1 siRNA before irradiation. Silencing of CAV-1 also promoted DNA damage 24 h after irradiation. Colony formation assays verified that cells could be radiosensitized after knockdown of CAV-1. Furthermore, G2/M cell cycle arrest and apoptosis enhancement may also contribute to the radiosensitizing effect of CAV-1 siRNA. Our results support the hypothesis that CAV-1 knockdown by siRNA causes increased radiosensitivity in basal-like TNBC cells. The mechanisms associated with this effect are reduced DNA repair through delayed CAV-1-associated EGFR nuclear accumulation and induction of G2/M arrest and apoptosis through the combined effects of CAV-1 siRNA and radiation. © 2017 The Author(s). Published by S. Karger AG, Basel.

Demyelination of subcortical nuclei in multiple sclerosis

NASA Astrophysics Data System (ADS)

Krutenkova, E.; Aitmagambetova, G.; Khodanovich, M.; Bowen, J.; Gangadharan, B.; Henson, L.; Mayadev, A.; Repovic, P.; Qian, P.; Yarnykh, V.

2016-02-01

Myelin containing in basal ganglia in multiple sclerosis patients was evaluated using new noninvasive quantitative MRI method fast whole brain macromolecular proton fraction mapping. Myelin level in globus pallidus and putamen significantly decreased in multiple sclerosis patients as compared with healthy control subjects but not in substantia nigra and caudate nucleus.

An uncommon disorder with multiple skeletal anomalies: Gorlin-Goltz syndrome.

PubMed

Keçeli, Onur; Coskun-Benlidayı, İlke; Benlidayı, M Emre; Erdoğan, Özgür

2014-01-01

Gorlin-Goltz syndrome is an uncommon disorder transmitted through autosomal dominant inheritance. This syndrome is characterized by multiple odontogenic keratocysts, along with congenital skeletal anomalies and basal cell carcinomas. A 16-year-old girl was admitted with a complaint of swelling on the lower jaw. She had multiple basal cell nevi on both hands. Multiple lytic bone lesions on radiographs were defined as odontogenic keratocysts following the biopsy. The patient was referred to the Department of Physical Medicine and Rehabilitation for detailed musculoskeletal evaluation. Adam's forward bend test revealed a hump on the right side representing right thoracic scoliosis. Cervical kyphosis, thoracic lordosis and scoliosis, bifid rib and sacral and lumbar spina bifida on plain radiographs led to the diagnosis of Gorlin-Goltz syndrome. Since early diagnosis may provide optimum surveillance for related neoplasms, it is of paramount importance for pediatricians as well as physicians dealing with the musculoskeletal system to be aware of this rare condition.

The effects of acute stress on Pavlovian-instrumental transfer in rats.

PubMed

Pielock, Steffi M; Braun, Stephanie; Hauber, Wolfgang

2013-03-01

Pavlovian stimuli invigorate ongoing instrumental action, a phenomenon termed the Pavlovian-instrumental transfer (PIT) effect. Acute stressors can markedly enhance the release of corticotropin-releasing factor (CRF), and CRF injection into the nucleus accumbens increases the PIT effect. However, it is unknown whether acute stressors by themselves would amplify the PIT effect. Here, we examined the effects of acute stressors on PIT. Rats first received Pavlovian and instrumental training, and then the impact of the Pavlovian stimuli on instrumental responding was analyzed in the subsequent PIT test. Acute stressors were applied prior to the PIT test. Because the effects of acute stressors critically depend on stressor type and time of day, we used two acute stressors that involved one or several distinct stressors (denoted here as "single" vs. "multiple" stressors) applied either in the light or the dark period of the light:dark cycle. The results revealed that single and multiple stressors applied in the light period did not alter the PIT effect--that is, the ability of an appetitive Pavlovian stimulus to enhance leverpressing--or the basal leverpress rate. When applied in the dark period, single and multiple stressors also did not alter the PIT effect, but they did markedly reduce the basal leverpress rate. Diazepam pretreatment did not counteract the declines in basal instrumental responding in the PIT test that were induced by either a single or multiple stressors. Our findings suggest that acute stressors were unable to amplify the incentive salience of reward-predictive Pavlovian stimuli to activate instrumental responding, but, depending on the time of day of stressor exposure, they did reduce basal instrumental responding.

Sclerodermiform basal cell carcinoma: how much can we rely on dermatoscopy to differentiate from non-aggressive basal cell carcinomas? Analysis of 1256 cases.

PubMed

Husein-ElAhmed, Husein

2018-03-01

The behaviour of each basal cell carcinoma is known to be different according to the histological growth pattern. Among these aggressive lesions, sclerodermiform basal cell carcinomas are the most common type. This is a challenging-to-treat lesion due to its deep tissue invasion, rapid growth, risk of metastasis and overall poor prognosis if not diagnosed in early stages. To investigate if sclerodermiform basal cell carcinomas are diagnosed later compared to non-sclerodermiform basal cell carcinoma Method: All lesions excised from 2000 to 2010 were included. A pathologist classified the lesions in two cohorts: one with specimens of non-aggressive basal cell carcinoma (superficial, nodular and pigmented), and other with sclerodermiform basal cell carcinoma. For each lesion, we collected patient's information from digital medical records regarding: gender, age when first attending the clinic and the tumor location. 1256 lesions were included, out of which 296 (23.6%) corresponded to sclerodermiform basal cell carcinoma, whereas 960 (76.4%) were non-aggressive subtypes of basal cell carcinoma. The age of diagnosis was: 72.78±12.31 years for sclerodermiform basal cell and 69.26±13.87 years for non-aggressive basal cell carcinoma (P<.0001). Sclerodermiform basal cell carcinomas are diagnosed on average 3.52 years later than non-aggressive basal cell carcinomas. Sclerodermiform basal cell carcinomas were diagnosed 3.40 years and 2.34 years later than non-aggressive basal cell carcinomas in younger and older patients respectively (P=.002 and P=.03, respectively). retrospective design. The diagnostic accuracy and primary clinic conjecture of sclerodermiform basal cell carcinomas is quite low compared to other forms of basal cell carcinoma such as nodular, superficial and pigmented. The dermoscopic vascular patterns, which is the basis for the diagnosis of non-melanocytic nonpigmented skin tumors, may not be particularly useful in identifying sclerodermiform basal cell carcinomas in early stages. As a distinct entity, sclerodermiform basal cell carcinomas show a lack of early diagnosis compared to less-aggressive subtypes of BCC, and thus, more accurate diagnostic tools apart from dermatoscopy are required to reach the goal of early-stage diagnosis of sclerodermiform basal cell carcinomas.

Omitting late-night eating may cause hypoglycemia in "well controlled" basal insulin-treated type 2 diabetes.

PubMed

King, Allen B; Clark, Dawn

2015-03-01

To assess hypoglycemia caused by eating the last meal of the day earlier or its omission in "well controlled" type 2 diabetes mellitus patients treated with once-nightly basal insulin. Previously basal insulin-titrated subjects (n = 20) (fasting plasma glucose, FPG, <110 mg/dL and no self-reported hypoglycemia) underwent continuous glucose monitoring (CGM) during 3 consecutive eating conditions of 3 days each; (1) usual eating, (2) the last meal restricted to 18:00, and (3) 1 sequential meal omitted/day thereby creating a fasting day after transposing the 4-hour period after a meal with that when the meal was omitted. One 24-hour (00:00 to 00:00) period within each eating condition was selected for comparison. The mean duration in all hypoglycemic ranges doubled (P = .0584 or greater) when the last meal was omitted or eaten at 18:09 ± 0:39 instead of 19:43 ± 1:01, the usual time for the subjects' undisturbed eating. The mean duration of hypoglycemia was greatest between 00:00 to 06:00 compared to the 3 other 6-hour periods of the day. Increased hypoglycemia occurs when the subject's last meal is eaten earlier or omitted and may not be recognized because it occurs predominately during sleep. When titrating basal insulin from the morning FPG, considerations should be given to the effect of the last meal of the day and possible hypoglycemia between 00:00 and 06:00 to avoid excessive basal insulin treatment.

Gorlin syndrome.

PubMed

Devi, Basanti; Behera, Binodini; Patro, Sibasish; Pattnaik, Subhransu S; Puhan, Manas R

2013-05-01

Gorlin Syndrome, a rare genodermatosis, otherwise known as Nevoid basal cell carcinoma syndrome (NBCCS) is a multisystem disease affecting skin, nervous system, eyes, endocrine glands, and bones. It is characterized by multiple basal cell carcinomas, palmoplantar pits, jaw cysts, and bony deformities like kyphoscoliosis and frontal bossing. We would like to report a case of Gorlin syndrome with classical features, as this is a rare genodermatosis.

Studies on the mechanism of salicylate-induced increase of insulin secretion in man.

PubMed

Giugliano, D; Cozzolino, D; Ceriello, A; Cerciello, T; Varano, R; Saccomanno, F; Torella, R

1988-01-01

Salicylate compounds are known to increase basal and stimulated insulin secretion in man. In our studies, infusion of lysine acetylsalicylate (72 mg/min) increased basal insulin levels and amplified insulin responses to glucose (5 g i.v.), arginine (5 g i.v.) and tolbutamide (1 g i.v.). Verapamil, an organic calcium antagonist, did not modify LAS-induced increase of basal insulin levels, but reduced the effect of LAS on glucose-induced insulin secretion. Calcitonin and somatostatin, two agents that inhibit basal and glucose-stimulated insulin secretion, inhibited the insulin response to glucose in presence of LAS infusion. The ability of salicylate compounds to augment insulin secretion might be due to multiple sites of action in the Beta-cells.

Basal Ganglia Neuromodulation Over Multiple Temporal and Structural Scales—Simulations of Direct Pathway MSNs Investigate the Fast Onset of Dopaminergic Effects and Predict the Role of Kv4.2

PubMed Central

Lindroos, Robert; Dorst, Matthijs C.; Du, Kai; Filipović, Marko; Keller, Daniel; Ketzef, Maya; Kozlov, Alexander K.; Kumar, Arvind; Lindahl, Mikael; Nair, Anu G.; Pérez-Fernández, Juan; Grillner, Sten; Silberberg, Gilad; Hellgren Kotaleski, Jeanette

2018-01-01

The basal ganglia are involved in the motivational and habitual control of motor and cognitive behaviors. Striatum, the largest basal ganglia input stage, integrates cortical and thalamic inputs in functionally segregated cortico-basal ganglia-thalamic loops, and in addition the basal ganglia output nuclei control targets in the brainstem. Striatal function depends on the balance between the direct pathway medium spiny neurons (D1-MSNs) that express D1 dopamine receptors and the indirect pathway MSNs that express D2 dopamine receptors. The striatal microstructure is also divided into striosomes and matrix compartments, based on the differential expression of several proteins. Dopaminergic afferents from the midbrain and local cholinergic interneurons play crucial roles for basal ganglia function, and striatal signaling via the striosomes in turn regulates the midbrain dopaminergic system directly and via the lateral habenula. Consequently, abnormal functions of the basal ganglia neuromodulatory system underlie many neurological and psychiatric disorders. Neuromodulation acts on multiple structural levels, ranging from the subcellular level to behavior, both in health and disease. For example, neuromodulation affects membrane excitability and controls synaptic plasticity and thus learning in the basal ganglia. However, it is not clear on what time scales these different effects are implemented. Phosphorylation of ion channels and the resulting membrane effects are typically studied over minutes while it has been shown that neuromodulation can affect behavior within a few hundred milliseconds. So how do these seemingly contradictory effects fit together? Here we first briefly review neuromodulation of the basal ganglia, with a focus on dopamine. We furthermore use biophysically detailed multi-compartmental models to integrate experimental data regarding dopaminergic effects on individual membrane conductances with the aim to explain the resulting cellular level dopaminergic effects. In particular we predict dopaminergic effects on Kv4.2 in D1-MSNs. Finally, we also explore dynamical aspects of the onset of neuromodulation effects in multi-scale computational models combining biochemical signaling cascades and multi-compartmental neuron models. PMID:29467627

The clinical characteristics and therapy of syndrome of craniocerebral-cervical vertebral injury.

PubMed

Liu, Sheng; Liu, Yuan-xin; Wang, Cheng

2005-06-01

To explore the clinical characteristics and new treatment for syndrome of craniocerebral-cervical vertebral injury. The clinical data of 52 patients with head injury accompanied by neck injury were analyzed retrospectively. Craniocerebral injury could result in damage to cervical vertebrae, muscles, vessels and nerves, and even cause vertebral artery injury, which may lead to insufficient blood-supply of vertebral-basal artery. All patients were treated with cervical vertebral traction and the results were good. Acute craniocerebral injury with symptom of insufficient blood-supply of vertebral-basal artery, evident neurosis and atlas-axis half-dislocation in X-ray should be treated by cervical vertebral traction, which will yield better outcome.

The Evaluation of Basal Respiration for Various Soil Textures in Ecologically Sensitive Area

NASA Astrophysics Data System (ADS)

Huličová, P.; Kotorová, D.; Fazekašová, D.; Hynšt, J.

2017-10-01

The present contribution was focused on monitoring changes in the soil basal respiration in different textures of soil in the dry polder Beša. The research was conducted between 2012 and 2014 on soil type Fluvisol locations on three soil textures: clay - loam soil, clayey soil and clay soil in three soil depths. The basal respiration (BR) has been determine by soil CO2 production measuring from incubated soil samples in serum bottles in laboratory condition. Release Co2 has been analysed by gas chromatography. Content of clay particles were in the range 52.18 % to 81.31%, indicating the high difference between the minimum and maximum content. By using of multiple LSD-test we recorded statistically significant impact of clay on basal respiration. Results confirm the values of basal respiration with the depth of the soil profile decreased.

Syndrome in question: Gorlin-Goltz syndrome.

PubMed

Ribeiro, Pauline Lyrio; Souza, João Basílio de; Abreu, Karina Demoner de; Brezinscki, Marisa Simon; Pignaton, Christine Chambo

2016-01-01

The Nevoid Basal Cell Carcinoma Syndrome (NBCCS) is an uncommon disorder caused by a mutation in Patched, tumor suppressor gene. It is mainly characterized by numerous early onset basal cell carcinomas, odontogenic cysts of jaw and skeletal abnormalities. Due to the wide clinical spectrum, treatment and management of its modalities are not standardized and should be individualized and monitored by a multidisciplinary team. We report a typical case in a 30-year-old man with multiple basal cell carcinomas, keratotic pits of palmar creases and bifid ribs, with a history of several corrective surgeries for keratocystic odontogenic tumors, among other lesions characteristic of the syndrome.

Successful Treatment of Passive Fecal Incontinence in an Animal Model Using Engineered Biosphincters: A 3‐Month Follow‐Up Study

PubMed Central

Bohl, Jaime L.; Zakhem, Elie

2017-01-01

Abstract Fecal incontinence (FI) is the involuntary passage of fecal material. Current treatments have limited successful outcomes. The objective of this study was to develop a large animal model of passive FI and to demonstrate sustained restoration of fecal continence using anorectal manometry in this model after implantation of engineered autologous internal anal sphincter (IAS) biosphincters. Twenty female rabbits were used in this study. The animals were divided into three groups: (a) Non‐treated group: Rabbits underwent IAS injury by hemi‐sphincterectomy without treatment. (b) Treated group: Rabbits underwent IAS injury by hemi‐sphincterectomy followed by implantation of autologous biosphincters. (c) Sham group: Rabbits underwent IAS injury by hemi‐sphincterectomy followed by re‐accessing the surgical site followed by immediate closure without implantation of biosphincters. Anorectal manometry was used to measure resting anal pressure and recto‐anal inhibitory reflex (RAIR) at baseline, 1 month post‐sphincterectomy, up to 3 months after implantation and post‐sham. Following sphincterectomy, all rabbits had decreased basal tone and loss of RAIR, indicative of FI. Anal hygiene was also lost in the rabbits. Decreases in basal tone and RAIR were sustained more than 3 months in the non‐treated group. Autologous biosphincters were successfully implanted into eight donor rabbits in the treated group. Basal tone and RAIR were restored at 3 months following biosphincter implantation and were significantly higher compared with rabbits in the non‐treated and sham groups. Histologically, smooth muscle reconstruction and continuity was restored in the treated group compared with the non‐treated group. Results in this study provided promising outcomes for treatment of FI. Results demonstrated the feasibility of developing and validating a large animal model of passive FI. This study also showed the efficacy of the engineered biosphincters to restore fecal continence as demonstrated by manometry. Stem Cells Translational Medicine 2017;6:1795–1802 PMID:28678378

Characteristics and Treatment of Breakthrought Pain (BTcP) in Palliative Care

PubMed Central

Husic, Samir; Imamovic, Semir; Matic, Srecko; Sukalo, Aziz

2017-01-01

Introduction: This research was to follow characteristics of breakthrough pain caused by cancer (BTcP) and other most common sympthoms (ESAS) at patients in advanced stage of cancer disease in palliative care. Patients and methods: Prospective study included 433 patients which were treated in Palliative Care Centre in UKC Tuzla, Bosnia and Herzegovina. Group 1 was consisted of 353 patients whose basal cancer pain of intensity 4-7 NRS was treated weak opiates (basal analgetic- fixed combination of tramadol/paracetamol (37.5 mg/325 mg) in initial dose 3x1tbl for pain intensity 4, to 4x2tbl (for pain intensity 7). In Group 2 (80 patients) basal pain of intensity 8-10 was treated strong opiates as basal analgetic (oral morphine and transdermal fentanil). If the previous day were 2 or more breakthrough pain that required ‘’rescue dose’’ of analgetics (tramadol 50-100 mg orally in group 1 ie. Oral morphine 8-12 mg in the group 2), the dose of basal analgetic was increased. Results: The total number of reported breakthrough pain in all 433 patients for 10 days of treatment was 3 369 (0.78 BTcP /per patient/day), where at Group 1 patients showed significantly lower BTcP (0.56 BTcP/patient/day). The average intensity of BTcP was 5.91 where in the Group1 was 4.51 while in the Group 2 8.04. 582 (17.28%) was rated grade 7, of which 539 were successfully coupled by strong and 43 (7.39%) successfully coupled by weak opiates. From 556 BTcP who were rated with 8, 540 of them were coupled strong and only 16 successfully coupled by weak opiates. 1967 (58.39 %) of breakthrough pain has occured in the evening hours (18-06 h), while 1402 (41.62%) BTCP occured during day hours (06-18h). Most (1290 or 38.29%) of breakthrough pain lasted less than 10 minutes, 882 (26.18%) between 16 and 20 minutes, 752 (22.32%) between 11 and 15 minutes, 407 (12.8%) between 21 and 30 minutes and 38 (1.13%) lasted longer than 20 minutes. Conclusion: Duriong our study, we noted a relatively large number of breakthrough pain with lower intensity (3-6) in patients treated with weak opiates, which are also adversely affected patients satisfaction with pain treatment and required additional doses of analgetics. In the small percentage is possible the breakthrough pain of stronger intensity (7-8) treat by maximum doses of weak opiates. PMID:28974843

Regression modeling and mapping of coniferous forest basal area and tree density from discrete-return lidar and multispectral data

Treesearch

Andrew T. Hudak; Nicholas L. Crookston; Jeffrey S. Evans; Michael K. Falkowski; Alistair M. S. Smith; Paul E. Gessler; Penelope Morgan

2006-01-01

We compared the utility of discrete-return light detection and ranging (lidar) data and multispectral satellite imagery, and their integration, for modeling and mapping basal area and tree density across two diverse coniferous forest landscapes in north-central Idaho. We applied multiple linear regression models subset from a suite of 26 predictor variables derived...

Giant basal cell carcinoma of the face: surgical management and challenges for reconstruction.

PubMed

Maimaiti, A; Mijiti, A; Yarbag, A; Moming, A

2016-02-01

Giant basal cell carcinoma, in which the tumour measures 5 cm or greater in diameter, is a very rare skin malignancy that accounts for less than 1 per cent of all basal cell tumours. Very few studies have reported on the incidence, resection and reconstruction of this lesion worldwide. In total, 17 patients with giant basal cell carcinoma of the head and neck region underwent surgical excision and reconstruction at our hospital. Medical charts were retrospectively reviewed and analysed. The lesion was usually in the forehead, eyelid, lips or nasal-cheek region. The greatest diameter ranged from 5 to 11 cm, with 5-6 cm being the most common size at the time of presentation. All patients had their tumour resected and reconstructed in a single-stage procedure, mostly with a local advancement flap, and with no post-operative flap failure. Giant basal cell carcinoma of the head and neck can be successfully treated with a local flap in a single-stage approach.

Deconstructing breast cancer heterogeneity: clinical implications for women with Basal-like tumors.

PubMed

Rattani, Nabila S; Swift-Scanlan, Theresa

2014-11-01

To compare and contrast the molecular and environmental factors contributing to basal-like breast cancer and highlight the clinical implications for women with this phenotype. CINAHL® and PubMed databases, journals, and citation indices were searched using the key word basal-like in combination with breast cancer, epigenetic, treatment, subtype, risk factor, and BRCA1 to synthesize the literature on the multiple underpinnings of basal-like breast cancer. Research findings related to the molecular foundation of basal-like breast cancer were integrated with knowledge of nongenetic contributing risk factors. Approved therapies and those under development were summarized with the goal of improving understanding for research and practice. Of the five subtypes of breast cancer, the basal-like subtype has the shortest survival and poorest prognosis. The development of gene expression assays with epigenetic studies has enabled reliable identification of the basal-like subtype and has shed light on novel therapeutic possibilities. Clinical trials for basal-like breast cancer are underway, and the potential for individualized treatments for women with this subtype show promise. The main difficulties with basal-like breast cancer are its aggressive course, treatment refractory nature, and complex biology, all of which pose real challenges for clinical management and patient education. Oncology nurses play a pivotal role in providing holistic care and patient support. Therefore, nurses must understand the complexity of the clinical presentation and the underlying biology of this cancer subtype.

Multiple jaw cysts-unveiling the Gorlin-Goltz syndrome.

PubMed

Manjima, S; Naik, Zameera; Keluskar, Vaishali; Bagewadi, Anjana

2015-03-01

Gorlin-Goltz syndrome or basal cell nevus syndrome is a comparatively rare syndrome characterized by basal cell nevi, odontogenic keratocysts, and skeletal anomalies. Diagnosis is based on the major and minor clinical and radiographic criteria. Dentist plays a major role in the diagnosis of this disease due to the oral and maxillofacial manifestations of the syndrome. In some cases, jaw cysts are diagnosed by routine radiographs advised by the dentists. Odontogenic keratocysts in such syndromic patients will be multiple and extensive and in some cases results in cortical expansion and facial disfigurement. Thorough clinical examination and investigations prompt an early confirmation of the syndrome, which is very essential to avoid morbidity associated with the syndrome. Here, we report a case of multiple odontogenic cysts in a 16-year-old patient which later was diagnosed as a case of Gorlin Goltz syndrome.

Multiple jaw cysts-unveiling the Gorlin-Goltz syndrome

PubMed Central

Manjima, S.; Naik, Zameera; Keluskar, Vaishali; Bagewadi, Anjana

2015-01-01

Gorlin-Goltz syndrome or basal cell nevus syndrome is a comparatively rare syndrome characterized by basal cell nevi, odontogenic keratocysts, and skeletal anomalies. Diagnosis is based on the major and minor clinical and radiographic criteria. Dentist plays a major role in the diagnosis of this disease due to the oral and maxillofacial manifestations of the syndrome. In some cases, jaw cysts are diagnosed by routine radiographs advised by the dentists. Odontogenic keratocysts in such syndromic patients will be multiple and extensive and in some cases results in cortical expansion and facial disfigurement. Thorough clinical examination and investigations prompt an early confirmation of the syndrome, which is very essential to avoid morbidity associated with the syndrome. Here, we report a case of multiple odontogenic cysts in a 16-year-old patient which later was diagnosed as a case of Gorlin Goltz syndrome. PMID:25821359

Brooke-Spiegler syndrome presenting multiple concurrent cutaneous and parotid gland neoplasms: cytologic findings on fine-needle sample and description of a novel mutation of the CYLD gene.

PubMed

Malzone, Maria Gabriella; Campanile, Anna Cipolletta; Losito, Nunzia Simona; Longo, Francesco; Perri, Francesco; Caponigro, Francesco; Schiavone, Concetta; Ionna, Franco; Maiello, Francesco; Martinuzzi, Claudia; Nasti, Sabina; Botti, Gerardo; Fulciniti, Franco

2015-08-01

Multiple dermal cylindromas and membranous basal cell adenoma of parotid gland in a 67-year-old woman with Brooke-Spiegler syndrome (BSS) were examined by fine-needle cytology. Histology, immunochemistry, and CYLD germline mutation testing were also performed. Cytomorphology and immunochemistry of the two lesions showed basaloid neoplasms, remarkably similar, composed by proliferating epithelial cells of basal type accompanied by a smaller proportion of myoepithelial cells. CYLD gene showed a novel germline splice acceptor site mutation (c.2042-1G>C) with skipping of the entire exon 15. The occurrence of analogous tumors, dermal cylindromas, and membranous basal cell adenoma of the parotid gland, in the same patient may result from the action of a single gene on ontogenetically similar stem cells. Therefore, patients with BSS should be offered a genetic counselling for an early and correct diagnosis. © 2015 Wiley Periodicals, Inc.

Basal cell carcinoma of the nipple-areola complex: a case report.

PubMed

Huang, Ching-Wen; Pan, Ching-Kuen; Shih, Teng-Fu; Tsai, Cheng-Chien; Juan, Chung-Chou; Ker, Chen-Guo

2005-10-01

Basal cell carcinoma (BCC) of the nipple-areola complex is very rare. Only 24 cases were reported in the literature and 17 (70.8%) of these cases arose in men. Most of the cases were treated with simple excision. We report on a case of BCC of the nipple-areola complex in a 46-year-old woman, treated with partial mastectomy. Metastasis to the axillary lymph nodes had been noted in 3 (12.5%) of the 24 reported cases of BCC of the nipple-areola complex. Thus, we applied the concept of the sentinel lymph node to detect possible metastases of axillary lymph nodes, letting us avoid the unnecessary axillary lymph node dissection and possible future morbidity.

Basal ganglia and Dopamine Contributions to Probabilistic Category Learning

PubMed Central

Shohamy, D.; Myers, C.E.; Kalanithi, J.; Gluck, M.A.

2009-01-01

Studies of the medial temporal lobe and basal ganglia memory systems have recently been extended towards understanding the neural systems contributing to category learning. The basal ganglia, in particular, have been linked to probabilistic category learning in humans. A separate parallel literature in systems neuroscience has emerged, indicating a role for the basal ganglia and related dopamine inputs in reward prediction and feedback processing. Here, we review behavioral, neuropsychological, functional neuroimaging, and computational studies of basal ganglia and dopamine contributions to learning in humans. Collectively, these studies implicate the basal ganglia in incremental, feedback-based learning that involves integrating information across multiple experiences. The medial temporal lobes, by contrast, contribute to rapid encoding of relations between stimuli and support flexible generalization of learning to novel contexts and stimuli. By breaking down our understanding of the cognitive and neural mechanisms contributing to different aspects of learning, recent studies are providing insight into how, and when, these different processes support learning, how they may interact with each other, and the consequence of different forms of learning for the representation of knowledge. PMID:18061261

Inhibition of RHO-ROCK signaling enhances ICM and suppresses TE characteristics through activation of Hippo signaling in the mouse blastocyst

PubMed Central

Kono, Kanako; Tamashiro, Dana Ann A.; Alarcon, Vernadeth B.

2014-01-01

Specification of the trophectoderm (TE) and inner cell mass (ICM) lineages in the mouse blastocyst correlates with cell position, as TE derives from outer cells whereas ICM from inner cells. Differences in position are reflected by cell polarization and Hippo signaling. Only in outer cells, the apical-basal cell polarity is established, and Hippo signaling is inhibited in such a manner that LATS1 and 2 (LATS1/2) kinases are prevented from phosphorylating YAP, a key transcriptional co-activator of the TE-specifying gene Cdx2. However, the molecular mechanisms that regulate these events are not fully understood. Here, we showed that inhibition of RHO-ROCK signaling enhances ICM and suppresses TE characteristics through activation of Hippo signaling and disruption of apical-basal polarity. Embryos treated with ROCK inhibitor Y-27632 exhibited elevated expression of ICM marker NANOG and reduced expression of CDX2 at the blastocyst stage. Y-27632-treated embryos failed to accumulate YAP in the nucleus, although it was rescued by concomitant inhibition of LATS1/2. Segregation between apical and basal polarity regulators, namely PARD6B, PRKCZ, SCRIB, and LLGL1, was dampened by Y-27632 treatment, whereas some of the polarization events at the late 8-cell stage such as compaction and apical localization of p-ERM and tyrosinated tubulin occurred normally. Similar abnormalities of Hippo signaling and apical-basal polarization were also observed in embryos that were treated with RHO GTPases inhibitor. These results suggest that RHO-ROCK signaling plays an essential role in regulating Hippo signaling and cell polarization to enable proper specification of the ICM and TE lineages. PMID:24997360

Predictive model for photodynamic therapy with gold nanoparticles as vehicle for the photosensitizer delivery

NASA Astrophysics Data System (ADS)

Salas-García, I.; Fanjul-Vélez, F.; Ortega-Quijano, N.; Arce-Diego, J. L.

2013-06-01

Photodynamic Therapy offers multiple advantages to treat nonmelanoma skin cancer compared to conventional treatment techniques such as surgery, radiotherapy or chemotherapy. Among these advantages are particularly relevant its noninvasive nature, the use of non ionizing radiation and its high selectivity. However the therapeutic efficiency of the current clinical protocol is not complete in all the patients and depends on the type of pathology. Emerging strategies to overcome its current shortcomings include the use of nanostructures that can act as carriers for conventional photosensitizers and improve the treatment selectivity and provide a controlled release of the photoactive agent. In this work, a model for photodynamic therapy combined with gold nanocarriers for a photosensitizer commonly used in dermatology is presented and applied to a basal cell carcinoma in order to predict the cytotoxic agent spatial and temporal evolution.

Comparison of liraglutide plus basal insulin and basal-bolus insulin therapy (BBIT) for glycemic control, body weight stability, and treatment satisfaction in patients treated using BBIT for type 2 diabetes without severe insulin deficiency: A randomized prospective pilot study.

PubMed

Yamamoto, Saki; Hayashi, Toshiyuki; Ohara, Makoto; Goto, Satoshi; Sato, Jun; Nagaike, Hiroe; Fukase, Ayako; Sato, Nobuko; Hiromura, Munenori; Tomoyasu, Masako; Nakanishi, Noriko; Lee, Soushou; Osamura, Anna; Yamamoto, Takeshi; Fukui, Tomoyasu; Hirano, Tsutomu

2018-03-26

We examined whether 0.9 mg/day liraglutide plus basal insulin (Lira-basal) is superior to basal-bolus insulin therapy (BBIT) for type 2 diabetes (T2DM) without severe insulin deficiency as determined by glucagon stimulation. Fifty patients receiving BBIT were enrolled in this 24-week, prospective, randomized, open-labeled study. After excluding subjects with fasting C-peptide immunoreactivity (CPR) < 1.0 ng/mL and CPR increase < 1.0 ng/mL at 6 min post glucagon injection, 25 were randomly allocated to receive Lira-basal (n = 12) or continued BBIT (n = 13). Primary endpoint was change in HbA1c. Secondary endpoints were changes in body weight (BW), 7-point self-monitored blood glucose (SMBG), and Diabetes Treatment Satisfaction Questionnaire status (DTSQs) scores. The Lira-basal group demonstrated reduced HbA1c, whereas the BBIT group showed no change. BW was reduced in the Lira-basal group but increased in the BBIT group. The Lira-basal group also exhibited significantly reduced pre-breakfast and pre-lunch SMBG. DTSQs scores improved in the Lira-basal group but not the BBIT group. Plasma lipids, liver function, and kidney function were not significantly changed in either group. Lira-basal therapy is superior to BBIT for T2DM without severe insulin deficiency. This study was registered with UMIN Clinical Trials Registry (UMIN000028313). Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Subthalamic nucleus stimulation does not influence basal glucose metabolism or insulin sensitivity in patients with Parkinson's disease.

PubMed

Lammers, Nicolette M; Sondermeijer, Brigitte M; Twickler, Th B Marcel; de Bie, Rob M; Ackermans, Mariëtte T; Fliers, Eric; Schuurman, P Richard; La Fleur, Susanne E; Serlie, Mireille J

2014-01-01

Animal studies have shown that central dopamine signaling influences glucose metabolism. As a first step to show this association in an experimental setting in humans, we studied whether deep brain stimulation (DBS) of the subthalamic nucleus (STN), which modulates the basal ganglia circuitry, alters basal endogenous glucose production (EGP) or insulin sensitivity in patients with Parkinson's disease (PD). We studied 8 patients with PD treated with DBS STN, in the basal state and during a hyperinsulinemic euglycemic clamp using a stable glucose isotope, in the stimulated and non-stimulated condition. We measured EGP, hepatic insulin sensitivity, peripheral insulin sensitivity (Rd), resting energy expenditure (REE), glucoregulatory hormones, and Parkinson symptoms, using the Unified Parkinson's Disease Rating Scale (UPDRS). Basal plasma glucose and EGP did not differ between the stimulated and non-stimulated condition. Hepatic insulin sensitivity was similar in both conditions and there were no significant differences in Rd and plasma glucoregulatory hormones between DBS on and DBS off. UPDRS was significantly higher in the non-stimulated condition. DBS of the STN in patients with PD does not influence basal EGP or insulin sensitivity. These results suggest that acute modulation of the motor basal ganglia circuitry does not affect glucose metabolism in humans.

Confocal and dermoscopic features of basal cell carcinoma in Gorlin-Goltz syndrome: A case report.

PubMed

Casari, Alice; Argenziano, Giuseppe; Moscarella, Elvira; Lallas, Aimilios; Longo, Caterina

2017-05-01

Gorlin-Goltz (GS) syndrome is an autosomal dominant disease linked to a mutation in the PTCH gene. Major criteria include the onset of multiple basal cell carcinoma (BCC), keratocystic odontogenic tumours in the jaws and bifid ribs. Dermoscopy and reflectance confocal microscopy represent imaging tools that are able to increase the diagnostic accuracy of skin cancer in a totally noninvasive manner, without performing punch biopsies. Here we present a case of a young woman in whom the combined approach of dermoscopy and RCM led to the identification of multiple small inconspicuous lesions as BCC and thus to the diagnosis of GS syndrome. © 2016 The Australasian College of Dermatologists.

Modified temporal approach for a rostro-temporal basal meningioma in a cat.

PubMed

Forterre, Franck; Jaggy, André; Rohrbach, Helene; Dickomeit, Marc; Konar, Martin

2009-06-01

An 11-year-old neutered female domestic shorthair indoor cat was presented to our hospital for treatment of a left-sided rostro-temporal basal meningioma. Focal seizures in the facial muscles had been observed sporadically for 1 year. Two weeks prior to presentation the cat had developed generalised seizures and was treated with symptomatic anticonvulsive treatment. Focal facial seizures, especially on the right side, persisted after medical therapy. From the computed tomography scan, a basal meningioma was suspected by the treating veterinarian. A left-sided suprazygomatical temporobasal approach to the zygomatic arch was chosen because it causes less soft tissue damage. After craniotomy, durotomy and gentle dorsal retraction of the left piriform lobe, the meningioma was removed. Postoperative magnetic resonance imaging confirmed complete excision of the tumour. One day after surgery the cat was alert and a left-sided facial nerve palsy was noticed. Otherwise the neurological examination was normal. Anticonvulsive and eye moistening therapy was continued for 3 months. Six months after surgery the cat was clinically normal without any recurrence of seizures.

Quantitative EEG abnormalities in major depressive disorder with basal ganglia stroke with lesions in different hemispheres.

PubMed

Wang, Chunfang; Chen, Yuanyuan; Zhang, Ying; Chen, Jin; Ding, Xiaojing; Ming, Dong; Du, Jingang

2017-06-01

This study aimed to examine the aberrant EEG oscillation in major depressive subjects with basal ganglia stroke with lesions in different hemispheres. Resting EEG of 16 electrodes in 58 stroke subjects, 26 of whom had poststroke depression (13 with left-hemisphere lesion and 13 with right) and 32 of whom did not (18 with left lesion and 14 with right), was recorded to obtain spectral power analysis for several frequency bands. Multiple analysis of variance and receiver operating characteristic (ROC) curves were used to identify differences between poststroke depression (PSD) and poststroke non-depression (PSND), treating the different lesion hemispheres separately. Moreover, Pearson linear correlation analysis was conducted to test the severity of depressive symptoms and EEG indices. PSD with left-hemisphere lesion showed increased beta2 power in frontal and central areas, but PSD with right-hemisphere lesion showed increased theta and alpha power mainly in occipital and temporal regions. Additionally, for left-hemisphere lesions, beta2 power in central and right parietal regions provided high discrimination between PSD and PSND, and for right-hemisphere lesions, theta power was similarly discriminative in most regions, especially temporal regions. We also explored the association between symptoms of depression and the power of abnormal bands, but we found no such relationship. The sample size was relatively small and included subjects with different lesions of the basal ganglia. The aberrant EEG oscillation in subjects with PSD differs between subjects with lesions of the left and right hemispheres, suggesting a complex association between depression and lesion location in stroke patients. Copyright © 2017 Elsevier B.V. All rights reserved.

Bladder, bowel, and sexual dysfunction in Parkinson's disease.

PubMed

Sakakibara, Ryuji; Kishi, Masahiko; Ogawa, Emina; Tateno, Fuyuki; Uchiyama, Tomoyuki; Yamamoto, Tatsuya; Yamanishi, Tomonori

2011-01-01

Bladder dysfunction (urinary urgency/frequency), bowel dysfunction (constipation), and sexual dysfunction (erectile dysfunction) (also called "pelvic organ" dysfunctions) are common nonmotor disorders in Parkinson's disease (PD). In contrast to motor disorders, pelvic organ autonomic dysfunctions are often nonresponsive to levodopa treatment. The brain pathology causing the bladder dysfunction (appearance of overactivity) involves an altered dopamine-basal ganglia circuit, which normally suppresses the micturition reflex. By contrast, peripheral myenteric pathology causing slowed colonic transit (loss of rectal contractions) and central pathology causing weak strain and paradoxical anal sphincter contraction on defecation (PSD, also called as anismus) are responsible for the bowel dysfunction. In addition, hypothalamic dysfunction is mostly responsible for the sexual dysfunction (decrease in libido and erection) in PD, via altered dopamine-oxytocin pathways, which normally promote libido and erection. The pathophysiology of the pelvic organ dysfunction in PD differs from that in multiple system atrophy; therefore, it might aid in differential diagnosis. Anticholinergic agents are used to treat bladder dysfunction in PD, although these drugs should be used with caution particularly in elderly patients who have cognitive decline. Dietary fibers, laxatives, and "prokinetic" drugs such as serotonergic agonists are used to treat bowel dysfunction in PD. Phosphodiesterase inhibitors are used to treat sexual dysfunction in PD. These treatments might be beneficial in maximizing the patients' quality of life.

Bladder, Bowel, and Sexual Dysfunction in Parkinson's Disease

PubMed Central

Sakakibara, Ryuji; Kishi, Masahiko; Ogawa, Emina; Tateno, Fuyuki; Uchiyama, Tomoyuki; Yamamoto, Tatsuya; Yamanishi, Tomonori

2011-01-01

Bladder dysfunction (urinary urgency/frequency), bowel dysfunction (constipation), and sexual dysfunction (erectile dysfunction) (also called “pelvic organ” dysfunctions) are common nonmotor disorders in Parkinson's disease (PD). In contrast to motor disorders, pelvic organ autonomic dysfunctions are often nonresponsive to levodopa treatment. The brain pathology causing the bladder dysfunction (appearance of overactivity) involves an altered dopamine-basal ganglia circuit, which normally suppresses the micturition reflex. By contrast, peripheral myenteric pathology causing slowed colonic transit (loss of rectal contractions) and central pathology causing weak strain and paradoxical anal sphincter contraction on defecation (PSD, also called as anismus) are responsible for the bowel dysfunction. In addition, hypothalamic dysfunction is mostly responsible for the sexual dysfunction (decrease in libido and erection) in PD, via altered dopamine-oxytocin pathways, which normally promote libido and erection. The pathophysiology of the pelvic organ dysfunction in PD differs from that in multiple system atrophy; therefore, it might aid in differential diagnosis. Anticholinergic agents are used to treat bladder dysfunction in PD, although these drugs should be used with caution particularly in elderly patients who have cognitive decline. Dietary fibers, laxatives, and “prokinetic” drugs such as serotonergic agonists are used to treat bowel dysfunction in PD. Phosphodiesterase inhibitors are used to treat sexual dysfunction in PD. These treatments might be beneficial in maximizing the patients' quality of life. PMID:21918729

Inhibiting the Hedgehog Pathway in Patients with the Basal-Cell Nevus Syndrome

PubMed Central

Tang, Jean Y.; Mackay-Wiggan, Julian M.; Aszterbaum, Michelle; Yauch, Robert L.; Lindgren, Joselyn; Chang, Kris; Coppola, Carol; Chanana, Anita M.; Marji, Jackleen; Bickers, David R.; Epstein, Ervin H.

2012-01-01

BACKGROUND Dysregulated hedgehog signaling is the pivotal molecular abnormality underlying basal-cell carcinomas. Vismodegib is a new orally administered hedgehog-pathway inhibitor that produces objective responses in locally advanced and metastatic basal-cell carcinomas. METHODS We tested the anti–basal-cell carcinoma efficacy of vismodegib in a randomized, double-blind, placebo-controlled trial in patients with the basal-cell nevus syndrome at three clinical centers from September 2009 through January 2011. The primary end point was reduction in the incidence of new basal-cell carcinomas that were eligible for surgical resection (surgically eligible) with vismodegib versus placebo after 3 months; secondary end points included reduction in the size of existing basal-cell carcinomas. RESULTS In 41 patients followed for a mean of 8 months (range, 1 to 15) after enrollment, the per-patient rate of new surgically eligible basal-cell carcinomas was lower with vismodegib than with placebo (2 vs. 29 cases per group per year, P<0.001), as was the size (percent change from baseline in the sum of the longest diameter) of existing clinically significant basal-cell carcinomas (−65% vs. −11%, P = 0.003). In some patients, all basal-cell carcinomas clinically regressed. No tumors progressed during treatment with vismodegib. Patients receiving vismodegib routinely had grade 1 or 2 adverse events of loss of taste, muscle cramps, hair loss, and weight loss. Overall, 54% of patients (14 of 26) receiving vismodegib discontinued drug treatment owing to adverse events. At 1 month, vismodegib use had reduced the hedgehog target-gene expression by basal-cell carcinoma by 90% (P<0.001) and diminished tumor-cell proliferation, but apoptosis was not affected. No residual basal-cell carcinoma was detectable in 83% of biopsy samples taken from sites of clinically regressed basal-cell carcinomas. CONCLUSIONS Vismodegib reduces the basal-cell carcinoma tumor burden and blocks growth of new basal-cell carcinomas in patients with the basal-cell nevus syndrome. The adverse events associated with treatment led to discontinuation in over half of treated patients. (Funded by Genentech and others; ClinicalTrials.gov number, NCT00957229.) PMID:22670904

Treating Japanese barberry (Berberis thunbergii) during the dormant season

Treesearch

Jeffrey S. Ward; Scott C. Williams

2013-01-01

Japanese barberry (Berberis thunbergii) is an invasive shrub that can suppress forest regeneration and increase the risk of exposure to Lyme disease. In 2008, we began a study in central Connecticut to examine the efficacy of treating barberry infestations during the dormant season (October-March). Techniques included basal spray (triclopyr in oil)...

Neuroprotection and aging of the cholinergic system: a role for the ergoline derivative nicergoline (Sermion).

PubMed

Giardino, L; Giuliani, A; Battaglia, A; Carfagna, N; Aloe, L; Calza', L

2002-01-01

The aging brain is characterized by selective neurochemical changes involving several neural populations. A deficit in the cholinergic system of the basal forebrain is thought to contribute to the development of cognitive symptoms of dementia. Attempts to prevent age-associated cholinergic vulnerability and deterioration therefore represent a crucial point for pharmacotherapy in the elderly. In this paper we provide evidence for the protective effect of nicergoline (Sermion) on the degeneration of cholinergic neurons induced by nerve growth factor deprivation. Nerve growth factor deprivation was induced by colchicine administration in rats 13 and 18 months old. Colchicine induces a rapid and substantial down-regulation of choline acetyltransferase messenger RNA level in the basal forebrain in untreated adult, middle-aged and old rats. Colchicine failed to cause these effects in old rats treated for 120 days with nicergoline 10 mg/kg/day, orally. Moreover, a concomitant increase of both nerve growth factor and brain-derived neurotrophic factor content was measured in the basal forebrain of old, nicergoline-treated rats. Additionally, the level of messenger RNA for the brain isoform of nitric oxide synthase in neurons of the basal forebrain was also increased in these animals. Based on the present findings, nicergoline proved to be an effective drug for preventing neuronal vulnerability due to experimentally induced nerve growth factor deprivation.

Observation of a unique case of metastatic basal cell carcinoma found by radiographic evaluation in a patient with oculocutaneous albinism

PubMed Central

Johnston, Mickaila

2014-01-01

Background: Basal cell carcinoma is one of the more common cancers worldwide; 2.8 million are diagnosed annually in the USA.  However, the rate at which it metastasizes is considered very low, between 0.0028 and 0.5%.  For those rare cases in which metastases occur, approximately one third metastasize to the lung.  Case: Presented is a 62-year-old Caucasian male with oculocutaneous albinism and a history of basal cell carcinomas occurring in multiple anatomic sites, most recently at the bilateral forearm and back.  Surveillance PET/CT imaging led to the discovery of no less than 30 lung nodules which were consistent with basal cell carcinoma on biopsy.  Histological features were remarkably similar in both the primary tumor and in the metastases. Conclusion:  An unusual case of a non-head and neck primary basal cell carcinoma metastatic to the lung was discovered on surveillance PET/CT imaging, in a patient with oculocutaneous albinism. PMID:24555117

Cytokine effects on the basal ganglia and dopamine function: the subcortical source of inflammatory malaise.

PubMed

Felger, Jennifer C; Miller, Andrew H

2012-08-01

Data suggest that cytokines released during the inflammatory response target subcortical structures including the basal ganglia as well as dopamine function to acutely induce behavioral changes that support fighting infection and wound healing. However, chronic inflammation and exposure to inflammatory cytokines appears to lead to persisting alterations in the basal ganglia and dopamine function reflected by anhedonia, fatigue, and psychomotor slowing. Moreover, reduced neural responses to hedonic reward, decreased dopamine metabolites in the cerebrospinal fluid and increased presynaptic dopamine uptake and decreased turnover have been described. This multiplicity of changes in the basal ganglia and dopamine function suggest fundamental effects of inflammatory cytokines on dopamine synthesis, packaging, release and/or reuptake, which may sabotage and circumvent the efficacy of current treatment approaches. Thus, examination of the mechanisms by which cytokines alter the basal ganglia and dopamine function will yield novel insights into the treatment of cytokine-induced behavioral changes and inflammatory malaise. Copyright © 2012 Elsevier Inc. All rights reserved.

Effects of chronic ammonium sulfate treatment on the forest at the Bear Brook Watershed in Maine.

PubMed

Elvir, Jose Alexander; Wiersma, G Bruce; Bethers, Suzanne; Kenlan, Peter

2010-12-01

At the Bear Brook Watershed in Maine (BBWM), the forest tree composition was characterized and the effects of the chronic ammonium sulfate ((NH(4))(2)SO(4)) treatment on basal area growth, foliar chemistry, and gas exchange were investigated on forest species. The BBWM is a paired watershed forest ecosystem study with one watershed, West Bear (WB), treated since 1989 with 26.6 kg N ha(-1) year(-1) and 30 kg S ha(-1) year(-1)applied bimonthly as (NH(4))(2)SO(4), while the other watershed, East Bear (EB), serves as a reference. Tree species richness, density, and mortality were found to be similar between watersheds. Basal area increment was estimated from red spruce and sugar maple, showing that, for the first 7 years of treatment, it was significantly higher for sugar maple growing in WB compared to EB, but no differences were observed for red spruce between watersheds. However, the initial higher sugar maple basal area growth in WB subsequently decreased after 8 years of treatment. Foliar chemical analysis performed in trees, saplings, and ground flora showed higher N concentrations in the treated WB compared to the reference EB. But, foliar cation concentrations, especially Ca and Mg, were significantly lower for most of the species growing in WB compared with those growing in EB. For sugar maple, foliar N was higher on WB, but there were no differences in foliar Ca and Mg concentrations between treated and reference watersheds. In addition, only sugar maple trees in the treated WB showed significantly higher photosynthetic rates compared to reference EB trees.

Multiple Risks, Emotion Regulation Skill, and Cortisol in Low-Income African American Youth: A Prospective Study

ERIC Educational Resources Information Center

Kliewer, Wendy; Reid-Quinones, Kathryn; Shields, Brian J.; Foutz, Lauren

2009-01-01

Associations between multiple risks, emotion regulation skill, and basal cortisol levels were examined in a community sample of 69 African American youth (mean age = 11.30 years; 49% male) living in an urban setting. Multiple risks were assessed at Time 1 and consisted of 10 demographic and psychosocial risk factors including parent, child, and…

Breeding birds in managed forests on public conservation lands in the Mississippi Alluvial Valley

USGS Publications Warehouse

Twedt, Daniel J.; Wilson, R. Randy

2017-01-01

Managers of public conservation lands in the Mississippi Alluvial Valley have implemented forest management strategies to improve bottomland hardwood habitat for target wildlife species. Through implementation of various silvicultural practices, forest managers have sought to attain forest structural conditions (e.g., canopy cover, basal area, etc.) within values postulated to benefit wildlife. We evaluated data from point count surveys of breeding birds on 180 silviculturally treated stands (1049 counts) that ranged from 1 to 20 years post-treatment and 134 control stands (676 counts) that had not been harvested for >20 years. Birds detected during 10-min counts were recorded within four distance classes and three time intervals. Avian diversity was greater on treated stands than on unharvested stands. Of 42 commonly detected species, six species including Prothonotary Warbler (Prothonotaria citrea) and Acadian Flycatcher (Empidonax virescens) were indicative of control stands. Similarly, six species including Indigo Bunting (Passerina cyanea) and Yellow-breasted Chat (Icteria virens) were indicative of treated stands. Using a removal model to assess probability of detection, we evaluated occupancy of bottomland forests at two spatial scales (stands and points within occupied stands). Wildlife-forestry treatment improved predictive models of species occupancy for 18 species. We found years post treatment (range = 1–20), total basal area, and overstory canopy were important species-specific predictors of occupancy, whereas variability in basal area was not. In addition, we used a removal model to estimate species-specific probability of availability for detection, and a distance model to estimate effective detection radius. We used these two estimated parameters to derive species densities and 95% confidence intervals for treated and unharvested stands. Avian densities differed between treated and control stands for 16 species, but only Common Yellowthroat (Geothlypis trichas) and Yellow-breasted Chat had greater densities on treated stands.

Restoration of normal sperm characteristics in hypoprolactinemic infertile men treated with metoclopramide and exogenous human prolactin.

PubMed

Ufearo, C S; Orisakwe, O E

1995-09-01

We investigated the effects of induced increase in prolactin levels on spermatogenesis in 20 infertile men with hypoprolactinemia using exogenous human prolactin (hPRL) and metoclopramide. The subjects were selected from a population of 175 infertile men in whom the prevalence of hypoprolactinemia was 33.14%. Mean basal plasma prolactin was 2.79 +/- 0.62 ng.ml-1 in the infertile men and 9.57 +/- 2.14 ng.ml-1 in the normal control subjects. At the sixteenth week, mean plasma prolactin was 9.41 +/- 1.3 ng.ml-1 in subjects treated with exogenous hPRL and 5.2 +/- 0.7 ng.ml-1 in subjects treated with metoclopramide. Mean basal sperm concentration was approximately 8.8 million per milliliter in the infertile men and 41.5 million per milliliter in the normal control subjects. Mean sperm concentration was approximately 37 million per milliliter in subjects treated with exogenous hPRL, whereas the peak mean value was 23 million per milliliter in subjects treated with metoclopramide for 16 weeks. At basal conditions, the mean percentages of abnormal sperm were 66.75% +/- 14.93% and 21.36% +/- 4.78% in infertile and normal subjects, respectively. In subjects treated with exogenous hPRL and metoclopramide, the mean percentage of abnormal sperm were 24.7% and 31%, respectively, at week 16. Mean plasma prolactin, mean sperm concentration and the mean percentage of abnormal sperm were 3.3 +/- 1.4 ng.ml-1, 7 million per milliliter, and 60.5, respectively, in the infertile subjects after drug withdrawal at week 14. In normal control subjects, there was no significant difference (p = 0.01) in the plecebo effect. We therefore conclude that the low prolactin levels in this group of infertile men may be one of the primary causes of their infertility.

Multiple keratocysts of the mandible in association with Gorlin-Goltz syndrome: A rare case report

PubMed Central

Kulkarni, Gayithri Harish; Khaji, Shahanavaj I.; Metkari, Suryakant; Kulkarni, Harish S.; Kulkarni, Reshma

2014-01-01

Nevoid basal cell carcinoma syndrome is a syndrome with wide variety of manifestations ranging from oral lesions to skeletal deformities. It calls for due responsibility of maxillofacial surgeon to diagnose the syndrome because very often they are the first health professionals to see the patient for the treatment of keratocystic odontogenic tumor. Keratocystic odontogenic tumor has been the topic of numerous investigators, is known for its potentially aggressive behavior, significant rate of recurrences. KCOT often occurs as a solitary lesion, in some instances multiple keratocysts may occur in association with a syndrome called Gorlin-Goltz syndrome (nevoid BCC, jaw cyst bifid rib basal cell nevus syndrome). Here, we present a case of multiple keratocysts in the mandible in association with skeletal, ocular, cutaneous anomalies in the given clinical scenario, which has profound relevance in the clinical dental practice. PMID:25191087

Multiple keratocysts of the mandible in association with Gorlin-Goltz syndrome: A rare case report.

PubMed

Kulkarni, Gayithri Harish; Khaji, Shahanavaj I; Metkari, Suryakant; Kulkarni, Harish S; Kulkarni, Reshma

2014-07-01

Nevoid basal cell carcinoma syndrome is a syndrome with wide variety of manifestations ranging from oral lesions to skeletal deformities. It calls for due responsibility of maxillofacial surgeon to diagnose the syndrome because very often they are the first health professionals to see the patient for the treatment of keratocystic odontogenic tumor. Keratocystic odontogenic tumor has been the topic of numerous investigators, is known for its potentially aggressive behavior, significant rate of recurrences. KCOT often occurs as a solitary lesion, in some instances multiple keratocysts may occur in association with a syndrome called Gorlin-Goltz syndrome (nevoid BCC, jaw cyst bifid rib basal cell nevus syndrome). Here, we present a case of multiple keratocysts in the mandible in association with skeletal, ocular, cutaneous anomalies in the given clinical scenario, which has profound relevance in the clinical dental practice.

Phosphorylation of NHE3-S719 regulates NHE3 activity through the formation of multiple signaling complexes

PubMed Central

Sarker, Rafiquel; Cha, Boyoung; Kovbasnjuk, Olga; Cole, Robert; Gabelli, Sandra; Tse, Chung Ming; Donowitz, Mark

2017-01-01

Casein kinase 2 (CK2) binds to the NHE3 C-terminus and constitutively phosphorylates a downstream site (S719) that accounts for 40% of basal NHE3 activity. The role of CK2 in regulation of NHE3 activity in polarized Caco-2/bbe cells was further examined by mutation of NHE3-S719 to A (not phosphorylated) or D (phosphomimetic). NHE3-S719A but not -S719D had multiple changes in NHE3 activity: 1) reduced basal NHE3 activity—specifically, inhibition of the PI3K/AKT-dependent component; 2) reduced acute stimulation of NHE3 activity by LPA/LPA5R stimulation; and 3) reduced acute inhibition of NHE3 activity—specifically, elevated Ca2+ related (carbachol/Ca2+ ionophore), but there was normal inhibition by forskolin and hyperosmolarity. The S719A mutant had reduced NHE3 complex size, reduced expression in lipid rafts, increased BB mobile fraction, and reduced binding to multiple proteins that bind throughout the NHE3 intracellular C-terminus, including calcineurin homologous protein, the NHERF family and SNX27 (related PDZ domains). These studies show that phosphorylation of the NHE3 at a single amino acid in the distal part of the C-terminus affects multiple aspects of NHE3 complex formation and changes the NHE3 lipid raft distribution, which cause changes in specific aspects of basal as well as acutely stimulated and inhibited Na+/H+ exchange activity. PMID:28495796

Switching to multiple daily injection therapy with glulisine improves glycaemic control, vascular damage and treatment satisfaction in basal insulin glargine-injected diabetic patients.

PubMed

Yanagisawa, Katsuyuki; Ashihara, Junya; Obara, Shinji; Wada, Norio; Takeuchi, Masayoshi; Nishino, Yuri; Maeda, Sayaka; Ishibashi, Yuji; Yamagishi, Sho-ichi

2014-11-01

Basal and bolus insulin therapy is required for strict blood control in diabetic patients, which could lead to prevention of vascular complications in diabetes. However, the optimal combination regimen is not well established. Fifty-nine diabetic patients (49 type 1 and 10 type 2; 52.9 ± 13.3 years old) whose blood glucose levels were uncontrolled (HbA1c  > 6.2%) by combination treatment of basal insulin glargine with multiple daily pre-meal injections of bolus short-acting insulin [aspart (n = 19), lispro (n = 37) and regular human insulin (n = 3)] for at least 8 weeks were enrolled in this study. We examined whether glycaemic control and vascular injury were improved by replacement of short-acting insulin with glulisine. Patient satisfaction was assessed with Diabetes Treatment Satisfaction Questionnaire. Although bolus and basal insulin doses were almost unchanged before and after replacement therapy, switching to glulisine insulin for 24 weeks significantly decreased level of HbA1c , advanced glycation end products (AGEs), soluble receptor for AGEs (sRAGE), monocyte chemoattractant protein-1 (MCP-1) and urinary albumin excretion. In multiple stepwise regression analysis, change in MCP-1 values from baseline (ΔMCP-1) was a sole determinant of log urinary albumin excretion. ΔAGEs and ΔsRAGE were independently correlated with each other. The relationship between ΔMCP-1 and ΔsRAGE was marginally significant (p = 0.05). Replacement of short-acting insulin by glulisine significantly increased Diabetes Treatment Satisfaction Questionnaire scores. Our present study suggests that combination therapy of glargine with multiple daily pre-meal injections of glulisine might show superior efficacy in controlling blood glucose, preventing vascular damage and improving treatment satisfaction in diabetic patients. Copyright © 2014 John Wiley & Sons, Ltd.

Aging and Intermittent Fasting Impact on Transcriptional Regulation and Physiological Responses of Adult Drosophila Neuronal and Muscle Tissues

PubMed Central

Zhang, Sharon; Ratliff, Eric P.; Molina, Brandon; El-Mecharrafie, Nadja; Mastroianni, Jessica; Kotzebue, Roxanne W.; Achal, Madhulika; Mauntz, Ruth E.; Gonzalez, Arysa; Barekat, Ayeh; Bray, William A.; Macias, Andrew M.; Daugherty, Daniel; Harris, Greg L.; Edwards, Robert A.; Finley, Kim D.

2018-01-01

The progressive decline of the nervous system, including protein aggregate formation, reflects the subtle dysregulation of multiple functional pathways. Our previous work has shown intermittent fasting (IF) enhances longevity, maintains adult behaviors and reduces aggregates, in part, by promoting autophagic function in the aging Drosophila brain. To clarify the impact that IF-treatment has upon aging, we used high throughput RNA-sequencing technology to examine the changing transcriptome in adult Drosophila tissues. Principle component analysis (PCA) and other analyses showed ~1200 age-related transcriptional differences in head and muscle tissues, with few genes having matching expression patterns. Pathway components showing age-dependent expression differences were involved with stress response, metabolic, neural and chromatin remodeling functions. Middle-aged tissues also showed a significant increase in transcriptional drift-variance (TD), which in the CNS included multiple proteolytic pathway components. Overall, IF-treatment had a demonstrably positive impact on aged transcriptomes, partly ameliorating both fold and variance changes. Consistent with these findings, aged IF-treated flies displayed more youthful metabolic, behavioral and basal proteolytic profiles that closely correlated with transcriptional alterations to key components. These results indicate that even modest dietary changes can have therapeutic consequences, slowing the progressive decline of multiple cellular systems, including proteostasis in the aging nervous system. PMID:29642630

Aging and Intermittent Fasting Impact on Transcriptional Regulation and Physiological Responses of Adult Drosophila Neuronal and Muscle Tissues.

PubMed

Zhang, Sharon; Ratliff, Eric P; Molina, Brandon; El-Mecharrafie, Nadja; Mastroianni, Jessica; Kotzebue, Roxanne W; Achal, Madhulika; Mauntz, Ruth E; Gonzalez, Arysa; Barekat, Ayeh; Bray, William A; Macias, Andrew M; Daugherty, Daniel; Harris, Greg L; Edwards, Robert A; Finley, Kim D

2018-04-10

The progressive decline of the nervous system, including protein aggregate formation, reflects the subtle dysregulation of multiple functional pathways. Our previous work has shown intermittent fasting (IF) enhances longevity, maintains adult behaviors and reduces aggregates, in part, by promoting autophagic function in the aging Drosophila brain. To clarify the impact that IF-treatment has upon aging, we used high throughput RNA-sequencing technology to examine the changing transcriptome in adult Drosophila tissues. Principle component analysis (PCA) and other analyses showed ~1200 age-related transcriptional differences in head and muscle tissues, with few genes having matching expression patterns. Pathway components showing age-dependent expression differences were involved with stress response, metabolic, neural and chromatin remodeling functions. Middle-aged tissues also showed a significant increase in transcriptional drift-variance (TD), which in the CNS included multiple proteolytic pathway components. Overall, IF-treatment had a demonstrably positive impact on aged transcriptomes, partly ameliorating both fold and variance changes. Consistent with these findings, aged IF-treated flies displayed more youthful metabolic, behavioral and basal proteolytic profiles that closely correlated with transcriptional alterations to key components. These results indicate that even modest dietary changes can have therapeutic consequences, slowing the progressive decline of multiple cellular systems, including proteostasis in the aging nervous system.

The ABC Model and its Applicability to Basal Angiosperms

PubMed Central

Soltis, Douglas E.; Chanderbali, André S.; Kim, Sangtae; Buzgo, Matyas; Soltis, Pamela S.

2007-01-01

Background Although the flower is the central feature of the angiosperms, little is known of its origin and subsequent diversification. The ABC model has long been the unifying paradigm for floral developmental genetics, but it is based on phylogenetically derived eudicot models. Synergistic research involving phylogenetics, classical developmental studies, genomics and developmental genetics has afforded valuable new insights into floral evolution in general, and the early flower in particular. Scope and Conclusions Genomic studies indicate that basal angiosperms, and by inference the earliest angiosperms, had a rich tool kit of floral genes. Homologues of the ABCE floral organ identity genes are also present in basal angiosperm lineages; however, C-, E- and particularly B-function genes are more broadly expressed in basal lineages. There is no single model of floral organ identity that applies to all angiosperms; there are multiple models that apply depending on the phylogenetic position and floral structure of the group in question. The classic ABC (or ABCE) model may work well for most eudicots. However, modifications are needed for basal eudicots and, the focus of this paper, basal angiosperms. We offer ‘fading borders’ as a testable hypothesis for the basal-most angiosperms and, by inference, perhaps some of the earliest (now extinct) angiosperms. PMID:17616563

Cortical stimulation evokes abnormal responses in the dopamine-depleted rat basal ganglia.

PubMed

Kita, Hitoshi; Kita, Takako

2011-07-13

The motor cortex (MC) sends massive projections to the basal ganglia. Motor disabilities in patients and animal models of Parkinson's disease (PD) may be caused by dopamine (DA)-depleted basal ganglia that abnormally process the information originating from MC. To study how DA depletion alters signal transfer in the basal ganglia, MC stimulation-induced (MC-induced) unitary responses were recorded from the basal ganglia of control and 6-hydroxydopamine-treated hemi-parkinsonian rats anesthetized with isoflurane. This report describes new findings about how DA depletion alters MC-induced responses. MC stimulation evokes an excitation in normally quiescent striatal (Str) neurons projecting to the globus pallidus external segment (GPe). After DA-depletion, the spontaneous firing of Str-GPe neurons increases, and MC stimulation evokes a shorter latency excitation followed by a long-lasting inhibition that was invisible under normal conditions. The increased firing activity and the newly exposed long inhibition generate tonic inhibition and a disfacilitation in GPe. The disfacilitation in GPe is then amplified in basal ganglia circuitry and generates a powerful long inhibition in the basal ganglia output nucleus, the globus pallidus internal segment. Intra-Str injections of a behaviorally effective dose of DA precursor l-3,4-dihydroxyphenylalanine effectively reversed these changes. These newly observed mechanisms also support the generation of pauses and burst activity commonly observed in the basal ganglia of parkinsonian subjects. These results suggest that the generation of abnormal response sequences in the basal ganglia contributes to the development of motor disabilities in PD and that intra-Str DA supplements effectively suppress abnormal signal transfer.

Perceptions of diabetes control among people with type 2 diabetes treated with basal insulin in Sweden, Switzerland, and the United Kingdom.

PubMed

Brod, Meryl; Pfeiffer, Kathryn M; Barnett, Anthony H; Berntorp, Kerstin; Vilsbøll, Tina; Weissenberger, Benno

2016-07-11

To investigate perceptions of control among people with uncontrolled and well controlled type 2 diabetes (T2D) treated with basal insulin, as well as differences in perceptions and diabetes management practices between the two groups. Web surveys of 1012 people with uncontrolled T2D (HbA 1c >8.0% or 64 mmol/mol) on basal insulin in Sweden, Switzerland, and the UK and 295 people with well controlled T2D (HbA 1c <7.5% or 58 mmol/mol) on basal insulin in the UK were conducted. People with uncontrolled T2D perceived a wide range of factors as very/extremely important for deciding whether they are well controlled, including diet (80.7%), HbA 1c value (78.9%), times per day insulin taken (78.8%), insulin units taken per day (77.6%), and energy levels (74.5%). Fifty-one percent of uncontrolled respondents considered the past week or more recently when thinking about control. Perceived major obstacles to control included stress (75.4%), other health issues (70.8%), medicine side effects (69.9%), food cravings (69.8%), doctor not understanding individual situation (67.6%), and life crises (66.9%). Many uncontrolled respondents reported that diabetes was very/extremely interfering with their lives, including energy level (71.0%), performance at work (70.0%), general health (69.9%), and doing what one wants (69.3%). Analyses showed significant differences between well controlled and uncontrolled UK respondents. Compared to the uncontrolled, people with well controlled T2D were significantly more likely to consider the last 24 hours/current time when thinking about control (50% vs. 21%, p < 0.001) and reported greater healthcare contact related to diabetes and more frequent glucose measurement. Study limits include potential selection bias of web surveys and possible recall bias in patient-reported data. The results illuminate how people with T2D treated with basal insulin perceive control and show important differences between the well controlled and uncontrolled. Findings may have implications for improving patient and physician education and diabetes management.

A review of the new GLP-1 receptor agonist/basal insulin fixed-ratio combination products.

PubMed

Nuffer, Wesley; Guesnier, Ashley; Trujillo, Jennifer M

2018-03-01

There have been several new treatment approaches established for the management of hyperglycemia in type 2 diabetes (T2D), with treatment guidelines listing both glucagon-like peptide 1 receptor agonists (GLP-1 RAs) and basal insulin therapies as considerations for patients who have failed to control their blood glucose with oral antidiabetic agents. New studies have highlighted the importance of initiating combination therapy earlier in the T2D disease process to avoid clinical inertia and prevent the long-term complications arising from uncontrolled diabetes. Until recently, both GLP-1 RAs and basal insulin therapies were only available as single agents, but there are now two combination pen devices that deliver both a GLP-1 RA and basal insulin simultaneously. This article reviews the current clinical evidence evaluating the use of these combination GLP-1 RA/basal insulin preparations to treat T2D, presents both potential benefits as well as possible downsides with the use of these agents, and discusses the current place in therapy these products represent in the management of T2D.

Usefulness of (18)F-FDG PET/CT in recurrent basal cell carcinoma: Report of a case.

PubMed

Ayala, S; Perlaza, P; Puig, S; Prats, E; Vidal-Sicart, S

2016-01-01

We analyze the case of a patient with left periorbital infiltrating basal cell carcinoma treated with surgical excision in October 2010. Surgery included orbital exenteration and reconstruction using skin graft and radiotherapy. In May 2013 a MR imaging showed a mass in the left orbital fossa, suggesting a recurrence in the graft. A basal cell carcinoma recurrence with perineural invasion was confirmed in the biopsy. On (18)F-FDG PET/CT performed, a hypermetabolic activity was observed in the left periorbital area with extension to surrounding sinus and bones. The use of (18)F-FDG PET/CT in patients with advanced basal cell carcinoma has not been fully explored due to the rarity of this entity. This case demonstrates the usefulness of this technique to determine the extent of non-melanocytic recurrent skin tumors, and its value in the staging and treatment control, supporting the incorporation of (18)F-FDG PET/CT in the management of advanced basal cell carcinoma. Copyright © 2015 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

Vismodegib Therapy for Basal Cell Carcinoma in an 8-Year-Old Chinese Boy with Xeroderma Pigmentosum.

PubMed

Fife, Douglas; Laitinen, Marko A; Myers, David J; Landsteiner, Pamela B

2017-03-01

Vismodegib is an oral inhibitor of the Hedgehog signaling pathway and has been used to treat basal cell carcinoma (BCC) in adults. This article reports clearance of a nodular BCC of the nasal tip in an 8-year-old boy with xeroderma pigmentosum (XP). BCC can pose therapeutic challenges when located in areas that are not amenable to traditional therapies such as Mohs micrographic surgery or topical agents. Vismodegib was used at a dose of 150 mg/day to treat the boy's BCC. After 4 months of therapy, we achieved complete clinical clearance. During 21 months of follow-up, the patient's nose remained clinically clear of tumor. Vismodegib was successfully used to treat a child with XP and nodular BCC. Our goal in using vismodegib was tumor regression while avoiding cosmetic and functional disfigurement. Vismodegib was effective in clinically clearing the tumor, and the patient has shown no signs of recurrence. Further studies are warranted. © 2017 Wiley Periodicals, Inc.

Clinical inertia with regard to intensifying therapy in people with type 2 diabetes treated with basal insulin.

PubMed

Khunti, K; Nikolajsen, A; Thorsted, B L; Andersen, M; Davies, M J; Paul, S K

2016-04-01

To investigate whether clinical inertia, the failure to intensify treatment regimens when required, exists in people with type 2 diabetes treated with basal insulin. This was a retrospective cohort study involving patients with type 2 diabetes in the UK Clinical Practice Research Datalink database between January 2004 and December 2011, with follow-up until December 2013. A total of 11 696 patients were included in the analysis. Among all patients, 36.5% had their treatment intensified during the study period; of these, the treatment of 50.0, 42.5 and 7.4% was intensified with bolus or premix insulin or glucagon-like peptide-1 receptor agonists, respectively. The median time from initiation of basal insulin to treatment intensification was 4.3 years [95% confidence interval (CI) 4.1, 4.6]. Among patients clinically eligible for treatment intensification [glycated haemoglobin (HbA1c) ≥7.5% (58 mmol/mol)], 30.9% had their treatment regimen intensified. The median time to intensification in this group was 3.7 years (95% CI 3.4, 4.0). Increasing age, duration of diabetes, oral antihyperglycaemic agent usage and Charlson comorbidity index score were associated with a significant delay in the time to intensification (p < 0.05). Among patients with HbA1c ≥7.5% (58 mmol/mol), 32.1% stopped basal insulin therapy. Strategies should be developed to increase the number of patients undergoing therapy intensification and to reduce the delay in intensifying therapy for suitable patients on basal insulin. Initiatives to support patients continuing on insulin are also required. © 2016 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Surgical management of Gorlin syndrome: a 4-decade experience using local excision technique.

PubMed

Griner, Devan; Sutphin, Daniel; Sargent, Larry A

2015-04-01

Basal cell nevus syndrome (aka Gorlin syndrome, Gorlin-Goltz syndrome, nevoid basal cell carcinoma syndrome, and fifth phacomatosis) is a rare but well-described autosomal dominant condition with variable penetrance. We present a female patient who has been successfully treated using local surgical excision and diligent skin surveillance for more than 4 decades, demonstrating that simple local incision is an efficacious and reasonable surgical alternative that may circumvent the specialization and expense of Mohs technique.

Deep Brain Stimulation for Movement Disorders of Basal Ganglia Origin: Restoring Function or Functionality?

PubMed

Wichmann, Thomas; DeLong, Mahlon R

2016-04-01

Deep brain stimulation (DBS) is highly effective for both hypo- and hyperkinetic movement disorders of basal ganglia origin. The clinical use of DBS is, in part, empiric, based on the experience with prior surgical ablative therapies for these disorders, and, in part, driven by scientific discoveries made decades ago. In this review, we consider anatomical and functional concepts of the basal ganglia relevant to our understanding of DBS mechanisms, as well as our current understanding of the pathophysiology of two of the most commonly DBS-treated conditions, Parkinson's disease and dystonia. Finally, we discuss the proposed mechanism(s) of action of DBS in restoring function in patients with movement disorders. The signs and symptoms of the various disorders appear to result from signature disordered activity in the basal ganglia output, which disrupts the activity in thalamocortical and brainstem networks. The available evidence suggests that the effects of DBS are strongly dependent on targeting sensorimotor portions of specific nodes of the basal ganglia-thalamocortical motor circuit, that is, the subthalamic nucleus and the internal segment of the globus pallidus. There is little evidence to suggest that DBS in patients with movement disorders restores normal basal ganglia functions (e.g., their role in movement or reinforcement learning). Instead, it appears that high-frequency DBS replaces the abnormal basal ganglia output with a more tolerable pattern, which helps to restore the functionality of downstream networks.

Non-Syndromic Recurrent Multiple Odontogenic Keratocysts: A Case Report

PubMed Central

Bartake, AR.; Shreekanth, NG.; Prabhu, S.; Gopalkrishnan, K.

2011-01-01

Odontogenic keratocysts (OKCs) are one of the most frequent features of nevoid basal cell carcinoma syndrome (NBS). It is linked with mutation in the PTCH gene. Partial expression of the gene may result in occurrence of only multiple recurring OKC. Our patient presented with nine cysts with multiple recurrences over a period of 11 years without any other manifestation of the syndrome. PMID:21998815

Basal ganglia dysfunction

MedlinePlus

... disease Metabolic problems Multiple sclerosis (MS) Poisoning with copper, manganese, or other heavy metals Stroke Tumors A ... the brain) Wilson disease (disorder causing too much copper in the body's tissues)

Successful treatment of multiple basaliomas with bleomycin-based electrochemotherapy: a case series of three patients with Gorlin-Goltz syndrome.

PubMed

Kis, Erika; Baltás, Eszter; Kinyó, Agnes; Varga, Erika; Nagy, Nikoletta; Gyulai, Rolland; Kemény, Lajos; Oláh, Judit

2012-11-01

Gorlin-Goltz syndrome is a rare multisystemic disease, characterized by numerous basal cell carcinomas. The ideal approach for patients with the syndrome would be a treatment with a high cure rate, minimal scarring, short healing time and mild side-effects. Electrochemo-therapy is a novel therapeutic option that ablates tumours with electrical current and simultaneously administered anticancer drugs. Three patients with Gorlin-Goltz syndrome were treated with electrochemotherapy using intravenous bleomycin. Clinical response was obtained in 98 (99%) of the lesions, 86 (87%) of them showed complete response. In 2 tumours, regression was confirmed with histological examination. Long-term cosmetic results were excellent. We consider electrochemotherapy to be an additional tool in the therapeutic armamentarium for Gorlin-Goltz syndrome, and suggest using it as early as possible in selected patients to avoid disfiguring scarring.

Dermatoscopy-guided therapy of pigmented basal cell carcinoma with imiquimod*

PubMed Central

Husein-ElAhmed, Husein; Fernandez-Pugnaire, Maria Antonia

2016-01-01

BACKGROUND Dermatoscopy is a non-invasive diagnostic tool used to examine skin lesions with an optical magnification. It has been suggested as a useful tool for monitoring therapeutic response in lentigo maligna patients treated with imiquimod. OBJECTIVE To examine the accuracy of dermatoscopy as a tool to monitor the therapeutic response of pigmented basal cell carcinoma treated with imiquimod. METHOD The authors designed a prospective study. Patients with pigmented basal cell carcinoma were included and data regarding the dermatoscopy features were collected following the Menzies criteria, prior to initiating the imiquimod treatment. Subsequent dermatoscopic evaluations were performed at weeks 4 and 8, following imiquimod discontinuation. RESULTS Twenty lesions were included. The most common pigmented dermatoscopy features were large blue-grey ovoid nests (80%), followed by blue-grey globules (50%) and leaf-like areas (30%). No spoke wheel areas were observed. In 17 out of 20 patients, a response was noted during the first evaluation at 4 weeks, while the clearance was noted at the second check-up after 8 weeks. In two patients, the clearance was found at the initial evaluation at 4 weeks, while in one patient, the response remained unchanged. Blue-grey globules were the fastest to exhibit clearance (50% at week 4), followed by leaf-like areas (15%) and large blue-grey ovoid nests (6.25%). CONCLUSION According to our results, dermatoscopic evaluation enhances the accuracy in the assessment of the clinical response to imiquimod in pigmented basal cell carcinoma. PMID:28099598

Protective Effects of Trehalose on the Corneal Epithelial Cells

PubMed Central

Aragona, Pasquale; Colosi, Pietro; Colosi, Francesca; Pisani, Antonina; Puzzolo, Domenico; Micali, Antonio

2014-01-01

Purpose. Aim of the present work was to evaluate the effects of the trehalose on the corneal epithelium undergoing alcohol delamination. Methods. Twelve patients undergoing laser subepithelial keratomileusis (LASEK) were consecutively included in the study. The right eyes were pretreated with 3% trehalose eye drops, whilst left eyes were used as control. Epithelial specimens were processed for cells vitality assessment, apoptosis, and light and transmission electron microscopy; a morphometric analysis was performed in both groups. Results. In both trehalose-untreated eyes (TUE) and trehalose-treated eyes (TTE), the percentage of vital cells was similar and no apoptotic cells were observed. In TUE, the corneal epithelium showed superficial cells with reduced microfolds, wing cells with vesicles and dilated intercellular spaces, and dark basal cells with vesicles and wide clefts. In TTE, superficial and wing cells were better preserved, and basal cells were generally clear with intracytoplasmatic vesicles. The morphometric analysis showed statistically significant differences between the two groups: the TTE epithelial height was higher, the basal cells showed larger area and clearer cytoplasm. The distribution of desmosomes and hemidesmosomes was significantly different between the groups. Conclusions. Trehalose administration better preserved morphological and morphometric features of alcohol-treated corneal epithelium, when compared to controls. PMID:25045743

Protective effects of trehalose on the corneal epithelial cells.

PubMed

Aragona, Pasquale; Colosi, Pietro; Rania, Laura; Colosi, Francesca; Pisani, Antonina; Puzzolo, Domenico; Micali, Antonio

2014-01-01

Aim of the present work was to evaluate the effects of the trehalose on the corneal epithelium undergoing alcohol delamination. Twelve patients undergoing laser subepithelial keratomileusis (LASEK) were consecutively included in the study. The right eyes were pretreated with 3% trehalose eye drops, whilst left eyes were used as control. Epithelial specimens were processed for cells vitality assessment, apoptosis, and light and transmission electron microscopy; a morphometric analysis was performed in both groups. In both trehalose-untreated eyes (TUE) and trehalose-treated eyes (TTE), the percentage of vital cells was similar and no apoptotic cells were observed. In TUE, the corneal epithelium showed superficial cells with reduced microfolds, wing cells with vesicles and dilated intercellular spaces, and dark basal cells with vesicles and wide clefts. In TTE, superficial and wing cells were better preserved, and basal cells were generally clear with intracytoplasmatic vesicles. The morphometric analysis showed statistically significant differences between the two groups: the TTE epithelial height was higher, the basal cells showed larger area and clearer cytoplasm. The distribution of desmosomes and hemidesmosomes was significantly different between the groups. Trehalose administration better preserved morphological and morphometric features of alcohol-treated corneal epithelium, when compared to controls.

Effect of perinatal asphyxia and carbamazepine treatment on cortical dopamine and DOPAC levels.

PubMed

López-Pérez, Silvia J; Morales-Villagrán, Alberto; Medina-Ceja, Laura

2015-02-13

One of the most important manifestations of perinatal asphyxia is the occurrence of seizures, which are treated with antiepileptic drugs, such as carbamazepine. These early seizures, combined with pharmacological treatments, may influence the development of dopaminergic neurotransmission in the frontal cortex. This study aimed to determine the extracellular levels of dopamine and its main metabolite DOPAC in 30-day-old rats that had been asphyxiated for 45 min in a low (8%) oxygen chamber at a perinatal age and treated with daily doses of carbamazepine. Quantifications were performed using microdialysis coupled to a high-performance liquid chromatography (HPLC) system in basal conditions and following the use of the chemical stimulus. Significant decreases in basal and stimulated extracellular dopamine and DOPAC content were observed in the frontal cortex of the asphyxiated group, and these decreases were partially recovered in the animals administered daily doses of carbamazepine. Greater basal dopamine concentrations were also observed as an independent effect of carbamazepine. Perinatal asphyxia plus carbamazepine affects extracellular levels of dopamine and DOPAC in the frontal cortex and stimulated the release of dopamine, which provides evidence for the altered availability of dopamine in cortical brain areas during brain development.

Endotoxin-induced basal respiration alterations of renal HK-2 cells: A sign of pathologic metabolism down-regulation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Quoilin, C., E-mail: cquoilin@ulg.ac.be; Mouithys-Mickalad, A.; Duranteau, J.

Highlights: Black-Right-Pointing-Pointer A HK-2 cells model of inflammation-induced acute kidney injury. Black-Right-Pointing-Pointer Two oximetry methods: high resolution respirometry and ESR spectroscopy. Black-Right-Pointing-Pointer Oxygen consumption rates of renal cells decrease when treated with LPS. Black-Right-Pointing-Pointer Cells do not recover normal respiration when the LPS treatment is removed. Black-Right-Pointing-Pointer This basal respiration alteration is a sign of pathologic metabolism down-regulation. -- Abstract: To study the mechanism of oxygen regulation in inflammation-induced acute kidney injury, we investigate the effects of a bacterial endotoxin (lipopolysaccharide, LPS) on the basal respiration of proximal tubular epithelial cells (HK-2) both by high-resolution respirometry and electron spin resonancemore » spectroscopy. These two complementary methods have shown that HK-2 cells exhibit a decreased oxygen consumption rate when treated with LPS. Surprisingly, this cellular respiration alteration persists even after the stress factor was removed. We suggested that this irreversible decrease in renal oxygen consumption after LPS challenge is related to a pathologic metabolic down-regulation such as a lack of oxygen utilization by cells.« less

The effect of melatonin from slow-release implants on basic and TLR-4-mediated gene expression of inflammatory cytokines and their receptors in the choroid plexus in ewes.

PubMed

Kowalewska, M; Herman, A P; Szczepkowska, A; Skipor, J

2017-08-01

The present study concerns the effect of melatonin from slow-release implants on the expression of genes coding interleukin-1β (Il1B), inerleukin-6 (Il6), tumour necrosis factor α (Tnf) and their receptors: IL-1 receptor type I (Il1r1) and type II (Il1r2), IL-6 receptor (Il6r) and signal transducer (Il6st), TNFα receptor type I (Tnfrsf1a) and II (Tnfrsf1b) and retinoid-related orphan receptor α (RorA) and Rev.-erbα in the ovine choroid plexus (CP) under basal and lipopolysaccharide (LPS)-challenged conditions. Studies were performed on four groups: 1) sham-implanted and placebo-treated, 2) melatonin-implanted (Melovine, 18mg) and placebo-treated, 3) sham-implanted and LPS-treated (400ng/kg of body weight) and 4) melatonin-implanted and LPS-treated. Under basal conditions, we observed weak expression of Tnf, low expression of Il1B, Il6 and Il1r2 and intermediate expression of other cytokines receptors. LPS treatment induced (P≤0.05) expression in all cytokines and their receptors, except Il6r 3h after the administration. Melatonin attenuated (P≤0.05) LPS-induced up-regulation of Il6 but had no effect on other cytokines and their receptors and up-regulated (P≤0.05) Rev.-erbα expression under basal conditions. This indicates that melatonin from slow-release implants suppresses TLR4-mediated Il6 expression in the ovine CP via a mechanism likely involving clock genes. Copyright © 2017 Elsevier Ltd. All rights reserved.

A Magnetic Resonance Spectroscopy Study of Lovastatin for Treating Bipolar Mood Disorder: A 4-Week Randomized Double-Blind, Placebo- Controlled Clinical Trial.

PubMed

Lotfi, Mehrzad; Shafiee, Sara; Ghanizadeh, Ahmd; Sigaroudi, Motahar O; Razeghian, Leila

2017-01-01

No trial has examined the effect of lovastatin on the brain metabolites in patients with bipolar mood disorder. Current medications for treating bipolar disorders cause metabolic syndrome. It is supposed that lovastatin not only decreases the rate of metabolic syndrome but also impacts some brain metabolites and their ratio like common treatments that are measured by Magnetic Resonance Spectroscopy. 27 Manic phase patients were randomly allocated into two groups, lovastatin and placebo as their adjuant medication. Clinical symptoms were assessed at baseline, weeks 2, 4. The brain metabolites were measured at baseline and week 4. Regarding the change of clinical symptoms, no significant difference was found between two groups. However, lovastatin significantly increased the level of NAA in cingulate gyrus in comparison to the placebo group. Moreover, lovastatin more than placebo increased creatine in the left basal ganglia. Furthermore, choline/ creatine showed a significant decrease in the left basal ganglia in lovastatin group. Using MRS after treating with lovastatin showed lovastatin increases NAA in cingulate gyrus, indicating the possible effect of NAA for increasing the reduced viable neuron. Moreover, the increment of Cr by lovastatin in the left basal ganglia suggests the role of lovastatin for maintaining energy homeostasis, anti-apoptotic activity and ATP production in bipolar disorder. Some patents using lovastatin as an adjuant therapy for treating bipolar patients and depression in MDD patients are also outlined. This trial was registered in the Iranian Clinical Trials Registry (http://www.irct.ir/) (IRCT201302203930N18). Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Experimentally quantifying critical stresses associated with basal slip and twinning in magnesium using micro-pillars

DOE PAGES

Liu, Yue; Li, Nan; Mariyappan, Arul Kumar; ...

2017-06-07

Basal slip and {01more » $$\\bar{1}$$2} twinning are two major plastic deformation mechanisms in hexagonal closed-packed magnesium. Here in this paper, we quantify the critical stresses associated with basal slip and twinning in single-crystal and bi-crystal magnesium samples by performing in situ compression of micropillars with different diameters in a scanning electron microscope. The micropillars are designed to favor either slip or twinning under uniaxial compression. Compression tests imply a negligible size effect related to basal slip and twinning as pillar diameter is greater than 10 μm. The critical resolved shear stresses are deduced to be 29 MPa for twinning and 6 MPa for basal slip from a series of micropillar compression tests. Employing full-field elasto-visco-plastic simulations, we further interpret the experimental observations in terms of the local stress distribution associated with multiple twinning, twin nucleation, and twin growth. Our simulation results suggest that the twinning features being studied should not be close to the top surface of the micropillar because of local stress perturbations induced by the hard indenter.« less

A time- and matrix-dependent TGFBR3–JUND–KRT5 regulatory circuit in single breast epithelial cells and basal-like premalignancies

PubMed Central

Wang, Chun-Chao; Bajikar, Sameer S.; Jamal, Leen; Atkins, Kristen A.; Janes, Kevin A.

2014-01-01

Basal-like breast carcinoma is characterized by poor prognosis and high intratumor heterogeneity. In an immortalized basal-like breast epithelial cell line, we identified two anti-correlated gene-expression programs that arise among single extracellular matrix (ECM)-attached cells during organotypic 3D culture. The first contains multiple TGFβ-related genes including TGFBR3, whereas the second contains JUND and the basal-like marker, KRT5. TGFBR3 and JUND interconnect through four negative-feedback loops to form a circuit that exhibits spontaneous damped oscillations in 3D culture. The TGFBR3–JUND circuit appears conserved in some premalignant lesions that heterogeneously express KRT5. The circuit depends on ECM engagement, as detachment causes a rewiring that is triggered by RPS6 dephosphorylation and maintained by juxtacrine tenascin C, which is critical for intraductal colonization of basal-like breast cancer cells in vivo. Intratumor heterogeneity need not stem from partial differentiation and could instead reflect dynamic toggling of cells between expression states that are not cell autonomous. PMID:24658685

Skin Cancer

MedlinePlus

... States. The two most common types are basal cell cancer and squamous cell cancer. They usually form on the head, face, ... If not treated, some types of skin cancer cells can spread to other tissues and organs. Treatments ...

Ascl1 (Mash1) Knockout Perturbs Differentiation of Nonneuronal Cells in Olfactory Epithelium

PubMed Central

Jang, Woochan; Wildner, Hendrik; Schwob, James E.

2012-01-01

The embryonic olfactory epithelium (OE) generates only a very few olfactory sensory neurons when the basic helix-loop-helix transcription factor, ASCL1 (previously known as MASH1) is eliminated by gene mutation. We have closely examined the structure and composition of the OE of knockout mice and found that the absence of neurons dramatically affects the differentiation of multiple other epithelial cell types as well. The most prominent effect is observed within the two known populations of stem and progenitor cells of the epithelium. The emergence of horizontal basal cells, a multipotent progenitor population in the adult epithelium, is anomalous in the Ascl1 knockout mice. The differentiation of globose basal cells, another multipotent progenitor population in the adult OE, is also aberrant. All of the persisting globose basal cells are marked by SOX2 expression, suggesting a prominent role for SOX2 in progenitors upstream of Ascl1. However, NOTCH1-expressing basal cells are absent from the knockout; since NOTCH1 signaling normally acts to suppress Ascl1 via HES1 and drives sustentacular (Sus) cell differentiation during adult epithelial regeneration, its absence suggests reciprocity between neurogenesis and the differentiation of Sus cells. Indeed, the Sus cells of the mutant mice express a markedly lower level of HES1, strengthening that notion of reciprocity. Duct/gland development appears normal. Finally, the expression of cKIT by basal cells is also undetectable, except in those small patches where neurogenesis escapes the effects of Ascl1 knockout and neurons are born. Thus, persistent neurogenic failure distorts the differentiation of multiple other cell types in the olfactory epithelium. PMID:23284756

Dark exposure of petunia cuttings strongly improves adventitious root formation and enhances carbohydrate availability during rooting in the light.

PubMed

Klopotek, Yvonne; Haensch, Klaus-Thomas; Hause, Bettina; Hajirezaei, Mohammad-Reza; Druege, Uwe

2010-05-01

The effect of temporary dark exposure on adventitious root formation (ARF) in Petuniaxhybrida 'Mitchell' cuttings was investigated. Histological and metabolic changes in the cuttings during the dark treatment and subsequent rooting in the light were recorded. Excised cuttings were exposed to the dark for seven days at 10 degrees C followed by a nine-day rooting period in perlite or were rooted immediately for 16 days in a climate chamber at 22/20 degrees C (day/night) and a photosynthetic photon flux density (PPFD) of 100micromolm(-2)s(-1). Dark exposure prior to rooting increased, accelerated and synchronized ARF. The rooting period was reduced from 16 days (non-treated cuttings) to 9 days (treated cuttings). Under optimum conditions, despite the reduced rooting period, dark-exposed cuttings produced a higher number and length of roots than non-treated cuttings. An increase in temperature to 20 degrees C during the dark treatment or extending the cold dark exposure to 14 days caused a similar enhancement of root development compared to non-treated cuttings. Root meristem formation had already started during the dark treatment and was enhanced during the subsequent rooting period. Levels of soluble sugars (glucose, fructose and sucrose) and starch in leaf and basal stem tissues significantly decreased during the seven days of dark exposure. This depletion was, however, compensated during rooting after 6 and 24h for soluble sugars in leaves and the basal stem, respectively, whereas the sucrose level in the basal stem was already increased at 6h. The association of higher carbohydrate levels with improved rooting in previously dark-exposed versus non-treated cuttings indicates that increased post-darkness carbohydrate availability and allocation towards the stem base contribute to ARF under the influence of dark treatment and provide energy for cell growth subject to a rising sink intensity in the base of the cutting. Copyright 2009 Elsevier GmbH. All rights reserved.

Evaluation of Agrilus planipennis (Coleoptera: Buprestidae) control provided by emamectin benzoate and two neonicotinoid insecticides, one and two seasons after treatment.

PubMed

McCullough, Deborah G; Poland, Therese M; Anulewicz, Andrea C; Lewis, Phillip; Cappaert, David

2011-10-01

Effective methods are needed to protect ash trees (Fraxinus spp.) from emerald ash borer, Agrilus planipennis Fairmaire (Coleoptera: Buprestidae), an invasive buprestid that has killed millions of North American ash (Fraxinus spp.) trees. We randomly assigned 175 ash trees (11.5-48.1 cm in diameter) in 25 blocks located in three study sites in Michigan to one of seven insecticide treatments in May 2007. Treatments included 1) trunk-injected emamectin benzoate; 2) trunk-injected imidacloprid; 3) basal trunk spray of dinotefuran with or 4) without Pentra-Bark, an agricultural surfactant; 5) basal trunk spray of imidacloprid with or 6) without Pentra-Bark; or (7) control. Foliar insecticide residues (enzyme-linked immunosorbent assay) and toxicity of leaves to adult A. planipennis (4-d bioassays) were quantified at 3-4-wk intervals posttreatment. Seven blocks of trees were felled and sampled in fall 2007 to quantify A. planipennis larval density. Half of the remaining blocks were retreated in spring 2008. Bioassays and residue analyses were repeated in summer 2008, and then all trees were sampled to assess larval density in winter. Foliage from emamectin benzoate-treated trees was highly toxic to adult A. planipennis, and larval density was < 1% of that in comparable control trees, even two seasons posttreatment. Larval densities in trees treated with trunk-injected imidacloprid in 2007 + 2008 were similar to control trees. Dinotefuran and imidacloprid were effectively translocated within trees treated with the noninvasive basal trunk sprays; the surfactant did not appreciably enhance A. planipennis control. In 2008, larval densities were 57-68% lower in trees treated with dinotefuran or imidacloprid trunk sprays in 2007 + 2008 than on controls, but densities in trees treated only in 2007 were similar to controls. Highly effective control provided by emamectin benzoate for > or = 2 yr may reduce costs or logistical issues associated with treatment.

Basal Cell Carcinoma Arising in a Breast Augmentation Scar.

PubMed

Edwards, Lisa R; Cresce, Nicole D; Russell, Mark A

2017-04-01

We report a case of a 46-year-old female who presented with a persistent lesion on the inferior right breast. The lesion was located within the scar from a breast augmentation procedure 12 years ago. The lesion had been treated as several conditions with no improvement. Biopsy revealed a superficial and nodular basal cell carcinoma, and the lesion was successfully removed with Mohs micrographic surgery. Basal cell carcinoma arising in a surgical scar is exceedingly rare with only 13 reported cases to date. This is the first reported case of basal cell carcinoma arising in a breast augmentation scar. We emphasize the importance of biopsy for suspicious lesions or those refractory to treatment, particularly those lesions that form within a scar. Level of Evidence V This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Identification and characterization of a gibberellin-regulated protein, which is ASR5, in the basal region of rice leaf sheaths.

PubMed

Takasaki, Hironori; Mahmood, Tariq; Matsuoka, Makoto; Matsumoto, Hiroshi; Komatsu, Setsuko

2008-04-01

Gibberellins (GAs) regulate growth and development in higher plants. To identify GA-regulated proteins during rice leaf sheath elongation, a proteomic approach was used. Proteins from the basal region of leaf sheath in rice seedling treated with GA(3) were analyzed by fluorescence two-dimensional difference gel electrophoresis. The levels of abscisic acid-stress-ripening-inducible 5 protein (ASR5), elongation factor-1 beta, translationally controlled tumor protein, fructose-bisphosphate aldolase and a novel protein increased; whereas the level of RuBisCO subunit binding-protein decreased by GA(3) treatment. ASR5 out of these six proteins was significantly regulated by GA(3) at the protein level but not at the mRNA level in the basal region of leaf sheaths. Since this protein is regulated not only by abscisic acid but also by GA(3), these results indicate that ASR5 might be involved in plant growth in addition to stress in the basal regions of leaf sheaths.

Modulation of hippocampal ACh release by chronic nicergoline treatment in freely moving young and aged rats.

PubMed

Carfagna, N; Di Clemente, A; Cavanus, S; Damiani, D; Gerna, M; Salmoiraghi, P; Cattaneo, B; Post, C

1995-09-15

The effects of nicergoline on basal and K(+)-stimulated release of ACh in the hippocampus of 3- and 19-month old rats has been studied by microdialysis. A significant decrease of basal ACh release (59%) was found in aged vehicle treated rats in comparison to young rats. High-K+ (100 mM) in the perfusate strongly increased the release of ACh by up to 6-fold over the baseline of both young and aged rats. Chronic oral administration of nicergoline to aged rats (5 mg/kg b.i.d. for 6 weeks) significantly reversed (93%) the age-related decrease of basal release of ACh, leaving the increase due to K+ depolarization unchanged. In young animals, nicergoline did not affect the basal output of ACh, but enhanced the K(+)-evoked release of ACh by 39%. Results from this study demonstrate that nicergoline treatment increases the ability of hippocampal cholinergic terminals to release ACh, and suggest that this drug can reset the cholinergic impairement associated with aging.

Dishevelled links basal body docking and orientation in ciliated epithelial cells

PubMed Central

Vladar, Eszter K.; Axelrod, Jeffrey D.

2014-01-01

Some epithelia contain cells with multiple, motile cilia that beat in a concerted fashion. New tools and experimental systems have facilitated molecular studies of cilium biogenesis and of the coordinated planar polarization of cilia that leads to their concerted motility. Recent, elegant work by Park and colleagues, using embryonic frog epidermis, demonstrates that Dishevelled (Dvl), a key regulator of both the Wnt/β-catenin and Planar Cell Polarity (PCP) pathways, controls both the docking and planar polarization of ciliary basal bodies. PMID:18819800

Circular RNA expression in basal cell carcinoma.

PubMed

Sand, Michael; Bechara, Falk G; Sand, Daniel; Gambichler, Thilo; Hahn, Stephan A; Bromba, Michael; Stockfleth, Eggert; Hessam, Schapoor

2016-05-01

Circular RNAs (circRNAs), are nonprotein coding RNAs consisting of a circular loop with multiple miRNA, binding sites called miRNA response elements (MREs), functioning as miRNA sponges. This study was performed to identify differentially expressed circRNAs and their MREs in basal cell carcinoma (BCC). Microarray circRNA expression profiles were acquired from BCC and control followed by qRT-PCR validation. Bioinformatical target prediction revealed multiple MREs. Sequence analysis was performed concerning MRE interaction potential with the BCC miRNome. We identified 23 upregulated and 48 downregulated circRNAs with 354 miRNA response elements capable of sequestering miRNA target sequences of the BCC miRNome. The present study describes a variety of circRNAs that are potentially involved in the molecular pathogenesis of BCC.

Efficacy of Vismodegib (Erivedge) for Basal Cell Carcinoma Involving the Orbit and Periocular Area.

PubMed

Demirci, Hakan; Worden, Francis; Nelson, Christine C; Elner, Victor M; Kahana, Alon

2015-01-01

Evaluate the effectiveness of vismodegib in the management of basal cell carcinoma with orbital extension and/or extensive periocular involvement. Retrospective chart review of 6 consecutive patients with biopsy-proven orbital basal cell carcinoma and 2 additional patients with extensive periocular basal cell carcinoma who were treated with oral vismodegib (150 mg/day) was performed. Basal cell carcinoma extended in the orbit in 6 of 8 patients (involving orbital bones in 1 patient), and 2 of 8 patients had extensive periocular involvement (1 with basal cell nevus syndrome). Vismodegib therapy was the only treatment in 6 patients, off-label neoadjuvant in 1 patient, and adjuvant treatment in 1 patient. Orbital tumors in all 4 patients who received vismodegib as sole treatment showed partial response with a mean 83% shrinkage in tumor size after a median of 7 months of therapy. In the 2 patients receiving vismodegib as neoadjuvant or adjuvant therapies, there was complete response after a median of 7 months of therapy and no evidence of clinical recurrence after discontinuing therapy for a median of 15 months. The 2 patients with extensive periocular involvement experienced complete clinical response after a median 14 months of treatment. During treatment, the most common side effects were muscle spasm (75%) followed by alopecia (50%), dysgeusia (25%), dysosmia, and episodes of diarrhea and constipation (13%). Basal cell carcinoma with orbital extension and extensive periocular involvement responds to vismodegib therapy. The long-term prognosis remains unknown, and additional prospective studies are indicated.

Finasteride Treatment Alters Tissue Specific Androgen Receptor Expression in Prostate Tissues

PubMed Central

Bauman, Tyler M.; Sehgal, Priyanka D.; Johnson, Karen A.; Pier, Thomas; Bruskewitz, Reginald C.; Ricke, William A.; Huang, Wei

2014-01-01

BACKGROUND Normal and pathologic growth of the prostate is dependent on the synthesis of dihydrotestosterone (DHT) from testosterone by 5α-reductase. Finasteride is a selective inhibitor of 5α-reductase 2, one isozyme of 5α-reductase found in abundance in the human prostate. The objective of this study was to investigate the effects of finasteride on androgen receptor expression and tissue morphology in human benign prostatic hyperplasia specimens. METHODS Patients undergoing transurethral resection of the prostate and either treated or not treated with finasteride between 2004 and 2010 at the University of Wisconsin-Hospital were retrospectively identified using an institutional database. Prostate specimens from each patient were triple-stained for androgen receptor, prostate-specific antigen, and basal marker cytokeratin 5. Morphometric analysis was performed using the multispectral imaging, and results were compared between groups of finasteride treated and non-treated patients. RESULTS Epithelial androgen receptor but not stromal androgen receptor expression was significantly lower in patients treated with finasteride than in non-treated patients. Androgen receptor-regulated prostate-specific antigen was not significantly decreased in finasteride-treated patients. Significant luminal epithelial atrophy and basal cell hyperplasia were prevalent in finasteride treated patients. Epithelial androgen receptor expression was highly correlated to the level of luminal epithelial atrophy. CONCLUSIONS In this study, finasteride decreased the expression of epithelial androgen receptor in a tissue specific manner. The correlation between epithelial androgen receptor and the extent of luminal epithelial atrophy suggests that epithelial androgen receptor may be directly regulating the atrophic effects observed with finasteride treatment. PMID:24789081

Basal cell carcinoma: PD-L1/PD-1 checkpoint expression and tumor regression after PD-1 blockade.

PubMed

Lipson, Evan J; Lilo, Mohammed T; Ogurtsova, Aleksandra; Esandrio, Jessica; Xu, Haiying; Brothers, Patricia; Schollenberger, Megan; Sharfman, William H; Taube, Janis M

2017-01-01

Monoclonal antibodies that block immune regulatory proteins such as programmed death-1 (PD-1) have demonstrated remarkable efficacy in controlling the growth of multiple tumor types. Unresectable or metastatic basal cell carcinoma, however, has largely gone untested. Because PD-Ligand-1 (PD-L1) expression in other tumor types has been associated with response to anti-PD-1, we investigated the expression of PD-L1 and its association with PD-1 expression in the basal cell carcinoma tumor microenvironment. Among 40 basal cell carcinoma specimens, 9/40 (22%) demonstrated PD-L1 expression on tumor cells, and 33/40 (82%) demonstrated PD-L1 expression on tumor-infiltrating lymphocytes and associated macrophages. PD-L1 was observed in close geographic association to PD-1+ tumor infiltrating lymphocytes. Additionally, we present, here, the first report of an objective anti-tumor response to pembrolizumab (anti-PD-1) in a patient with metastatic PD-L1 (+) basal cell carcinoma, whose disease had previously progressed through hedgehog pathway-directed therapy. The patient remains in a partial response 14 months after initiation of therapy. Taken together, our findings provide a rationale for testing anti-PD-1 therapy in patients with advanced basal cell carcinoma, either as initial treatment or after acquired resistance to hedgehog pathway inhibition.

Basal C-peptide Level as a Surrogate Marker of Subclinical Atherosclerosis in Type 2 Diabetic Patients

PubMed Central

Kim, Sung-Tae; Kim, Byung-Joon; Song, In-Geol; Jung, Jang-Han; Lee, Kang-Woo; Park, Keun-Young; Cho, Youn-Zoo; Lee, Dae-Ho; Koh, Gwan-Pyo

2011-01-01

Background Recent studies have revealed that C-peptide induces smooth muscle cell proliferation and causes human atherosclerotic lesions in diabetic patients. The present study was designed to examine whether the basal C-peptide levels correlate with cardiovascular risk in type 2 diabetes mellitus (T2DM) patients. Methods Data was obtained from 467 patients with T2DM from two institutions who were followed for four years. The medical findings of all patients were reviewed, and patients with creatinine >1.4 mg/dL, any inflammation or infection, hepatitis, or type 1 DM were excluded. The relationships between basal C-peptide and other clinical values were statistically analyzed. Results A simple correlation was found between basal C-peptide and components of metabolic syndrome (MS). Statistically basal C-peptide levels were significantly higher than the three different MS criteria used in the present study, the Adult Treatment Panel III (ATP III) of the National Cholesterol Education Program's (NCEP's), World Health Organization (WHO), and the International Diabetes Federation (IDF) criteria (NCEP-ATP III, P=0.001; IDF, P<0.001; WHO, P=0.029). The multiple regression analysis between intima-media thickness (IMT) and clinical values showed that basal C-peptide significantly correlated with IMT (P=0.043), while the analysis between the 10-year coronary heart disease risk by the United Kingdom Prospective Diabetes Study risk engine and clinical values showed that basal C-peptide did not correlate with IMT (P=0.226). Conclusion Basal C-peptide is related to cardiovascular predictors (IMT) of T2DM, suggesting that basal C-peptide does provide a further indication of cardiovascular disease. PMID:21537412

Expression of basic fibroblast growth factor and its receptors FGFR1 and FGFR2 in human benign prostatic hyperplasia treated with finasteride.

PubMed

Sáez, C; González-Baena, A C; Japón, M A; Giráldez, J; Segura, D I; Rodríguez-Vallejo, J M; González-Esteban, J; Miranda, G; Torrubia, F

1999-07-01

The development of benign prostatic hyperplasia (BPH) is an androgen-dependent process which may be mediated by a number of locally produced growth factors. One of these, the basic fibroblast growth factor (bFGF or FGF2), has a mitogenic effect on prostatic stroma. High expression levels of bFGF have been reported in BPH. FGFR1 and FGFR2 receptors, that exhibit affinity for bFGF, have been identified in normal and hyperplastic prostate. Finasteride, a 5alpha-reductase inhibitor, is an effective drug in the treatment of BPH, inducing regressive changes in the prostate of treated patients, even though its mechanisms of action are not yet completely elucidated. This study was designed to assess the effects of finasteride on the expression levels of bFGF, FGFR1, and FGFR2 in patients with BPH. The expression levels of bFGF, FGFR1, and FGFR2 in 9 patients with prostatic hyperplasia treated with finasteride were assessed by immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR) analysis of mRNA expression and were compared with those of 9 control patients with untreated BPH. Immunohistochemistry showed strong bFGF immunoreactivity in the prostatic stroma of untreated patients, this being somewhat weaker in the epithelium. In treated patients, epithelial immunoreactivity was practically negative, and a considerable reduction in stromal immunoreactivity was seen. These findings were also confirmed by RT-PCR. FGFR1 showed a weak immunoreactivity in the stroma and in basal epithelial cells. FGFR1 showed a weak immunoreactivity in the stroma and in basal epithelial cells. FGFR2 exhibited strong stromal immunoreactivity, becoming weaker in the basal epithelium. No differences were seen in the expression of both receptors between the groups of treated and untreated patients. A marked reduction in bFGF levels is seen in BPH treated with finasteride in comparison to untreated BPH. In our opinion, finasteride may act as a negative regulator of bFGF expression, counteracting the role of bFGF in the development of BPH.

Outcome of in vitro fertilization in women with subclinical hypothyroidism.

PubMed

Cai, YunYing; Zhong, LanPing; Guan, Jie; Guo, RuiJin; Niu, Ben; Ma, YanPing; Su, Heng

2017-05-25

Previous studies examining associations between subclinical hypothyroidism (SCH) with in vitro fertilization (IVF) outcome indicate some benefits of levothyroxine (LT4) treatment. But IVF outcomes in treated SCH women whose serum Thyroid Stimulating Hormone (TSH) concentration did and did not exceed 2.5 mIU/L before the IVF cycle has not been studied thoroughly. In this study, we performed a prospective cohort study with 270 treated subclinical hypothyroidism patients undergoing their first IVF retrieval cycle at a single cite. SCH in women receiving LT4 replacement with a basal TSH level between 0.2-2.5mIU/L displayed a similar rate of clinical pregnancy (47.4% vs 38.7%, P = .436), miscarriage (7.4% vs 16.7%, P = .379) and live birth (43.9% vs 32.3%, P = .288) compared to women with a basal TSH level between 2.5-4.2 mIU/L. Strictly controlled TSH (less than 2.5 mIU/L) before IVF may have no effect on the pregnancy rate in LT4 treated SCH women.

[Exenteration of the Orbit for Basal Cell Carcinoma].

PubMed

Furdová, A; Horkovičová, K; Krčová, I; Krásnik, V

2015-08-01

Primary treatment of basal cell carcinoma of the lower eyelid and the inner corner is essentially surgical, but advanced lesions require extensive surgical interventions. In some cases it is necessary to continue with the mutilating surgery--exenteration of the orbit. In this work we evaluate the indications of radical solutions in patients with basal cell carcinoma invading the orbit and the subsequent possibility for individually made prosthesis to cover the defect of the cavity. Indications to exenteration of the orbit in patients with basal cell carcinoma findings in 2008-2013. Case report of 2 patients. In period 2008-20013 at the Dept. of Ophthalmology, Comenius University in Bratislava totally 221 patients with histologically confirmed basal cell carcinoma of the eyelids and the inner corner were treated. In 5 cases (2.7 %) with infiltration of the orbit the radical surgical procedure, exenteration was necessary. In 3 patients exenteration was indicated as the first surgical procedure in the treatment of basal cell carcinoma, since they had never visited ophthalmologist before only at in the stage of infiltration of the orbit (stage T4). In one case was indicated exenteration after previous surgical interventions and relapses. After healing the cavity patients got individually prepared epithesis. Surgical treatment of basal cell carcinoma involves the radical removal of the neoplasm entire eyelid and stage T1 or T2 can effectively cure virtually all tumors with satisfactory cosmetic and functional results. In advanced stages (T4 stage) by infiltrating the orbit by basal cell carcinoma exenteration of the orbit is necessary. This surgery is a serious situation for the patient and also for his relatives. Individually made prosthesis helps the patient to be enrolled to the social environment.

Efficacy and Safety of Vildagliptin as an Add-On Therapy in Inadequately Controlled Type 2 Diabetes Patients Treated With Basal Insulin.

PubMed

Saito, Daisuke; Kanazawa, Akio; Shigihara, Nayumi; Sato, Fumihiko; Uchida, Toyoyoshi; Sato, Junko; Goto, Hiromasa; Miyatsuka, Takeshi; Ikeda, Fuki; Ogihara, Takeshi; Ohmura, Chie; Watada, Hirotaka

2017-03-01

The aim of this study was to investigate the efficacy and safety of vildagliptin as an add-on therapy for patients with type 2 diabetes mellitus inadequately controlled with basal insulin. Twenty-four patients treated with basal insulin and oral anti-diabetes drugs were randomly allocated into two groups: the control group (did not receive any add-on drugs) and vildagliptin group (received vildagliptin 100 mg/day for 6 months). The primary outcome was changes in hemoglobin A1c (HbA1c) from baseline to end of study. Treatment with vildagliptin significantly reduced HbA1c from 8.1±0.7% at baseline to 7.1±0.7% (P < 0.01), while there was no significant change of HbA1c in the control group. Vildagliptin group showed significant reduction of HbA1c compared with control group (-1.0±0.3% vs. 0.2±0.8%, P < 0.01). In addition, vildagliptin group showed a significant increase in 1,5-anhydroglucitol compared with the control group (4.5 ± 3.4 vs. 0.5 ± 4.1 μg/mL, P < 0.05). Mild hypoglycemia was reported in one patient of the vildagliptin group and two patients of the control group. Vildagliptin improved glycemic control without increasing hypoglycemia in Japanese type 2 diabetes inadequately controlled with basal insulin treatment and other oral anti-diabetes drugs. This study was registered with UMIN (University Hospital Medical Information Network ID#000010849).

A comparison of the direct medical costs for individuals with or without basal or squamous cell skin cancer: A study from Australia.

PubMed

Rowell, David; Gordon, Louisa G; Olsen, Catherine M; Whiteman, David C

2016-01-01

The composition of the medical costs incurred by people treated for basal cell and squamous cell carcinomas (hereafter keratinocyte cancers) is not adequately understood. We sought to compare the medical costs of individuals with or without keratinocyte cancers. We used national health insurance data to analyze the direct medical costs of 2000 cases and 2000 controls nested within the QSkin prospective cohort study (n = 43,794) conducted in Australia. We reconstructed the medical history of patients using medical and pharmaceutical item codes and then compared the health service costs of individuals treated for keratinocyte cancers with those not treated for keratinocyte cancers. Individuals treated for keratinocyte cancers consumed on average AUD$1320 per annum more in medical services than those without keratinocyte cancers. Only 23.2% of costs were attributed to the explicit treatment of keratinocyte cancers. The principal drivers of the residual costs were medical attendances, surgical procedures on the skin, and histopathology services. We found significant positive associations between history of treatment for keratinocyte cancers with treatments for other health conditions, including melanoma, cardiovascular disease, lipidemia, osteoporosis, rheumatoid arthritis, colorectal cancer, prostate cancer, and tuberculosis. Individuals treated for keratinocyte cancers have substantially higher medical costs overall than individuals without keratinocyte cancers. The direct costs of skin cancer excision account for only one-fifth of this difference.

Pharmacological interaction between valproic acid and carbapenem: what about levels in pediatrics?

PubMed

Miranda Herrero, M Concepción; Alcaraz Romero, Andrés J; Escudero Vilaplana, Vicente; Fernández Lafever, Sarah Nicole; Fernández-Llamazares, Cecilia Martínez; Barredo Valderrama, Estibaliz; Vázquez López, María; de Castro, Pedro

2015-03-01

Valproic acid (VPA) is the most commonly used antiepileptic drug in pediatric patients, but its major drawback is its multiple pharmacological interactions. To study children who had been simultaneously treated with carbapenems and valproic acid, considering drug levels, pharmacological interactions and clinical follow-up. Retrospective study of children who simultaneously received treatment with VPA and carbapenems between January 2003 and December 2011. Demographic variables, indication of treatment, dose, VPA plasma levels, interactions, clinical manifestations and medical management were analyzed. 28 children with concomitant treatment with both drugs were included in the study. 64.3% were males. 78.6% of the interactions were observed in the Intensive Care Unit. 60.7% of children had been previously treated VPA and its major indication were generalized seizures. Basal plasma levels of VPA were recorded in 53% and at 24 h after admittance in 60%. "40% of basal VPA levels were below therapeutic range prior to the administration of carbapenem. After the introduction of carbapenem 88% of level determinations were below therapeutic range". 54.5% of the patients that were chronically receiving VPA and had good control of epilepsy before admission had seizures during the coadministration. One patient that was on VPA before admission but with bad control of epilepsy worsened, and one patient that acutely received VPA did not achieve seizure freedom. In these cases it was necessary to either increase VPA dose or change to a different antiepileptic drug. Little is known about the mechanism of pharmacologic interactions between carbapenems and VPA, but it leads to a reduction in plasma levels that may cause a loss of seizure control, so simultaneous use of both drugs should be avoided when possible. If not, VPA levels should be monitored. Copyright © 2014 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Gorlin syndrome and bilateral ovarian fibroma

PubMed Central

Pirschner, Fernanda; Bastos, Pollyana Marçal; Contarato, George Luiz; Bimbato, Anna Carolina Bon Lima; Filho, Antônio Chambô

2012-01-01

INTRODUCTION Gorlin syndrome (GS), also known as nevoid basal cell carcinoma syndrome (NBCCS), is a rare hereditary, autosomal dominant disease that affects various systems. Its prevalence is estimated at 1/57,000 to 1/256,000 of the population. It is characterized by basal cell carcinomas, multiple odontogenic keratocysts, skeletal abnormalities and ovarian fibroma, among other disorders. PRESENTATION OF CASE To report the case of a young patient with Gorlin syndrome and bilateral ovarian fibroma. DISCUSSION A 20-year old patient with Gorlin syndrome presented with facial asymmetry, broad nasal root, dental abnormalities, micrognathism, convergent strabismus, multiple pigmented lesions on the trunk and face, pectus excavatum, kyphoscoliosis and a palpable mass in the abdomen occupying the entire pelvic region. CONCLUSION Gorlin–Goltz syndrome is a hereditary pathology that includes numerous clinical manifestations. Diagnosis is clinical and genetic confirmation is unnecessary. PMID:22771908

Giant Cornu Cutaneum Superimposed on Basal Cell Carcinoma.

PubMed

Agirgol, S; Mansur, A T; Bozkurt, K; Azakli, H N; Babacan, A; Dikmen, A

2015-09-01

Cornu cutaneum (CC) is a clinical term that describes the horn-like keratotic lesions extending vertically from the skin. Benign, premalignant or malignant lesions may be present at the base of CC. Seborrhoeic keratosis and squamous cell carcinoma (SCC) are the most commonly reported benign and malignant forms, respectively. Basal cell carcinoma (BCC) at the base is rare. Here, we report on an 85-year old female patient having multiple CC lesions, one being giant on her face and two of the lesions diagnosed with BCC at the base. This case is of significance due to the presence of giant and multiple CC and detection of BCC at the base of more than one lesion. This present case indicates the need for the treatment of possible malignant lesions underlying CC in the elderly by total surgical excision.

Nevoid basal cell carcinoma syndrome (Gorlin-Goltz syndrome)

PubMed Central

Kiran, N. K.; Tilak Raj, T. N.; Mukunda, K. S.; Rajashekar Reddy, V.

2012-01-01

The Gorlin-Goltz syndrome, also known as nevoid basal cell carcinoma syndrome (NBCCS), is an infrequent multisystemic disease inherited in a dominant autosomal way, which shows a high level of penetrance and variable expressiveness. It is characterized by odontogenic keratocysts in the jaw, multiple basal cell nevi carcinomas and skeletal abnormalities. This syndrome may be diagnosed early by a dentist by routine radiographic exams in the first decade of life, since the odontogenic keratocysts are usually one of the first manifestations of the syndrome. This case report presents a patient diagnosed as NBCCS by clinical, radiographic and histological findings in a 13-year-old boy. This paper highlights the importance of early diagnosis of NBCCS which can help in preventive multidisciplinary approach to provide a better prognosis for the patient. PMID:23633824

Nevoid basal cell carcinoma syndrome (Gorlin-Goltz syndrome).

PubMed

Kiran, N K; Tilak Raj, T N; Mukunda, K S; Rajashekar Reddy, V

2012-10-01

The Gorlin-Goltz syndrome, also known as nevoid basal cell carcinoma syndrome (NBCCS), is an infrequent multisystemic disease inherited in a dominant autosomal way, which shows a high level of penetrance and variable expressiveness. It is characterized by odontogenic keratocysts in the jaw, multiple basal cell nevi carcinomas and skeletal abnormalities. This syndrome may be diagnosed early by a dentist by routine radiographic exams in the first decade of life, since the odontogenic keratocysts are usually one of the first manifestations of the syndrome. This case report presents a patient diagnosed as NBCCS by clinical, radiographic and histological findings in a 13-year-old boy. This paper highlights the importance of early diagnosis of NBCCS which can help in preventive multidisciplinary approach to provide a better prognosis for the patient.

Fine genetic mapping of the gene for nevoid basal cell carcinoma syndrome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wicking, C.; Berkman, J.; Wainwright, B.

1994-08-01

Nevoid basal cell carcinoma syndrome (NBCCS, or Gorlin syndrome) is a cancer predisposition syndrome characterized by multiple basal cell carcinomas and diverse developmental defects. The gene responsible for NBCCS, which is most likely to be a tumor suppressor gene, has previously been mapped to 9q22.3-q31 in a 12-cM interval between the microsatellite marker loci D9S12.1 and D9S109. Combined multipoint and haplotype analyses of additional polymorphisms in this region in our collection of Australasian pedigrees have further refined the localization of the gene to between the markers D9S196 and D9S180, an interval reported to be approximately 2 cM. 27 refs., 4more » figs., 1 tab.« less

Amnesia Associated with Bilateral Hippocampal and Bilateral Basal Ganglia Lesions in Anoxia with Stimulant Use

PubMed Central

Haut, Marc W.; Hogg, Jeffery P.; Marshalek, Patrick J.; Suter, Blair C.; Miller, Liv E.

2017-01-01

We report a case of a 55-year-old man with ischemic lesions of the bilateral hippocampus and bilateral basal ganglia following a myocardial infarction during an episode of multiple drug use with subsequent anoxia requiring resuscitation. He presented for a neuropsychological evaluation with an anterograde amnesia for both explicit and procedural memory. There are two main points to this case, the unique aspects of the bilateral multifocal lesions and the functional, cognitive impact of these lesions. We hypothesize that his rare focal bilateral lesions of both the hippocampus and basal ganglia are a result of anoxia acting in synergy with his stimulant drug use (cocaine and/or 3,4-methylenedioxy-methamphetamine). Second, his unique lesions produced an explicit and implicit/procedural anterograde amnesia. PMID:28228745

Amnesia Associated with Bilateral Hippocampal and Bilateral Basal Ganglia Lesions in Anoxia with Stimulant Use.

PubMed

Haut, Marc W; Hogg, Jeffery P; Marshalek, Patrick J; Suter, Blair C; Miller, Liv E

2017-01-01

We report a case of a 55-year-old man with ischemic lesions of the bilateral hippocampus and bilateral basal ganglia following a myocardial infarction during an episode of multiple drug use with subsequent anoxia requiring resuscitation. He presented for a neuropsychological evaluation with an anterograde amnesia for both explicit and procedural memory. There are two main points to this case, the unique aspects of the bilateral multifocal lesions and the functional, cognitive impact of these lesions. We hypothesize that his rare focal bilateral lesions of both the hippocampus and basal ganglia are a result of anoxia acting in synergy with his stimulant drug use (cocaine and/or 3,4-methylenedioxy-methamphetamine). Second, his unique lesions produced an explicit and implicit/procedural anterograde amnesia.

Task-phase-specific dynamics of basal forebrain neuronal ensembles

PubMed Central

Tingley, David; Alexander, Andrew S.; Kolbu, Sean; de Sa, Virginia R.; Chiba, Andrea A.; Nitz, Douglas A.

2014-01-01

Cortically projecting basal forebrain neurons play a critical role in learning and attention, and their degeneration accompanies age-related impairments in cognition. Despite the impressive anatomical and cell-type complexity of this system, currently available data suggest that basal forebrain neurons lack complexity in their response fields, with activity primarily reflecting only macro-level brain states such as sleep and wake, onset of relevant stimuli and/or reward obtainment. The current study examined the spiking activity of basal forebrain neuron populations across multiple phases of a selective attention task, addressing, in particular, the issue of complexity in ensemble firing patterns across time. Clustering techniques applied to the full population revealed a large number of distinct categories of task-phase-specific activity patterns. Unique population firing-rate vectors defined each task phase and most categories of task-phase-specific firing had counterparts with opposing firing patterns. An analogous set of task-phase-specific firing patterns was also observed in a population of posterior parietal cortex neurons. Thus, consistent with the known anatomical complexity, basal forebrain population dynamics are capable of differentially modulating their cortical targets according to the unique sets of environmental stimuli, motor requirements, and cognitive processes associated with different task phases. PMID:25309352

Classification of volcanic ash particles using a convolutional neural network and probability.

PubMed

Shoji, Daigo; Noguchi, Rina; Otsuki, Shizuka; Hino, Hideitsu

2018-05-25

Analyses of volcanic ash are typically performed either by qualitatively classifying ash particles by eye or by quantitatively parameterizing its shape and texture. While complex shapes can be classified through qualitative analyses, the results are subjective due to the difficulty of categorizing complex shapes into a single class. Although quantitative analyses are objective, selection of shape parameters is required. Here, we applied a convolutional neural network (CNN) for the classification of volcanic ash. First, we defined four basal particle shapes (blocky, vesicular, elongated, rounded) generated by different eruption mechanisms (e.g., brittle fragmentation), and then trained the CNN using particles composed of only one basal shape. The CNN could recognize the basal shapes with over 90% accuracy. Using the trained network, we classified ash particles composed of multiple basal shapes based on the output of the network, which can be interpreted as a mixing ratio of the four basal shapes. Clustering of samples by the averaged probabilities and the intensity is consistent with the eruption type. The mixing ratio output by the CNN can be used to quantitatively classify complex shapes in nature without categorizing forcibly and without the need for shape parameters, which may lead to a new taxonomy.

Red Dot Basal Cell Carcinoma: Report of Cases and Review of This Unique Presentation of Basal Cell Carcinoma.

PubMed

Cohen, Philip R

2017-03-22

Red dot basal cell carcinoma is a unique variant of basal cell carcinoma. Including the three patients described in this report, red dot basal cell carcinoma has only been described in seven individuals. This paper describes the features of two males and one female with red dot basal cell carcinoma and reviews the characteristics of other patients with this clinical subtype of basal cell carcinoma. A 70-year-old male developed a pearly-colored papule with a red dot in the center on his nasal tip. A 71-year-old male developed a red dot surrounded by a flesh-colored papule on his left nostril. Lastly, a 74-year-old female developed a red dot within an area of erythema on her left mid back. Biopsy of the lesions all showed nodular and/or superficial basal cell carcinoma. Correlation of the clinical presentation and pathology established the diagnosis of red dot basal cell carcinoma. The tumors were treated by excision using the Mohs surgical technique. Pubmed was searched with the keyword: basal, cell, cancer, carcinoma, dot, red, and skin. The papers generated by the search and their references were reviewed. Red dot basal cell carcinoma has been described in three females and two males; the gender was not reported in two patients. The tumor was located on the nose (five patients), back (one patient) and thigh (one patient). Cancer presented as a solitary small red macule or papule; often, the carcinoma was surrounded by erythema or a flesh-colored papule. Although basal cell carcinomas usually do not blanch after a glass microscope slide is pressed against them, the red dot basal cell carcinoma blanched after diascopy in two of the patients, resulting in a delay of diagnosis in one of these individuals. Dermoscopy may be a useful non-invasive modality for evaluating skin lesions when the diagnosis of red dot basal cell carcinoma is considered. Mohs surgery is the treatment of choice; in some of the patients, the ratio of the area of the postoperative wound to that of the preoperative cancer was greater than 12:1, demonstrating a significant lateral spread of the tumor beyond the observed clinical margins of the neoplasm. In conclusion, in a patient with a personal history of actinic keratosis or nonmelanoma skin cancer, the appearance of a new red dot in a sun-exposed site should prompt additional evaluation of the skin lesion to exclude or establish the diagnosis of red dot basal cell carcinoma.

Red Dot Basal Cell Carcinoma: Report of Cases and Review of This Unique Presentation of Basal Cell Carcinoma

PubMed Central

2017-01-01

Red dot basal cell carcinoma is a unique variant of basal cell carcinoma. Including the three patients described in this report, red dot basal cell carcinoma has only been described in seven individuals. This paper describes the features of two males and one female with red dot basal cell carcinoma and reviews the characteristics of other patients with this clinical subtype of basal cell carcinoma. A 70-year-old male developed a pearly-colored papule with a red dot in the center on his nasal tip. A 71-year-old male developed a red dot surrounded by a flesh-colored papule on his left nostril. Lastly, a 74-year-old female developed a red dot within an area of erythema on her left mid back. Biopsy of the lesions all showed nodular and/or superficial basal cell carcinoma. Correlation of the clinical presentation and pathology established the diagnosis of red dot basal cell carcinoma. The tumors were treated by excision using the Mohs surgical technique. Pubmed was searched with the keyword: basal, cell, cancer, carcinoma, dot, red, and skin. The papers generated by the search and their references were reviewed. Red dot basal cell carcinoma has been described in three females and two males; the gender was not reported in two patients. The tumor was located on the nose (five patients), back (one patient) and thigh (one patient). Cancer presented as a solitary small red macule or papule; often, the carcinoma was surrounded by erythema or a flesh-colored papule. Although basal cell carcinomas usually do not blanch after a glass microscope slide is pressed against them, the red dot basal cell carcinoma blanched after diascopy in two of the patients, resulting in a delay of diagnosis in one of these individuals. Dermoscopy may be a useful non-invasive modality for evaluating skin lesions when the diagnosis of red dot basal cell carcinoma is considered. Mohs surgery is the treatment of choice; in some of the patients, the ratio of the area of the postoperative wound to that of the preoperative cancer was greater than 12:1, demonstrating a significant lateral spread of the tumor beyond the observed clinical margins of the neoplasm. In conclusion, in a patient with a personal history of actinic keratosis or nonmelanoma skin cancer, the appearance of a new red dot in a sun-exposed site should prompt additional evaluation of the skin lesion to exclude or establish the diagnosis of red dot basal cell carcinoma. PMID:28465868

Nicergoline increases serum substance P levels in patients with an ischaemic stroke.

PubMed

Nishiyama, Yasuhiro; Abe, Arata; Ueda, Masayuki; Katsura, Ken-ichiro; Katayama, Yasuo

2010-01-01

Aspiration pneumonia is one of the most important complications following ischaemic stroke, and a leading cause of mortality in stroke patients. This is particularly prevalent in patients with involvement of the basal ganglia, which may be due to impaired neurotransmission through lack of production of substance P. Consecutive patients in the chronic stage, 1-3 months after cerebral ischaemic infarction, were assessed for basal ganglia involvement by magnetic resonance imaging. The patients were randomised to 4 weeks of treatment with (n = 25) or without (n = 25) nicergoline (15 mg t.i.d.). Serum concentration of substance P was measured by radioimmunoassay. At entry to the study, mean concentration of substance P was significantly (p < 0.001) lower in patients with bilateral basal ganglia lesions than in patients with no or unilateral basal ganglia involvement. Nicergoline administration caused a significant (p = 0.021) increase from baseline in mean substance P concentration. No significant change was seen in the nicergoline-untreated patients (p = 0.626). Among the patients who received nicergoline, 11 patients had bilateral basal ganglia involvement and there was no significant mean change in substance P in these patients, whereas there was a significant increase (p = 0.032) in the 14 nicergoline-treated patients with no or unilateral basal ganglia involvement. The present study suggests a possible effect of nicergoline to increase substance P level in ischaemic stroke patients with partial damage to basal ganglia, who have a decreased swallowing response and consequent risk of aspiration pneumonia. Further trials of nicergoline treatment in patients at risk for aspiration pneumonia are warranted. (c) 2009 S. Karger AG, Basel.

Gorlin-Goltz syndrome: a rare case report.

PubMed

Mohan, Ravi Prakash Sasankoti; Verma, Sankalp; Agarwal, Neha; Singh, Udita

2013-06-27

Gorlin-Goltz syndrome (GS), also known as nevoid basal cell carcinoma syndrome, is an infrequent multisystem disease inherited in a dominant autosomal way, which shows a high level of penetrance and variable expressiveness. It is characterised by keratocystic odontogenic tumours (KCOT) in the jaw, multiple basal cell nevi carcinomas and skeletal abnormalities. This syndrome may be diagnosed early by a dentist by routine radiographical examinations in the first decade of life, since the KCOTs are usually one of the first manifestations of the syndrome. This article describes an 11-year-old boy with GS.

Gorlin-Goltz syndrome: a rare case report

PubMed Central

Mohan, Ravi Prakash Sasankoti; Verma, Sankalp; Agarwal, Neha; Singh, Udita

2013-01-01

Gorlin-Goltz syndrome (GS), also known as nevoid basal cell carcinoma syndrome, is an infrequent multisystem disease inherited in a dominant autosomal way, which shows a high level of penetrance and variable expressiveness. It is characterised by keratocystic odontogenic tumours (KCOT) in the jaw, multiple basal cell nevi carcinomas and skeletal abnormalities. This syndrome may be diagnosed early by a dentist by routine radiographical examinations in the first decade of life, since the KCOTs are usually one of the first manifestations of the syndrome. This article describes an 11-year-old boy with GS. PMID:23814215

Congenital Mirror Movements in Gorlin Syndrome: A Case Report With DTI and Functional MRI Features.

PubMed

Sag, Erdal; Gocmen, Rahsan; Yildiz, F Gokcem; Ozturk, Zeynelabidin; Temucin, Cagri; Teksam, Ozlem; Utine, Eda

2016-03-01

Congenital mirror movements are rare conditions that define the inability to perform unimanual movements. Gorlin syndrome, also known as nevoid basal cell carcinoma syndrome, is a genetic disorder with multiple nevi predisposing to basal cell carcinoma, odontogenic keratocysts, and skeletal malformations. Herein we report on an adolescent patient with Gorlin syndrome and coexisting congenital mirror movements. To our knowledge, this is the first patient in the literature who has both of these very rare conditions. Copyright © 2016 by the American Academy of Pediatrics.

The Basal Ganglia and Adaptive Motor Control

NASA Astrophysics Data System (ADS)

Graybiel, Ann M.; Aosaki, Toshihiko; Flaherty, Alice W.; Kimura, Minoru

1994-09-01

The basal ganglia are neural structures within the motor and cognitive control circuits in the mammalian forebrain and are interconnected with the neocortex by multiple loops. Dysfunction in these parallel loops caused by damage to the striatum results in major defects in voluntary movement, exemplified in Parkinson's disease and Huntington's disease. These parallel loops have a distributed modular architecture resembling local expert architectures of computational learning models. During sensorimotor learning, such distributed networks may be coordinated by widely spaced striatal interneurons that acquire response properties on the basis of experienced reward.

Mental Symptoms in Huntington's Disease and a Possible Primary Aminergic Neuron Lesion

NASA Astrophysics Data System (ADS)

Mann, J. John; Stanley, Michael; Gershon, Samuel; Rossor, M.

1980-12-01

Monoamine oxidase activity was higher in the cerebral cortex and basal ganglia of patients dying from Huntington's disease than in controls. Enzyme kinetics and multiple substrate studies indicated that the increased activity was due to elevated concentrations of monoamine oxidase type B. Concentrations of homovanillic acid were increased in the cerebral cortex but not in the basal ganglia of brains of patients with Huntington's disease. These changes may represent a primary aminergic lesion that could underlie some of the mental symptoms of this disease.

Does Reducing Basal Insulin During Ramadan Fasting by Children and Adolescents with Type 1 Diabetes Decrease the Risk of Symptomatic Hypoglycemia?

PubMed

Deeb, Asma; Al Qahtani, Nabras; Attia, Salima; Al Suwaidi, Hana; Nagelkerke, Nico

2016-09-01

Ramadan fasting by patients with type 1 diabetes might predispose them to hypoglycemia. There are no data on the optimal way of adjusting basal insulin during fasting. We aim at studying whether reducing basal insulin during Ramadan reduces the frequency of symptomatic hypoglycemia. We enrolled children and adolescents with type 1 diabetes who intended to fast during Ramadan. Logbooks were given to subjects to mark days fasted, symptomatic hypoglycemia, and dose of basal insulin on all days of Ramadan. Logbooks were examined. Glucometers and insulin pumps were downloaded. Seventy-five patients were enrolled. The age was 10.2-18.9 (14.5) years. Sixty-eight patients had results analyzed. Forty-one patients were on pumps, and 27 patients were on multiple daily injections (MDI). Mean HbA1c was 7.9 (1.2) and 8.4 (1.3) for the pump and the MDI, respectively (P = 0.007). Thirty-nine patients had hypoglycemia leading to breaking fast. The mean number of episodes of breaking fast was 3 (1-8). Thirty-five of the 68 patients had reduced basal insulin. The difference in the frequency of hypoglycemia in those who reduced/did not reduce insulin was not statistically significant (P > 0.10). Fifteen patients on MDI and 24 patients on pumps had at least one episode of breaking fast. Six and 18 of the patients on MDI and pumps, respectively, reduced basal insulin (P > 0.10). This is the first study examining the impact of reduction of basal insulin on hypoglycemia in adolescents. Reducing basal insulin during Ramadan fasting does not decrease the risk of symptomatic hypoglycemia. Use of the insulin pump does not appear to be different from MDI in the frequency of occurrence of hypoglycemia.

The incidence and multiplicity rates of keratinocyte cancers in Australia.

PubMed

Pandeya, Nirmala; Olsen, Catherine M; Whiteman, David C

2017-10-16

To assess the incidence and multiplicity of keratinocyte cancers (basal cell carcinoma [BCC] and squamous cell carcinoma [SCC]) excised in Australia, and to examine variations by age, sex, state, and prior skin cancer history. Analysis of individual-level Medicare data for keratinocyte cancer treatments (identified by eight specific MBS item codes) during 2011-2014. Histological data from the QSkin prospective cohort study were analysed to estimate BCC and SCC incidence. A 10% systematic random sample of all people registered with Medicare during 1997-2014. People aged at least 20 years in 2011 who made at least one claim for any MBS medical service during 2011-2014 (1 704 193 individuals). Age-standardised incidence rates (ASRs) and standardised incidence ratios (SIRs). The person-based incidence of keratinocyte cancer excisions in Australia was 1531 per 100 000 person-years; incidence increased with age, and was higher for men than women (SIR, 1.43; 95% CI, 1.42-1.45). Lesion-based incidence was 3154 per 100 000 person-years. The estimated ASRs for BCC and SCC were 770 per 100 000 and 270 per 100 000 person-years respectively. During 2011-2014, 3.9% of Australians had one keratinocyte cancer excised, 2.7% had more than one excised; 74% of skin cancers were excised from patients who had two or more lesions removed. Multiplicity was strongly correlated with age; most male patients over 70 were treated for multiple lesions. Keratinocyte cancer incidence was eight times as high among people with a prior history of excisions as among those without. The incidence and multiplicity of keratinocyte cancer in Australia are very high, causing a large disease burden that has not previously been quantified.

Loss of 50% of excess weight using a very low energy diet improves insulin-stimulated glucose disposal and skeletal muscle insulin signalling in obese insulin-treated type 2 diabetic patients.

PubMed

Jazet, I M; Schaart, G; Gastaldelli, A; Ferrannini, E; Hesselink, M K; Schrauwen, P; Romijn, J A; Maassen, J A; Pijl, H; Ouwens, D M; Meinders, A E

2008-02-01

Both energy restriction (ER) per se and weight loss improve glucose metabolism in obese insulin-treated type 2 diabetic patients. Short-term ER decreases basal endogenous glucose production (EGP) but not glucose disposal. In contrast the blood glucose-lowering mechanism of long-term ER with substantial weight loss has not been fully elucidated. The aim of this study was to investigate the effect of loss of 50% of excess weight [50% excess weight reduction (EWR)] on EGP, whole-body insulin sensitivity and the disturbed myocellular insulin-signalling pathway in ten obese insulin-treated type 2 diabetic patients. A euglycaemic-hyperinsulinaemic clamp with stable isotopes ([6,6-(2)H2]glucose and [2H5]glycerol) combined with skeletal muscle biopsies was performed during a very low energy diet (VLED; 1,883 kJ/day) on day 2 and again after 50% EWR. Oral blood glucose-lowering agents and insulin were discontinued 3 weeks prior to the VLED and at the start of the VLED, respectively. Loss of 50% EWR (20.3+/-2.2 kg from day 2 to day of 50% EWR) normalised basal EGP and improved insulin sensitivity, especially insulin-stimulated glucose disposal (18.8+/-2.0 to 39.1+/-2.8 micromol kg fat-free mass(-1) min(-1), p=0.001). The latter was accompanied by improved insulin signalling at the level of the recently discovered protein kinase B/Akt substrates AS160 and PRAS40 along with a decrease in intramyocellular lipid (IMCL) content. Considerable weight loss in obese, insulin-treated type 2 diabetic patients normalises basal EGP and improves insulin sensitivity resulting from an improvement in insulin signal transduction in skeletal muscle. The decrease in IMCL might contribute to this effect.

Neonatal nociception elevated baseline blood pressure and attenuated cardiovascular responsiveness to noxious stress in adult rats.

PubMed

Chu, Ya-Chun; Yang, Cheryl C H; Lin, Ho-Tien; Chen, Pin-Tarng; Chang, Kuang-Yi; Yang, Shun-Chin; Kuo, Terry B J

2012-10-01

Neonatal nociception has significant long-term effects on sensory perception in adult animals. Although neonatal adverse experience affect future responsiveness to stressors is documented, little is known about the involvement of early nociceptive experiences in the susceptibility to subsequent nociceptive stress exposure during adulthood. The aim of this study is to explore the developmental change in cardiovascular regulating activity in adult rats that had been subjected to neonatal nociceptive insults. To address this question, we treated neonatal rats with an intraplantar injection of saline (control) or carrageenan at postnatal day 1. The carrageenan-treated rats exhibited generalized hypoalgesia at basal state, and localized hyperalgesia after re-nociceptive challenge induced by intraplantar injections of complete Freund's adjuvant (CFA) as adults. Then we recorded baseline cardiovascular variables and 24-h responsiveness to an injection of CFA in the free-moving adult rats with telemetric technique. The carrageenan-treated rats showed significantly higher basal blood pressures (110.3±3.16 vs. control 97.0±4.28 mmHg). In control animals, baroreceptor reflex sensitivity (BRS) decreased, sympathetic vasomotor activity increased, and parasympathetic activity was inhibited after CFA injection. Blood pressure elevation was evident (107.0±2.75 vs. pre-injection 97.0±4.28 mmHg). Comparatively, the carrageenan-treated rats showed a higher BRS (BrrLF 1.03±0.09 vs. control 0.70±0.06 ms/mmHg) and higher parasympathetic activity [0.93±0.17 vs. control 0.32±0.02 ln(ms²)] after CFA injection. The change in blood pressure is negligible (111.9±4.05 vs. pre-injection 110.3±3.16 mmHg). Our research has shown that neonatal nociception alters future pain sensation, raises basal blood pressure level, and attenuates cardiovascular responsiveness to nociceptive stress in adult rats. Copyright © 2012 ISDN. Published by Elsevier Ltd. All rights reserved.

SU-F-P-58: Squamous Cell and Basal Cell Carcinoma of the Skin Treated with a Freiburg Flap Applicator

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dou, K; Li, B; Jacobs, M

Purpose: To treat squamous cell and basal cell carcinoma of the skin with the Freiburg flap applicator using a high dose rate modality of an Elekta Flexitron or MicroSelectron for radiation delivery by compensating the dose deviation resulting from the incomplete scatter environment. Methods: Patients were selected to have lesions greater than or equal to 2cm. A mask might be needed depending on special locations. The lesions on the eyelid and face presented in this research were, however, treated without a mask. Cutting the flap into a shape conformal to the target and attaching it to the mask were usedmore » in order to make the treatment reproducible. Patients were scanned with a Philips Big Bore Brilliant CT. A 1cm margin was added to the lesion. An Elekta Oncentra Brachy treatment planning system ver. 4.3 was used for treatment planning. 40 Gy in 10 or 8 fractions was prescribed to the 1cm depth. The Freiburg flap was aligned and verified by CT scanning prior to treatment. Results: Three patients with squamous cell and basal cell carcinoma of the skin were treated with the Freiburg flap applicator. Lesion sizes ranged from 2cm to 6 cm in a maximum dimension. With treatment planning, we made a dose correction for compensating the dose deviation resulting from the incomplete scatter environment of the flap applicators exposed to air. The flap was also covered by a 4cm bolus in order to obtain more back scattered radiation during treatment. Six month follow up showed a very good cosmetic result. Conclusion: The Freiburg flap brachytherapy offers a non-invasive skin cancer treatment with a high skin dose delivered to the tumor while a low dose sparing the surrounding health tissue. It is a promising alternative to skin cancer surgery or external beam radiation therapy.« less

Effects of Electrical and Optogenetic Deep Brain Stimulation on Synchronized Oscillatory Activity in Parkinsonian Basal Ganglia.

PubMed

Ratnadurai-Giridharan, Shivakeshavan; Cheung, Chung C; Rubchinsky, Leonid L

2017-11-01

Conventional deep brain stimulation of basal ganglia uses high-frequency regular electrical pulses to treat Parkinsonian motor symptoms but has a series of limitations. Relatively new and not yet clinically tested, optogenetic stimulation is an effective experimental stimulation technique to affect pathological network dynamics. We compared the effects of electrical and optogenetic stimulation of the basal gangliaon the pathologicalParkinsonian rhythmic neural activity. We studied the network response to electrical stimulation and excitatory and inhibitory optogenetic stimulations. Different stimulations exhibit different interactions with pathological activity in the network. We studied these interactions for different network and stimulation parameter values. Optogenetic stimulation was found to be more efficient than electrical stimulation in suppressing pathological rhythmicity. Our findings indicate that optogenetic control of neural synchrony may be more efficacious than electrical control because of the different ways of how stimulations interact with network dynamics.

Implant-retained skull prosthesis to cover a large defect of the hairy skull resulting from treatment of a basal cell carcinoma: A clinical report.

PubMed

Hoekstra, Jitske; Vissink, Arjan; Raghoebar, Gerry M; Visser, Anita

2017-05-01

Skin carcinoma, particularly basal cell carcinoma, and its treatment can result in large defects of the hairy skull. A 53-year-old man is described who was surgically treated for a large basal cell carcinoma invading the skin and underlying tissue at the top of the hairy skull. Treatment consisted of resecting the tumor and external part of the skull bone. To protect the brain and to cover the defect of the hairy skull, an acrylic resin skull prosthesis with hair was designed to mask the defect. The skull prosthesis was retained on 8 extraoral implants placed at the margins of the defect in the skull bone. The patient was satisfied with the treatment outcome. Copyright © 2016 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

Modulation of phosphoinositide turnover by chronic nicergoline in rat brain.

PubMed

Carfagna, N; Cavanus, S; Damiani, D; Salmoiraghi, P; Fariello, R; Post, C

1996-05-17

Basal and agonist-stimulated phosphoinositide (PI) turnover and inositol 1,4,5 -trisphospate (InsP3) content in rat brain were investigated after chronic nicergoline (SERMION) treatment. Oral administration of nicergoline (5 mg/kg b.i.d. for 7 weeks) enhanced the basal turnover of PI in the cerebral cortex compared to controls. This effect was paralleled by a significant rise of cortical InsP3 levels. No significant changes of noradrenaline- or carbachol-induced accumulation of [3H]-inositol-I-phophate ([3H]-InsP1) were found in cortices from nicergoline-treated rats. On the contrary, in the striatum nicergoline significantly potentiated the responsiveness of noradrenaline- and carbachol-stimulated PI turnover, leaving unchanged the basal production of [3H]-InsP1 and InsP3 levels. The results suggest that the interaction of nicergoline with PI transducing pathway might have relevance to the mechanisms of action of nicergoline.

Gorlin syndrome and bilateral ovarian fibroma.

PubMed

Pirschner, Fernanda; Bastos, Pollyana Marçal; Contarato, George Luiz; Bimbato, Anna Carolina Bon Lima; Filho, Antônio Chambô

2012-01-01

Gorlin syndrome (GS), also known as nevoid basal cell carcinoma syndrome (NBCCS), is a rare hereditary, autosomal dominant disease that affects various systems. Its prevalence is estimated at 1/57,000 to 1/256,000 of the population. It is characterized by basal cell carcinomas, multiple odontogenic keratocysts, skeletal abnormalities and ovarian fibroma, among other disorders. To report the case of a young patient with Gorlin syndrome and bilateral ovarian fibroma. A 20-year old patient with Gorlin syndrome presented with facial asymmetry, broad nasal root, dental abnormalities, micrognathism, convergent strabismus, multiple pigmented lesions on the trunk and face, pectus excavatum, kyphoscoliosis and a palpable mass in the abdomen occupying the entire pelvic region. Gorlin-Goltz syndrome is a hereditary pathology that includes numerous clinical manifestations. Diagnosis is clinical and genetic confirmation is unnecessary. Copyright © 2012 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

Nevoid basal cell carcinoma syndrome (Gorlin-Goltz syndrome). Case report.

PubMed

Fini, G; Belli, E; Mici, E; Virciglio, P; Moricca, L M; D'Itri, L; Leonardi, A; Malavenda, M S; Krizzuk, D; Merola, R; Maturo, A; Pasta, V

2013-01-01

Gorlin-Goltz syndrome or nevoid basal cell carcinoma syndrome (NBCCS) comprises multiple basal cell carcinomas, keratocysts of the jaw, palmar/plantar pits, spine and rib anomalies, calcifications of the falx cerebri etc. The diagnosis is made according to clinical criteria (Kimonis Criteria) and genetic ones. We studied one family where father and then his sun resulted affected by each syndrome. Gorlin-Goltz syndrome is a rare disease diagnosed according to clinical criteria sometimes difficult to integrate. The family case we presented shows how you can get diagnosis even in older age and after numerous surgeries. Patients should be given special attention and therefore should be monitorized and need multidisciplinary treatments continued in time, even a trivial change of signs and symptoms may be an important indicator of a precipitating event which puts the patient's life under threat.

Nevoid basal cell carcinoma syndrome (Gorlin-Goltz syndrome). Case report

PubMed Central

FINI, G.; BELLI, E.; MICI, E.; VIRCIGLIO, P.; MORICCA, L.M.; D’ITRI, L.; LEONARDI, A.; MALAVENDA, M.S.; KRIZZUK, D.; MEROLA, R.; MATURO, A.; PASTA, V.

2013-01-01

Summary: Gorlin-Goltz syndrome or nevoid basal cell carcinoma syndrome (NBCCS) comprises multiple basal cell carcinomas, keratocysts of the jaw, palmar/plantar pits, spine and rib anomalies, calcifications of the falx cerebri etc. The diagnosis is made according to clinical criteria (Kimonis Criteria) and genetic ones. We studied one family where father and then his sun resulted affected by each syndrome. Gorlin-Goltz syndrome is a rare disease diagnosed according to clinical criteria sometimes difficult to integrate. The family case we presented shows how you can get diagnosis even in older age and after numerous surgeries. Patients should be given special attention and therefore should be monitorized and need multidisciplinary treatments continued in time, even a trivial change of signs and symptoms may be an important indicator of a precipitating event which puts the patient’s life under threat. PMID:23837959

Learning Reward Uncertainty in the Basal Ganglia

PubMed Central

Bogacz, Rafal

2016-01-01

Learning the reliability of different sources of rewards is critical for making optimal choices. However, despite the existence of detailed theory describing how the expected reward is learned in the basal ganglia, it is not known how reward uncertainty is estimated in these circuits. This paper presents a class of models that encode both the mean reward and the spread of the rewards, the former in the difference between the synaptic weights of D1 and D2 neurons, and the latter in their sum. In the models, the tendency to seek (or avoid) options with variable reward can be controlled by increasing (or decreasing) the tonic level of dopamine. The models are consistent with the physiology of and synaptic plasticity in the basal ganglia, they explain the effects of dopaminergic manipulations on choices involving risks, and they make multiple experimental predictions. PMID:27589489

Computational models of basal-ganglia pathway functions: focus on functional neuroanatomy

PubMed Central

Schroll, Henning; Hamker, Fred H.

2013-01-01

Over the past 15 years, computational models have had a considerable impact on basal-ganglia research. Most of these models implement multiple distinct basal-ganglia pathways and assume them to fulfill different functions. As there is now a multitude of different models, it has become complex to keep track of their various, sometimes just marginally different assumptions on pathway functions. Moreover, it has become a challenge to oversee to what extent individual assumptions are corroborated or challenged by empirical data. Focusing on computational, but also considering non-computational models, we review influential concepts of pathway functions and show to what extent they are compatible with or contradict each other. Moreover, we outline how empirical evidence favors or challenges specific model assumptions and propose experiments that allow testing assumptions against each other. PMID:24416002

Oligo-carrageenan kappa increases NADPH, ascorbate and glutathione syntheses and TRR/TRX activities enhancing photosynthesis, basal metabolism, and growth in Eucalyptus trees.

PubMed

González, Alberto; Moenne, Fabiola; Gómez, Melissa; Sáez, Claudio A; Contreras, Rodrigo A; Moenne, Alejandra

2014-01-01

In order to analyze the effect of OC kappa in redox status, photosynthesis, basal metabolism and growth in Eucalyptus globulus, trees were treated with water (control), with OC kappa at 1 mg mL(-1), or treated with inhibitors of NAD(P)H, ascorbate (ASC), and glutathione (GSH) syntheses and thioredoxin reductase (TRR) activity, CHS-828, lycorine, buthionine sulfoximine (BSO), and auranofin, respectively, and with OC kappa, and cultivated for 4 months. Treatment with OC kappa induced an increase in NADPH, ASC, and GSH syntheses, TRR and thioredoxin (TRX) activities, photosynthesis, growth and activities of basal metabolism enzymes such as rubisco, glutamine synthetase (GlnS), adenosine 5'-phosphosulfate reductase (APR), involved in C, N, and S assimilation, respectively, Krebs cycle and purine/pyrimidine synthesis enzymes. Treatment with inhibitors and OC kappa showed that increases in ASC, GSH, and TRR/TRX enhanced NADPH synthesis, increases in NADPH and TRR/TRX enhanced ASC and GSH syntheses, and only the increase in NADPH enhanced TRR/TRX activities. In addition, the increase in NADPH, ASC, GSH, and TRR/TRX enhanced photosynthesis and growth. Moreover, the increase in NADPH, ASC and TRR/TRX enhanced activities of rubisco, Krebs cycle, and purine/pyrimidine synthesis enzymes, the increase in GSH, NADPH, and TRR/TRX enhanced APR activity, and the increase in NADPH and TRR/TRX enhanced GlnS activity. Thus, OC kappa increases NADPH, ASC, and GSH syntheses leading to a more reducing redox status, the increase in NADPH, ASC, GSH syntheses, and TRR/TRX activities are cross-talking events leading to activation of photosynthesis, basal metabolism, and growth in Eucalyptus trees.

Effects of Lactofermented Beetroot Juice Alone or with N-nitroso-N-methylurea on Selected Metabolic Parameters, Composition of the Microbiota Adhering to the Gut Epithelium and Antioxidant Status of Rats.

PubMed

Klewicka, Elżbieta; Zduńczyk, Zenon; Juśkiewicz, Jerzy; Klewicki, Robert

2015-07-16

An objective of this work was to assess the biological activity of beetroot juice (Chrobry variety, Beta vulgaris L. ssp. vulgaris), which was lactofermented by probiotic bacteria Lactobacillus brevis 0944 and Lactobacillus paracasei 0920. The oxidative status of blood serum, kidneys, and liver of rats consuming the fermented beetroot juice were determined. The experimental rats were divided into four groups on diet type: Basal diet, basal diet supplemented with fermented beetroot juice, basal diet and N-nitroso-N-methylurea treatment, and basal diet supplemented with fermented beetroot juice and N-nitroso-N-methylurea treatment. Mutagen N-nitroso-N-methylurea, which was added to diet in order to induce aberrant oxidative and biochemical processes and disadvantageous changes in the count and metabolic activity of the gut epithelium microbiota. The nutritional in vivo study showed that supplementing the diet of the rats with the lactofermented beetroot juice reduced the level of ammonia by 17% in the group treated with N-nitroso-N-methylurea. Furthermore, the positive modulation of the gut microflora and its metabolic activity was observed in groups of rats fed with the diet supplemented with the fermented beetroot juice. A concomitant decrease in the b-glucuronidase activity was a consequence of the gut epithelium microbiota modulation. The antioxidant capacity of blood serum aqueous fraction was increased by about 69% in the group of rats treated N-nitroso-N-methylurea mixed with the fermented beetroot juice and N-nitroso-N-methylurea versus to the N-nitroso-N-methylurea treatment, whereas the antioxidant parameters of the blood serum lipid fraction, kidneys, and liver remained unchanged.

Differential effects of pyrethroid insecticides on extracellular dopamine in the striatum of freely moving rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mubarak Hossain, Muhammad; Suzuki, Tadahiko; United Graduate School of Veterinary Sciences, Gifu University, Gifu 501-1193

2006-11-15

In order to obtain a more complete understanding of pyrethroid neurotoxicity, effects of the pyrethroid insecticides, allethrin (type I), cyhalothrin (type II) and deltamethrin (type II) on extracellular levels of dopamine (DA) and its metabolites in the striatum of conscious rats were studied by in vivo microdialysis. Rats were treated i.p. with pyrethroids or vehicle. Allethrin had a dual effect on DA release. The increase in the extracellular level of striatal DA by 10 mg/kg allethrin reached a maximum of 178% of baseline but 20 and 60 mg/kg inhibited DA release to 63% and 52% of baseline with a peakmore » effect at 60-80 min after injection. Cyhalothrin 10, 20 and 60 mg/kg inhibited DA release to 65%, 56% and 45% of basal release, respectively, with a peak time of inhibition 40-80 min past injection. Deltamethrin (10 and 20 mg/kg) increased DA release to maximum of 187% and 252% of basal release whereas 60 mg/kg first reduced the efflux for 40 min to 50% of basal release and then increased the efflux to a maximum of 344% of basal release with a peak time of 120 min. Local infusion of 1 {mu}M tetrodotoxin, a Na{sup +} blocker through the dialysis probe completely prevented the effect of allethrin (10 and 60 mg/kg), cyhalothrin (60 mg/kg) and deltamethrin (20 mg/kg) on DA release but only partially blocked the effects of 60 mg/kg deltamethrin. The effect of deltamethrin (60 mg/kg) on DA release was completely prevented by local infusion of 10 {mu}M nimodipine, an L-type Ca{sup ++} channel blocker. All three pyrethroids did not alter the extracellular levels of DOPAC, 3-MT and HVA except that 20 and 60 mg/kg of allethrin and cyhalothrin increased 3-MT levels. Effect of the pyrethroids on synaptosomal DA uptake was also examined. The DA uptake was decreased in rats exposed to 60 mg/kg of allethrin and cyhalothrin but was increased in rats exposed to 60 mg/kg of deltamethrin. Our results demonstrate that striatal DA release and DA uptake are differentially affected by type I and the two type II pyrethroids indicating that dopaminergic circuitry, striatal DA in particular, may be a pyrethroid target and that pyrethroids may be acting on striatal DA by multiple mechanisms.« less

[Hypogonadism caused by Gorlin-Goltz syndrome].

PubMed

Marín Romero, Olivia; Hernández Marín, Imelda; Ayala Ruiz, Aquiles R

2006-09-01

The Gorlin-Goltz syndrome is a dominant autosomic disorder characterized by cancerigenic predisposition and multiple development defects, apparently without reproductive compromise. The complex is characterized by four primary symptoms, which include nevoid basal cell epitheliomas malignantly prone, keratocystic jaw, skeletal abnormalities and intracranial calcifications. Apparently, reproductive problems reported had been rarely associated with this syndrome. We present the case of a patient with clinic stigmatae of Gorlin-Goltz syndrome, who had a characteristic progress as seen in the literature; he was the fifth product of a 43 year-old female (father was 48 years old); who at birth disclosed right eye microftalmy, bilateral cryptorchidism surgically treated at age of six. At puberty, an odontogenic cyst of the jaw was noted and enucleated. He also showed facial nevi in neck, thorax and abdomen. When he was admitted being 14 years old in our clinic, he had recurrent bilateral cryptorchidism, sexual immatturity and infertility. It is important to take into consideration Gorlin-Goltz stigmatae in cases of hypogonadism in order to recognize a further genetic influence.

Cancer of the head and neck region in solid organ transplant recipients.

PubMed

Rabinovics, Naomi; Mizrachi, Aviram; Hadar, Tuvia; Ad-El, Dean; Feinmesser, Raphael; Guttman, Dan; Shpitzer, Thomas; Bachar, Gideon

2014-02-01

Solid organ recipients are at an increased risk of developing various malignancies. We investigated the incidence, clinical features, and outcome of patients diagnosed with head and neck cancer after organ transplantation. A retrospective analysis was undertaken of patients who underwent solid organ transplantation (kidney, liver, lung, heart) treated at our institution from 1992 to 2010. Of 2817 organ recipients, 175 patients (6.1%) developed 391 head and neck malignancies. Cutaneous malignancies were the most common (93%): squamous cell carcinoma (SCC; 51%) and basal cell carcinoma (BCC; 42%). The average interval from transplantation to diagnosis of head and neck malignancy was 7.3 years, with liver recipients diagnosed earlier. Eighteen percent of patients presented with an aggressive pattern of head and neck cancer, including 24% of patients with cutaneous SCC. Organ transplantation recipients are at a higher risk to develop head and neck cancer with an aggressive behavior characterized by multiple recurrences and decreased survival. Copyright © 2013 Wiley Periodicals, Inc.

Blue light versus red light for photodynamic therapy of basal cell carcinoma in patients with Gorlin syndrome: A bilaterally controlled comparison study.

PubMed

Maytin, Edward V; Kaw, Urvashi; Ilyas, Muneeb; Mack, Judith A; Hu, Bo

2018-06-01

Photodynamic therapy (PDT) is a non-scarring alternative for treating basal cell carcinoma (BCC) in patients with Basal Cell Nevus Syndrome (BCNS), also known as Gorlin syndrome. In Europe, red light (635 nm) is the predominant source for PDT, whereas in the United States blue light (400 nm) is more widely available. The objective of this study was to conduct a head-to-head comparison of blue light and red light PDT in the same BCNS patients. In a pilot study of three patients with 141 BCC lesions, 5-aminolevulinate (20% solution) was applied to all tumors. After 4 h, half of the tumors were illuminated with blue light and the remainder with red light. To ensure safety while treating this many tumors simultaneously, light doses were escalated gradually. Six treatments were administered in three biweekly sessions over 4 months, with a final evaluation at 6 months. Tumor status was documented with high-resolution photographs. Persistent lesions were biopsied at 6 months. Clearance rates after blue light (98%) were slightly better than after red light (93%), with blue light shown to be statistically non-inferior to red light. Eight suspicious lesions were biopsied, 5 after red light (5/5 were BCC) and 3 after blue light (1 was BCC). Blue light PDT was reportedly less painful. Blue light and red light PDT appear to be equally safe and perhaps equally effective for treating BCC tumors in BCNS patients. Further studies to evaluate long-term clearance after blue light PDT are needed. Copyright © 2018 Elsevier B.V. All rights reserved.

On the association between nandrolone-mediated testosterone reduction during alcohol intoxication and attenuated voluntary alcohol intake in rats.

PubMed

Etelälahti, T J; Eriksson, C J P

2013-11-01

Human studies have indicated that the use of anabolic androgenic steroids may be associated with the abuse of alcohol and other drugs. Also, experimental animal research has indicated that chronic nandrolone administration subsequently increases voluntary alcohol drinking. The aim of our study was to test our hypothesis that alcohol-induced testosterone elevation, especially associated with stress conditions derived by nandrolone treatment, could be the underlying factor in causing increased alcohol drinking. Male alcohol-preferring AA and low drinking Wistar rats were randomly divided into control and nandrolone decanoate treated (15 mg/kg for 14 days) groups. Basal serum testosterone and corticosterone were determined before the first nandrolone treatment, after 7 days of treatment, and after an additional (7-day) washout period, during which also the acute effect of alcohol (1.5 g/kg) on steroid hormones was determined. Hereafter followed a (5-week) voluntary alcohol consumption period, during the last 2 weeks of which the rats were treated again with nandrolone. Both normal and reversed dark- vs. light-cycle experimental designs were used. Contrary to our hypothesis, nandrolone treatment decreased voluntary alcohol consumption in both AA and Wistar rats. Also, instead of stress causation, elevated basal testosterone and lowered basal corticosterone levels were observed after nandrolone treatment in both AA rats and Wistars. During acute alcohol intoxication the frequency of testosterone decreases was higher in the nandrolone-treated groups compared with control AA and Wistar rats. Present data support the hypothesis that nandrolone-treatment mediated attenuation of alcohol intake in both AA and Wistar rats may be the result of negative reinforcement caused by alcohol-mediated testosterone reduction. © 2013.

TP53 supports basal-like differentiation of mammary epithelial cells by preventing translocation of deltaNp63 into nucleoli

NASA Astrophysics Data System (ADS)

Munne, Pauliina M.; Gu, Yuexi; Tumiati, Manuela; Gao, Ping; Koopal, Sonja; Uusivirta, Sanna; Sawicki, Janet; Wei, Gong-Hong; Kuznetsov, Sergey G.

2014-04-01

Multiple observations suggest a cell type-specific role for TP53 in mammary epithelia. We developed an in vitro assay, in which primary mouse mammary epithelial cells (mMECs) progressed from lumenal to basal-like phenotypes based on expression of Krt18 or ΔNp63, respectively. Such transition was markedly delayed in Trp53-/- mMECs suggesting that Trp53 is required for specification of the basal, but not lumenal cells. Evidence from human basal-like cell lines suggests that TP53 may support the activity of ΔNp63 by preventing its translocation from nucleoplasm into nucleoli. In human lumenal cells, activation of TP53 by inhibiting MDM2 or BRCA1 restored the nucleoplasmic expression of ΔNp63. Trp53-/- mMECs eventually lost epithelial features resulting in upregulation of MDM2 and translocation of ΔNp63 into nucleoli. We propose that TP63 may contribute to TP53-mediated oncogenic transformation of epithelial cells and shed light on tissue- and cell type-specific biases observed for TP53-related cancers.

TP53 supports basal-like differentiation of mammary epithelial cells by preventing translocation of deltaNp63 into nucleoli.

PubMed

Munne, Pauliina M; Gu, Yuexi; Tumiati, Manuela; Gao, Ping; Koopal, Sonja; Uusivirta, Sanna; Sawicki, Janet; Wei, Gong-Hong; Kuznetsov, Sergey G

2014-04-11

Multiple observations suggest a cell type-specific role for TP53 in mammary epithelia. We developed an in vitro assay, in which primary mouse mammary epithelial cells (mMECs) progressed from lumenal to basal-like phenotypes based on expression of Krt18 or ΔNp63, respectively. Such transition was markedly delayed in Trp53(-/-) mMECs suggesting that Trp53 is required for specification of the basal, but not lumenal cells. Evidence from human basal-like cell lines suggests that TP53 may support the activity of ΔNp63 by preventing its translocation from nucleoplasm into nucleoli. In human lumenal cells, activation of TP53 by inhibiting MDM2 or BRCA1 restored the nucleoplasmic expression of ΔNp63. Trp53(-/-) mMECs eventually lost epithelial features resulting in upregulation of MDM2 and translocation of ΔNp63 into nucleoli. We propose that TP63 may contribute to TP53-mediated oncogenic transformation of epithelial cells and shed light on tissue- and cell type-specific biases observed for TP53-related cancers.

Further localization of the gene for nevoid basal cell carcinoma syndrome (NBCCS) in 15 Australasian families: Linkage and loss of heterozygosity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chenevix-Trench, G.; Wicking, C.; Berkman, J.

Nevoid basal cell carcinoma syndrome (NBCCS; basal cell nevus syndrome or Gorlin syndrome) is a cancer-predisposition syndrome characterized by multiple basal cell carcinomas (BCCs) and diverse developmental defects. The gene for NBCCS has been mapped to 9q23.1-q31 in North Americal and European families. In addition, loss of heterozygosity (LOH) for genetic markers in this region has been detected in sporadic BCCs, indicating that the NBCCs gene is probably a tumor-suppressor gene. In this study the authors have determined that the NBCCS gene is also linked to this region in Australasian pedigrees and that there is no significant evidence of heterogeneity.more » They have defined the localization of the gene by multipoint and haplotype analysis of 15 families, using four microsatellite markers. LOH at these loci was detected in 50% of sporadic BCCs, a rate that is significantly higher than that in other skin lesions used as controls. 21 refs., 3 figs., 2 tabs.« less

ALD1 Regulates Basal Immune Components and Early Inducible Defense Responses in Arabidopsis.

PubMed

Cecchini, Nicolás M; Jung, Ho Won; Engle, Nancy L; Tschaplinski, Timothy J; Greenberg, Jean T

2015-04-01

Robust immunity requires basal defense machinery to mediate timely responses and feedback cycles to amplify defenses against potentially spreading infections. AGD2-LIKE DEFENSE RESPONSE PROTEIN 1 (ALD1) is needed for the accumulation of the plant defense signal salicylic acid (SA) during the first hours after infection with the pathogen Pseudomonas syringae and is also upregulated by infection and SA. ALD1 is an aminotransferase with multiple substrates and products in vitro. Pipecolic acid (Pip) is an ALD1-dependent bioactive product induced by P. syringae. Here, we addressed roles of ALD1 in mediating defense amplification as well as the levels and responses of basal defense machinery. ALD1 needs immune components PAD4 and ICS1 (an SA synthesis enzyme) to confer disease resistance, possibly through a transcriptional amplification loop between them. Furthermore, ALD1 affects basal defense by controlling microbial-associated molecular pattern (MAMP) receptor levels and responsiveness. Vascular exudates from uninfected ALD1-overexpressing plants confer local immunity to the wild type and ald1 mutants yet are not enriched for Pip. We infer that, in addition to affecting Pip accumulation, ALD1 produces non-Pip metabolites that play roles in immunity. Thus, distinct metabolite signals controlled by the same enzyme affect basal and early defenses versus later defense responses, respectively.

Micropropagation of an exotic ornamental plant, Calathea crotalifera, for production of high quality plantlets.

PubMed

Rozali, Shahril Efzueni; Rashid, Kamaludin A; Taha, Rosna Mat

2014-01-01

A successful protocol was established for micropropagation in two selected varieties of exotic ornamental plants, Calathea crotalifera. The effects of different sterilization techniques, explant type, and the combination and concentration of plant growth regulators on shoots induction were studied. The axillary shoot buds explants sprouted from rhizomes in soil free conditions showed high induction rate of shoots with lowest contamination percentage when treated with combination of 30% (v/v) NaOCl, 70% (v/v) ethanol, and 0.3% (w/v) HgCl2. In the present study, the highest number of multiple shoots was obtained in MS basal medium supplemented with 3.5 mg/L 6-Benzylaminopurine (BAP), 1.0 mg/L 1-Naphthaleneacetic acid (NAA), 3% sucrose, and 6 g/L plant agar for both varieties and was used as multiplication medium. Microshoots were highly induced when the young shoot bud explants were incised longitudinally prior subculture. Chlorophyll analysis was studied to test the effects of activated charcoal and L-glutamine on reduction of necrosis problem. The maximum roots induction was recorded on MS medium supplemented with 1.0 mg/L 1-Naphthaleneacetic acid (NAA) compared to indolebutyric acid (IBA). The complete regenerated plantlets were successfully acclimatized in the soilless medium under greenhouse condition. This is the first report of rapid mass propagation for C. crotalifera.

[Evaluation and perioperative management of patients with diabetes mellitus. A challenge for the anesthesiologist].

PubMed

Pontes, João Paulo Jordão; Mendes, Florentino Fernandes; Vasconcelos, Mateus Meira; Batista, Nubia Rodrigues

Diabetes mellitus (DM) is characterized by alteration in carbohydrate metabolism, leading to hyperglycemia and increased perioperative morbidity and mortality. It evolves with diverse and progressive physiological changes, and the anesthetic management requires attention regarding this disease interference in multiple organ systems and their respective complications. Patient's history, physical examination, and complementary exams are important in the preoperative management, particularly glycosylated hemoglobin (HbA1c), which has a strong predictive value for complications associated with diabetes. The goal of surgical planning is to reduce the fasting time and maintain the patient's routine. Patients with Type 1 DM must receive insulin (even during the preoperative fast) to meet the basal physiological demands and avoid ketoacidosis. Whereas patients with Type 2 DM treated with multiple injectable and/or oral drugs are susceptible to develop a hyperglycemic hyperosmolar state (HHS). Therefore, the management of hypoglycemic agents and different types of insulin is fundamental, as well as determining the surgical schedule and, consequently, the number of lost meals for dose adjustment and drug suspension. Current evidence suggests the safe target to maintain glycemic control in surgical patients, but does not conclude whether it should be obtained with either moderate or severe glycemic control. Copyright © 2017 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

Basal Cell Carcinoma in Cases with or without Xeroderma Pigmentosum.

PubMed

Ghartimagar, Dilasma; Ghosh, Arnab; Shrestha, Sushil Ram; Shrestha, Sachet; Thapa, Sushma; Narasimhan, Raghavan; Talwar, O P

2017-01-01

Basal cell carcinoma is the most common form of cancer in humans and comprises the vast majority of skin cancers. It predominantly affects fair-skinned individuals, and its incidence is rapidly increasing. The objective of the study is to identify the epidemiology, its topography and different histological subtypes of basal cell carcinoma in patients with or without Xeroderma Pigmentosum. A cross-sectional descriptive study was conducted at Manipal Teaching Hospital, Pokhara from Jan 2009 to Dec 2016. Ethical approval was taken from MEMG/IRC/GA. The study included patients with a confirmed diagnosis of basal cell carcinoma irrespective of their age and sex. This study showed 77 individuals with 91 biopsies of BCC including 5 cases of Xeroderma Pigmentosum. The predominant histological subtype was nodular with 41 (53.94%) cases, followed by the 14 (18.42%) cases of pigmented and 10 (13.15%) cases baso-squamous subtype. The most frequent sites of involvement were the head and neck, with predominance in the nasal and orbital region. The mean age was 57.68 years but the basal cell carcinoma in cases of Xeroderma Pigmentosum was seen more in younger age groups. There were 43 (55.84 %) male patients and 34 (44.16 %) female patients with a male to female ratio of 1.26:1. Nodular and pigmented varieties were the most frequent subtypes with nose being the commonest site of involvement. Basal cell carcinomas in cases of Xeroderma Pigmentosum were noted in younger age group with multiple lesions.

Photodynamic treatment of basal cell carcinoma and squamous cell carcinoma with hypericin.

PubMed

Alecu, M; Ursaciuc, C; Hãlãlãu, F; Coman, G; Merlevede, W; Waelkens, E; de Witte, P

1998-01-01

Hypericin displays antiproliferative and cytotoxic effects on tumor cells. This effect depends on photodynamic activation with visible light and oxygen. Hence, we explored its potential use in treating skin cancer. Eight patients with squamous cell carcinoma (SCC) and eleven patients with basal cell carcinoma (BCC) were treated topically with hypericin. After intralesional injection, the hypericin was irradiated with visible light. Patients with SCC were given 40-100 micrograms hypericin intralesionally, 3-5 times per week for 2-4 weeks; patients with BCC 40-200 micrograms hypericin 3-5 times per week for 2-6 weeks. Hypericin displayed selective tumor-targeting: penetration in the surrounding tissues did not induce necrosis or cell loss and even the generation of a new epithelium at the surface of the malignancy was noticed. The effectiveness of the therapy depends on the concentration and total dose of hypericin, the frequency and duration of the therapy; clinical remissions can be expected after 6-8 weeks.

Basal cell carcinoma of the nipple-areola complex.

PubMed

Ferguson, Mark S; Nouraei, S A Reza; Davies, Ben J H; McLean, N R

2009-11-01

Basal cell carcinoma (BCC) of the nipple-areola complex is uncommon. It has been suggested that BCCs in this region behave more aggressively, with a higher potential for distant spread, than in other anatomical sites. To address questions about etiology, behavior, optimal treatment, and prognosis of this entity. A literature search identifying all cases of BCC of the nipple and nipple-areola complex in the English literature from 1893 to 2008. Thirty-four cases of BCC of the nipple, areola, or both were identified, mostly affecting middle-aged men. The majority of patients were treated with tissue-sparing surgery. There was a metastatic rate of 9.1%, and one patient died from the disease (3.0%). The optimal treatment of this condition should be local excision, but patients with this condition should be followed up for primary site recurrence and axillary metastasis, because there is greater incidence than with BCC at other anatomical sites. Furthermore, proven axillary metastasis should be surgically treated.

Midline Shift is Unrelated to Subjective Pupillary Reactivity Assessment on Admission in Moderate and Severe Traumatic Brain Injury.

PubMed

Nourallah, Basil; Menon, David K; Zeiler, Frederick A

2018-04-04

This study aims to determine the relationship between pupillary reactivity, midline shift and basal cistern effacement on brain computed tomography (CT) in moderate-to-severe traumatic brain injury (TBI). All are important diagnostic and prognostic measures, but their relationship is unclear. A total of 204 patients with moderate-to-severe TBI, documented pupillary reactivity, and archived neuroimaging were included. Extent of midline shift and basal cistern effacement were extracted from admission brain CT. Mean midline shift was calculated for each ordinal category of pupillary reactivity and basal cistern effacement. Sequential Chi-square analysis was used to calculate a threshold midline shift for pupillary abnormalities and basal cistern effacement. Univariable and multiple logistic regression analyses were performed. Pupils were bilaterally reactive in 163 patients, unilaterally reactive in 24, and bilaterally unreactive in 17, with mean midline shift (mm) of 1.96, 3.75, and 2.56, respectively (p = 0.14). Basal cisterns were normal in 118 patients, compressed in 45, and absent in 41, with mean midline shift (mm) of 0.64, 2.97, and 5.93, respectively (p < 0.001). Sequential Chi-square analysis identified a threshold for abnormal pupils at a midline shift of 7-7.25 mm (p = 0.032), compressed basal cisterns at 2 mm (p < 0.001), and completely effaced basal cisterns at 7.5 mm (p < 0.001). Logistic regression revealed no association between midline shift and pupillary reactivity. With effaced basal cisterns, the odds ratio for normal pupils was 0.22 (95% CI 0.08-0.56; p = 0.0016) and for at least one unreactive pupil was 0.061 (95% CI 0.012-0.24; p < 0.001). Basal cistern effacement strongly predicted midline shift (OR 1.27; 95% CI 1.17-1.40; p < 0.001). Basal cistern effacement alone is associated with pupillary reactivity and is closely associated with midline shift. It may represent a uniquely useful neuroimaging marker to guide intervention in traumatic brain injury.

Cost-effectiveness of once daily GLP-1 receptor agonist lixisenatide compared to bolus insulin both in combination with basal insulin for the treatment of patients with type 2 diabetes in Norway.

PubMed

Huetson, Pernilla; Palmer, James L; Levorsen, Andrée; Fournier, Marie; Germe, Maeva; McLeod, Euan

2015-01-01

Lixisenatide is a potent, selective and short-acting once daily prandial glucagon-like peptide-1 receptor agonist which lowers glycohemoglobin and body weight by clinically significant amounts in patients with type 2 diabetes treated with basal insulin, with limited risk of hypoglycemia. To assess the cost-effectiveness of lixisenatide versus bolus insulin, both in combination with basal insulin, in patients with type 2 diabetes in Norway. The IMS CORE Diabetes Model, a non-product-specific and validated simulation model, was used to make clinical and cost projections. Transition probabilities, risk adjustments and the progression of complication risk factors were derived from the UK Prospective Diabetes Study, supplemented with Norwegian data. Patients were assumed to receive combination treatment with basal insulin, lixisenatide or bolus insulin therapy for 3 years, followed by intensification of a basal-bolus insulin regimen for their remaining lifetime. Simulated healthcare costs, taken from the public payer perspective, were derived from microcosting and diagnosis related groups, discounted at 4% per annum and reported in Norwegian krone (NOK). Productivity costs were also captured based on extractions from the Norwegian Labor and Welfare Administration. Health state utilities were derived from a systematic literature review. Sensitivity and scenario analyses were performed. Lixisenatide in combination with basal insulin was associated with increased quality-adjusted life years (QALYs) and reduced lifetime healthcare costs compared to bolus insulin in combination with basal insulin in patients with Type 2 diabetes, and can be considered dominant. The net monetary benefit of lixisenatide versus bolus insulin was NOK 39,369 per patient. Results were sensitive to discounting, the application of excess body weight associated disutility and uncertainty surrounding the changes in HbA1c. Lixisenatide may be considered an economically efficient therapy in combination with basal insulin in the Norwegian setting, due to cost savings, weight loss and associated gains in health-related quality of life.

Anti-dopamine beta-hydroxylase immunotoxin-induced sympathectomy in adult rats

NASA Technical Reports Server (NTRS)

Picklo, M. J.; Wiley, R. G.; Lonce, S.; Lappi, D. A.; Robertson, D.

1995-01-01

Anti-dopamine beta-hydroxylase immunotoxin (DHIT) is an antibody-targeted noradrenergic lesioning tool comprised of a monoclonal antibody against the noradrenergic enzyme, dopamine beta-hydroxylase, conjugated to saporin, a ribosome-inactivating protein. Noradrenergic-neuron specificity and completeness and functionality of sympathectomy were assessed. Adult, male Sprague-Dawley rats were given 28.5, 85.7, 142 or 285 micrograms/kg DHIT i.v. Three days after injection, a 6% to 73% decrease in the neurons was found in the superior cervical ganglia of the animals. No loss of sensory, nodose and dorsal root ganglia, neurons was observed at the highest dose of DHIT. In contrast, the immunotoxin, 192-saporin (142 micrograms/kg), lesioned all three ganglia. To assess the sympathectomy, 2 wk after treatment (285 micrograms/kg), rats were anesthetized with urethane (1 g/kg) and cannulated in the femoral artery and vein. DHIT-treated animals' basal systolic blood pressure and heart rate were significantly lower than controls. Basal plasma norepinephrine levels were 41% lower in DHIT-treated animals than controls. Tyramine-stimulated release of norepinephrine in DHIT-treated rats was 27% of controls. Plasma epinephrine levels of DHIT animals were not reduced. DHIT-treated animals exhibited a 2-fold hypersensitivity to the alpha-adrenergic agonist phenylephrine. We conclude that DHIT selectively delivered saporin to noradrenergic neurons resulting in destruction of these neurons. Anti-dopamine beta-hydroxylase immunotoxin administration produces a rapid, irreversible sympathectomy.

Role of angiotensin in renal sympathetic activation in cirrhotic rats.

PubMed

Voigt, M D; Jones, S Y; DiBona, G F

1999-08-01

Central nervous system (CNS) renin-angiotensin activity influences the basal level of renal sympathetic nerve activity (RSNA) and its reflex regulation. The effect of type 1 angiotensin II (ANG II)-receptor antagonist treatment (losartan) on cardiac baroreflex regulation of RSNA and renal sodium handling was examined in rats with cirrhosis due to common bile duct ligation (CBDL). Basal levels of heart rate, mean arterial pressure (MAP), RSNA, and urinary sodium excretion were not affected by intracerebroventricular administration of either losartan or vehicle to CBDL rats. After acute intravenous isotonic saline loading (10% body wt) in vehicle-treated CBDL rats, MAP was unchanged and the decrease in RSNA seen in normal rats did not occur. However, in losartan-treated CBDL rats, there were significant concurrent but transient decreases in MAP (-20 +/- 2 mmHg) and RSNA (-25 +/- 3%). The natriuretic response to acute volume loading in losartan-treated CBDL rats was significantly less than that in vehicle-treated CBDL rats only at those time points where there were significant decreases in MAP. Antagonism of CNS ANG II type 1 receptors augments the renal sympathoinhibitory response to acute volume loading in CBDL. However, the natriuretic response to the acute volume loading is not improved, likely due to the strong antinatriuretic influence of the concomitant marked decrease in MAP (renal perfusion pressure) mediated by widespread sympathetic withdrawal from the systemic vasculature.

Gonadotropin Promotion of Adventitious Root Production on Cuttings of Begonia semperflorens and Vitis vinifera 1

PubMed Central

Leshem, Y.; Lunenfeld, B.

1968-01-01

Adventitious rooting of Begonia semperflorens cv. Indian Maid and Vitis vinifera cv. Semillon stem cuttings was significantly promoted by human chorionic gonadotropin (HCG). Basal sections of HCG treated cuttings upon which promoted rooting took place had markedly less endogenous gibberellin (GA) activity than non-treated controls or apical sections of treated ones, while changes in auxin levels were not found. HCG also inhibited GA3-induced reducing sugar release from embryoless barley endosperm halves. These findings are discussed in the light of a possible analogy to gonadotropin action in animal systems. PMID:5641189

In vitro evaluation of mitochondrial dysfunction and treatment with adeno-associated virus vector in fibroblasts from Doberman Pinschers with dilated cardiomyopathy and a pyruvate dehydrogenase kinase 4 mutation.

PubMed

Sosa, Ivan; Estrada, Amara H; Winter, Brandy D; Erger, Kirsten E; Conlon, Thomas J

2016-02-01

To compare mitochondrial oxygen consumption rate (OCR) of fibroblasts from Doberman Pinschers with and without dilated cardiomyopathy (DCM) and mutation of the gene for pyruvate dehydrogenase kinase isozyme 4 (PDK4) and to evaluate in vitro whether treatment with adeno-associated virus (AAV) vector (i.e., gene therapy) would alter metabolic efficiency. 10 Doberman Pinschers screened for DCM and PDK4 mutation. PROCEDURES Fibroblasts were harvested from skin biopsy specimens obtained from Doberman Pinschers, and dogs were classified as without DCM or PDK4 mutation (n = 3) or with occult DCM and heterozygous (4) or homozygous (3) for PDK4 mutation. Fibroblasts were or were not treated with tyrosine mutant AAV type 2 vector containing PDK4 at multiplicities of infection of 1,000. Mitochondrial OCR was measured to evaluate mitochondrial metabolism. The OCR was compared among dog groups and between untreated and treated fibroblasts within groups. Mean ± SD basal OCR of fibroblasts from heterozygous (74 ± 8 pmol of O2/min) and homozygous (58 ± 12 pmol of O2/min) dogs was significantly lower than that for dogs without PDK4 mutation (115 ± 9 pmol of O2/min). After AAV transduction, OCR did not increase significantly in any group (mutation-free group, 121 ± 26 pmol of O2/min; heterozygous group, 88 ± 6 pmol of O2/min; homozygous group, 59 ± 3 pmol of O2/min). Mitochondrial function was altered in skin fibroblasts of Doberman Pinschers with DCM and PDK4 mutation. Change in mitochondrial function after in vitro gene therapy at the multiplicities of infection used in this study was not significant.

Canceling actions involves a race between basal ganglia pathways

PubMed Central

Schmidt, Robert; Leventhal, Daniel K.; Mallet, Nicolas; Chen, Fujun; Berke, Joshua D.

2013-01-01

Salient cues can prompt the rapid interruption of planned actions. It has been proposed that fast, reactive behavioral inhibition involves specific basal ganglia pathways, and we tested this by comparing activity in multiple rat basal ganglia structures during performance of a stop-signal task. Subthalamic nucleus (STN) neurons showed low-latency responses to Stop cues, irrespective of whether actions were successfully canceled or not. By contrast, neurons downstream in the substantia nigra pars reticulata (SNr) responded to Stop cues only in trials with successful cancellation. Recordings and simulations together indicate that this sensorimotor gating arises from the relative timing of two distinct inputs to neurons in the SNr dorsolateral “core” subregion: cue-related excitation from STN and movement-related inhibition from striatum. Our results support race models of action cancellation, with successful stopping requiring Stop cue information to be transmitted from STN to SNr before increased striatal input creates a point of no return. PMID:23852117

Growth mechanism of extension twin variants during annealing of pure magnesium: An ‘ex situ’ electron backscattered diffraction investigation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sabat, R.K.

Pure magnesium was subjected to plastic deformation through CSM (continuous stiffness measurement) indentation followed by annealing at 200 °C for 30 min. Nucleation of no new grains was observed neither at the twin–twin intersections nor at the multiple twin variants of a grain after annealing. Significant growth of off-basal twin orientation compared to basal twin orientation was observed in the sample after annealing and is attributed to the partial coherent nature of twin boundary in the later case. Further, growth of twins was independent of the strain distribution between parent and twinned grains. - Highlights: • An ‘ex situ’ EBSDmore » of pure Mg during annealing was investigated. • Nucleation of no new grains was observed. • Significant growth of off-basal twin orientation was observed. • Growth of twins may be attributed to the partial coherent nature of twin boundary.« less

The effect of aniracetam on cerebral glucose metabolism in rats after lesioning of the basal forebrain measured by PET.

PubMed

Ouchi, Y; Kakiuchi, T; Okada, H; Nishiyama, S; Tsukada, H

1999-03-15

To evaluate the effect of aniracetam, a potent modulator of the glutamatergic and cholinergic systems, on the altered cerebral glucose metabolism after lesioning of the basal forebrain, we measured the cerebral metabolic rate of glucose (CMRGlc) with positron emission tomography and the choline acetyltransferase (ChAT) activity in the frontal cortex of the lesioned rats after treating them with aniracetam. Continuous administration of aniracetam for 7 days after the surgery prevented CMRGlc reduction in the frontal cortex ipsilateral to the lesion while the lesioned rats without aniracetam showed significant CMRGlc reduction in the frontal cortex. The level of CMRGlc in the lesion-side basal forebrain was lower in all rats regardless of the aniracetam treatment. Biochemical studies showed that aniracetam did not alter the reduction in the frontal ChAT activity. These results showed that aniracetam prevents glucose metabolic reduction in the cholinergically denervated frontal cortex with little effect on the cortical cholinergic system. The present study suggested that a neurotransmitter system other than the cholinergic system, e.g. the glutamatergic system, plays a central role in the cortical metabolic recovery after lesioning of the basal forebrain.

Mutiple keratocystic odontogenic tumors (KCOT) in a patient with Gorlin syndrome: a case report with late presentation and absence of skin manifestations.

PubMed

Hashmi, Atif Ali; Edhi, Muhammad Muzzammil; Faridi, Naveen; Hosein, Mervyn; Khan, Mehmood

2016-07-22

Gorlin syndrome is a rare autosomal dominant syndrome characterized by multiple basal cell carcinomas, keratocystic odontogenic tumors (KOT) and falx cerebral calcifications, which occur due to mutation in PTCH gene. A 36 year old Asian patient presented with jaw swelling and pain. Radiographic examination revealed six cysts in maxilla and mandible which were excised and histologically were compatable with keratocystic odontogenic tumors. CT scan also revealed falx cerebral calcification which led to the diagnosis of Gorlin syndrome confirmed on genetic testing. There was no evidence of basal cell carcinoma and other manifestations of Gorlin syndrome were absent. Multiple KCOT are hallmark of Gorlin syndrome and should always leads to its suspicion even in the absence of other manifestations and late presentation. Moreover, keratocystic odontogenic tumors have a particularly higher risk of recurrence and patients with Gorlin syndrome are prone to develop additional keratocystic odontogenic tumors from basal cells of oral epithelium. Therefore we suggest a stepwise approach to manage such patients which include a preoperative biopsy to establish a definitive diagnosis and complete removal of all keratocystic odontogenic tumors to prevent recurrence followed by close clinical follow up and early removal of any newly developed or recurrent cyst. Additionally thorough clinical examination is necessary to rule out the possibility of Gorlin syndrome in any patient with keratocystic odontogenic tumors as there are only subtle differences in histology of those cysts with a syndromic association and clinical features of Gorlin syndrome are markedly variable. Hence late occurrence of keratocystic odontogenic tumors and absence of skin manifestations like basal cell carcinoma should not preclude a diagnosis of Gorlin syndrome.

Expression analysis of the speech-related genes FoxP1 and FoxP2 and their relation to singing behavior in two songbird species.

PubMed

Chen, Qianqian; Heston, Jonathan B; Burkett, Zachary D; White, Stephanie A

2013-10-01

Humans and songbirds are among the rare animal groups that exhibit socially learned vocalizations: speech and song, respectively. These vocal-learning capacities share a reliance on audition and cortico-basal ganglia circuitry, as well as neurogenetic mechanisms. Notably, the transcription factors Forkhead box proteins 1 and 2 (FoxP1, FoxP2) exhibit similar expression patterns in the cortex and basal ganglia of humans and the zebra finch species of songbird, among other brain regions. Mutations in either gene are associated with language disorders in humans. Experimental knock-down of FoxP2 in the basal ganglia song control region Area X during song development leads to imprecise copying of tutor songs. Moreover, FoxP2 levels decrease naturally within Area X when zebra finches sing. Here, we examined neural expression patterns of FoxP1 and FoxP2 mRNA in adult Bengalese finches, a songbird species whose songs exhibit greater sequence complexity and increased reliance on audition for maintaining their quality. We found that FoxP1 and FoxP2 expression in Bengalese finches is similar to that in zebra finches, including strong mRNA signals for both factors in multiple song control nuclei and enhancement of FoxP1 in these regions relative to surrounding brain tissue. As with zebra finches, when Bengalese finches sing, FoxP2 is behaviorally downregulated within basal ganglia Area X over a similar time course, and expression negatively correlates with the amount of singing. This study confirms that in multiple songbird species, FoxP1 expression highlights song control regions, and regulation of FoxP2 is associated with motor control of song.

Expression analysis of the speech-related genes FoxP1 and FoxP2 and their relation to singing behavior in two songbird species

PubMed Central

Chen, Qianqian; Heston, Jonathan B.; Burkett, Zachary D.; White, Stephanie A.

2013-01-01

SUMMARY Humans and songbirds are among the rare animal groups that exhibit socially learned vocalizations: speech and song, respectively. These vocal-learning capacities share a reliance on audition and cortico-basal ganglia circuitry, as well as neurogenetic mechanisms. Notably, the transcription factors Forkhead box proteins 1 and 2 (FoxP1, FoxP2) exhibit similar expression patterns in the cortex and basal ganglia of humans and the zebra finch species of songbird, among other brain regions. Mutations in either gene are associated with language disorders in humans. Experimental knock-down of FoxP2 in the basal ganglia song control region Area X during song development leads to imprecise copying of tutor songs. Moreover, FoxP2 levels decrease naturally within Area X when zebra finches sing. Here, we examined neural expression patterns of FoxP1 and FoxP2 mRNA in adult Bengalese finches, a songbird species whose songs exhibit greater sequence complexity and increased reliance on audition for maintaining their quality. We found that FoxP1 and FoxP2 expression in Bengalese finches is similar to that in zebra finches, including strong mRNA signals for both factors in multiple song control nuclei and enhancement of FoxP1 in these regions relative to surrounding brain tissue. As with zebra finches, when Bengalese finches sing, FoxP2 is behaviorally downregulated within basal ganglia Area X over a similar time course, and expression negatively correlates with the amount of singing. This study confirms that in multiple songbird species, FoxP1 expression highlights song control regions, and regulation of FoxP2 is associated with motor control of song. PMID:24006346

Effects of nonfiction guided interactive read-alouds and think-alouds on fourth grader's depth of content area science vocabulary knowledge and comprehension

NASA Astrophysics Data System (ADS)

Hanna, Tania Tamara

Effects of nonfiction guided interactive read-alouds and think-alouds as a supplement to basal science textbooks on three vocabulary measures, definitions, examples, and characteristics, and one multiple-choice comprehension measure were assessed for 127 fourth graders over three time periods: pretest, posttest, and a 2-week delayed posttest. Two of three fourth-grade elementary science teachers implemented a series of 12 content-enhanced guided interactive scripted lessons. Two of these teachers implemented two treatments each. The first condition employed basal science textbooks as the text for guided interactive read-alouds and think-alouds while the second treatment employed basal science textbooks in conjunction with nonfiction text sets as the texts for guided interactive read-alouds and think-alouds. The third teacher, guided by traditional lesson plans, provided students with silent independent reading instruction using basal science textbooks. Multivariate analyses of variance and analyses of variance tests showed that mean scores for both treatment groups significantly improved on definitions and characteristics measures at posttest and either stabilized or slightly declined at delayed posttest. The treatment-plus group lost considerably on the examples posttest measure. The treatment group improved mean scores on the examples posttest measure, outperforming the treatment-plus group and the control group. Alternately, the control group significantly improved on the delayed posttest examples measure. Additionally, the two groups implementing guided interactive read-alouds and think-alouds performed better than the independent reading group on multiple-choice comprehension measures at posttest and sustained those gains 2 weeks later on delayed posttests. Findings maintain the incremental nature of vocabulary acquisition and development research and emphasize the roles of listening and speaking as critical features for integrating vocabulary into long-term memory.

GLUTAMATE NEUROTOXICITY IN THE DEVELOPING RAT COCHLEA: PHYSIOLOGICAL AND MORPHOLOGICAL APPROACHES

EPA Science Inventory

The neurotoxic effects of exogenous glutamate were studied in the rat cochlea. lutamate-treated rats (4g/kg/day ip, postnatal days 2 through 9) exhibited electrophysiologically-measured elevations in high frequency thresholds usually associated with hair cell loss in the basal re...

Calcified basal ganglionic mass 12 years after radiation therapy for medulloblastoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lichtor, T.; Wollmann, R.L.; Brown, F.D.

1984-04-01

A patient treated 12 years previously with an operation and radiation therapy for a medulloblastoma developed weakness of the left hand and perivascular calcification involving the right internal capsule and caudate nucleus. These findings are considered possible long-term complications of the radiation therapy.

1,1-Bis(3'-indolyl)-1-(p-biphenyl)methane inhibits basal-like breast cancer growth in athymic nude mice

PubMed Central

Su, Yunpeng; Vanderlaag, Kathryn; Ireland, Courtney; Ortiz, Janelle; Grage, Henry; Safe, Stephen; Frankel, Arthur E

2007-01-01

Introduction 1,1-Bis (3'-indolyl)-1-(p-biphenyl) methane (CDIM9) has been identified as a new peroxisome proliferator-activated receptor (PPAR)-γ agonist that exhibits both receptor dependent and independent antitumor activities. CDIM9 has not previously been studied with respect to its effects against basal-like breast cancer. Our goal in the present study was to investigate the anti-basal-like breast tumor activity of CDIM9 in vitro and in vivo. Methods The effects of CDIM9 on cell protein and DNA syntheses were determined in basal-like breast cancer MDA-MB231 and BT549 cells in vitro. Maximum tolerated dose and dose-limited toxicity were determined in BalB/c mice, and antitumor growth activities were assessed in MDA-MB231 basal-like breast tumor xenografts in athymic nude mice. Results CDIM9 exhibited selective cell cytotoxicity and anti-proliferation effects on basal-like breast cancer lines. In MDA-MB231 cell, CDIM9 induced caveolin-1 and p27 expression, which was significantly downregulated by co-treatment with the PPAR-γ antagonist GW9662. Nonsteroidal anti-inflammatory drug-activated gene-1 and activating transcription factor-3 were upregulated by CDIM9 through a PPAR-γ independent pathway. CDIM9 (40 mg/kg daily, intraperitoneally, for 35 days) inhibited the growth of subcutaneous MDA-MB231 tumor xenografts by 87%, and produced a corresponding decrease in proliferation index. Nearly half of the treated mice (46%) had complete durable remissions, confirmed by histology. The growth of an established tumor was inhibited by CDIM9 treatment (64 mg/kg daily, intraperitoneally, for 10 days), with a mean tumor growth inhibition of 67% as compared with controls. CDIM9 induced increases in tumor caveolin-1 and p27 in vivo, which may contribute to its antitumor activity in basal-like breast cancer. Conclusion CDIM9 showed potent antiproliferative effects on basal-like breast cancer cell in tissue culture and dramatic growth inhibition in animal models at safe doses. These findings justify further development of this drug for treatment of basal-like breast cancer. PMID:17764562

Distribution and co-localization of choline acetyltransferase and p75 neurotrophin receptors in the sheep basal forebrain: implications for the use of a specific cholinergic immunotoxin.

PubMed

Ferreira, G; Meurisse, M; Tillet, Y; Lévy, F

2001-01-01

The basal forebrain cholinergic system is involved in different forms of memory. To study its role in social memory in sheep, an immunotoxin, ME20.4 immunoglobulin G (IgG)-saporin, was developed that is specific to basal forebrain cholinergic neurons bearing the p75 neurotrophin receptor. The distribution of sheep cholinergic neurons was mapped with an antibody against choline acetyltransferase. To assess the localization of the p75 receptor on basal forebrain cholinergic neurons, the distribution of p75 receptor-immunoreactive neurons with ME20.4 IgG was examined, and a double-labeling study with antibodies against choline acetyltransferase and p75 receptor was undertaken. The loss of basal forebrain cholinergic neurons and acetylcholinesterase fibers in basal forebrain projection areas was assessed in ewes that had received intracerebroventricular injections of the immunotoxin (50, 100 or 150 microg) alone, as well as, in some of the ewes treated with the highest dose, with bilateral immunotoxin injections in the nucleus basalis (11 microg/side). Results indicated that choline acetyltransferase- and p75 receptor-immunoreactive cells had similar distributions in the medial septum, the vertical and horizontal limbs of the band of Broca, and the nucleus basalis. The double-labeling procedure revealed that 100% of the cholinergic neurons are also p75 receptor positive in the medial septum and in the vertical and horizontal limbs of the band of Broca, and 82% in the nucleus basalis. Moreover, 100% of the p75 receptor-immunoreactive cells of these four nuclei were cholinergic. Combined immunotoxin injections into ventricles and the nucleus basalis produced a near complete loss (80-95%) of basal forebrain cholinergic neurons and acetylcholinesterase-positive fibers in the hippocampus, olfactory bulb and entorhinal cortex. This study provides the first anatomical data concerning the basal forebrain cholinergic system in ungulates. The availability of a selective cholinergic immunotoxin effective in sheep provides a new tool to probe the involvement of basal forebrain cholinergic neurons in cognitive processes in this species.

Basal cell carcinoma and World War II-era cathode ray oscilloscope exposure.

PubMed

Cognetta, Armand B; Green, W Harris; Marks, Maria M; Manausa, Robert M; Horenstein, Marcelo G

2005-02-01

There is a high prevalence of skin cancer in World War II servicemen stationed in the Pacific theater as a result of various risk factors such as exposure to ultraviolet radiation and genetic predisposition. We sought to describe whether a possible association exists between basal cell carcinoma (BCC) development and the use of high-voltage cathode ray tube (CRT) oscilloscopes manufactured around 1940 to 1955, which were a source of X-radiation. We present a case series of 9 men aged 65 to 93 years who presented with similar head and neck distributions of BCC and a history of extensive use of early CRT oscilloscopes during and shortly after the World War II era. The patients were interviewed and their medical records reviewed to determine CRT exposure times and BCC location, subtype, and treatment. Representative BCC histologic sections were reviewed. A total of 230 BCCs of the head and neck region were identified and mapped. Questionnaires determined a minimum exposure of 600 (range, 624-9600) hours within a 60-cm distance of early CRT screens in all patients. The average number of aggressive histologic subtypes was 23.5%. The average number of Mohs micrographic surgery layers required to obtain negative margins was 1.99 compared with 1.63 in the control group treated by the same Mohs micrographic surgeon (P < .002). This descriptive study is the first to suggest that ionizing radiation from early CRT oscilloscopes may be a factor in the development of multiple BCCs of the head and neck with increased subclinical spread.

Subthalamic nucleus deep brain stimulation impacts language in early Parkinson's disease.

PubMed

Phillips, Lara; Litcofsky, Kaitlyn A; Pelster, Michael; Gelfand, Matthew; Ullman, Michael T; Charles, P David

2012-01-01

Although deep brain stimulation (DBS) of the basal ganglia improves motor outcomes in Parkinson's disease (PD), its effects on cognition, including language, remain unclear. This study examined the impact of subthalamic nucleus (STN) DBS on two fundamental capacities of language, grammatical and lexical functions. These functions were tested with the production of regular and irregular past-tenses, which contrast aspects of grammatical (regulars) and lexical (irregulars) processing while controlling for multiple potentially confounding factors. Aspects of the motor system were tested by contrasting the naming of manipulated (motor) and non-manipulated (non-motor) objects. Performance was compared between healthy controls and early-stage PD patients treated with either DBS/medications or medications alone. Patients were assessed on and off treatment, with controls following a parallel testing schedule. STN-DBS improved naming of manipulated (motor) but not non-manipulated (non-motor) objects, as compared to both controls and patients with just medications, who did not differ from each other across assessment sessions. In contrast, STN-DBS led to worse performance at regulars (grammar) but not irregulars (lexicon), as compared to the other two subject groups, who again did not differ. The results suggest that STN-DBS negatively impacts language in early PD, but may be specific in depressing aspects of grammatical and not lexical processing. The finding that STN-DBS affects both motor and grammar (but not lexical) functions strengthens the view that both depend on basal ganglia circuitry, although the mechanisms for its differential impact on the two (improved motor, impaired grammar) remain to be elucidated.

Effects of Ascorbyl-2-phosphate Magnesium on Human Keratinocyte Toxicity and Pathological Changes by Sorafenib.

PubMed

Yamamoto, Kazuhiro; Shichiri, Hiroaki; Ishida, Takahiro; Kaku, Kenta; Nishioka, Tatsuya; Kume, Manabu; Makimoto, Hiroo; Nakagawa, Tsutomu; Hirano, Takeshi; Bito, Toshinori; Nishigori, Chikako; Yano, Ikuko; Hirai, Midori

2017-01-01

Hand-foot skin reaction is recognized as one of the most common adverse events related to multiple tyrosine kinase inhibitors, but an effective prevention method has not been identified. The chief aim of this study was to find a mechanism-based preventive method for the skin toxicity induced by sorafenib using vitamin C derivatives. The effects of ascorbyl-2-phosphate magnesium (P-VC-Mg) on the molecular and pathological changes induced by sorafenib were investigated in human keratinocyte HaCaT cells. The cell growth inhibition and apoptotic effects of sorafenib were attenuated by P-VC-Mg. Moreover, P-VC-Mg inhibited the decrease of signal transducer and activator of transcription 3 (STAT3) phosphorylation and the expression of apoptosis suppressors treated by sorafenib. HaCaT cells transfected with the STAT3 dominant-negative form (STAT3DN) and STAT3 small interfering RNA (siRNA) combined with P-VC-Mg did not exhibit the attenuation of cell growth inhibition. Interestingly, after exposure to sorafenib in a three dimensional (3D) skin model assay, the basal layer was significantly thickened and the granular and spinous layers became thinner. In contrast, after exposure to sorafenib with P-VC-Mg, the thickness of the basal, granular, and spinous layers was similar to that of the control image. These findings suggest that P-VC-Mg attenuates sorafenib-induced apoptosis and pathological changes in human keratinocyte cells and in the 3D skin model mediated by the maintenance of STAT3 activity.

Subthalamic Nucleus Deep Brain Stimulation Impacts Language in Early Parkinson's Disease

PubMed Central

Phillips, Lara; Litcofsky, Kaitlyn A.; Pelster, Michael; Gelfand, Matthew

2012-01-01

Although deep brain stimulation (DBS) of the basal ganglia improves motor outcomes in Parkinson's disease (PD), its effects on cognition, including language, remain unclear. This study examined the impact of subthalamic nucleus (STN) DBS on two fundamental capacities of language, grammatical and lexical functions. These functions were tested with the production of regular and irregular past-tenses, which contrast aspects of grammatical (regulars) and lexical (irregulars) processing while controlling for multiple potentially confounding factors. Aspects of the motor system were tested by contrasting the naming of manipulated (motor) and non-manipulated (non-motor) objects. Performance was compared between healthy controls and early-stage PD patients treated with either DBS/medications or medications alone. Patients were assessed on and off treatment, with controls following a parallel testing schedule. STN-DBS improved naming of manipulated (motor) but not non-manipulated (non-motor) objects, as compared to both controls and patients with just medications, who did not differ from each other across assessment sessions. In contrast, STN-DBS led to worse performance at regulars (grammar) but not irregulars (lexicon), as compared to the other two subject groups, who again did not differ. The results suggest that STN-DBS negatively impacts language in early PD, but may be specific in depressing aspects of grammatical and not lexical processing. The finding that STN-DBS affects both motor and grammar (but not lexical) functions strengthens the view that both depend on basal ganglia circuitry, although the mechanisms for its differential impact on the two (improved motor, impaired grammar) remain to be elucidated. PMID:22880117

Dysregulation of apoptosis and autophagy gene expression in PBMCs of efficiently treated HIV-infected patients.

PubMed

Serrano, Amandine; El Haddad, Saïd; Moal, Frédéric; Prazuck, Thierry; Legac, Eric; Robin, Chloé; Brule, Fabienne; Charpentier, Stéphane; Normand, Thierry; Legrand, Alain; Hocqueloux, Laurent; Mollet, Lucile

2018-05-03

We measure the transcript levels of the pro-apoptotic GALIG, anti-apoptotic MCL1 genes and those of the autophagy genes BECN1, MAP1LC3B, ATG9a, P62/SQSTM1, GABARAP, GABARAPL1 and GABARAPL2 to define if mRNA alteration can characterize HIV infected patients effectively treated with combined antiretroviral therapy (cART). Monocentric pilot study conducted on PBMC of 40 uninfected donors and 27 HIV positive patients effectively treated by cART for at least 8.4 years. Transcripts of the various genes were quantified by RT-qPCR and RT- droplet digital PCR, and compared using the standard statistical Mann-Whitney U test and machine learning algorithms. A concomitant overexpression of GALIG and MCL1 is detected in PBMC of effectively cART-treated patients. Overexpression of MAP1LC3B and GABARAPL1 is also measured while BECN1 is under-expressed. Finally, accurate classification (94.5%) of our PBMC samples as HIV negative donors or HIV positive cART-treated is obtained in 3 separate machine-learning algorithms with GABARAPL1 and ATG9a as input variables. cART-treated HIV patients display altered transcript levels for 3 genes of basal autophagy. Some of these alterations may appear contradictory: BECN1 and ATG9a, both key actors in the formation of mammalian autophagosome, exhibit decreased amount of transcripts while mRNA from the ATG8 family increase. Given the known role of impaired basal autophagy in immune senescence and chronic inflammation, the functional significance of our findings should be explored in larger studies.

Visualizing Iron Deposition in Multiple Sclerosis Cadaver Brains

DOE Office of Scientific and Technical Information (OSTI.GOV)

Habib, A.C.; Zheng, W.; Haacke, E.M.

To visualize and validate iron deposition in two cases of multiple sclerosis using rapid scanning X-Ray Fluorescence (RS-XRF) and Susceptibility Weighted Imaging (SWI). Two (2) coronal cadaver brain slices from patients clinically diagnosed with multiple sclerosis underwent magnetic resonance imaging (MRI), specifically SWI to image iron content. To confirm the presence of iron deposits and the absence of zinc-rich myelin in lesions, iron and zinc were mapped using RS-XRF. MS lesions were visualized using FLAIR and correlated with the absence of zinc by XRF. XRF and SWI showed that in the first MS case, there were large iron deposits proximalmore » to the draining vein of the caudate nucleus as well as iron deposits associated with blood vessels throughout the globus pallidus. Less iron was seen in association with lesions than in the basal ganglia. The presence of larger amounts of iron correlated reasonably well between RS-XRF and SWI. In the second case, the basal ganglia appeared normal and acute perivascular iron deposition was absent. Perivascular iron deposition is seen in some but not all MS cases, giving credence to the use of SWI to assess iron involvement in MS pathology in vivo.« less

Visualizing Iron Deposition in Multiple Sclerosis Cadaver Brains

NASA Astrophysics Data System (ADS)

Habib, Charbel A.; Zheng, Weili; Mark Haacke, E.; Webb, Sam; Nichol, Helen

2010-07-01

Aim: To visualize and validate iron deposition in two cases of multiple sclerosis using rapid scanning X-Ray Fluorescence (RS-XRF) and Susceptibility Weighted Imaging (SWI). Material and Methods: Two (2) coronal cadaver brain slices from patients clinically diagnosed with multiple sclerosis underwent magnetic resonance imaging (MRI), specifically SWI to image iron content. To confirm the presence of iron deposits and the absence of zinc-rich myelin in lesions, iron and zinc were mapped using RS-XRF. Results: MS lesions were visualized using FLAIR and correlated with the absence of zinc by XRF. XRF and SWI showed that in the first MS case, there were large iron deposits proximal to the draining vein of the caudate nucleus as well as iron deposits associated with blood vessels throughout the globus pallidus. Less iron was seen in association with lesions than in the basal ganglia. The presence of larger amounts of iron correlated reasonably well between RS-XRF and SWI. In the second case, the basal ganglia appeared normal and acute perivascular iron deposition was absent. Conclusion: Perivascular iron deposition is seen in some but not all MS cases, giving credence to the use of SWI to assess iron involvement in MS pathology in vivo.

Sex Roles in Reading.

ERIC Educational Resources Information Center

Gunderson, Doris V.

Sex roles in two disparate areas, reading and literature, are treated separately in this paper. Sex-related factors listed which may attribute to the high incidence of boys experiencing reading difficulty were: (1) predominance of female teachers in the primary grades, (2) boys' lack of interest in basal readers, (3) adults considering reading a…

Preoperative prediction of histopathological outcome in basal cell carcinoma: flat surface and multiple small erosions predict superficial basal cell carcinoma in lighter skin types.

PubMed

Ahnlide, I; Zalaudek, I; Nilsson, F; Bjellerup, M; Nielsen, K

2016-10-01

Prediction of the histopathological subtype of basal cell carcinoma (BCC) is important for tailoring optimal treatment, especially in patients with suspected superficial BCC (sBCC). To assess the accuracy of the preoperative prediction of subtypes of BCC in clinical practice, to evaluate whether dermoscopic examination enhances accuracy and to find dermoscopic criteria for discriminating sBCC from other subtypes. The main presurgical diagnosis was compared with the histopathological, postoperative diagnosis of routinely excised skin tumours in a predominantly fair-skinned patient cohort of northern Europe during a study period of 3 years (2011-13). The study period was split in two: during period 1, dermoscopy was optional (850 cases with a pre- or postoperative diagnosis of BCC), while during period 2 (after an educational dermoscopic update) dermoscopy was mandatory (651 cases). A classification tree based on clinical and dermoscopic features for prediction of sBCC was applied. For a total of 3544 excised skin tumours, the sensitivity for the diagnosis of BCC (any subtype) was 93·3%, specificity 91·8%, and the positive predictive value (PPV) 89·0%. The diagnostic accuracy as well as the PPV and the positive likelihood ratio for sBCC were significantly higher when dermoscopy was mandatory. A flat surface and multiple small erosions predicted sBCC. The study shows a high accuracy for an overall diagnosis of BCC and increased accuracy in prediction of sBCC for the period when dermoscopy was applied in all cases. The most discriminating findings for sBCC, based on clinical and dermoscopic features in this fair-skinned population, were a flat surface and multiple small erosions. © 2016 British Association of Dermatologists.

Glycemic control and maternal and fetal outcomes in pregnant women with type 1 diabetes according to the type of basal insulin.

PubMed

Chico, A; Herranz, L; Corcoy, R; Ramírez, O; Goya, M M; Bellart, J; González-Romero, S; Codina, M; Sánchez, P; Cortázar, A; Acosta, D; Picón, M J; Rubio, J A; Megía, A; Sancho, M A; Balsells, M; Solá, E; González, N L; López-López, J

2016-11-01

To examine the potential role of the type of basal insulin on glycemic control and maternal and foetal outcomes in pregnant women with type 1 diabetes (T1DM). Retrospective cohort study of pregnancies attended at 18 Spanish tertiary hospitals. T1DM, singleton pregnancies, delivery between 2002-2010, and use of the same basal and prandial insulin from before pregnancy until delivery. A total of 1534 pregnancies were included. The basal insulin most commonly used was Neutral Protamine Hagedorn (NPH) (51.7%), followed by glargine (23.2%) and continuous subcutaneous insulin infusion (CSII) (21.1%). CSII users had longer diabetes duration. Multiple logistic regression analysis showed that CSII was independently associated with lower doses of insulin, higher glycated haemoglobin (HbA 1c ) in all trimesters, and higher rates of miscarriage, preterm birth and neonatal hypoglycemia. Glargine was related to a higher risk of preterm birth and a small-for-gestational age infant (SGA). The odds ratios (OR) of the associations between insulin type and clinical outcomes (from 0.642 to 4.894) have a relevant magnitude. In this observational study of pregnant women with T1DM, the type of basal insulin was independently associated with metabolic variables and foetal outcomes. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Surgical excision versus imiquimod 5% cream for nodular and superficial basal-cell carcinoma (SINS): a multicentre, non-inferiority, randomised controlled trial.

PubMed

Bath-Hextall, Fiona; Ozolins, Mara; Armstrong, Sarah J; Colver, Graham B; Perkins, William; Miller, Paul S J; Williams, Hywel C

2014-01-01

Basal-cell carcinoma is the most common form of skin cancer and its incidence is increasing worldwide. We aimed to assess the effectiveness of imiquimod cream versus surgical excision in patients with low-risk basal-cell carcinoma. We did a multicentre, parallel-group, pragmatic, non-inferiority, randomised controlled trial at 12 centres in the UK, in which patients were recruited between June 19, 2003, and Feb 22, 2007, with 3 year follow-up from June 26, 2006, to May 26, 2010. Participants of any age were eligible if they had histologically confirmed primary nodular or superficial basal-cell carcinoma at low-risk sites. We excluded patients with morphoeic or recurrent basal-cell carcinoma and those with Gorlin syndrome. Participants were randomly assigned (1:1) via computer-generated blocked randomisation, stratified by centre and tumour type, to receive either imiquimod 5% cream once daily for 6 weeks (superficial) or 12 weeks (nodular), or surgical excision with a 4 mm margin. The randomisation sequence was concealed from study investigators. Because of the nature of the interventions, masking of participants was not possible and masking of outcome assessors was only partly possible. The trial statistician was masked to allocation until all analyses had been done. The primary outcome was the proportion of participants with clinical success, defined as absence of initial treatment failure or signs of recurrence at 3 years from start of treatment. We used a prespecified non-inferiority margin of a relative risk (RR) of 0.87. Analysis was by a modified intention-to-treat population and per protocol. This study is registered as an International Standard Randomised Controlled Trial (ISRCTN48755084), and with ClinicalTrials.gov, number NCT00066872. 501 participants were randomly assigned to the imiquimod group (n=254) or the surgical excision group (n=247). At year 3, 401 (80%) patients were included in the modified intention-to-treat group. At 3 years, 178 (84%) of 213 participants in the imiquimod group were treated successfully compared with 185 (98%) of 188 participants in the surgery group (RR 0.84, 98% CI 0.78-0.91; p<0.0001). No clear difference was noted between groups in patient-assessed cosmetic outcomes. The most common adverse events were itching (211 patients in the imiquimod group vs 129 in the surgery group) and weeping (160 vs 81). We recorded serious adverse events in 99 (40%) of 249 participants in the imiquimod group and 97 (42%) of 229 in the surgery group had serious adverse events, but none were regarded as related to treatment. 12 (5%) participants in the imiquimod group withdrew because of adverse events compared with four (2%) in the surgery group. Imiquimod was inferior to surgery according to our predefined non-inferiority criterion. Although excisional surgery remains the best treatment for low-risk basal-cell carcinoma, imiquimod cream might still be a useful treatment option for small low-risk superficial or nodular basal-cell carcinoma dependent on factors such as patient preference, size and site of the lesion, and whether the patient has more than one lesion. Cancer Research UK. Copyright © 2014 Elsevier Ltd. All rights reserved.

Investigation of the dependence of deformation mechanisms on solute content in polycrystalline Mg–Al magnesium alloys by neutron diffraction and acoustic emission

DOE PAGES

Mathis, Kristian; Capek, J.; Clausen, Bjorn; ...

2015-04-20

Influence of aluminium content on the deformation mechanisms in Mg–Al binary alloys has been studied using in-situ neutron diffraction and acoustic emission technique. Here, it is shown that the addition of the solute increases the critical resolved shear stress for twinning. Further, the role of aluminium on the solid solution hardening of the basal plane and softening of non-basal planes are discussed using results of the convolutional multiple peak profile analysis of diffraction patterns. In conclusion, the results indicate that the density of both prismatic and pyramidal dislocations increases with increasing alloying content.

The BET bromodomain inhibitor CPI203 improves lenalidomide and dexamethasone activity in in vitro and in vivo models of multiple myeloma by blockade of Ikaros and MYC signaling

PubMed Central

Díaz, Tania; Rodríguez, Vanina; Lozano, Ester; Mena, Mari-Pau; Calderón, Marcos; Rosiñol, Laura; Martínez, Antonio; Tovar, Natalia; Pérez-Galán, Patricia; Bladé, Joan; Roué, Gaël; de Larrea, Carlos Fernández

2017-01-01

Most patients with multiple myeloma treated with current therapies, including immunomodulatory drugs, eventually develop relapsed/refractory disease. Clinical activity of lenalidomide relies on degradation of Ikaros and the consequent reduction in IRF4 expression, both required for myeloma cell survival and involved in the regulation of MYC transcription. Thus, we sought to determine the combinational effect of an MYC-interfering therapy with lenalidomide/dexamethasone. We analyzed the potential therapeutic effect of the combination of the BET bromodomain inhibitor CPI203 with the lenalidomide/dexamethasone regimen in myeloma cell lines. CPI203 exerted a dose-dependent cell growth inhibition in cell lines, indeed in lenalidomide/dexamethasone-resistant cells (median response at 0.5 μM: 65.4%), characterized by G1 cell cycle blockade and a concomitant inhibition of MYC and Ikaros signaling. These effects were potentiated by the addition of lenalidomide/dexamethasone. Results were validated in primary plasma cells from patients with multiple myeloma co-cultured with the mesenchymal stromal cell line stromaNKtert. Consistently, the drug combination evoked a 50% reduction in cell proliferation and correlated with basal Ikaros mRNA expression levels (P=0.04). Finally, in a SCID mouse xenotransplant model of myeloma, addition of CPI203 to lenalidomide/dexamethasone decreased tumor burden, evidenced by a lower glucose uptake and increase in the growth arrest marker GADD45B, with simultaneous downregulation of key transcription factors such as MYC, Ikaros and IRF4. Taken together, our data show that the combination of a BET bromodomain inhibitor with a lenalidomide-based regimen may represent a therapeutic approach to improve the response in relapsed/refractory patients with multiple myeloma, even in cases with suboptimal prior response to immunomodulatory drugs. PMID:28751557

Exquisite sensitivity of TP53 mutant and basal breast cancers to a dose-dense epirubicin-cyclophosphamide regimen.

PubMed

Bertheau, Philippe; Turpin, Elisabeth; Rickman, David S; Espié, Marc; de Reyniès, Aurélien; Feugeas, Jean-Paul; Plassa, Louis-François; Soliman, Hany; Varna, Mariana; de Roquancourt, Anne; Lehmann-Che, Jacqueline; Beuzard, Yves; Marty, Michel; Misset, Jean-Louis; Janin, Anne; de Thé, Hugues

2007-03-01

In breast cancers, only a minority of patients fully benefit from the different chemotherapy regimens currently in use. Identification of markers that could predict the response to a particular regimen would thus be critically important for patient care. In cell lines or animal models, tumor protein p53 (TP53) plays a critical role in modulating the response to genotoxic drugs. TP53 is activated in response to DNA damage and triggers either apoptosis or cell-cycle arrest, which have opposite effects on cell fate. Yet, studies linking TP53 status and chemotherapy response have so far failed to unambiguously establish this paradigm in patients. Breast cancers with a TP53 mutation were repeatedly shown to have a poor outcome, but whether this reflects poor response to treatment or greater intrinsic aggressiveness of the tumor is unknown. In this study we analyzed 80 noninflammatory breast cancers treated by frontline (neoadjuvant) chemotherapy. Tumor diagnoses were performed on pretreatment biopsies, and the patients then received six cycles of a dose-dense regimen of 75 mg/m(2) epirubicin and 1,200 mg/m(2) cyclophosphamide, given every 14 days. After completion of chemotherapy, all patients underwent mastectomies, thus allowing for a reliable assessment of chemotherapy response. The pretreatment biopsy samples were used to determine the TP53 status through a highly efficient yeast functional assay and to perform RNA profiling. All 15 complete responses occurred among the 28 TP53-mutant tumors. Furthermore, among the TP53-mutant tumors, nine out of ten of the highly aggressive basal subtypes (defined by basal cytokeratin [KRT] immunohistochemical staining) experienced complete pathological responses, and only TP53 status and basal subtype were independent predictors of a complete response. Expression analysis identified many mutant TP53-associated genes, including CDC20, TTK, CDKN2A, and the stem cell gene PROM1, but failed to identify a transcriptional profile associated with complete responses among TP53 mutant tumors. In patients with unresponsive tumors, mutant TP53 status predicted significantly shorter overall survival. The 15 patients with responsive TP53-mutant tumors, however, had a favorable outcome, suggesting that this chemotherapy regimen can overcome the poor prognosis generally associated with mutant TP53 status. This study demonstrates that, in noninflammatory breast cancers, TP53 status is a key predictive factor for response to this dose-dense epirubicin-cyclophosphamide regimen and further suggests that the basal subtype is exquisitely sensitive to this association. Given the well-established predictive value of complete responses for long-term survival and the poor prognosis of basal and TP53-mutant tumors treated with other regimens, this chemotherapy could be particularly suited for breast cancer patients with a mutant TP53, particularly those with basal features.

Effect of hexavalent chromium on electron leakage of respiratory chain in mitochondria isolated from rat liver.

PubMed

Xie, Ying; Zhong, Caigao; Zeng, Ming; Guan, Lan; Luo, Lei

2013-01-01

In the present study, we explored reactive axygen species (ROS) production in mitochondria, the mechanism of hexavalent chromium (Cr(VI)) hepatotoxicity, and the role of protection by GSH. Intact mitochondria were isolated from rat liver tissues and mitochondrial basal respiratory rates of NADH and FADH2 respiratory chains were determined. Mitochondria were treated with Cr(VI), GSH and several complex inhibitors. Mitochondria energized by glutamate/malate were separately or jointly treated with Rotenone (Rot), diphenyleneiodonium (DPI) and antimycinA (Ant), while mitochondria energized by succinate were separately or jointly treated with Rot, DPI ' thenoyltrifluoroacetone (TTFA) and Ant. Cr(VI) concentration-dependently induced ROS production in the NADH and FADH2 respiratory chain in liver mitochondria. Basal respiratory rate of the mitochondrial FADH2 respiratory chain was significantly higher than that of NADH respiratory chain. Hepatic mitochondrial electron leakage induced by Cr(VI) from NADH respiratory chain were mainly from ubiquinone binding sites of complex I and complex III. Treatment with 50µM Cr(VI) enhances forward movement of electrons through FADH2 respiratory chain and leaking through the ubiquinone binding site of complex III. Moreover, the protective effect of GSH on liver mitochondria electron leakage is through removing excess H2O2 and reducing total ROS. Copyright © 2013 S. Karger AG, Basel.

Abnormal brain MRI signals in the splenium of the corpus callosum, basal ganglia and internal capsule in a suspected case with tuberculous meningitis.

PubMed

Hirotani, Makoto; Yabe, Ichiro; Hamada, Shinsuke; Tsuji, Sachiko; Kikuchi, Seiji; Sasaki, Hidenao

2007-01-01

A 34-year-old man visited the hospital with chief complaints of headache, fever, and disturbance of consciousness. In view of his clinical condition, the course of the disease, and results of examination, he was diagnosed with viral meningitis and treated accordingly. However, his clinical condition worsened, and MRI revealed abnormal signals in the splenium of the corpus callosum, in the basal ganglia and in the internal capsule, as well as the presence of severe inflammation in the base of the brain. Since he had a high ADA level in the cerebrospinal fluid and was consequently suspected to have tuberculous meningitis, he was placed on antitubercular agents. Then, his clinical condition began to improve. Additional steroid pulse therapy further improved his condition, and abnormal signals in the splenium of the corpus callosum and the basal ganglia resolved. This valuable case suggests that an immune mechanism contributed to the occurrence of central nervous system symptoms associated with tuberculous meningitis.

Immunoprevention of Basal Cell Carcinomas with Recombinant Hedgehog-interacting Protein

PubMed Central

Vogt, Annika; Chuang, Pao-Tien; Hebert, Jennifer; Hwang, Jimmy; Lu, Ying; Kopelovich, Levy; Athar, Mohammad; Bickers, David R.; Epstein, Ervin H.

2004-01-01

Basal cell carcinomas (BCCs) are driven by abnormal hedgehog signaling and highly overexpress several hedgehog target genes. We report here our use of one of these target genes, hedgehog-interacting protein (Hip1), as a tumor-associated antigen for immunoprevention of BCCs in Ptch1+/− mice treated with ionizing radiation. Hip1 mRNA is expressed in adult mouse tissues at levels considerably lower than those in BCCs. Immunization with either of two large recombinant Hip1 polypeptides was well tolerated in Ptch1+/− mice, induced B and T cell responses detectable by enzyme-linked immunosorbent assay, Western blot, delayed type hypersensitivity, and enzyme-linked immunospot assay, and reduced the number of BCCs by 42% (P < 0.001) and 32% (P < 0.01), respectively. We conclude that immunization with proteins specifically up-regulated by hedgehog signaling may hold promise as a preventive option for patients such as those with the basal cell nevus syndrome who are destined to develop large numbers of BCCs. PMID:15024045

Inserting ex vivo fluorescence confocal microscopy perioperatively in Mohs micrographic surgery expedites bedside assessment of excision margins in recurrent basal cell carcinoma.

PubMed

Longo, Caterina; Ragazzi, Moira; Castagnetti, Fabio; Gardini, Stefano; Palmieri, Tamara; Lallas, Aimilios; Moscarella, Elvira; Piana, Simonetta; Pellacani, Giovanni; Zalaudek, Iris; Argenziano, Giuseppe

2013-01-01

Mohs micrographic surgery can be employed in recurrent basal cell carcinoma, although it is a time-consuming technique. Recently, ex vivo fluorescence confocal microscopy (FCM) has been employed to obtain a fast assessment of tumor margins at the bedside. In our case we successfully employed ex vivo FCM to assess the tumor margins and we treated the persistent tumor with intensity-modulated radiation therapy. Our case demonstrates that a multidisciplinary approach is very efficient in managing complex and recurrent tumors and highlights the benefits of FCM as a new technique that can be used in the surgical theater to speed up the entire procedure.

TP53 supports basal-like differentiation of mammary epithelial cells by preventing translocation of deltaNp63 into nucleoli

PubMed Central

Munne, Pauliina M.; Gu, Yuexi; Tumiati, Manuela; Gao, Ping; Koopal, Sonja; Uusivirta, Sanna; Sawicki, Janet; Wei, Gong-Hong; Kuznetsov, Sergey G.

2014-01-01

Multiple observations suggest a cell type-specific role for TP53 in mammary epithelia. We developed an in vitro assay, in which primary mouse mammary epithelial cells (mMECs) progressed from lumenal to basal-like phenotypes based on expression of Krt18 or ΔNp63, respectively. Such transition was markedly delayed in Trp53−/− mMECs suggesting that Trp53 is required for specification of the basal, but not lumenal cells. Evidence from human basal-like cell lines suggests that TP53 may support the activity of ΔNp63 by preventing its translocation from nucleoplasm into nucleoli. In human lumenal cells, activation of TP53 by inhibiting MDM2 or BRCA1 restored the nucleoplasmic expression of ΔNp63. Trp53−/− mMECs eventually lost epithelial features resulting in upregulation of MDM2 and translocation of ΔNp63 into nucleoli. We propose that TP63 may contribute to TP53-mediated oncogenic transformation of epithelial cells and shed light on tissue- and cell type-specific biases observed for TP53-related cancers. PMID:24722541

Loss of MACF1 Abolishes Ciliogenesis and Disrupts Apicobasal Polarity Establishment in the Retina.

PubMed

May-Simera, Helen L; Gumerson, Jessica D; Gao, Chun; Campos, Maria; Cologna, Stephanie M; Beyer, Tina; Boldt, Karsten; Kaya, Koray D; Patel, Nisha; Kretschmer, Friedrich; Kelley, Matthew W; Petralia, Ronald S; Davey, Megan G; Li, Tiansen

2016-10-25

Microtubule actin crosslinking factor 1 (MACF1) plays a role in the coordination of microtubules and actin in multiple cellular processes. Here, we show that MACF1 is also critical for ciliogenesis in multiple cell types. Ablation of Macf1 in the developing retina abolishes ciliogenesis, and basal bodies fail to dock to ciliary vesicles or migrate apically. Photoreceptor polarity is randomized, while inner retinal cells laminate correctly, suggesting that photoreceptor maturation is guided by polarity cues provided by cilia. Deletion of MACF1 in adult photoreceptors causes reversal of basal body docking and loss of outer segments, reflecting a continuous requirement for MACF1 function. MACF1 also interacts with the ciliary proteins MKKS and TALPID3. We propose that a disruption of trafficking across microtubles to actin filaments underlies the ciliogenesis defect in cells lacking MACF1 and that MKKS and TALPID3 are involved in the coordination of microtubule and actin interactions. Published by Elsevier Inc.

The brain map of gait variability in aging, cognitive impairment and dementia. A systematic review

PubMed Central

Tian, Qu; Chastan, Nathalie; Bair, Woei-Nan; Resnick, Susan M.; Ferrucci, Luigi; Studenski, Stephanie A.

2017-01-01

While gait variability may reflect subtle changes due to aging or cognitive impairment (CI), associated brain characteristics remain unclear. We summarize structural and functional neuroimaging findings associated with gait variability in older adults with and without CI and dementia. We identified 17 eligible studies; all were cross-sectional; few examined multiple brain areas. In older adults, temporal gait variability was associated with structural differences in medial areas important for lower limb coordination and balance. Both temporal and spatial gait variability were associated with structural and functional differences in hippocampus and primary sensorimotor cortex and structural differences in anterior cingulate cortex, basal ganglia, association tracts, and posterior thalamic radiation. In CI or dementia, some associations were found in primary motor cortex, hippocampus, prefrontal cortex and basal ganglia. In older adults, gait variability may be associated with areas important for sensorimotor integration and coordination. To comprehend the neural basis of gait variability with aging and CI, longitudinal studies of multiple brain areas are needed. PMID:28115194

Conditions for a steady ice sheet ice shelf junction

NASA Astrophysics Data System (ADS)

Nowicki, S. M. J.; Wingham, D. J.

2008-01-01

This paper investigates the conditions under which a marine ice sheet may adopt a steady profile. The ice is treated as a linear viscous fluid caused to flow from a rigid base to and over water, treated as a denser but inviscid fluid. The solutions in the region around the point of flotation, or 'transition' zone, are calculated numerically. In-flow and out-flow conditions appropriate to ice sheet and ice shelf flow are applied at the ends of the transition zone and the rigid base is specified; the flow and steady free surfaces are determined as part of the solutions. The basal stress upstream, and the basal deflection downstream, of the flotation point are examined to determine which of these steady solutions satisfy 'contact' conditions that would prevent (i) the steady downstream basal deflection contacting the downstream base, and (ii) the upstream ice commencing to float in the event it was melted at the base. In the case that the upstream bed is allowed to slide, we find only one mass flux that satisfies the contact conditions. When no sliding is allowed at the bed, however, we find a range of mass fluxes satisfy the contact conditions. The effect of 'backpressure' on the solutions is investigated, and is found to have no affect on the qualitative behaviour of the junctions. To the extent that the numerical, linearly viscous treatment may be applied to the case of ice flowing out over the ocean, we conclude that when sliding is present, Weertman's 'instability' hypothesis holds.

A chemical potentiator of copper-accumulation used to investigate the iron-regulons of Saccharomyces cerevisiae.

PubMed

Foster, Andrew W; Dainty, Samantha J; Patterson, Carl J; Pohl, Ehmke; Blackburn, Hannah; Wilson, Clare; Hess, Corinna R; Rutherford, Julian C; Quaranta, Laura; Corran, Andy; Robinson, Nigel J

2014-07-01

The extreme resistance of Saccharomyces cerevisiae to copper is overcome by 2-(6-benzyl-2-pyridyl)quinazoline (BPQ), providing a chemical-biology tool which has been exploited in two lines of discovery. First, BPQ is shown to form a red (BPQ)2 Cu(I) complex and promote Ctr1-independent copper-accumulation in whole cells and in mitochondria isolated from treated cells. Multiple phenotypes, including loss of aconitase activity, are consistent with copper-BPQ mediated damage to mitochondrial iron-sulphur clusters. Thus, a biochemical basis of copper-toxicity in S. cerevisiae is analogous to other organisms. Second, iron regulons controlled by Aft1/2, Cth2 and Yap5 that respond to mitochondrial iron-sulphur cluster status are modulated by copper-BPQ causing iron hyper-accumulation via upregulated iron-import. Comparison of copper-BPQ treated, untreated and copper-only treated wild-type and fra2Δ by RNA-seq has uncovered a new candidate Aft1 target-gene (LSO1) and paralogous non-target (LSO2), plus nine putative Cth2 target-transcripts. Two lines of evidence confirm that Fra2 dominates basal repression of the Aft1/2 regulons in iron-replete cultures. Fra2-independent control of these regulons is also observed but CTH2 itself appears to be atypically Fra2-dependent. However, control of Cth2-target transcripts which is independent of CTH2 transcript abundance or of Fra2, is also quantified. Use of copper-BPQ supports a substantial contribution of metabolite repression to iron-regulation. © 2014 The Authors. Molecular Microbiology published by John Wiley & Sons Ltd.

A chemical potentiator of copper-accumulation used to investigate the iron-regulons of Saccharomyces cerevisiae

PubMed Central

Foster, Andrew W; Dainty, Samantha J; Patterson, Carl J; Pohl, Ehmke; Blackburn, Hannah; Wilson, Clare; Hess, Corinna R; Rutherford, Julian C; Quaranta, Laura; Corran, Andy; Robinson, Nigel J

2014-01-01

The extreme resistance of Saccharomyces cerevisiae to copper is overcome by 2-(6-benzyl-2-pyridyl)quinazoline (BPQ), providing a chemical-biology tool which has been exploited in two lines of discovery. First, BPQ is shown to form a red (BPQ)2Cu(I) complex and promote Ctr1-independent copper-accumulation in whole cells and in mitochondria isolated from treated cells. Multiple phenotypes, including loss of aconitase activity, are consistent with copper-BPQ mediated damage to mitochondrial iron–sulphur clusters. Thus, a biochemical basis of copper-toxicity in S. cerevisiae is analogous to other organisms. Second, iron regulons controlled by Aft1/2, Cth2 and Yap5 that respond to mitochondrial iron–sulphur cluster status are modulated by copper-BPQ causing iron hyper-accumulation via upregulated iron-import. Comparison of copper-BPQ treated, untreated and copper-only treated wild-type and fra2Δ by RNA-seq has uncovered a new candidate Aft1 target-gene (LSO1) and paralogous non-target (LSO2), plus nine putative Cth2 target-transcripts. Two lines of evidence confirm that Fra2 dominates basal repression of the Aft1/2 regulons in iron-replete cultures. Fra2-independent control of these regulons is also observed but CTH2 itself appears to be atypically Fra2-dependent. However, control of Cth2-target transcripts which is independent of CTH2 transcript abundance or of Fra2, is also quantified. Use of copper-BPQ supports a substantial contribution of metabolite repression to iron-regulation. PMID:24895027

Optimizing Glycemic Control Through Titration of Insulin Glargine 100 U/mL: A Review of Current and Future Approaches with a Focus on Asian Populations.

PubMed

Deerochanawong, Chaicharn; Bajpai, Shailendra; Dwipayana, I Made Pande; Hussein, Zanariah; Mabunay, Maria Aileen; Rosales, Reynaldo; Tsai, Shih-Tzer; Tsang, Man Wo

2017-12-01

Various data have demonstrated inadequate glycemic control amongst Asians with type 2 diabetes mellitus (T2DM), possibly on account of suboptimal titration of basal insulin-an issue which needs to be further examined. Here we review the available global and Asia-specific data on titration of basal insulin, with a focus on the use of insulin glargine 100 U/mL (Gla-100). We also discuss clinical evidence on the efficacy and safety of titrating Gla-100, different approaches to titration, including some of the latest technological advancements, and guidance on the titration of basal insulin from international and local Asian guidelines. The authors also provide their recommendations for the initiation and titration of basal insulin for Asian populations. Discussion of the data included in this review and in relation to the authors' clinical experience with treating T2DM in Asian patients is also included. Briefly, clinical studies demonstrate the achievement of adequate glycemic control in adults with T2DM through titration of Gla-100. However, studies investigating approaches to titration, specifically in Asian populations, are lacking and need to be conducted. Given that the management of insulin therapy is a multidisciplinary team effort involving endocrinologists, primary care physicians, nurse educators, and patients, greater resources and education targeted at these groups are needed regarding the optimal titration of basal insulin. Technological advancements in the form of mobile or web-based applications for automated dose adjustment can aid different stakeholders in optimizing the dose of basal insulin, enabling a larger number of patients in Asia to reach their target glycemic goals with improved outcomes.

Description of Patients Undergoing Mohs Surgery in Spain: Initial Report on Data From the Spanish Registry of Mohs Surgery (REGESMOHS).

PubMed

Ruiz-Salas, V; Garcés, J R; Miñano Medrano, R; Alonso-Alonso, T; Rodríguez-Prieto, M Á; López-Estebaranz, J L; Sanmartín-Jiménez, O; Guillén Barona, C; Delgado Jiménez, Y; Toll-Abelló, A; Vargas Diez, E; Ciudad Blanco, C; Alfaro Rubio, A; Allende Markixana, I; de Eusebio Murillo, E; Manubens-Mercadé, E; Vázquez-Veiga, H; Barchino Ortiz, L; García-Doval, I; Redondo Bellón, P

2015-09-01

The Spanish registry of Mohs micrographic surgery started collecting data in July 2013. The aim of the registry is to report on the use of this technique in Spain and the outcomes achieved. In the present article, we describe the characteristics of patients and the tumors treated. This is a prospective cohort study of patients treated with Mohs micrographic surgery. The participating centers are hospitals where at least one intervention of this type is performed each week. All patients considered for Mohs micrographic surgery in participating centers are included in the registry except those who have been declared legally incompetent. Between July 2013 and October 2014, data from 655 patients were included in the registry. The most common tumor involved was basal cell carcinoma, and the most common histological subtype was infiltrative basal cell carcinoma. Most of the tumors treated were located on the face or scalp, and the most common site was the nose. Almost 40% of the tumors treated were recurrent or persistent, and preoperative tumor size was similar to that reported in other European studies and in Australia. In total, 45.5% of patients had received previous surgical treatment. The findings are similar to those reported in other studies, and the data collected are useful for assessing whether the results of studies carried out elsewhere are applicable in Spain. Copyright © 2014 Elsevier España, S.L.U. and AEDV. All rights reserved.

A three-dimensional histological atlas of the human basal ganglia. II. Atlas deformation strategy and evaluation in deep brain stimulation for Parkinson disease.

PubMed

Bardinet, Eric; Bhattacharjee, Manik; Dormont, Didier; Pidoux, Bernard; Malandain, Grégoire; Schüpbach, Michael; Ayache, Nicholas; Cornu, Philippe; Agid, Yves; Yelnik, Jérôme

2009-02-01

The localization of any given target in the brain has become a challenging issue because of the increased use of deep brain stimulation to treat Parkinson disease, dystonia, and nonmotor diseases (for example, Tourette syndrome, obsessive compulsive disorders, and depression). The aim of this study was to develop an automated method of adapting an atlas of the human basal ganglia to the brains of individual patients. Magnetic resonance images of the brain specimen were obtained before extraction from the skull and histological processing. Adaptation of the atlas to individual patient anatomy was performed by reshaping the atlas MR images to the images obtained in the individual patient using a hierarchical registration applied to a region of interest centered on the basal ganglia, and then applying the reshaping matrix to the atlas surfaces. Results were evaluated by direct visual inspection of the structures visible on MR images and atlas anatomy, by comparison with electrophysiological intraoperative data, and with previous atlas studies in patients with Parkinson disease. The method was both robust and accurate, never failing to provide an anatomically reliable atlas to patient registration. The registration obtained did not exceed a 1-mm mismatch with the electrophysiological signatures in the region of the subthalamic nucleus. This registration method applied to the basal ganglia atlas forms a powerful and reliable method for determining deep brain stimulation targets within the basal ganglia of individual patients.

Tropical pasture hay utilization with slaframine and cottonseed meal: ruminal characteristics and digesta passage in wethers.

PubMed

Bird, A R; Croom, W J; Bailey, J V; O'Sullivan, B M; Hagler, W M; Gordon, G L; Martin, P R

1993-06-01

Sixteen mature, ruminally cannulated wethers (average BW = 41 +/- 1 kg) were fed a low-quality hay diet with or without a cottonseed meal (CSM) supplement and the parasympathomimetic agonist slaframine (SF). Treatments were basal diet (Mitchell grass hay, 4.8% CP, 46.8% ADF) available on an ad libitum basis, basal diet plus SF (8 micrograms/kg BW, 2 x daily i.m. injection), basal diet plus CSM (41.0% CP; 100 g/d), or basal diet plus SF and CSM. Treatments were arranged as a 2 x 2 factorial within a replicated 4 x 4 Latin square with 20-d periods followed by a 10-d adjustment during which only the basal diet was fed. All measurements were performed within the final 10 d of each period. Slaframine increased salivary flow by 10 to 35% (P < .07), ruminal fluid dilution rate by 8 to 11% (P < .10), and pH by 3 to 4% (P < .001). A twofold increase (P < .05) in ruminal cellulolytic bacteria numbers occurred in SF-treated wethers. Despite these SF-induced changes in the ruminal environment, whole-tract apparent nutrient digestibility, N and mineral balance, and ruminal VFA concentrations were not changed. Cottonseed meal increased forage intake by 34 to 54% (P < .001) and DM digestibility by 30% (P < .001). Cottonseed meal supplementation of a Mitchell grass hay diet improved nutritional status and attenuated live weight loss.

Topical Imiquimod in the Treatment of Conjunctival Actinic Keratosis.

PubMed

Rowlands, Megan A; Giacometti, Joseph N; Servat, Javier; Materin, Miguel A; Levin, Flora

Conjunctival actinic keratosis is rare and difficult to treat, as recurrences are common. Imiquimod, an immune response modulator, is currently Food and Drug Administration-approved for cutaneous actinic keratosis and superficial basal cell carcinomas. Emerging reports have shown it to be effective in treating some periocular and conjunctival lesions. The authors present a case of a 68-year-old white man with recurrent actinic keratosis involving the pretarsal conjunctiva, which was successfully treated with 5% topical imiquimod following previous failure with cryotherapy and interferon α-2b. The patient had ocular irritation that resolved on cessation of treatment. To the authors' knowledge, this is the first report of conjunctival actinic keratosis being treated with and successfully eradicated by topical imiquimod.

Patient-reported frequency, awareness and patient-physician communication of hypoglycaemia in Belgium.

PubMed

Peene, B; D'Hooge, D; Vandebrouck, T; Mathieu, C

2014-12-01

Limited data exist on the frequency of non-severe hypoglycaemic events in patients with insulin-treated diabetes outside of clinical trial settings. Our study investigated the rates of self-reported non-severe events in a sample of Belgian patients. We also investigated self-reported awareness of the symptoms of hypoglycaemia and communication about hypoglycaemia between patients and their physicians. Patients aged >15 years with Type 1 (T1DM) and insulin-treated Type 2 (T2DM) diabetes were recruited via existing panels in Belgium to complete four questionnaires at weekly intervals. In addition to demographics, data on frequency of non-severe hypoglycaemic events (7-day recall), severe hypoglycaemic events (1-year recall), awareness of hypoglycaemia and reporting of hypoglycaemia to physicians were recorded. In total, 412 patients (44% T1DM, 56% T2DM) completed 1148 patient-week records. Mean insulin-treatment duration was 11 years, mean HbA(1c) 7·7%. Mean reported non-severe hypoglycaemic events per patient-week were 2·3 in T1DM patients, 0·3 in T2DM patients receiving basal-only therapy, 0·7 in T2DM patients receiving basal-bolus therapy and 0·8 in T2DM patients receiving another form of insulin. Mean reported annual frequencies of severe hypoglycaemic events were 0·9 in T1DM and 0·4 in T2DM. Impaired awareness or unawareness of hypoglycaemia was reported by 70% of T1DM patients, 55% of T2DM patients receiving basal-only therapy, 61% of T2DM patients receiving basal-bolus therapy and 73% of T2DM patients receiving another form of insulin. Overall, 60% of T1DM patients and 46% of T2DM patients rarely/never discuss hypoglycaemia with their GP/specialist. In addition, 10% of T1DM patients and 13% of T2DM patients stated that GPs/specialists did not ask them about their hypoglycaemia in routine appointments. Hypoglycaemic events and unawareness of these events are common in Belgian insulin-treated diabetes patients. Patients often fail to report hypoglycaemic events to their physician and many physicians do not inquire about hypoglycaemia, meaning the current burden of hypoglycaemic events may be underestimated.

Efficacy and Safety of LixiLan, a Titratable Fixed-Ratio Combination of Insulin Glargine Plus Lixisenatide in Type 2 Diabetes Inadequately Controlled on Basal Insulin and Metformin: The LixiLan-L Randomized Trial.

PubMed

Aroda, Vanita R; Rosenstock, Julio; Wysham, Carol; Unger, Jeffrey; Bellido, Diego; González-Gálvez, Guillermo; Takami, Akane; Guo, Hailing; Niemoeller, Elisabeth; Souhami, Elisabeth; Bergenstal, Richard M

2016-11-01

This study was conducted to demonstrate the efficacy and safety of LixiLan (iGlarLixi), a novel, titratable, fixed-ratio combination of insulin glargine (iGlar) (100 units) and lixisenatide, compared with iGlar in patients with type 2 diabetes inadequately controlled on basal insulin with or without up to two oral glucose-lowering agents. After a 6-week run-in when iGlar was introduced and/or further titrated, and oral antidiabetic drugs other than metformin were stopped, 736 basal insulin-treated patients (mean diabetes duration 12 years, BMI 31 kg/m 2 ) were randomized 1:1 to open-label, once-daily iGlarLixi or iGlar, both titrated to fasting plasma glucose <100 mg/dL (<5.6 mmol/L) up to a maximum dose of 60 units/day. The primary outcome was change in HbA 1c levels at 30 weeks. HbA 1c decreased from 8.5% (69 mmol/mol) to 8.1% (65 mmol/mol) during the run-in period. After randomization, iGlarLixi showed greater reductions in HbA 1c from baseline compared with iGlar (-1.1% vs. -0.6%, P < 0.0001), reaching a mean final HbA 1c of 6.9% (52 mmol/mol) compared with 7.5% (58 mmol/mol) for iGlar. HbA 1c <7.0% (53 mmol/mol) was achieved in 55% of iGlarLixi patients compared with 30% on iGlar. Mean body weight decreased by 0.7 kg with iGlarLixi and increased by 0.7 kg with iGlar (1.4 kg difference, P < 0.0001). Documented symptomatic hypoglycemia (≤70 mg/dL) was comparable between groups. Mild gastrointestinal adverse effects were very low but more frequent with iGlarLixi. Compared with iGlar, a substantially higher proportion of iGlarLixi-treated patients achieved glycemic targets with a beneficial effect on body weight, no additional risk of hypoglycemia, and low levels of gastrointestinal adverse effects in inadequately controlled, basal insulin-treated, long-standing type 2 diabetes. © 2016 by the American Diabetes Association.

Olfactory groove meningioma: report of 99 cases surgically treated at the Catholic University School of Medicine, Rome.

PubMed

Pallini, Roberto; Fernandez, Eduardo; Lauretti, Liverana; Doglietto, Francesco; D'Alessandris, Quintino Giorgio; Montano, Nicola; Capo, Gabriele; Meglio, Mario; Maira, Giulio

2015-02-01

We reviewed our series of olfactory groove meningiomas (OGMs) with the aim to relate the surgical approach with outcome and to define clinical and pathologic predictors of prognosis. Ninety-nine patients who underwent 113 craniotomies at our Institution between 1984 and 2010 were entered this study. The relationship between surgical approach (bifrontal, fronto-orbito-basal, and pterional) and either tumor diameter, extent of tumor resection, complication rate, need of reoperation, and Karnofsky Performance Status (KPS) was analyzed. The impact of age (≤ 70 vs. > 70 years), sex, tumor diameter (< 6 vs. ≥ 6 cm), pre- and postoperative KPS (< 80 vs. ≥ 80), Simpson grade (I-II vs. III-IV), and World Health Organization (WHO) histologic grade (I vs. II-III) on survival was assessed. Kaplan-Meier survival curves were plotted and differences in survival between groups of patients were compared. A multivariate analysis adjusted for age, pre- and postoperative KPS, Simpson grade, tumor diameter, and WHO histologic grade also was performed. The fronto-orbito-basal approach (n = 22) allowed a significantly greater percentage of Simpson I-II removals than the bifrontal (n = 70) and pterional approach (n = 21) (P = 0.0354 and P = 0.0485, respectively). The risk of life-threatening complications trended to be lower in patients operated upon either via the fronto-orbito-basal and via the pterional approach than in those treated via the bifrontal approach. Retraction-related brain swelling did not occur in any case after the fronto-orbito-basal approach (P = 0.0384); however, this approach was associated with a greater rate of cerebrospinal fluid leak (P = 0.0011). Among prognostic factors, age ≤ 70 years (P = 0.0044), tumor diameter <6 cm (P = 0.0455), pre- and postoperative KPS ≥ 80 (both P < 0.0001), Simpson grade I-II (P = 0.0096), and WHO histologic grade I (P = 0.0112) were significantly associated with longer overall survival. Age (P = 0.0393) and WHO histologic grade (P = 0.0418) emerged as independent prognostic factors for overall survival on multivariate analysis. In the largest series of OGMs published to date, the bifrontal approach was associated with a greater risk of life-threatening complications compared with the lateral pterional and fronto-orbito-basal approaches. The fronto-orbito-basal approach provided greater chances of total tumor removal than the bifrontal and pterional approaches. Two independent factors for overall survival of patients with OGM were identified, namely age and WHO grade. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

MHC2TA mRNA levels and human herpesvirus 6 in multiple sclerosis patients treated with interferon beta along two-year follow-up

PubMed Central

2012-01-01

Background In previous studies we found that MHC2TA +1614 genotype frequency was very different when MS patients with and without human herpesvirus 6 (HHV-6) in serum samples were compared; a different clinical behavior was also described. The purpose of the study was: 1. To evaluate if MHC2TA expression in MS patients was influenced by interferon beta (IFN-beta) treatment. 2. To study MHC2TA expression in MS patients with and without minor allele C. 3. To analyze the relation between MHC2TA mRNA levels and HHV-6 active infection in MS patients. Methods Blood and serum samples of 154 MS patients were collected in five programmed visits: basal (prior to beginning IFN-beta treatment), six, twelve, eighteen and twenty-four months later. HHV-6 in serum and MHC2TA mRNA levels were evaluated by PCR and RT-PCR, respectively. Neutralizing antibodies (NAbs) against IFN-beta were analyzed by the cytopathic effect assay. Results We found that MHC2TA mRNA levels were significantly lower among MS patients with HHV-6 active infection at the basal visit (without treatment) than in those MS patients without HHV-6 active infection at the basal visit (p = 0.012); in all the positive samples we only found variant A. Furthermore, 58/99 (58.6%) MS patients without HHV-6 along the five programmed visits and an increase of MHC2TA expression after two-years of IFN-beta treatment were clinical responders vs. 5/21 (23.8%) among those MS patients with HHV-6 and a decrease of MHC2TA mRNA levels along the two-years with IFN-beta treatment (p = 0.004); no differences were found between patients with and without NAbs. Conclusions MHC2TA mRNA levels could be decreased by the active replication of HHV-6; the absence of HHV-6 in serum and the increase of MHC2TA expression could be further studied as markers of good clinical response to IFN-beta treatment. PMID:23009575

Nevoid basal cell carcinoma syndrome (Gorlin syndrome)

PubMed Central

Lo Muzio, Lorenzo

2008-01-01

Nevoid basal cell carcinoma syndrome (NBCCS), also known as Gorlin syndrome, is a hereditary condition characterized by a wide range of developmental abnormalities and a predisposition to neoplasms. The estimated prevalence varies from 1/57,000 to 1/256,000, with a male-to-female ratio of 1:1. Main clinical manifestations include multiple basal cell carcinomas (BCCs), odontogenic keratocysts of the jaws, hyperkeratosis of palms and soles, skeletal abnormalities, intracranial ectopic calcifications, and facial dysmorphism (macrocephaly, cleft lip/palate and severe eye anomalies). Intellectual deficit is present in up to 5% of cases. BCCs (varying clinically from flesh-colored papules to ulcerating plaques and in diameter from 1 to 10 mm) are most commonly located on the face, back and chest. The number of BBCs varies from a few to several thousand. Recurrent jaw cysts occur in 90% of patients. Skeletal abnormalities (affecting the shape of the ribs, vertebral column bones, and the skull) are frequent. Ocular, genitourinary and cardiovascular disorders may occur. About 5–10% of NBCCS patients develop the brain malignancy medulloblastoma, which may be a potential cause of early death. NBCCS is caused by mutations in the PTCH1 gene and is transmitted as an autosomal dominant trait with complete penetrance and variable expressivity. Clinical diagnosis relies on specific criteria. Gene mutation analysis confirms the diagnosis. Genetic counseling is mandatory. Antenatal diagnosis is feasible by means of ultrasound scans and analysis of DNA extracted from fetal cells (obtained by amniocentesis or chorionic villus sampling). Main differential diagnoses include Bazex syndrome, trichoepithelioma papulosum multiplex and Torre's syndrome (Muir-Torre's syndrome). Management requires a multidisciplinary approach. Keratocysts are treated by surgical removal. Surgery for BBCs is indicated when the number of lesions is limited; other treatments include laser ablation, photodynamic therapy and topical chemotherapy. Radiotherapy should be avoided. Vitamin A analogs may play a preventive role against development of new BCCs. Life expectancy in NBCCS is not significantly altered but morbidity from complications can be substantial. Regular follow-up by a multi-specialist team (dermatologist, neurologist and odontologist) should be offered. Patients with NBCCS should strictly avoid an excessive sun exposure. PMID:19032739

Basal ganglia, movement disorders and deep brain stimulation: advances made through non-human primate research.

PubMed

Wichmann, Thomas; Bergman, Hagai; DeLong, Mahlon R

2018-03-01

Studies in non-human primates (NHPs) have led to major advances in our understanding of the function of the basal ganglia and of the pathophysiologic mechanisms of hypokinetic movement disorders such as Parkinson's disease and hyperkinetic disorders such as chorea and dystonia. Since the brains of NHPs are anatomically very close to those of humans, disease states and the effects of medical and surgical approaches, such as deep brain stimulation (DBS), can be more faithfully modeled in NHPs than in other species. According to the current model of the basal ganglia circuitry, which was strongly influenced by studies in NHPs, the basal ganglia are viewed as components of segregated networks that emanate from specific cortical areas, traverse the basal ganglia, and ventral thalamus, and return to the frontal cortex. Based on the presumed functional domains of the different cortical areas involved, these networks are designated as 'motor', 'oculomotor', 'associative' and 'limbic' circuits. The functions of these networks are strongly modulated by the release of dopamine in the striatum. Striatal dopamine release alters the activity of striatal projection neurons which, in turn, influences the (inhibitory) basal ganglia output. In parkinsonism, the loss of striatal dopamine results in the emergence of oscillatory burst patterns of firing of basal ganglia output neurons, increased synchrony of the discharge of neighboring basal ganglia neurons, and an overall increase in basal ganglia output. The relevance of these findings is supported by the demonstration, in NHP models of parkinsonism, of the antiparkinsonian effects of inactivation of the motor circuit at the level of the subthalamic nucleus, one of the major components of the basal ganglia. This finding also contributed strongly to the revival of the use of surgical interventions to treat patients with Parkinson's disease. While ablative procedures were first used for this purpose, they have now been largely replaced by DBS of the subthalamic nucleus or internal pallidal segment. These procedures are not only effective in the treatment of parkinsonism, but also in the treatment of hyperkinetic conditions (such as chorea or dystonia) which result from pathophysiologic changes different from those underlying Parkinson's disease. Thus, these interventions probably do not counteract specific aspects of the pathophysiology of movement disorders, but non-specifically remove the influence of the different types of disruptive basal ganglia output from the relatively intact portions of the motor circuitry downstream from the basal ganglia. Knowledge gained from studies in NHPs remains critical for our understanding of the pathophysiology of movement disorders, of the effects of DBS on brain network activity, and the development of better treatments for patients with movement disorders and other neurologic or psychiatric conditions.

Isolated Limb Perfusion With Melphalan in Treating Patients With Stage IIIB-IV Melanoma or Sarcoma

ClinicalTrials.gov

2015-07-22

Basal Cell Carcinoma of the Skin; Eccrine Carcinoma of the Skin; Recurrent Adult Soft Tissue Sarcoma; Recurrent Melanoma; Recurrent Skin Cancer; Squamous Cell Carcinoma of the Skin; Stage III Adult Soft Tissue Sarcoma; Stage IIIB Melanoma; Stage IIIC Melanoma; Stage IV Adult Soft Tissue Sarcoma; Stage IV Melanoma

Topical 5% 5-fluorouracil in the treatment of multifocal basal cell carcinoma of the face: A novel chemotherapeutic approach.

PubMed

Naik, Mayuresh P; Mehta, Anuj; Abrol, Sangeeta; Kumar, Sandeep; Gupta, Vishnu S

2016-12-01

To determine the safety and efficacy of topical 5-fluorouracil (5-FU) 5% ointment in treatment of non-syndromic multifocal basal cell carcinoma. A 55-year-old male patient, with 8 hours of daily sun exposure, having histologically proven and radiologically non-syndromic, multifocal basal cell carcinoma with involvement of 6 sites on the face, was treated with topical 5-FU 5% ointment twice daily over all sites except the site involving lid margin to prevent corneal toxicity. Left lid lesion underwent wide surgical excision with 5-mm clear margins and reconstruction with nasal septal mucoperichondrium and local skin mobilization. Pharmacologic effects first appeared at 4 weeks and by 8 weeks, the lesions had scabbed and had fallen off with no induration but residual mild perilesional erythema. Patient had post-op histopathological clear margins and recovered uneventfully. No recurrence in 6 months. A topical 5-FU 5% ointment represents a paradigm shift in the treatment of BCC from invasive and disfiguring options (surgery and chemoradiotherapy) to cheap, convenient, effective, non-invasive, non-disfiguring topical chemotherapy. Topical 5% 5-FU is a safe and effective modality of treatment of superficial spreading multifocal basal carcinoma, especially lesions larger than 10 mm, where margins cannot be identified clearly and recurrent lesions.

Effects of turmeric (Curcuma longa) and vitamin E on histopathological lesions induced in bursa of Fabricius of broiler chicks by salinomycin.

PubMed

Sayrafi, Reza; Mirzakhani, Navideh; Mobaseri, Reza

2017-01-01

The aim of this study was to evaluate the protective effects of the turmeric in comparison to vitamin E on bursal damages induced by salinomycin in broiler chickens. In this study, forty one day-old broiler chicks were randomly divided into four treatment groups: 1- basal diet as control, 2- basal diet plus salinomycin, 3- basal diet plus salinomycin (SLM) and vitamin E (Vit. E) and 4- basal diet plus salinomycin and turmeric powder. The chicks were treated for two weeks. At the end of the experiment, the bursal tissues were removed and fixed in 10% formalin solution. Tissue sections were stained with hematoxylin and eosin stain for histopathological studies. Light microscopic observations showed that, SLM diminished cortex thickness of bursal tissue, enhanced its medulla zone and caused severe lymphocytic necrosis. In addition, SLM led to fibrosis of interstitium along with sever edema of medulla zone in the bursal tissue of the chicken. Administration of Vit. E and TP significantly inhibited the SLM-induced derangements and comparing the Vit. E and TP showed no significant differences. The results of this study indicated that the turmeric may protect bursa of Fabricius against toxicity induced by salinomycin in chicks.

Vidarabine, an Anti-Herpes Virus Agent, Protects Against the Development of Heart Failure With Relatively Mild Side-Effects on Cardiac Function in a Canine Model of Pacing-Induced Dilated Cardiomyopathy.

PubMed

Nakamura, Takashi; Fujita, Takayuki; Kishimura, Megumi; Suita, Kenji; Hidaka, Yuko; Cai, Wenqian; Umemura, Masanari; Yokoyama, Utako; Uechi, Masami; Ishikawa, Yoshihiro

2016-11-25

In heart failure patients, chronic hyperactivation of sympathetic signaling is known to exacerbate cardiac dysfunction. In this study, the cardioprotective effect of vidarabine, an anti-herpes virus agent, which we identified as a cardiac adenylyl cyclase inhibitor, in dogs with pacing-induced dilated cardiomyopathy (DCM) was evaluated. In addition, the adverse effects of vidarabine on basal cardiac function was compared to those of the β-blocker, carvedilol.Methods and Results:Vidarabine and carvedilol attenuated the development of pacing-induced systolic dysfunction significantly and with equal effectiveness. Both agents also inhibited the development of cardiac apoptosis and fibrosis and reduced the Na + -Ca 2+ exchanger-1 protein level in the heart. Importantly, carvedilol significantly enlarged the left ventricle and atrium; vidarabine, in contrast, did not. Vidarabine-treated dogs maintained cardiac response to β-AR stimulation better than carvedilol-treated dogs did. Vidarabine may protect against pacing-induced DCM with less suppression of basal cardiac function than carvedilol in a dog model. (Circ J 2016; 80: 2496-2505).

Multiple encephalogaleoperiosteal synangiosis for bilateral carotid artery stenosis in a 13-year-old girl: a case report.

PubMed

Inamura, Akinori; Nomura, Sadahiro; Sadahiro, Hirokazu; Oku, Takayuki; Ishihara, Hideyuki; Suzuki, Michiyasu

2016-05-01

Encephalogaleoperiosteal synangiosis (EGS) has been widely used to treat children with moyamoya disease (MMD). We present the first case of successful multiple EGS in a patient with brain ischemic disease who presented with different cerebrovascular findings from MMD. A 13-year-old girl had an increased frequency of transient ischemic attacks that affected her right extremities. Digital subtraction angiography showed tapering of the internal carotid artery (ICA). The anterior cerebral artery (ACA) and middle cerebral artery (MCA) were visible on vertebral angiogram, but not on carotid angiogram. The intact circle of Willis and lack of hypervascularity of the lenticulostriate arteries were observed. Decreased regional cerebral blood flow (CBF) in the bilateral ACA and MCA territories quantified by (123)I-N-isopropyl-p-iodoamphetamine-single photon emission computed tomography indicated the need for extracranial-intracranial bypass surgery. Multiple EGS procedures were performed instead of direct anastomosis, which is the standard procedure for intracranial ICA stenosis, because the space for the craniotomy was limited by transdural anastomosis. Despite the fact that the diagnosis of MMD was questionable, the hemispheres were well vascularized, and the neurology and CBF improved postoperatively. The preserved circle of Willis and lack of moyamoya vessels were inconsistent with the features of MMD. However, childhood onset, bilateralness, chronic intracranial ICA stenosis, and transdural anastomosis indicated the same underling pathogenicity as MMD. It is hypothesized that ICA stenosis occurred immediately proximal to the posterior communicating artery in this case. This would have produced the atypical finding of the remaining circle of Willis without growth of the basal moyamoya vessels.

Biochemistry of epidermal stem cells.

PubMed

Eckert, Richard L; Adhikary, Gautam; Balasubramanian, Sivaprakasam; Rorke, Ellen A; Vemuri, Mohan C; Boucher, Shayne E; Bickenbach, Jackie R; Kerr, Candace

2013-02-01

The epidermis is an important protective barrier that is essential for maintenance of life. Maintaining this barrier requires continuous cell proliferation and differentiation. Moreover, these processes must be balanced to produce a normal epidermis. The stem cells of the epidermis reside in specific locations in the basal epidermis, hair follicle and sebaceous glands and these cells are responsible for replenishment of this tissue. A great deal of effort has gone into identifying protein epitopes that mark stem cells, in identifying stem cell niche locations, and in understanding how stem cell populations are related. We discuss these studies as they apply to understanding normal epidermal homeostasis and skin cancer. An assortment of stem cell markers have been identified that permit assignment of stem cells to specific regions of the epidermis, and progress has been made in understanding the role of these cells in normal epidermal homeostasis and in conditions of tissue stress. A key finding is the multiple stem cell populations exist in epidermis that give rise to different structures, and that multiple stem cell types may contribute to repair in damaged epidermis. Understanding epidermal stem cell biology is likely to lead to important therapies for treating skin diseases and cancer, and will also contribute to our understanding of stem cells in other systems. This article is part of a Special Issue entitled Biochemistry of Stem Cells. Copyright © 2012 Elsevier B.V. All rights reserved.

Biochemistry of epidermal stem cells☆

PubMed Central

Eckert, Richard L.; Adhikary, Gautam; Balasubramanian, Sivaprakasam; Rorke, Ellen A.; Vemuri, Mohan C.; Boucher, Shayne E.; Bickenbach, Jackie R.; Kerr, Candace

2014-01-01

Background The epidermis is an important protective barrier that is essential for maintenance of life. Maintaining this barrier requires continuous cell proliferation and differentiation. Moreover, these processes must be balanced to produce a normal epidermis. The stem cells of the epidermis reside in specific locations in the basal epidermis, hair follicle and sebaceous glands and these cells are responsible for replenishment of this tissue. Scope of review A great deal of effort has gone into identifying protein epitopes that mark stem cells, in identifying stem cell niche locations, and in understanding how stem cell populations are related. We discuss these studies as they apply to understanding normal epidermal homeostasis and skin cancer. Major conclusions An assortment of stem cell markers have been identified that permit assignment of stem cells to specific regions of the epidermis, and progress has been made in understanding the role of these cells in normal epidermal homeostasis and in conditions of tissue stress. A key finding is the multiple stem cell populations exist in epidermis that give rise to different structures, and that multiple stem cell types may contribute to repair in damaged epidermis. General significance Understanding epidermal stem cell biology is likely to lead to important therapies for treating skin diseases and cancer, and will also contribute to our understanding of stem cells in other systems. This article is part of a Special Issue entitled Biochemistry of Stem Cells. PMID:22820019

Micropropagation of an Exotic Ornamental Plant, Calathea crotalifera, for Production of High Quality Plantlets

PubMed Central

Efzueni Rozali, Shahril; Rashid, Kamaludin A.; Mat Taha, Rosna

2014-01-01

A successful protocol was established for micropropagation in two selected varieties of exotic ornamental plants, Calathea crotalifera. The effects of different sterilization techniques, explant type, and the combination and concentration of plant growth regulators on shoots induction were studied. The axillary shoot buds explants sprouted from rhizomes in soil free conditions showed high induction rate of shoots with lowest contamination percentage when treated with combination of 30% (v/v) NaOCl, 70% (v/v) ethanol, and 0.3% (w/v) HgCl2. In the present study, the highest number of multiple shoots was obtained in MS basal medium supplemented with 3.5 mg/L 6-Benzylaminopurine (BAP), 1.0 mg/L 1-Naphthaleneacetic acid (NAA), 3% sucrose, and 6 g/L plant agar for both varieties and was used as multiplication medium. Microshoots were highly induced when the young shoot bud explants were incised longitudinally prior subculture. Chlorophyll analysis was studied to test the effects of activated charcoal and L-glutamine on reduction of necrosis problem. The maximum roots induction was recorded on MS medium supplemented with 1.0 mg/L 1-Naphthaleneacetic acid (NAA) compared to indolebutyric acid (IBA). The complete regenerated plantlets were successfully acclimatized in the soilless medium under greenhouse condition. This is the first report of rapid mass propagation for C. crotalifera. PMID:25136669

Two-stage treatment protocol of keratocystic odontogenic tumour in young patients with Gorlin-Goltz syndrome: marsupialization and later enucleation with peripheral ostectomy. A 5-year-follow-up experience.

PubMed

Borgonovo, Andrea Enrico; Di Lascia, Stefano; Grossi, Giovanni; Maiorana, Carlo

2011-12-01

Keratocystic odontogenic tumour (KCOT) is a benign uni- or multicystic intraosseous odontogenic tumour with potential for local destruction and tendency for multiplicity, especially when associated with Gorlin-Goltz syndrome. We suggest a conservative surgical treatment based on marsupialization and later enucleation with peripheral ostectomy in order to preserve jaw's integrity in young patients. Three young patients affected of nevoid basal cell carcinoma syndrome (NBCCS or Gorlin-Goltz syndrome) presented large and multiple KCOTs, which have been treated following a two-stage surgical strategy. Initially marsupialization was performed and after a mean period of 10 months, contextually to evident reduction in radiological size image, enucleation with peripheral ostectomy was carried out. All the patients showed high collaboration in daily self-irrigation of the stomia with chlorhexidine 0.2% during the period of marsupialization. Definitive surgical intervention led to complete healing and no signs of recurrence have been observed during a 5-year-follow-up. The main advantage of this modality is the preservation of important anatomical structures involved in the lesion and jaw's continuity. Therefore in a selected group of cooperative patients, especially those affected of Gorlin-Goltz syndrome, the surgical protocol exposed allows for a less invasive approach with excellent results avoiding extensive disfiguring procedures. Copyright © 2011. Published by Elsevier Ireland Ltd.

Current status of cannabis treatment of multiple sclerosis with an illustrative case presentation of a patient with MS, complex vocal tics, paroxysmal dystonia, and marijuana dependence treated with dronabinol.

PubMed

Deutsch, Stephen I; Rosse, Richard B; Connor, Julie M; Burket, Jessica A; Murphy, Mary E; Fox, Fiona J

2008-05-01

Pain, spasticity, tremor, spasms, poor sleep quality, and bladder and bowel dysfunction, among other symptoms, contribute significantly to the disability and impaired quality of life of many patients with multiple sclerosis (MS). Motor symptoms referable to the basal ganglia, especially paroxysmal dystonia, occur rarely and contribute to the experience of distress. A substantial percentage of patients with MS report subjective benefit from what is often illicit abuse of extracts of the Cannabis sativa plant; the main cannabinoids include delta-9-tetrahydrocannabinol (delta9-THC) and cannabidiol. Clinical trials of cannabis plant extracts and synthetic delta9-THC provide support for therapeutic benefit on at least some patient self-report measures. An illustrative case is presented of a 52-year-old woman with MS, paroxysmal dystonia, complex vocal tics, and marijuana dependence. The patient was started on an empirical trial of dronabinol, an encapsulated form of synthetic delta9-THC that is usually prescribed as an adjunctive medication for patients undergoing cancer chemotherapy. The patient reported a dramatic reduction of craving and illicit use; she did not experience the "high" on the prescribed medication. She also reported an improvement in the quality of her sleep with diminished awakenings during the night, decreased vocalizations, and the tension associated with their emission, decreased anxiety and a decreased frequency of paroxysmal dystonia.

Gastric leiomyoma in a child with Gorlin-Goltz syndrome: First pediatric case.

PubMed

Virgone, Calogero; Decker, Emily; Mitton, Sally G; Mansour, Sahar; Giuliani, Stefano

2016-04-01

Gorlin-Goltz syndrome (GGS), also known as nevoid basal cell carcinoma syndrome (MIM 109 400), is a rare genetic condition with a prevalence between 1/56 000 and 1/256 000. Clinical presentation is usually characterized by multiple basal cell carcinomas, odontogenic jaw keratocysts, palmar or plantar pitting and skeletal anomalies. It is furthermore associated with the development of various tumors beside basal cell carcinoma, among which medulloblastoma is the most frequent. Increased incidence of other mesenchymal neoplasms, however, is also well known: recently the first adult case of gastric leiomyoma in GGS was reported, and the inclusion of "fibromas and leiomyomas of other organs" in the minor criteria for the diagnosis was suggested. We report the first case of a pediatric patient with GGS who also developed a gastric leiomyoma: the present case illustrates the need for this change to the diagnostic criteria to encompass the highly variable presentations and phenotype in GGS. © 2015 Japan Pediatric Society.

Ice stream motion facilitated by a shallow-deforming and accreting bed

PubMed Central

Spagnolo, Matteo; Phillips, Emrys; Piotrowski, Jan A.; Rea, Brice R.; Clark, Chris D.; Stokes, Chris R.; Carr, Simon J.; Ely, Jeremy C.; Ribolini, Adriano; Wysota, Wojciech; Szuman, Izabela

2016-01-01

Ice streams drain large portions of ice sheets and play a fundamental role in governing their response to atmospheric and oceanic forcing, with implications for sea-level change. The mechanisms that generate ice stream flow remain elusive. Basal sliding and/or bed deformation have been hypothesized, but ice stream beds are largely inaccessible. Here we present a comprehensive, multi-scale study of the internal structure of mega-scale glacial lineations (MSGLs) formed at the bed of a palaeo ice stream. Analyses were undertaken at macro- and microscales, using multiple techniques including X-ray tomography, thin sections and ground penetrating radar (GPR) acquisitions. Results reveal homogeneity in stratigraphy, kinematics, granulometry and petrography. The consistency of the physical and geological properties demonstrates a continuously accreting, shallow-deforming, bed and invariant basal conditions. This implies that ice stream basal motion on soft sediment beds during MSGL formation is accommodated by plastic deformation, facilitated by continuous sediment supply and an inefficient drainage system. PMID:26898399

Usefulness of confocal microscopy in distinguishing between basal cell carcinoma and intradermal melanocytic nevus on the face.

PubMed

Gamo, R; Floristan, U; Pampín, A; Caro, D; Pinedo, F; López-Estebaranz, J L

2015-10-01

The clinical distinction between basal cell carcinoma (BCC) and intradermal melanocytic nevus lesions on the face can be difficult, particularly in young patients or patients with multiple nevi. Dermoscopy is a useful tool for analyzing characteristic dermoscopic features of BCC, such as cartwheel structures, maple leaf-like areas, blue-gray nests and dots, and ulceration. It also reveals arborizing telangiectatic vessels and prominent curved vessels, which are typical of BCC, and comma vessels, which are typical of intradermal melanocytic nevi. It is, however, not always easy to distinguish between these 2 conditions, even when dermoscopy is used. We describe 2 facial lesions that posed a clinical and dermoscopic challenge in two 38-year-old patients; confocal microscopy showed separation between tumor nests and stroma and polarized nuclei, which are confocal microscopy features of basal cell carcinoma. Copyright © 2014 Elsevier España, S.L.U. y AEDV. All rights reserved.

Infection of Polarized MDCK Cells with Herpes Simplex Virus 1: Two Asymmetrically Distributed Cell Receptors Interact with Different Viral Proteins

NASA Astrophysics Data System (ADS)

Sears, Amy E.; McGwire, Bradford S.; Roizman, Bernard

1991-06-01

Herpes simplex virus 1 attaches to at least two cell surface receptors. In polarized epithelial (Madin-Darby canine kidney; MDCK) cells one receptor is located in the apical surface and attachment to the cells requires the presence of glycoprotein C in the virus. The second receptor is located in the basal surface and does not require the presence of glycoprotein C. Exposure of MDCK cells at either the apical or basal surface to wild-type virus yields plaques and viral products whereas infection by a glycoprotein C-negative mutant yields identical results only after exposure of MDCK cells to virus at the basal surface. Multiple receptors for viral entry into cells expand the host range of the virus. The observation that glycoprotein C-negative mutants are infectious in many nonpolarized cell lines suggests that cells in culture may express more than one receptor and explains why genes that specify the viral proteins that recognize redundant receptors, like glycoprotein C, are expendable.

Coordinated Beating of Algal Flagella is Mediated by Basal Coupling

NASA Astrophysics Data System (ADS)

Wan, Kirsty; Goldstein, Raymond

Cilia or flagella often exhibit synchronized behavior. This includes phase-locking, as seen in Chlamydomonas, and metachronal wave formation in the respiratory cilia of higher organisms. Since the observations by Gray and Rothschild of phase synchrony of nearby swimming spermatozoa, it has been a working hypothesis that synchrony arises from hydrodynamic interactions between beating filaments. Recent work on the dynamics of physically separated pairs of flagella isolated from the multicellular alga Volvox has shown that hydrodynamic coupling alone is sufficient for synchrony. However, the situation is more complex when considering multiple flagella on a single cell. We suggest that a mechanism, internal to the cell, provides an additional flagellar coupling. For instance, flagella of Chlamydomonas mutants deficient in filamentary connections between basal bodies are found to display markedly different synchronization from the wildtype. Diverse flagellar coordination strategies found in quadri-, octo- and hexadecaflagellates reveal further evidence that intracellular couplings between flagellar basal bodies compete with hydrodynamic interactions to determine the precise form of flagellar synchronization in unicellular algae.

Oral diffuse B-cell non-Hodgkin's lymphoma associated to Gorlin-Goltz syndrome: a case report with one year follow-up.

PubMed

Pereira, Cláudio M; Lopes, Ana Paula M; Meneghini, Alexandre J; Silva, Alberto F; Botelho, Tessa de L

2011-01-01

Nevoid cell carcinoma syndrome or Gorlin-Goltz syndrome is an autosomal dominant disorder characterized by multiple basal cell carcinoma, multiple keratocyst tumors, and skeletal anomalies. The Gorlin-Goltz syndrome has been associated with numerous benign and malignant neoplasms. The authors describe a case of Gorlin-Goltz syndrome in association with non-Hodgkin's lymphoma. To the best of our knowledge, this is the second case described in the English literature.

Insulin secretion enhancing activity of roselle calyx extract in normal and streptozotocin-induced diabetic rats

PubMed Central

Wisetmuen, Eamruthai; Pannangpetch, Patchareewan; Kongyingyoes, Bunkerd; Kukongviriyapan, Upa; Yutanawiboonchai, Wiboonchai; Itharat, Arunporn

2013-01-01

Background and Objective: Our recent study revealed the antihyperglycemic activity of an ethanolic extract of roselle calyxes (Hibiscus sabdariffa) in diabetic rats. The present study had, therefore, an objective to investigate the mechanism underlying this activity. Materials and Methods: Male Sprague Dawley rats were induced to be diabetes by intraperitoneal injection of 45 mg/kg streptozotocin (STZ). Normal rats as well as diabetic rats were administered with the ethanolic extract of H. sabdariffa calyxes (HS-EE) at 0.1 and 1.0 g/kg/day, respectively, for 6 weeks. Then, blood glucose and insulin levels, at basal and glucose-stimulated secretions, were measured. The pancreas was dissected to examine histologically. Results: HS-EE 1.0 g/kg/day significantly decreased the blood glucose level by 38 ± 12% in diabetic rats but not in normal rats. In normal rats, treatment with 1.0 g/kg HS-EE increased the basal insulin level significantly as compared with control normal rats (1.28 ± 0.25 and 0.55 ± 0.05 ng/ml, respectively). Interestingly, diabetic rats treated with 1.0 g/kg HS-EE also showed a significant increase in basal insulin level as compared with the control diabetic rats (0.30 ± 0.05 and 0.15 ± 0.01 ng/ml, respectively). Concerning microscopic histological examination, HS-EE 1.0 g/kg significantly increased the number of islets of Langerhans in both normal rats (1.2 ± 0.1 and 2.0 ± 0.1 islet number/10 low-power fields (LPF) for control and HS-EE treated group, respectively) and diabetic rats (1.0 ± 0.3 and 3.9 ± 0.6 islet number/10 LPF for control and HS-EE treated group, respectively). Conclusion: The antidiabetic activity of HS-EE may be partially mediated via the stimulating effect on insulin secretion. PMID:23798879

Protective effect of hexane and ethanol extract of piper longum L. On gentamicin-induced hair cell loss in neonatal cultures.

PubMed

Yadav, Mukesh Kumar; Choi, June; Song, Jae-Jun

2014-03-01

Gentamicin (GM) is a commonly used aminoglycoside antibiotic that generates free oxygen radicals within the inner ear, which can cause vestibulo-cochlear toxicity and permanent damage to the sensory hair cells and neurons. Piper longum L. (PL) is a well-known spice and traditional medicine in Asia and Pacific islands, which has been reported to exhibit a wide spectrum of activity, including antioxidant activity. In this study, we evaluated the effect of hexane:ethanol (2:8) PL extract (subfraction of PL [SPL] extract) on GM-induced hair cell loss in basal, middle and apical regions in a neonatal cochlea cultures. The protective effects of SPL extract were measured by phalloidin staining of cultures from postnatal day 2-3 mice with GM-induced hair cell loss. The anti-apoptosis activity of SPL extract was measured using double labeling by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and myosin-7a staining. The radical-scavenging activity of SPL extract was assessed using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. SPL extract at a concentration of 1 µg/mL significantly inhibited GM-induced hair cell loss at basal and middle region of cochlea, while 5 µg/mL was effective against apical region hair cell loss. The protective effect of SPL extract was concentration dependent and hair cells retained their stereocilia in explants treated with SPL extract prior to treatment with 0.3 mM GM. SPL extract decreased GM-induced apoptosis of hair cells as assessed by TUNEL staining. The outer hair and inner hair counts were not decreased in SPL extract treated groups in compare to GM treated explants. Additionally, SPL extract showed concentration dependent radical scavenging activity in a DPPH assay. An anti-apoptosis effect and potent radical scavenger activity of SPL extract protects from GM-induced hair cell loss at basal, middle and apical regions in neonatal cochlea cultures.

The molecular genetics of eyelid tumors: recent advances and future directions.

PubMed

Milman, Tatyana; McCormick, Steven A

2013-02-01

Unprecedented recent advances in the molecular genetics of cutaneous malignancies have markedly improved our ability to diagnose, treat, and counsel patients with skin tumors. This review provides an update on molecular genetics of periocular cutaneous basal cell carcinoma, squamous cell carcinoma, sebaceous carcinoma, Merkel cell carcinoma, and malignant melanoma and describes how the knowledge of molecular genetics is translated into clinical practice. A literature search of peer-reviewed and indexed publications from 1965 to 2012 using the PubMed search engine was performed. Key terms included: molecular genetics, eyelid, basal cell carcinoma, squamous cell carcinoma, sebaceous adenoma, sebaceous epithelioma, sebaceoma, sebaceous carcinoma, Merkel cell carcinoma, and melanoma. Seminal articles prior to 1965 were selected from primary sources and reviews from the initial search. Articles were chosen based on pertinence to clinical, genetic, and therapeutic topics reviewed in this manuscript. We reviewed the literature regarding the advances in molecular genetics of cutaneous basal cell carcinoma, squamous cell carcinoma, sebaceous neoplasia, Merkel cell carcinoma, and malignant melanoma, and possible future directions towards diagnosing and treating cutaneous tumors at the genetic level. Cell culture experiments, animal models, and molecular genetic studies on the patients' tumor tissues helped to elucidate genetic aberrations in these lesions. Cell culture experiments, animal studies and, ultimately, clinical trials provided means to test and develop novel therapeutic strategies, namely targeted therapy directed at specific molecular genetic defects. While remarkable progress has been made in this process, the complexity of the molecular genetics of skin tumors makes complete elucidation of the genetic mechanisms and the search for ideal therapies challenging. The recent studies focusing on molecular genetics of cutaneous malignancies show promising results, thereby improving our ability to diagnose, treat and counsel patients with these lesions. Future studies will hopefully help unravel further molecular mechanisms involved in cutaneous neoplasia and provide insights into novel preventative and therapeutic modalities.

Characterizing the efficacy of cancer therapeutics in patient-derived xenograft models of metastatic breast cancer.

PubMed

Turner, Tia H; Alzubi, Mohammad A; Sohal, Sahib S; Olex, Amy L; Dozmorov, Mikhail G; Harrell, J Chuck

2018-03-12

Basal-like breast cancers are aggressive and often metastasize to vital organs. Treatment is largely limited to chemotherapy. This study aims to characterize the efficacy of cancer therapeutics in vitro and in vivo within the primary tumor and metastatic setting, using patient-derived xenograft (PDX) models. We employed two basal-like, triple-negative PDX models, WHIM2 and WHIM30. PDX cells, obtained from mammary tumors grown in mice, were treated with twelve cancer therapeutics to evaluate their cytotoxicity in vitro. Four of the effective drugs-carboplatin, cyclophosphamide, bortezomib, and dacarbazine-were tested in vivo for their efficacy in treating mammary tumors, and metastases generated by intracardiac injection of tumor cells. RNA sequencing showed that global gene expression of PDX cells grown in the mammary gland was similar to those tested in culture. In vitro, carboplatin was cytotoxic to WHIM30 but not WHIM2, whereas bortezomib, dacarbazine, and cyclophosphamide were cytotoxic to both lines. Yet, these drugs were ineffective in treating both primary and metastatic WHIM2 tumors in vivo. Carboplatin and cyclophosphamide were effective in treating WHIM30 mammary tumors and reducing metastatic burden in the brain, liver, and lungs. WHIM2 and WHIM30 metastases showed distinct patterns of cytokeratin and vimentin expression, regardless of treatment, suggesting that different tumor cell subpopulations may preferentially seed in different organs. This study highlights the utility of PDX models for studying the efficacy of therapeutics in reducing metastatic burden in specific organs. The differential treatment responses between two PDX models of the same intrinsic subtype, in both the primary and metastatic setting, recapitulates the challenges faced in treating cancer patients and highlights the need for combination therapies and predictive biomarkers.

Transitional basal cells at the squamous-columnar junction generate Barrett’s oesophagus

PubMed Central

Jiang, Ming; Li, Haiyan; Zhang, Yongchun; Yang, Ying; Lu, Rong; Liu, Kuancan; Lin, Sijie; Lan, Xiaopeng; Wang, Haikun; Wu, Han; Zhu, Jian; Zhou, Zhongren; Xu, Jianming; Lee, Dong-Kee; Zhang, Lanjing; Lee, Yuan-Cho; Yuan, Jingsong; Abrams, Julian A.; Wang, Timothy G.; Sepulveda, Antonia R.; Wu, Qi; Chen, Huaiyong; Sun, Xin; She, Junjun; Chen, Xiaoxin; Que, Jianwen

2017-01-01

In several organ systems the transitional zone between different types of epithelia is a hotspot for pre-neoplastic metaplasia and malignancy1–3. However, the cell-of-origin for the metaplastic epithelium and subsequent malignancy, remains obscure1–3. In the case of Barrett’s oesophagus (BE), intestinal metaplasia occurs at the gastro-oesophageal junction, where stratified squamous epithelium transitions into simple columnar cells4. Based on different experimental models, several alternative cell types have been proposed as the source of the metaplasia, but in all cases the evidence is inconclusive and no model completely mimics BE with the presence of intestinal goblet cells5–8. Here, we describe a novel transitional columnar epithelium with distinct basal progenitor cells (p63+ KRT5+ KRT7+) in the squamous-columnar junction (SCJ) in the upper gastrointestinal tract of the mouse. We use multiple models and lineage tracing strategies to show that this unique SCJ basal cell population serves as a source of progenitors for the transitional epithelium. Moreover, upon ectopic expression of CDX2 these transitional basal progenitors differentiate into intestinal-like epithelium including goblet cells, thus reproducing Barrett’s metaplasia. A similar transitional columnar epithelium is present at the transitional zones of other mouse tissues, including the anorectal junction, and, importantly, at the gastro-oesophageal junction in the human gut. Acid reflux-induced oesophagitis and the multilayered epithelium (MLE) believed to be a precursor of BE are both characterized by the expansion of the transitional basal progenitor cells. Taken together our findings reveal the presence of a previously unidentified transitional zone in the epithelium of the upper gastrointestinal tract and provide evidence that the p63+ KRT7+ basal cells in this zone are the cell-of-origin for MLE and BE. PMID:29019984

Transitional basal cells at the squamous-columnar junction generate Barrett's oesophagus.

PubMed

Jiang, Ming; Li, Haiyan; Zhang, Yongchun; Yang, Ying; Lu, Rong; Liu, Kuancan; Lin, Sijie; Lan, Xiaopeng; Wang, Haikun; Wu, Han; Zhu, Jian; Zhou, Zhongren; Xu, Jianming; Lee, Dong-Kee; Zhang, Lanjing; Lee, Yuan-Cho; Yuan, Jingsong; Abrams, Julian A; Wang, Timothy C; Sepulveda, Antonia R; Wu, Qi; Chen, Huaiyong; Sun, Xin; She, Junjun; Chen, Xiaoxin; Que, Jianwen

2017-10-26

In several organ systems, the transitional zone between different types of epithelium is a hotspot for pre-neoplastic metaplasia and malignancy, but the cells of origin for these metaplastic epithelia and subsequent malignancies remain unknown. In the case of Barrett's oesophagus, intestinal metaplasia occurs at the gastro-oesophageal junction, where stratified squamous epithelium transitions into simple columnar cells. On the basis of a number of experimental models, several alternative cell types have been proposed as the source of this metaplasia but in all cases the evidence is inconclusive: no model completely mimics Barrett's oesophagus in terms of the presence of intestinal goblet cells. Here we describe a transitional columnar epithelium with distinct basal progenitor cells (p63 + KRT5 + KRT7 + ) at the squamous-columnar junction of the upper gastrointestinal tract in a mouse model. We use multiple models and lineage tracing strategies to show that this squamous-columnar junction basal cell population serves as a source of progenitors for the transitional epithelium. On ectopic expression of CDX2, these transitional basal progenitors differentiate into intestinal-like epithelium (including goblet cells) and thereby reproduce Barrett's metaplasia. A similar transitional columnar epithelium is present at the transitional zones of other mouse tissues (including the anorectal junction) as well as in the gastro-oesophageal junction in the human gut. Acid reflux-induced oesophagitis and the multilayered epithelium (believed to be a precursor of Barrett's oesophagus) are both characterized by the expansion of the transitional basal progenitor cells. Our findings reveal a previously unidentified transitional zone in the epithelium of the upper gastrointestinal tract and provide evidence that the p63 + KRT5 + KRT7 + basal cells in this zone are the cells of origin for multi-layered epithelium and Barrett's oesophagus.

Gorlin-Goltz syndrome and neoplasms: a case study.

PubMed

Lopes, Nilza N F; Caran, Eliana M; Lee, Maria Lucia; Silva, Nasjla Saba; Rocha, André Caroli; Macedo, Carla R D

2010-01-01

Gorlin syndrome is a rare autosomal dominant disorder exhibiting high penetrance and variable expressivity. It is characterized by facial dysmorphism, skeletal anomalies, multiple basal cell carcinomas, odontogenic keratocysts (OKC), palmar and plantar pits, bifid ribs, vertebral anomalies and a variety of other malformations. Various neoplasms, such as medulloblastomas, meningiomas, ovarian and cardiac fibromas are also found in this syndrome. To describe a twelve-year-old patient with Gorlin-Goltz syndrome, with basal cell carcinomas and promyelocytic leukemia developed after receiving craniospinal radiation for a medulloblastoma. Bifid ribs as well as mandibular and maxillar OKC were also diagnosed Conclusion: The patient with Gorlin-Goltz syndrome should receive close follow-up for early detection of malformations nd malignant neoplasias.

[Nevoid basal-cell carcinoma syndrome (Gorlin Syndrome): report of two cases and review of the literature].

PubMed

Castro-Mujica, María Del Carmen; Barletta-Carrillo, Claudia; Poterico, Julio A; Acosta, Marisa; Valer, Jesús; Cruz, Miguel De La

2017-01-01

Gorlin syndrome (GS) is a genetic disorder with an autosomal dominant inheritance pattern, with complete penetrance and variable expressivity. GS is caused by germline mutations in the genes PTCH1 or SUFU, which are components of the Sonic hedgehog molecular pathway. GS is characterized by the presence of multiple nevoid basal cell carcinomas, odontogenic cysts, calcification of the brain sickle, and lesions in the palms and soles. This study is the first to report cases in Peru of patients with GS who underwent genetic evaluation and counseling. We present two GS cases that meet the clinical criteria for the syndrome and review the literature.

Terminal zone glacial sediment transfer at a temperate overdeepened glacier system

NASA Astrophysics Data System (ADS)

Swift, D. A.; Cook, S. J.; Graham, D. J.; Midgley, N. G.; Fallick, A. E.; Storrar, R.; Toubes Rodrigo, M.; Evans, D. J. A.

2018-01-01

Continuity of sediment transfer through glacial systems is essential to maintain subglacial bedrock erosion, yet transfer at temperate glaciers with overdeepened beds, where subglacial fluvial sediment transport should be greatly limited by adverse slopes, remains poorly understood. Complex multiple transfer processes in temperate overdeepened systems has been indicated by the presence of large frontal moraine systems, supraglacial debris of mixed transport origin, thick basal ice sequences, and englacial thrusts and eskers. At Svínafellsjökull, thrusts comprising decimetre-thick debris-rich bands of stratified facies ice of basal origin, with a coarser size distribution and higher clast content than that observed in basal ice layers, contribute substantially to the transfer of subglacial material in the terminal zone. Entrainment and transfer of material occurs by simple shear along the upper surface of bands and by strain-induced deformation of stratified and firnified glacier ice below. Thrust material includes rounded and well-rounded clasts that are also striated, indicating that fluvial bedload is deposited as subglacial channels approach the overdeepening and then entrained along thrusts. Substantial transfer also occurs within basal ice, with facies type and debris content dependent on the hydrological connectedness of the adverse slope. A process model of transfer at glaciers with terminal overdeepenings is proposed, in which the geometry of the overdeepening influences spatial patterns of ice deformation, hydrology, and basal ice formation. We conclude that the significance of thrusting in maintaining sediment transfer continuity has likely been overlooked by glacier sediment budgets and glacial landscape evolution studies.

Untangling Basal Ganglia Network Dynamics and Function: Role of Dopamine Depletion and Inhibition Investigated in a Spiking Network Model.

PubMed

Lindahl, Mikael; Hellgren Kotaleski, Jeanette

2016-01-01

The basal ganglia are a crucial brain system for behavioral selection, and their function is disturbed in Parkinson's disease (PD), where neurons exhibit inappropriate synchronization and oscillations. We present a spiking neural model of basal ganglia including plausible details on synaptic dynamics, connectivity patterns, neuron behavior, and dopamine effects. Recordings of neuronal activity in the subthalamic nucleus and Type A (TA; arkypallidal) and Type I (TI; prototypical) neurons in globus pallidus externa were used to validate the model. Simulation experiments predict that both local inhibition in striatum and the existence of an indirect pathway are important for basal ganglia to function properly over a large range of cortical drives. The dopamine depletion-induced increase of AMPA efficacy in corticostriatal synapses to medium spiny neurons (MSNs) with dopamine receptor D2 synapses (CTX-MSN D2) and the reduction of MSN lateral connectivity (MSN-MSN) were found to contribute significantly to the enhanced synchrony and oscillations seen in PD. Additionally, reversing the dopamine depletion-induced changes to CTX-MSN D1, CTX-MSN D2, TA-MSN, and MSN-MSN couplings could improve or restore basal ganglia action selection ability. In summary, we found multiple changes of parameters for synaptic efficacy and neural excitability that could improve action selection ability and at the same time reduce oscillations. Identification of such targets could potentially generate ideas for treatments of PD and increase our understanding of the relation between network dynamics and network function.

Growth phenology of coast Douglas-fir seed sources planted in diverse environments.

PubMed

Gould, Peter J; Harrington, Constance A; St Clair, J Bradley

2012-12-01

The timing of periodic life cycle events in plants (phenology) is an important factor determining how species and populations will react to climate change. We evaluated annual patterns of basal-area and height growth of coast Douglas-fir (Pseudotusga menziesii var. menziesii (Mirb.) Franco) seedlings from four seed sources that were planted in four diverse environments as part of the Douglas-fir Seed-Source Movement Trial. Stem diameters and heights were measured periodically during the 2010 growing season on 16 open-pollinated families at each study installation. Stem diameters were measured on a subset of trees with electronic dendrometers during the 2010 and 2011 growing seasons. Trees from the four seed sources differed in phenology metrics that described the timing of basal-area and height-growth initiation, growth cessation and growth rates. Differences in the height-growth metrics were generally larger than differences in the basal-area growth metrics and differences among installations were larger than differences among seed sources, highlighting the importance of environmental signals on growth phenology. Variations in the height- and basal-area growth metrics were correlated with different aspects of the seed-source environments: precipitation in the case of height growth and minimum temperature in the case of basal-area growth. The detailed dendrometer measurements revealed differences in growth patterns between seed sources during distinct periods in the growing season. Our results indicate that multiple aspects of growth phenology should be considered along with other traits when evaluating adaptation of populations to future climates.

Correlation of p63 immunohistochemistry with histology and contrast enhanced MRI in characteristic lesions induced by minimally invasive thermal treatments in a dog prostate

NASA Astrophysics Data System (ADS)

Pascal, A.; Butts-Pauly, K.; Plata, J.; Sommer, G.; Daniel, B.; Bouley, D. M.

2017-03-01

Thermal ablation techniques are important tools to treat low grade tumors in the prostate gland. The use of Magnetic Resonance Imaging (MRI) has been an excellent tool to visualize and assess the thermally ablated areas in real time. In this study slides from dog prostates previously treated with cryoablation or High Intensity Focal Ultrasound (HIFU) were immunohistochemically stained with the biomarker p63, in order to determine if this marker would be helpful for differentiatiating between viable, sub lethally damaged and normal glands. Digitized slides were analyzed using Sedeen Viewer software, and compared with corresponding representative H&E slides and MR images. p63 staining in the cryoablated acute duration prostates was negative in the coagulation necrosis zone (region of interest subjected to the coldest temperatures). In acute duration HIFU treated prostates, the central heat-fixed zone (region of interest subjected to the hottest temperatures) still displayed + p63 staining. Cryoablated or HIFU subacute duration treated prostates were very hemorrhagic, but presented the same stain pattern in the treated areas as the acute duration prostates, and in chronic duration prostates, whether treated with cryo or HIFU, glands displayed robust p63 staining most prevalent in the outer edges of the lesion where there was extensive glandular regeneration. In conclusion, this study demonstrates the value of p63 IHC and its usefulness in detecting viable prostate basal cells in normal dog prostates following either cryoablation of HIFU. Our results suggest that the portions of the lesion with complete loss of p63 staining correspond well to the non-enhancing region in cryoablated prostates, as viewed with MRI. However, p63 staining in the heat-fixed zone in acute harvested HIFU treated prostates remains positive, suggesting either inadequate heat to destroy basal cells, or heat-fixation of the p63 antigen and false positive staining. Therefore p63 staining does not appear to be beneficial in determining cell viability in HIFU-treated tissues, and would not aid in predicting if unwanted tumor cells in a similarly treated area could regenerate.

Phase-sensitive radar on thick Antarctic ice - how well does it work?

NASA Astrophysics Data System (ADS)

Binder, Tobias; Eisen, Olaf; Helm, Veit; Humbert, Angelika; Steinhage, Daniel

2016-04-01

Phase-sensitive radar (pRES) has become one of the mostly used tools to determine basal melt rates as well as vertical strain in ice sheets. Whereas most applications are performed on ice shelves, only few experiments were conducted on thick ice in Greenland or Antarctica. The technical constrains on an ice shelf to deduce basal melt rates are less demanding than on inland ice of more than 2 km thickness. First, the ice itself is usually only several 100s of meters thick; and, second, the reflection coefficient at the basal interface between sea water and ice is the second strongest one possible. Although the presence of marine ice with higher conductivities might increase attenuation in the lower parts, most experiments on shelves were successful. To transfer this technology to inland regions, either for the investigation of basal melt rates of subglacial hydrological networks or for determining vertical strain rates in basal regions, a reliable estimate of the current system performance is necessary. To this end we conducted an experiment at and in the vicinity of the EPICA deep ice core drill site EDML in Dronning Maud Land, Antarctica. That site has been explored in extraordinary detail with different geophysical methods and provides an already well-studied ice core and borehole, in particular with respect to physical properties like crystal orientation fabric, dielectric properties and matching of internal radar horizons with conductivity signals. We present data from a commercially available pRES system initially recorded in January 2015 and repeated measurements in January 2016. The pRES data are matched to existing and already depth-calibrated airborne radar data. Apart from identifying prominent internal layers, e.g. the one originating from the deposits of the Toba eruption at around 75 ka, we put special focus on the identification of the basal reflection at multiple polarizations. We discuss the potential uncertainty estimates and requirements to unambiguously identify the basal melt rate on thick grounded ice in Antarctica.

Suppression of intestinal carcinogenesis in Apc-mutant mice by limonin.

PubMed

Shimizu, Satomi; Miyamoto, Shingo; Fujii, Gen; Nakanishi, Ruri; Onuma, Wakana; Ozaki, Yoshihiko; Fujimoto, Kyoko; Yano, Tomohiro; Mutoh, Michihiro

2015-07-01

Limonoids in citrus fruits are known to possess multiple biological functions, such as anti-proliferative functions in human cancer cell lines. Therefore, we aimed to investigate the suppressive effect of limonin on intestinal polyp development in Apc-mutant Min mice. Five-week-old female Min mice were fed a basal diet or a diet containing 250 or 500 ppm limonin for 8 weeks. The total number of polyps in mice treated with 500 ppm limonin decreased to 74% of the untreated control value. Neoplastic cell proliferation in the polyp parts was assessed by counting PCNA positive cells, and a tendency of reduction was obtained by limonin treatment. Moreover, expression levels of c-Myc and MCP-1 mRNA in the polyp part were reduced by administration of limonin. We finally confirmed the effects of limonin on β-catenin signaling, and found limonin significantly inhibited T-cell factor/lymphocyte enhancer factor-dependent transcriptional activity in a dose-dependent manner in the Caco-2 human colon cancer cell line. Our results suggest that limonin might be a candidate chemopreventive agent against intestinal carcinogenesis.

Micropropagation of Capparis decidua (Forsk.) Edgew. - a tree of arid horticulture.

PubMed

Deora, N S; Shekhawat, N S

1995-12-01

A method for micropropagation of mature trees of Capparis decidua was developed. Multiple shoots were obtained from nodal explants on Murashige and Skoog's (1962) medium+0.1mgl(-1) NAA+5.0mgl(-1)BAP+additives (50mgl(-1) ascorbic acid and25 mgl(-1) each of adenine sulphate, L-arginine and citric acid) at 28 ± 2°C, 12 h/dphotoperiod and 35-40 μmol m(-2)s(-1) photon flux density. The shoots were multiplied by (i) subculture of nodal shoot segments onto MS +0.1 mgl(--1) IAA+1.0mgl(-1) BAPH+additives, and (ii) repeated transfer of original explant onto MS+ 0.1mgl(-1) IAA+mg l(-1) BAP+additives, at intervals of 3 weeks. Sixty to 70% of the shoots rooted when pulse treated with 100 mg l(-1) IBA in half strength MS liquid medium for 4h, and then transferred onto hormone-free half-strength agar-gelled MS basal saltmedium. Incubation in dark at 33 ± 2°C for 6d favoured root induction. In vitro hardened plants were transferred to pots.

Methodological Aspects of Cognitive Rehabilitation with Eye Movement Desensitization and Reprocessing (EMDR)

PubMed Central

Zarghi, Afsaneh; Zali, Alireza; Tehranidost, Mehdi

2013-01-01

A variety of nervous system components such as medulla, pons, midbrain, cerebellum, basal ganglia, parietal, frontal and occipital lobes have role in Eye Movement Desensitization and Reprocessing (EMDR) processes. The eye movement is done simultaneously for attracting client's attention to an external stimulus while concentrating on a certain internal subject. Eye movement guided by therapist is the most common attention stimulus. The role of eye movement has been documented previously in relation with cognitive processing mechanisms. A series of systemic experiments have shown that the eyes’ spontaneous movement is associated with emotional and cognitive changes and results in decreased excitement, flexibility in attention, memory processing, and enhanced semantic recalling. Eye movement also decreases the memory's image clarity and the accompanying excitement. By using EMDR, we can reach some parts of memory which were inaccessible before and also emotionally intolerable. Various researches emphasize on the effectiveness of EMDR in treating and curing phobias, pains, and dependent personality disorders. Consequently, due to the involvement of multiple neural system components, this palliative method of treatment can also help to rehabilitate the neuro-cognitive system. PMID:25337334

Effect of Serum from Chickens Treated with Clenbuterol on Myosin Accumulation, Beta-Adrenergic Receptor Population, and Cyclic AM Synthesis in Embryonic Chicken Skeletal Muscle Cell Cultures

NASA Technical Reports Server (NTRS)

Young, R. B.; Bridge, K. Y.; Wuethrich, A. J.; Hancock, D. L.; Whitaker, Ann F. (Technical Monitor)

2001-01-01

Broiler chickens at 35 days of age were fed 1 ppm clenbuterol for 14 days. This level of dietary clenbuterol led to 5-7% increases in weights of leg and breast muscle tissue. At the end of the 14-day period, serum was prepared from both control and clenbuterol-treated chickens and was then employed as a component of cell culture media at a final concentration of 20% (v/v). Muscle cell cultures were prepared from both the leg and breast muscle groups of twelve-day chick embryos. Treatment groups included control chicken serum to which 10 nM, 50 nM, and 1 micron clenbuterol had been added, as well as cells grown in media containing 10% horse serum. Cultures were subjected to each treatment for 3 days beginning on the seventh day in culture. Neither the percent fusion nor the number of nuclei in myotubes were significantly affected by any of the treatments. The quantity of MHC was not increased by serum from clenbuterol-treated chickens in either breast and leg muscle cultures; however, MHC quantity was 50- 100% higher in cultures grown in control chicken serum to which 10 nM and 50 nM clenbuterol had also been added. The Beta-AR population was 4,000-7,000 Beta-AR per cell in cultures grown in chicken serum, with leg muscle cultures having approximately 25-30% more receptors than breast muscle cultures. Receptor population was not significantly affected by the presence of clenbuterol or by the presence of serum from clenbuterol-treated chickens. In contrast, the Beta-AR population in leg and breast muscle cultures grown in the presence of 10% horse serum was 18,000-20,000 Beta-AR per cell. Basal concentration of cAMP was not significantly affected by any of the treatments. When cultures grown in chicken serum were stimulated for 10 min with 1 micron isoproterenol, limited increases of 12-20% in cAMP concentration above basal levels were observed. However, when cultures grown in the presence of horse serum were stimulated with 1 micron isoproterenol, increases of 600-800 % in cAMP concentration above basal levels were observed. Thus, not only did cells grown in horse serum have a higher Beta-AR population, each receptor had a higher capacity for cAMP synthesis following isoproterenol stimulation. Finally, the hypothesis was tested that clenbuterol exerts its action on muscle protein content by changes in cAMP concentration. No correlation was apparent between basal cAMP concentration and MHC content.

Effect of Serum from Chickens Treated with Clenbuterol on Myosin Accumulation, Beta-Adrenergic Receptor Population, and Cyclic AMP Synthesis in Embryonic Chicken Skeletal Muscle Cell Cultures

NASA Technical Reports Server (NTRS)

Young, Ronald B.; Bridge, Kristin Y.; Wuethrich, Andrew J.; Hancock, Deana L.

2002-01-01

Broiler chickens at 35 d of age were fed 1 ppm clenbuterol for 14 d. This level of dietary clenbuterol led to 5-7% increases in the weights of leg and breast muscle tissue. At the end of the 14-d period, serum was prepared from both control and clenbuterol-treated chickens, and was then employed as a component of cell culture media at a final concentration of 20% (v/v). Muscle cell cultures were prepared from both the leg and the breast muscle groups of 12-d chick embryos. Treatment groups included control chicken serum to which 10 nM, 50 nM, and 1 uM clenbuterol had been added, as well as cells grown in media containing 10% horse serum. Cultures were subjected to each treatment for 3 d, beginning on the seventh d in culture. Neither the percent fusion nor the number of nuclei in myotubes was significantly affected by any of the treatments. The quantity of myosin heavy chains (MHCs) was not increased by serum from clenbuterol-treated chickens in either breast or leg muscle cultures; however, the MHC quantity was 50-150% higher in cultures grown in control chicken serum to which 10 and 50 nM clenbuterol had also been added. The B-adrenergic receptor (betaAR) population was 4000-7000 betaARs per cell in cultures grown in chicken serum with leg muscle cultures having approximately 25-30% more receptors than breast muscle Culture. Receptor population was not significantly affected by the presence of clenbuterol or by the presence of serum from clenbuterol-treated chickens. In contrast, the betaAR Population in leg and breast muscle cultures grown in the presence of 10% horse serum was 16,000-18,000 betaARs per cell. Basal concentration of cyclic adenosine 3':5'monophosphate (cAMP) was not significantly affected by the treatments. When cultures grown in chicken serum were stimulated for 10 min with 1 uM isoproterenol, limited increases of 12-20% in cAMP Concentration above the. basal levels were observed. However, when cultures grown in the presence of horse serum were stimulated with 1 uM isoproterenol, cAMP concentration was stimulated 5- to 9-fold above the basal levels. Thus, not only did cells, grown in horse serum have a higher PAR population, but also each receptor had a higher capacity for cAMP synthesis following isoproterenol stimulation. Finally, the hypothesis that clenbuterol exerts its action on muscle protein content by changes in cAMP concentration was tested. No correlation was apparent between basal cAMP concentration and MHC content.

Quetiapine responsive catatonia in an autistic patient with comorbid bipolar disorder and idiopathic basal ganglia calcification.

PubMed

Ishitobi, Makoto; Kawatani, Masao; Asano, Mizuki; Kosaka, Hirotaka; Goto, Takashi; Hiratani, Michio; Wada, Yuji

2014-10-01

Bipolar disorder (BD) has been linked with the manifestation of catatonia in subjects with autism spectrum disorders (ASD). Idiopathic basal ganglia calcification (IBGC) is characterized by movement disorders and various neuropsychiatric disturbances including mood disorder. We present a patient with ASD and IBGC who developed catatonia presenting with prominent dystonic feature caused by comorbid BD, which was treated effectively with quetiapine. In addition to considering the possibility of neurodegenerative disease, careful psychiatric interventions are important to avoid overlooking treatable catatonia associated with BD in cases of ASD presenting with both prominent dystonic features and apparent fluctuation of the mood state. Copyright © 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Gibberellin-regulated gene in the basal region of rice leaf sheath encodes basic helix-loop-helix transcription factor.

PubMed

Komatsu, Setsuko; Takasaki, Hironori

2009-07-01

Genes regulated by gibberellin (GA) during leaf sheath elongation in rice seedlings were identified using the transcriptome approach. mRNA from the basal regions of leaf sheaths treated with GA3 was analyzed by high-coverage gene expression profiling. 33,004 peaks were detected, and 30 transcripts showed significant changes in the presence of GA3. Among these, basic helix-loop-helix transcription factor (AK073385) was significantly upregulated. Quantitative PCR analysis confirmed that expression of AK073385 was controlled by GA3 in a time- and dose-dependent manner. Basic helix-loop-helix transcription factor (AK073385) is therefore involved in the regulation of gene expression by GA3.

Role of the human cytomegalovirus major immediate-early promoter's 19-base-pair-repeat cyclic AMP-response element in acutely infected cells.

PubMed

Keller, M J; Wheeler, D G; Cooper, E; Meier, J L

2003-06-01

Prior studies have suggested a role of the five copies of the 19-bp-repeat cyclic AMP (cAMP)-response element (CRE) in major immediate-early (MIE) promoter activation, the rate-limiting step in human cytomegalovirus (HCMV) replication. We used two different HCMV genome modification strategies to test this hypothesis in acutely infected cells. We report the following: (i) the CREs do not govern basal levels of MIE promoter activity at a high or low multiplicity of infection (MOI) in human foreskin fibroblast (HFF)- or NTera2-derived neuronal cells; (ii) serum and virion components markedly increase MIE promoter-dependent transcription at a low multiplicity of infection (MOI), but this increase is not mediated by the CREs; (iii) forskolin stimulation of the cAMP signaling pathway induces a two- to threefold increase in MIE RNA levels in a CRE-specific manner at a low MOI in both HFF- and NTera2-derived neuronal cells; and (iv) the CREs do not regulate basal levels of HCMV DNA replication at a high or low MOI in HFF. Their presence does impart a forskolin-induced increase in viral DNA replication at a low MOI but only when basal levels of MIE promoter activity are experimentally diminished. In conclusion, the 19-bp-repeat CREs add to the robust MIE promoter activity that occurs in the acutely infected stimulated cells, although the CREs' greater role may be in other settings.

Complex care by multiple medical and dental specialists of a patient with aggressive Gorlin-Goltz syndrome.

PubMed

Nagy, K; Kiss, E; Erdei, C; Oberna, F; Fejérdy, P; Márton, K; Vajo, Z

2008-06-01

Gorlin-Goltz syndrome is a genetically predisposed disease characterised by multiple basal cell carcinomas, odontogenic keratocysts and ectopic calcifications. The aim of this study was to show successful treatment of a 37-year-old male patient by cooperation between different dental and medical specialists. Because of the recurrence of a large basal cell carcinoma after multiple operations and a total dose telecobalt irradiation of 66 Gy, the patient's nose was ablated, with resection of the upper lip and part of the maxilla. The intraoral prosthetic treatment helped to restore the subtotal edentulousness. In order to enhance the application of the dental prosthesis, an Abbe plasty was performed at the second stage of surgery. As previous irradiation of the area precluded the use of facial implants immediately after the intraoral treatment, a temporary artificial nose prosthesis was created. The patient tolerated the procedures well and is completely disease-free 12 months after the surgery. Besides presenting a rare and complicated case of Gorlin-Goltz syndrome, the main purpose of this report is to show that, if different specialists in a dental-clinical team (maxillofacial surgeon, oncologist, radiation oncologist, prosthodontist and psychiatrist) combine their skills and expertise, successful management is possible even in a challenging complex case.

Disruption of spatial organization and interjoint coordination in Parkinson's disease, progressive supranuclear palsy, and multiple system atrophy.

PubMed

Leiguarda, R; Merello, M; Balej, J; Starkstein, S; Nogues, M; Marsden, C D

2000-07-01

Patients with basal ganglia diseases may exhibit ideomotor apraxia. To define the nature of the impairment of the action production system, we studied a repetitive gesture of slicing bread by three-dimensional computergraphic analysis in eight nondemented patients with Parkinson's disease in the "on" state, five with progressive supranuclear palsy and four with multiple system atrophy. Two patients with Parkinson's disease and two with progressive supranuclear palsy showed ideomotor apraxia for transitive movements on standard testing. A Selspott II system was used for kinematic analysis of wrist trajectories and angular motions of the shoulder and elbow joints. Patients with Parkinson's disease, progressive supranuclear palsy, and even some with multiple system atrophy exhibited kinematic deficits in the spatial precision of movement and velocity-curvature relationships; in addition, they failed to maintain proper angle/angle relationships and to apportion their relative joint amplitudes normally. Spatial disruption of wrist trajectories was more severe in patients with ideomotor apraxia. We posit that the basal ganglia are part of the parallel parieto-frontal circuits devoted to sensorimotor integration for object-oriented behavior. The severity and characteristics of spatial abnormalities of a transitive movement would therefore depend on the location and distribution of the pathologic process within these circuits.

Visualizing Iron Deposition in Multiple Sclerosis Cadaver Brains

DOE Office of Scientific and Technical Information (OSTI.GOV)

Habib, Charbel A.; Zheng Weili; Mark Haacke, E.

Aim: To visualize and validate iron deposition in two cases of multiple sclerosis using rapid scanning X-Ray Fluorescence (RS-XRF) and Susceptibility Weighted Imaging (SWI). Material and Methods: Two (2) coronal cadaver brain slices from patients clinically diagnosed with multiple sclerosis underwent magnetic resonance imaging (MRI), specifically SWI to image iron content. To confirm the presence of iron deposits and the absence of zinc-rich myelin in lesions, iron and zinc were mapped using RS-XRF. Results: MS lesions were visualized using FLAIR and correlated with the absence of zinc by XRF. XRF and SWI showed that in the first MS case, theremore » were large iron deposits proximal to the draining vein of the caudate nucleus as well as iron deposits associated with blood vessels throughout the globus pallidus. Less iron was seen in association with lesions than in the basal ganglia. The presence of larger amounts of iron correlated reasonably well between RS-XRF and SWI. In the second case, the basal ganglia appeared normal and acute perivascular iron deposition was absent. Conclusion: Perivascular iron deposition is seen in some but not all MS cases, giving credence to the use of SWI to assess iron involvement in MS pathology in vivo.« less

Differences in self-monitored, blood glucose test strip utilization by therapy for type 2 diabetes mellitus.

PubMed

Tavares, Ruben; Duclos, Marc; Brabant, Marie-Josée; Checchin, Daniella; Bosnic, Nevzeta; Turvey, Katherine; Terres, Jorge Alfonso Ross

2016-06-01

To determine whether blood glucose test strip (BGTS) utilization in patients with type 2 diabetes (T2D) is associated with the type of diabetes therapy, classified according to hypoglycemic risk. A retrospective, longitudinal (2006-2012) study of Canadian private drug plans (PDP) and Ontario Public Drug Programs (OPDP) prescription claims was conducted. Analyses were restricted to patients with T2D with or without a claim for BGTS. Daily BGTS utilization (TS/patient/day) was evaluated by diabetes therapy classified by hypoglycemic risk. Multivariate analyses were conducted to identify determinants of BGTS utilization. The T2D cohort comprised 5,759,591 observations from 1,949,129 claimants. Mean BGTS utilization was 0.84 TS/patient/day and differed between PDP and OPDP (0.66 vs. 1.00). Daily utilization was greatest in patients receiving therapy associated with a pre-defined high risk of hypoglycemia [insulin: basal + bolus (2.16), premixed (1.65), basal (1.16), other insulin regimens (2.13), and sulfonylureas (0.74)] versus non-sulfonylurea non-insulin-based regimens (0.52). For non-insulin therapy, BGTS utilization was greater for patients on multiple non-insulin therapies versus monotherapy (0.74 vs. 0.53 TS/patient/day). In multivariate analyses, drivers for BGTS utilization included insulin use, previous BGTS use, and female gender. Previous diabetes therapy and duration of therapy were negatively correlated with BGTS utilization. BGTS utilization varies depending on the type of therapy used to treat T2D according to hypoglycemic risk. Decision making regarding BGTS needs to account for robust analyses of current utilization and its value in those settings, including in patients not receiving diabetes therapy and the prevalence of circumstances conducive to more intensive monitoring.

Contributions of the three CYP1 monooxygenases to pro-inflammatory and inflammation-resolution lipid mediator pathways.

PubMed

Divanovic, Senad; Dalli, Jesmond; Jorge-Nebert, Lucia F; Flick, Leah M; Gálvez-Peralta, Marina; Boespflug, Nicholas D; Stankiewicz, Traci E; Fitzgerald, Jonathan M; Somarathna, Maheshika; Karp, Christopher L; Serhan, Charles N; Nebert, Daniel W

2013-09-15

All three cytochrome P450 1 (CYP1) monooxygenases are believed to participate in lipid mediator biosynthesis and/or their local inactivation; however, distinct metabolic steps are unknown. We used multiple-reaction monitoring and liquid chromatography-UV coupled with tandem mass spectrometry-based lipid-mediator metabololipidomics to identify and quantify three lipid-mediator metabolomes in basal peritoneal and zymosan-stimulated inflammatory exudates, comparing Cyp1a1/1a2/1b1(⁻/⁻) C57BL/6J-background triple-knockout mice with C57BL/6J wild-type mice. Significant differences between untreated triple-knockout and wild-type mice were not found for peritoneal cell number or type or for basal CYP1 activities involving 11 identified metabolic steps. Following zymosan-initiated inflammation, 18 lipid mediators were identified, including members of the eicosanoids and specialized proresolving mediators (i.e., resolvins and protectins). Compared with wild-type mice, Cyp1 triple-knockout mice exhibited increased neutrophil recruitment in zymosan-treated peritoneal exudates. Zymosan stimulation was associated with eight statistically significantly altered metabolic steps: increased arachidonic acid-derived leukotriene B₄ (LTB₄) and decreased 5S-hydroxyeicosatetraenoic acid; decreased docosahexaenoic acid-derived neuroprotectin D1/protectin D1, 17S-hydroxydocosahexaenoic acid, and 14S-hydroxydocosahexaenoic acid; and decreased eicosapentaenoic acid-derived 18R-hydroxyeicosapentaenoic acid (HEPE), 15S-HEPE, and 12S-HEPE. In neutrophils analyzed ex vivo, elevated LTB₄ levels were shown to parallel increased neutrophil numbers, and 20-hydroxy-LTB₄ formation was found to be deficient in Cyp1 triple-knockout mice. Together, these results demonstrate novel contributions of CYP1 enzymes to the local metabolite profile of lipid mediators that regulate neutrophilic inflammation.

α6β2* and α4β2* Nicotinic Acetylcholine Receptors As Drug Targets for Parkinson's Disease

PubMed Central

Wonnacott, Susan

2011-01-01

Parkinson's disease is a debilitating movement disorder characterized by a generalized dysfunction of the nervous system, with a particularly prominent decline in the nigrostriatal dopaminergic pathway. Although there is currently no cure, drugs targeting the dopaminergic system provide major symptomatic relief. As well, agents directed to other neurotransmitter systems are of therapeutic benefit. Such drugs may act by directly improving functional deficits in these other systems, or they may restore aberrant motor activity that arises as a result of a dopaminergic imbalance. Recent research attention has focused on a role for drugs targeting the nicotinic cholinergic systems. The rationale for such work stems from basic research findings that there is an extensive overlap in the organization and function of the nicotinic cholinergic and dopaminergic systems in the basal ganglia. In addition, nicotinic acetylcholine receptor (nAChR) drugs could have clinical potential for Parkinson's disease. Evidence for this proposition stems from studies with experimental animal models showing that nicotine protects against neurotoxin-induced nigrostriatal damage and improves motor complications associated with l-DOPA, the “gold standard” for Parkinson's disease treatment. Nicotine interacts with multiple central nervous system receptors to generate therapeutic responses but also produces side effects. It is important therefore to identify the nAChR subtypes most beneficial for treating Parkinson's disease. Here we review nAChRs with particular emphasis on the subtypes that contribute to basal ganglia function. Accumulating evidence suggests that drugs targeting α6β2* and α4β2* nAChR may prove useful in the management of Parkinson's disease. PMID:21969327

Proteomic and Metabolic Analyses of S49 Lymphoma Cells Reveal Novel Regulation of Mitochondria by cAMP and Protein Kinase A*

PubMed Central

Wilderman, Andrea; Guo, Yurong; Divakaruni, Ajit S.; Perkins, Guy; Zhang, Lingzhi; Murphy, Anne N.; Taylor, Susan S.; Insel, Paul A.

2015-01-01

Cyclic AMP (cAMP), acting via protein kinase A (PKA), regulates many cellular responses, but the role of mitochondria in such responses is poorly understood. To define such roles, we used quantitative proteomic analysis of mitochondria-enriched fractions and performed functional and morphologic studies of wild-type (WT) and kin− (PKA-null) murine S49 lymphoma cells. Basally, 75 proteins significantly differed in abundance between WT and kin− S49 cells. WT, but not kin−, S49 cells incubated with the cAMP analog 8-(4-chlorophenylthio)adenosine cAMP (CPT-cAMP) for 16 h have (a) increased expression of mitochondria-related genes and proteins, including ones in pathways of branched-chain amino acid and fatty acid metabolism and (b) increased maximal capacity of respiration on branched-chain keto acids and fatty acids. CPT-cAMP also regulates the cellular rate of ATP-utilization, as the rates of both ATP-linked respiration and proton efflux are decreased in WT but not kin− cells. CPT-cAMP protected WT S49 cells from glucose or glutamine deprivation, In contrast, CPT-cAMP did not protect kin− cells or WT cells treated with the PKA inhibitor H89 from glutamine deprivation. Under basal conditions, the mitochondrial structure of WT and kin− S49 cells is similar. Treatment with CPT-cAMP produced apoptotic changes (i.e. decreased mitochondrial density and size and loss of cristae) in WT, but not kin− cells. Together, these findings show that cAMP acts via PKA to regulate multiple aspects of mitochondrial function and structure. Mitochondrial perturbation thus likely contributes to cAMP/PKA-mediated cellular responses. PMID:26203188

Super-Resolution Imaging Reveals TCTN2 Depletion-Induced IFT88 Lumen Leakage and Ciliary Weakening.

PubMed

Weng, Rueyhung Roc; Yang, T Tony; Huang, Chia-En; Chang, Chih-Wei; Wang, Won-Jing; Liao, Jung-Chi

2018-06-01

The primary cilium is an essential organelle mediating key signaling activities, such as sonic hedgehog signaling. The molecular composition of the ciliary compartment is distinct from that of the cytosol, with the transition zone (TZ) gated the ciliary base. The TZ is a packed and organized protein complex containing multiple ciliopathy-associated protein species. Tectonic 2 (TCTN2) is one of the TZ proteins in the vicinity of the ciliary membrane, and its mutation is associated with Meckel syndrome. Despite its importance in ciliopathies, the role of TCTN2 in ciliary structure and molecules remains unclear. Here, we created a CRISPR/Cas9 TCTN2 knockout human retinal pigment epithelial cell line and conducted quantitative analysis of geometric localization using both wide-field and super-resolution microscopy techniques. We found that TCTN2 depletion resulted in partial TZ damage, loss of ciliary membrane proteins, leakage of intraflagellar transport protein IFT88 toward the basal body lumen, and cilium shortening and curving. The basal body lumen occupancy of IFT88 was also observed in si-RPGRIP1L cells and cytochalasin-D-treated wild-type cells, suggesting varying lumen accessibility for intraflagellar transport proteins under different perturbed conditions. Our findings support two possible models for the lumen leakage of IFT88, i.e., a tip leakage model and a misregulation model. Together, our quantitative image analysis augmented by super-resolution microscopy facilitates the observation of structural destruction and molecular redistribution in TCTN2 -/- cilia, shedding light on mechanistic understanding of TZ-protein-associated ciliopathies. Copyright © 2018 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Exquisite Sensitivity of TP53 Mutant and Basal Breast Cancers to a Dose-Dense Epirubicin−Cyclophosphamide Regimen

PubMed Central

Espié, Marc; de Reyniès, Aurélien; Feugeas, Jean-Paul; Plassa, Louis-François; Soliman, Hany; Varna, Mariana; de Roquancourt, Anne; Lehmann-Che, Jacqueline; Beuzard, Yves; Marty, Michel; Misset, Jean-Louis; Janin, Anne; de Thé, Hugues

2007-01-01

Background In breast cancers, only a minority of patients fully benefit from the different chemotherapy regimens currently in use. Identification of markers that could predict the response to a particular regimen would thus be critically important for patient care. In cell lines or animal models, tumor protein p53 (TP53) plays a critical role in modulating the response to genotoxic drugs. TP53 is activated in response to DNA damage and triggers either apoptosis or cell-cycle arrest, which have opposite effects on cell fate. Yet, studies linking TP53 status and chemotherapy response have so far failed to unambiguously establish this paradigm in patients. Breast cancers with a TP53 mutation were repeatedly shown to have a poor outcome, but whether this reflects poor response to treatment or greater intrinsic aggressiveness of the tumor is unknown. Methods and Findings In this study we analyzed 80 noninflammatory breast cancers treated by frontline (neoadjuvant) chemotherapy. Tumor diagnoses were performed on pretreatment biopsies, and the patients then received six cycles of a dose-dense regimen of 75 mg/m2 epirubicin and 1,200 mg/m2 cyclophosphamide, given every 14 days. After completion of chemotherapy, all patients underwent mastectomies, thus allowing for a reliable assessment of chemotherapy response. The pretreatment biopsy samples were used to determine the TP53 status through a highly efficient yeast functional assay and to perform RNA profiling. All 15 complete responses occurred among the 28 TP53-mutant tumors. Furthermore, among the TP53-mutant tumors, nine out of ten of the highly aggressive basal subtypes (defined by basal cytokeratin [KRT] immunohistochemical staining) experienced complete pathological responses, and only TP53 status and basal subtype were independent predictors of a complete response. Expression analysis identified many mutant TP53-associated genes, including CDC20, TTK, CDKN2A, and the stem cell gene PROM1, but failed to identify a transcriptional profile associated with complete responses among TP53 mutant tumors. In patients with unresponsive tumors, mutant TP53 status predicted significantly shorter overall survival. The 15 patients with responsive TP53-mutant tumors, however, had a favorable outcome, suggesting that this chemotherapy regimen can overcome the poor prognosis generally associated with mutant TP53 status. Conclusions This study demonstrates that, in noninflammatory breast cancers, TP53 status is a key predictive factor for response to this dose-dense epirubicin–cyclophosphamide regimen and further suggests that the basal subtype is exquisitely sensitive to this association. Given the well-established predictive value of complete responses for long-term survival and the poor prognosis of basal and TP53-mutant tumors treated with other regimens, this chemotherapy could be particularly suited for breast cancer patients with a mutant TP53, particularly those with basal features. PMID:17388661

Proximal tubule-specific glutamine synthetase deletion alters basal and acidosis-stimulated ammonia metabolism

PubMed Central

Lee, Hyun-Wook; Osis, Gunars; Handlogten, Mary E.; Lamers, Wouter H.; Chaudhry, Farrukh A.; Verlander, Jill W.

2016-01-01

Glutamine synthetase (GS) catalyzes the recycling of NH4+ with glutamate to form glutamine. GS is highly expressed in the renal proximal tubule (PT), suggesting ammonia recycling via GS could decrease net ammoniagenesis and thereby limit ammonia available for net acid excretion. The purpose of the present study was to determine the role of PT GS in ammonia metabolism under basal conditions and during metabolic acidosis. We generated mice with PT-specific GS deletion (PT-GS-KO) using Cre-loxP techniques. Under basal conditions, PT-GS-KO increased urinary ammonia excretion significantly. Increased ammonia excretion occurred despite decreased expression of key proteins involved in renal ammonia generation. After the induction of metabolic acidosis, the ability to increase ammonia excretion was impaired significantly by PT-GS-KO. The blunted increase in ammonia excretion occurred despite greater expression of multiple components of ammonia generation, including SN1 (Slc38a3), phosphate-dependent glutaminase, phosphoenolpyruvate carboxykinase, and Na+-coupled electrogenic bicarbonate cotransporter. We conclude that 1) GS-mediated ammonia recycling in the PT contributes to both basal and acidosis-stimulated ammonia metabolism and 2) adaptive changes in other proteins involved in ammonia metabolism occur in response to PT-GS-KO and cause an underestimation of the role of PT GS expression. PMID:27009341

The role of the basal ganglia in learning and memory: Insight from Parkinson's disease

PubMed Central

2013-01-01

It has long been known that memory is not a single process. Rather, there are different kinds of memory that are supported by distinct neural systems. This idea stemmed from early findings of dissociable patterns of memory impairments in patients with selective damage to different brain regions. These studies highlighted the role of the basal ganglia in non-declarative memory, such as procedural or habit learning, contrasting it with the known role of the medial temporal lobes in declarative memory. In recent years, major advances across multiple areas of neuroscience have revealed an important role for the basal ganglia in motivation and decision making. These findings have led to new discoveries about the role of the basal ganglia in learning and highlighted the essential role of dopamine in specific forms of learning. Here we review these recent advances with an emphasis on novel discoveries from studies of learning in patients with Parkinson's disease. We discuss how these findings promote the development of current theories away from accounts that emphasize the verbalizability of the contents of memory and towards a focus on the specific computations carried out by distinct brain regions. Finally, we discuss new challenges that arise in the face of accumulating evidence for dynamic and interconnected memory systems that jointly contribute to learning. PMID:21945835

CO2 laser debridement of sulphur mustard (bis-2-chloroethyl sulphide) induced cutaneous lesions accelerates production of a normal epidermis with elimination of cytological atypia.

PubMed

Smith, K J; Skelton, H G; Martin, J L; Hurst, C G; Hackley, B E

1997-10-01

Sulphur mustard (bis-2-chloroethyl sulphide; HD) exposure acutely produces lesions that vary from mild erythema, to blister formation, to necrosis. When blisters occur, with or without necrosis, healing of the lesions is delayed. Weanling pigs exposed to a mild erythema-producing dose of HD and to a moderate erythema-producing dose that consistently gave microblister formation were treated with CO2 laser (Tru-Pulse) debridement at 6, 24 or 48 h after exposure. The histopathological features observed at 14 days after exposure in control skin and skin exposed to both HD doses were compared with the features observed in CO2 laser-debrided skin in non-exposed and HD-exposed skin sites. The overlying epidermis in the non-laser treated lesions was thin, with cytological atypia and squamoid changes within the basal cell layer, as well as scattered apoptotic/necrotic keratinocytes. An increased inflammatory infiltrate and necrobiotic changes in the dermis were seen at the higher HD dose. All laser-treated lesions appeared identical, with a thick, differentiated epidermis and a well-formed basal cell layer. There was minimal inflammatory infiltrate. In the papillary dermis there were increased stromal cells. Laser debridement of mild clinical lesions induced by HD produced a more functional epidermis by 14 days as well as clearing the epidermis of damaged keratinocytes.

An analysis of the effects of acute and chronic fluoxetine on extracellular norepinephrine in the rat hippocampus during stress.

PubMed

Page, M E; Abercrombie, E D

1997-06-01

The locus coeruleus (LC) noradrenergic system is activated by a range of arousing and stressful stimuli. The serotonergic inputs to this structure have been shown to attenuate LC activation under some conditions. The present study examined the effect of fluoxetine, a selective serotonin reuptake inhibitor (SSRI) known to be a clinically effective antidepressant, on basal and stress-induced norepinephrine (NE) release. Basal and stress-induced NE efflux in the rat hippocampus were assessed using in vivo microdialysis techniques. The effect of a 30 minute tailpinch stressor on extracellular concentration of NE was compared in rats treated with fluoxetine either once prior to tailpinch or twice daily for 14 days and, respectively, in unhandled controls and vehicle-treated control animals. A single fluoxetine injection prior to tailpinch did not significantly alter the tailpinch-induced increase of extracellular NE as compared to naive controls. However, there was an enhanced NE response to tailpinch in chronic fluoxetine versus chronic vehicle-treated control rats. Thus, acute blockade of 5-HT uptake by fluoxetine does not affect NE release in response to tailpinch stress. Chronic fluoxetine administration, however, results in a potentiated evoked response of the LC-NE system. One action of chronic fluoxetine, which may relate to therapeutic efficacy, is an increase in responsivity of LC neurons.

Effects of dietary selenium of organic form against lead toxicity on the antioxidant system in Cyprinus carpio.

PubMed

Özkan-Yilmaz, Ferbal; Özlüer-Hunt, Arzu; Gündüz, Suna Gül; Berköz, Mehmet; Yalin, Serap

2014-04-01

In this study was evaluated potential protective effect of organic selenium (Se) on heavy metal stress induced by lead (Pb) in Cyprinus carpio. For this reason, C. carpio was exposed to sublethal concentration of Pb (1.5 mg/L Pb(NO3)2) for 14 days. The fish were fed a basal (control; measured 0.55 mg/kg Se) diet or a basal diet supplemented with 2.50 mg/kg (measured 2.92 mg/kg Se) organic Se (Sel-Plex(®)) during the experiment period. The variations in glutathione peroxidase (GSH-Px), glutathione S-transferase (GST) activities, and levels of reduced glutathione (GSH) with malondialdehyde (MDA) in liver and brain tissues of C. carpio were investigated in experimental groups. GSH levels in liver and brain tissues were significantly decreased by exposure to Pb. GST activity was significantly increased (p < 0.05) in liver tissue, but decreased in brain of treated fish by exposure to Pb. Also, GSH-Px activity was significantly increased in liver tissue, but decreased in brain of Pb-treated fish. Levels of MDA were increased in liver and brain of Pb-treated fish. The organic Se treatment for Pb-intoxicated animals improved activities of GSH-Px, GST and levels of MDA within normal limits. Supplemented Se could be able to improve Pb-induced oxidative stress by decreasing lipid peroxidation and regulating antioxidant defense system in tissues.

Girdling and Applying Chemicals Promote Rapid Rooting of Sycamore Cuttings

Treesearch

Robert C. Hare

1975-01-01

Shoots of 6- and 13-year-old sycamore (Platanus occidentalis L.) were girdled and treated with rooting powder 4 weeks before cuttings were taken. The powder, which contained auxins, sucrose, and cap tan, was also applied basally to nongirdled cuttings immediately before iwertion in a rooting medium. Thirteen days later, 100 percent of the...

Runoff Responses to Forest Thinning at Plot and Catchment Scales in a Headwater Catchment Draining Japanese Cypress Forest

EPA Science Inventory

We examined the effect of forest thinning on runoff generation at plot and catchment scales in headwater basins draining a Japanese cypress (Chamaecyparis obtusa) forest. We removed 58.3% of the stems (corresponding to 43.2% of the basal area) in the treated headwater basin (catc...

Platinum Based Chemotherapy or Capecitabine in Treating Patients With Residual Triple-Negative Basal-Like Breast Cancer Following Neoadjuvant Chemotherapy

ClinicalTrials.gov

2017-12-07

Estrogen Receptor Negative; HER2/Neu Negative; Invasive Breast Carcinoma; Progesterone Receptor Negative; Stage II Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage III Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Triple-Negative Breast Carcinoma

Multiple transcriptional regulatory domains in the human immunodeficiency virus type 1 long terminal repeat are involved in basal and E1A/E1B-induced promoter activity.

PubMed Central

Kliewer, S; Garcia, J; Pearson, L; Soultanakis, E; Dasgupta, A; Gaynor, R

1989-01-01

The human immunodeficiency virus (HIV) type 1 long terminal repeat (LTR) is the site of activation of the HIV tat protein. However, additional transactivators, such as the adenovirus E1A and herpesvirus ICPO proteins, have also been shown to be capable of activating the HIV LTR. Analysis of adenovirus mutants indicated that complete transactivation of the HIV LTR was dependent on both the E1A and E1B proteins. To determine which regions of the HIV LTR were important for complete E1A/E1B activation, a variety of oligonucleotide-directed mutations in HIV transcriptional regulatory domains were assayed both in vivo and in vitro. S1 nuclease analysis of RNA prepared after transfection of these HIV constructs into HeLa cells infected with wild-type adenovirus indicated that the enhancer, SP1, TATA, and a portion of the transactivation-responsive element were each required for complete E1A/E1B-mediated activation of the HIV LTR. These same promoter elements were required for both basal and E1A/E1B-induced levels of transcription in in vitro transcription reactions performed with cellular extracts prepared from cells infected with dl434, an E1A/E1B deletion mutant, or wild-type adenovirus. No mutations were found that reduced only E1A/E1B-induced expression without proportionally reducing basal levels of transcription, suggesting that E1A/E1B-mediated induction of the HIV LTR requires multiple promoter elements which are also required for basal transcriptional levels. Unlike activation by the tat protein, there was not a rigid dependence on maintenance of the transactivation-responsive stem base pairing for E1A/E1B-mediated activation either in vivo or in vitro, indicating that activation occurs by a mechanism distinct from that of tat induction. Images PMID:2529378

Non-syndromic odontogenic keratocysts: A rare case report

PubMed Central

Kurdekar, Raghavendra S.; Prakash, Jeevan; Rana, A. S.; Kalra, Puneet

2013-01-01

Odontogenic keratocysts are very well documented in the literature. Multiple odontogenic keratocysts (OKCs) are one of the most frequent features of nevoid basal cell carcinoma syndrome (NBCCS). It is linked with mutation in the PTCH gene (human homolog of the drosophila segment polarity gene, “patched”,). Partial expression of the gene may result in occurrence of only multiple recurring OKC without any associated systemic findings. A rare case of multiple odontogenic keratocysts unassociated with any syndrome is reported, so as to add to the growing number of such cases in the literature. The possibility of this case being a partial expression of the Gorlin-Goltz syndrome is discussed. PMID:24163561

Long-term follow-up of functional hypothalamic amenorrhea and prognostic factors.

PubMed

Falsetti, Leopoldo; Gambera, Alessandro; Barbetti, Lorena; Specchia, Cristina

2002-02-01

This study evaluated the prognosis of functional hypothalamic amenorrhea (FHA) and the predictive factors of recovery, through a long-term follow-up. Ninety-three women affected by FHA underwent a follow-up for an average period of 8.1 yr (range 7-9 yr). At the end of the follow-up, 65 (70.7%) patients recovered. Statistical analysis showed that there was no association between recovery and anamnestic causes of FHA or with the echographic ovarian morphology but identified the predictive factors of recovery as the basal body mass index (BMI), the basal cortisol, and androstenedione plasma levels. A higher basal BMI and A, and lower cortisol values are positive prognostic factors for the recovery. Also the BMI, acquired during the follow-up, is important for FHA resolution: in fact, in recovered women the BMI increased or remained stable, whereas in nonrecovered women it decreased or remained stable. At the end of the follow-up, 52 (74.3%) patients treated with hormone replacement therapy and 8 (80%) with no therapy recovered, but only 5 (41.7%) with oral contraceptive pills recovered.

What basal ganglia changes underlie the parkinsonian state? The significance of neuronal oscillatory activity

PubMed Central

Quiroga-Varela, A.; Walters, J.R.; Brazhnik, E.; Marin, C.; Obeso, J.A.

2014-01-01

One well accepted functional feature of the parkinsonian state is the recording of enhanced beta oscillatory activity in the basal ganglia. This has been demonstrated in patients with Parkinson's disease (PD) and in animal models such as the rat with 6-hydroxydopamine (6-OHDA)-induced lesion and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys, all of which are associated with severe striatal dopamine depletion. Neuronal hyper-synchronization in the beta (or any other) band is not present despite the presence of bradykinetic features in the rat and monkey models, suggesting that increased beta band power may arise when nigro-striatal lesion is advanced and that it is not an essential feature of the early parkinsonian state. Similar observations and conclusions have been previously made for increased neuronal firing rate in the subthalamic and globus pallidus pars interna nuclei. Accordingly, it is suggested that early parkinsonism may be associated with dynamic changes in basal ganglia output activity leading to reduced movement facilitation that may be an earlier feature of the parkinsonian state. PMID:23727447

Kinetics of the maintenance of the epidermis

NASA Astrophysics Data System (ADS)

Zhdanov, Vladimir P.; Cho, Nam-Joon

2013-08-01

The epidermis is the outermost layer of skin. It is comprised of keratin-containing cells called keratinocytes. Functionally, the epidermis serves as a physical barrier that can prevent infection and regulate body hydration. Maintenance and repair of the epidermis are important for human health. Mechanistically, these processes occur primarily via proliferation and differentiation of stem cells located in the basal monolayer. These processes are believed to depend on cell-cell communication and spatial constraints but existing kinetic models focus mainly on proliferation and differentiation. To address this issue, we present a mean-field kinetic model that takes these additional factors into account and describes the epidermis at a biosystem level. The corresponding equations operate with the populations of stem cells and differentiated cells in the basal layer. The keratinocytes located above the basal layer are treated at a more coarse-grained level by considering the thickness of the epidermis. The model clarifies the likely role of various negative feedbacks that may control the epidermis and, accordingly, provides insight into the cellular mechanisms underlying complex biological phenomena such as wound healing.

Effect of probiotic supplement on aflatoxicosis and gene expression in the liver of broiler chicken.

PubMed

Salem, Ramadan; El-Habashi, Nagwan; Fadl, Sabreen E; Sakr, Osama A; Elbialy, Zizy I

2018-06-01

The present study aimed to investigate the toxic effect of aflatoxin B1 (AFB1) and the effectiveness of a biological mycotoxin binder (Nutritox ® ) in detoxifying aflatoxicosis. Ninety one-day-old chicks were chosen and divided into 3 groups. The first group received standard basal diet only, the second group received a basal diet with AFB1 (0.25 mg/kg diet), and the third group received a basal diet with AFB1 (0.25 mg/kg diet) and Nutritox ® (1 kg/ton diet). AFB1 feed contamination significantly reduced growth performance and deteriorated FCR. Moreover, it significantly increased serum AST, ALT, and malondialdehyde and significantly decreased serum total protein, albumin, globulin, SOD, CAT activities and glutathione peroxidase gene expression as well. Aflatoxin residues were detected in the liver tissues. Furthermore, the liver and kidney of AFB1 treated group showed pathological changes. The supplementation of Nutritox ® significantly reduced aflatoxin levels in the liver and counteracted the negative effects of AFB1. Copyright © 2018 Elsevier B.V. All rights reserved.

Pubertal Development: Correspondence between Hormonal and Physical Development

ERIC Educational Resources Information Center

Shirtcliff, Elizabeth A.; Dahl, Ronald E.; Pollak, Seth D.

2009-01-01

Puberty is advanced by sex hormones, yet it is not clear how it is best measured. The interrelation of multiple indices of puberty was examined, including the Pubertal Development Scale (PDS), a picture-based interview about puberty (PBIP), and a physical exam. These physical pubertal measures were then associated with basal hormones responsible…

Hyporesponsive Reward Anticipation in the Basal Ganglia following Severe Institutional Deprivation Early in Life

ERIC Educational Resources Information Center

Mehta, Mitul A.; Gore-Langton, Emma; Golembo, Nicole; Colvert, Emma; Williams, Steven C. R.; Sonuga-Barke, Edmund

2010-01-01

Severe deprivation in the first few years of life is associated with multiple difficulties in cognition and behavior. However, the brain basis for these difficulties is poorly understood. Structural and functional neuroimaging studies have implicated limbic system structures as dysfunctional, and one functional imaging study in a heterogeneous…

Contrasting weight changes with LY2605541, a novel long-acting insulin, and insulin glargine despite similar improved glycaemic control in T1DM and T2DM.

PubMed

Jacober, S J; Rosenstock, J; Bergenstal, R M; Prince, M J; Qu, Y; Beals, J M

2014-04-01

The basal insulin analogue LY2605541, a PEGylated insulin lispro with prolonged duration of action, was previously shown to be associated with modest weight loss in Phase 2, randomized, open-label trials in type 2 (N=288) and type 1 (N=137) diabetes mellitus (T2DM and T1DM), compared with modest weight gain with insulin glargine. Exploratory analyses were conducted to further characterize these findings. Pearson correlations between change in body weight and other variables were calculated. Continuous variables were analysed using a mixed linear model with repeated measurements. Proportions of subjects with weight loss were analysed using Fisher's exact test for T2DM and Nagelkerke's method for T1DM. Weight loss was more common in LY2605541-treated patients than in patients treated with insulin glargine (T2DM: 56.9 vs. 40.2%, p=0.011; T1DM: 66.1 vs. 40.3%, p<0.001). More LY2605541-treated patients experienced ≥5% weight loss compared to patients treated with glargine (T2DM: 4.8 vs. 0%, p=0.033; T1DM: 11.9 vs. 0.8%, p<0.001). In both the T1DM and T2DM studies, weight change did not correlate with baseline body mass index (BMI), or change in HDL-cholesterol in either treatment group. No consistent correlations were found across both studies between weight change and any of the variables assessed; however, weight change was significantly correlated with hypoglycaemia rate in glargine-treated T2DM patients. In two Phase 2 trials, improved glycaemic control with long-acting basal insulin analogue LY2605541 is associated with weight loss in previously insulin-treated patients. This weight change is independent of baseline BMI or hypoglycaemia.

The sequential appearance of sperm abnormalities after scrotal insulation or dexamethasone treatment in bulls.

PubMed Central

Barth, A D; Bowman, P A

1994-01-01

Scrotal insulation and dexamethasone treatment were used as a model to compare the effect of testicular heating and stress on spermatogenesis. Insulation was applied to the scrotum of eight bulls (insulated) for a period of four days, eight bulls were treated daily for seven days with 20 mg dexamethasone injected intramuscularly, and four bulls were untreated controls. Semen from four bulls in each group was collected and evaluated over a six-week period after treatment. Blood samples for testosterone analysis were taken hourly for eight hours at the beginning and the end of the six-week period from the control bulls and before and after treatment from the four insulated and four dexamethasone-treated bulls that were not used for semen collection. At the end of the last blood sampling period, the four bulls in each group were castrated for the collection of testicular tissue for the determination of testosterone concentrations. Basal, peak episodic, and mean serum testosterone concentrations among control bulls, pre and postinsulated bulls, and pretreatment samples of dexamethasone-treated bulls were not different (p > 0.05); however, bulls that had received dexamethasone treatments had significantly lower basal, peak episodic, and mean testosterone concentrations (p < 0.05). Tissue concentrations of testosterone in control, insulated, and dexamethasone-treated bulls were not significantly different but tended to be lower in dexamethasone-treated bulls (p > 0.13). The spermiograms of the control bulls varied insignificantly over the six-week sampling period; however, there was a marked increase in sperm defects in insulated and dexamethasone-treated bulls. The types of sperm defects and the temporal relationships of rises and declines of sperm defects were quite similar for both treatments. All bulls recovered to approximately pretreatment levels of sperm defects by six weeks after the initiation of treatment. Results indicate that two of the most common types of insults to spermatogenesis in bulls, heat and stress, result in similar spermiograms. PMID:8069831

The effects of foliar fertilization with iron sulfate in chlorotic leaves are limited to the treated area. A study with peach trees (Prunus persica L. Batsch) grown in the field and sugar beet (Beta vulgaris L.) grown in hydroponics

PubMed Central

El-Jendoubi, Hamdi; Vázquez, Saúl; Calatayud, Ángeles; Vavpetič, Primož; Vogel-Mikuš, Katarina; Pelicon, Primož; Abadía, Javier; Abadía, Anunciación; Morales, Fermín

2014-01-01

Crop Fe deficiency is a worldwide problem. The aim of this study was to assess the effects of foliar Fe applications in two species grown in different environments: peach (Prunus persica L. Batsch) trees grown in the field and sugar beet (Beta vulgaris L. cv. “Orbis”) grown in hydroponics. The distal half of Fe-deficient, chlorotic leaves was treated with Fe sulfate by dipping and using a brush in peach trees and sugar beet plants, respectively. The re-greening of the distal (Fe-treated) and basal (untreated) leaf areas was monitored, and the nutrient and photosynthetic pigment composition of the two areas were also determined. Leaves were also studied using chlorophyll fluorescence imaging, low temperature-scanning electron microscopy microanalysis, scanning transmission ion microscopy-particle induced X-ray emission and Perls Fe staining. The distal, Fe-treated leaf parts of both species showed a significant increase in Fe concentrations (across the whole leaf volume) and marked re-greening, with significant increases in the concentrations of all photosynthetic pigments, as well as decreases in de-epoxidation of xanthophyll cycle carotenoids and increases in photochemical efficiency. In the basal, untreated leaf parts, Fe concentrations increased slightly, but little re-greening occurred. No changes in the concentrations of other nutrients were found. Foliar Fe fertilization was effective in re-greening treated leaf areas both in peach trees and sugar beet plants. Results indicate that the effects of foliar Fe-sulfate fertilization in Fe-deficient, chlorotic leaves were minor outside the leaf surface treated, indicating that Fe mobility within the leaf is a major constraint for full fertilizer effectiveness in crops where Fe-deficiency is established and leaf chlorosis occurs. PMID:24478782

The effects of foliar fertilization with iron sulfate in chlorotic leaves are limited to the treated area. A study with peach trees (Prunus persica L. Batsch) grown in the field and sugar beet (Beta vulgaris L.) grown in hydroponics.

PubMed

El-Jendoubi, Hamdi; Vázquez, Saúl; Calatayud, Angeles; Vavpetič, Primož; Vogel-Mikuš, Katarina; Pelicon, Primož; Abadía, Javier; Abadía, Anunciación; Morales, Fermín

2014-01-01

Crop Fe deficiency is a worldwide problem. The aim of this study was to assess the effects of foliar Fe applications in two species grown in different environments: peach (Prunus persica L. Batsch) trees grown in the field and sugar beet (Beta vulgaris L. cv. "Orbis") grown in hydroponics. The distal half of Fe-deficient, chlorotic leaves was treated with Fe sulfate by dipping and using a brush in peach trees and sugar beet plants, respectively. The re-greening of the distal (Fe-treated) and basal (untreated) leaf areas was monitored, and the nutrient and photosynthetic pigment composition of the two areas were also determined. Leaves were also studied using chlorophyll fluorescence imaging, low temperature-scanning electron microscopy microanalysis, scanning transmission ion microscopy-particle induced X-ray emission and Perls Fe staining. The distal, Fe-treated leaf parts of both species showed a significant increase in Fe concentrations (across the whole leaf volume) and marked re-greening, with significant increases in the concentrations of all photosynthetic pigments, as well as decreases in de-epoxidation of xanthophyll cycle carotenoids and increases in photochemical efficiency. In the basal, untreated leaf parts, Fe concentrations increased slightly, but little re-greening occurred. No changes in the concentrations of other nutrients were found. Foliar Fe fertilization was effective in re-greening treated leaf areas both in peach trees and sugar beet plants. Results indicate that the effects of foliar Fe-sulfate fertilization in Fe-deficient, chlorotic leaves were minor outside the leaf surface treated, indicating that Fe mobility within the leaf is a major constraint for full fertilizer effectiveness in crops where Fe-deficiency is established and leaf chlorosis occurs.

Should "Multiple Imputations" Be Treated as "Multiple Indicators"?

ERIC Educational Resources Information Center

Mislevy, Robert J.

1993-01-01

Multiple imputations for latent variables are constructed so that analyses treating them as true variables have the correct expectations for population characteristics. Analyzing multiple imputations in accordance with their construction yields correct estimates of population characteristics, whereas analyzing them as multiple indicators generally…

Breed- and age-related differences in canine mammary tumors

PubMed Central

Kim, Hyun-Woo; Lim, Ha-Young; Shin, Jong-Il; Seung, Byung-Joon; Ju, Jung-Hyung; Sur, Jung-Hyang

2016-01-01

Triple-negative breast cancer is a type of breast cancer that does not express the genes for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER-2). It is an important and clinically relevant condition as it has a poor prognosis and is difficult to treat. Basal-like triple-negative cancer is highly prevalent in both African-Americans and adolescents. We therefore examined whether such a cancer likewise occurs in specific breeds and age groups in dogs, focusing on basal-like triple-negative cancer in particular. In this study, 181 samples from dogs with malignant mammary carcinoma from the 5 most common breeds and 2 age groups in Korea were analyzed. Histological classification and molecular subtyping, including assessment of immunohistochemical findings, were carried out. Twenty-five of 28 (89.3%) triple-negative carcinomas were identified as basal-like triple-negative carcinomas. Analysis of associations of classified factors revealed that the shih tzu breed (9/25, 36.0%) and advanced-age (19/25, 76.0%) groups were characterized by higher prevalence of basal-like triple-negative tumors with diverse histological types and of a higher grade. These results suggest that breed- and age-related differences can be identified in canine mammary carcinoma and, notably, in the shih tzu breed and at older ages. Further investigation of these distinguishing characteristics of the shih tzu breed is warranted. PMID:27127342

Pilot-scale study on the treatment of basal aquifer water using ultrafiltration, reverse osmosis and evaporation/crystallization to achieve zero-liquid discharge.

PubMed

Loganathan, Kavithaa; Chelme-Ayala, Pamela; Gamal El-Din, Mohamed

2016-01-01

Basal aquifer water is deep groundwater found at the bottom of geological formations, underlying bitumen-saturated sands. Some of the concerns associated with basal aquifer water at the Athabasca oil sands are the high concentrations of hardness-causing compounds, alkalinity, and total dissolved solids. The objective of this pilot-scale study was to treat basal aquifer water to a quality suitable for its reuse in the production of synthetic oil. To achieve zero-liquid discharge (ZLD) conditions, the treatment train included chemical oxidation, polymeric ultrafiltration (UF), reverse osmosis (RO), and evaporation-crystallization technologies. The results indicated that the UF unit was effective in removing solids, with UF filtrate turbidity averaging 2.0 NTU and silt density index averaging 0.9. Membrane autopsies indicated that iron was the primary foulant on the UF and RO membranes. Laboratory and pilot-scale tests on RO reject were conducted to determine the feasibility of ZLD crystallization. Due to the high amounts of calcium, magnesium, and bicarbonate in the RO reject, softening of the feed was required to avoid scaling in the evaporator. Crystals produced throughout the testing were mainly sodium chloride. The results of this study indicated that the ZLD approach was effective in both producing freshwater and minimizing brine discharges. Copyright © 2015 Elsevier Ltd. All rights reserved.

Basal levels and GnRH-induced responses of peripheral testosterone and estrogen in Holstein bulls with poor semen quality.

PubMed

Devkota, Bhuminand; Takahashi, Ken-Ichi; Matsuzaki, Shigenori; Matsui, Motozumi; Miyamoto, Akio; Yamagishi, Norio; Osawa, Takeshi; Hashizume, Tsutomu; Izaike, Yoshiaki; Miyake, Yoh-Ichi

2011-06-01

The present study investigated the basal levels and GnRH-induced responses of peripheral testosterone and estrogen in Holstein bulls with poor semen quality. On the basis of semen parameters, bulls (n=5) having poor semen quality were selected as experimental bulls, and good semen quality bulls (n=4) were used as control bulls. Both groups were treated intramuscularly once with GnRH (250 µg of fertirelin acetate). Blood samples were collected at -1 day (d), -30 min and 0 h (treatment) followed by every 30 min for 5 h and 1, 3 and 5 d post-GnRH treatment (PGT), and LH, testosterone and estradiol-17β (E(2)) concentrations were measured. The pretreatment concentrations were used as basal levels. The percentage increments based on the 0-h levels were calculated per bull for each sampling time until 5 h PGT, and differences were compared between the experimental and control groups. The PGT concentrations of testosterone and basal and PGT concentrations of E(2) were significantly lower in the experimental group. The testosterone increment in the experimental group was delayed and significantly lower from 1 to 5 h PGT than those in the control group. It can be suggested that bulls with poor semen quality have delayed and lower GnRH-induced testosterone response and may also have lower estrogen levels.

Glucagon-like peptide-1 receptor agonists compared with basal insulins for the treatment of type 2 diabetes mellitus: a systematic review and meta-analysis.

PubMed

Singh, Sonal; Wright, Eugene E; Kwan, Anita Y M; Thompson, Juliette C; Syed, Iqra A; Korol, Ellen E; Waser, Nathalie A; Yu, Maria B; Juneja, Rattan

2017-02-01

Since 2005, several glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have been approved to treat people with type 2 diabetes. These agents are considered for use at the same point in the treatment paradigm as basal insulins. A comprehensive comparison of these drug classes, therefore, can help inform treatment decisions. This systematic review and meta-analysis assessed the clinical efficacy and safety of GLP-1 RAs compared with basal insulins. MEDLINE, EMBASE, CENTRAL and PubMed databases were searched. Randomized clinical trials (RCTs) of ≥16 weeks' duration comparing GLP-1 RAs vs basal insulins in adults with type 2 diabetes inadequately controlled with oral antihyperglycemic drugs were included. Data on the change from baseline to 26 weeks (±10 weeks) of treatment in hemoglobin A1c (HbA1c) and weight, as well as the proportion of patients experiencing hypoglycaemia, were extracted. Fixed-effect pairwise meta-analyses were conducted where data were available from ≥2 studies. Fifteen RCTs were identified and 11 were meta-analysed. The once-weekly GLP-1 RAs, exenatide long acting release (LAR) and dulaglutide, led to greater, statistically significant mean HbA1c reductions vs basal insulins (exenatide: -0.31% [95% confidence interval -0.42, -0.19], dulaglutide: -0.39% [-0.49, -0.29]) whilst once-daily liraglutide and twice-daily exenatide did not (liraglutide: 0.06% [-0.06, 0.18], exenatide: 0.01% [-0.11, 0.13]). Mean weight reduction was seen with all GLP-1 RAs while mean weight gain was seen with basal insulins. Interpretation of the analysis of hypoglycaemia was limited by inconsistent definitions and reporting. Because of the limited number of available studies sensitivity analyses to explore heterogeneity could not be conducted. Although weight reduction is seen with all GLP-1 RA's, only the once-weekly agents, exenatide LAR and dulaglutide, demonstrate significant HbA1c reductions when compared to basal insulins. © 2016 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Constraining Basal Conditions across the Amundsen Sea Embayment of West Antarctica using a Synthesis of the PASIN and HiCARS Radar Sounding Data

NASA Astrophysics Data System (ADS)

Hilger, A. M.; Schroeder, D. M.; Corr, H. F. J.; Blankenship, D. D.; Paden, J. D.

2017-12-01

Recent observational studies and models have shown that ocean forcing, bed topography, and basal conditions are major controls of the behavior of the Amundsen Sea Embayment of the West Antarctic Ice Sheet. This region contains Thwaites Glacier and Pine Island Glacier, the two most rapidly changing glaciers in Antarctica. Because they are adjacent, interactions between these two glaciers could potentially cause further destabilization as either glacier retreats. Accordingly, it is important to understand the basal conditions on the Thwaites-Pine Island boundary in order to accurately model the present and future behavior of these glaciers. Previous airborne geophysical surveys in this area have provided dense radar sounding coverage using multiple radar sounding systems, including the UTIG HiCARS system and the BAS PASIN system used in the 2004 AGASEA survey. Because the boundary region between Thwaites and Pine Island Glacier is at the respective boundaries of the UTIG and BAS surveys, accurate characterization of the basal conditions requires a synthesis of the data produced by the BAS and HiCARS systems. To this end, we present estimates of bed reflectivity spanning both glacier catchments. These estimates were produced using empirically determined attenuation rates. To improve the consistency of these attenuation rates, we fit across a two-dimensional area, rather than a one-dimensional line as in previous work. These estimates also include cross-calibration to account for the radar sounding systems' differing power and center frequency. This will provide the first cross-survey map of basal reflectivity spanning the entire Amundsen Sea Embayment.

Low plasma magnesium is associated with impaired brain metabolism in neonates with hypoxic-ischaemic encephalopathy.

PubMed

Chakkarapani, Elavazhagan; Chau, Vann; Poskitt, Kenneth J; Synnes, Anne; Kwan, Eddie; Roland, Elke; Miller, Steven P

2016-09-01

To determine the association between lowest plasma magnesium concentration and brain metabolism, and whether magnetic resonance imaging brain injury patterns moderated the association in hypoxic-ischemic encephalopathy. In 131 early (day-of-life 3) and 65 late (day-of-life 10) scans of term encephalopathic infants born between 2004 and 2012, we examined the association of lowest plasma magnesium (until day-of-life 3) on basal ganglia and white matter peak metabolite ratios on magnetic resonance spectroscopy independent of covariates, stratified by the predominant patterns of injury (normal, basal nuclei/total, watershed, multifocal) using multiple linear regression. Lowest plasma magnesium was associated with lower white matter N-acetyl-aspartate/choline in the multifocal pattern on early scan (regression-coefficient, β: 0.13; 95% CI: 0.04, 0.22) and in the basal nuclei/total pattern on late scan (β: 0.08; 95% CI: 0.02, 0.15), and was negatively associated with basal ganglia lactate/N-acetyl-aspartate (β: -0.16; 95% CI: -0.05, -0.28) and lactate/choline (β: -0.1; 95% CI: -0.03, -0.17) ratio in the basal nuclei/total pattern on late scan independent of hypomagnesaemia correction, cooling and postmenstrual age at scan. Lowest plasma magnesium was not associated with metabolite ratios in other brain injury patterns. In infants with hypoxic-ischaemic encephalopathy, predominant patterns of brain injury moderated the association between lowest plasma magnesium in the first three days of life and impaired brain metabolism. ©2016 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

Noble gas signatures in the Island of Maui, Hawaii: Characterizing groundwater sources in fractured systems

USGS Publications Warehouse

Niu, Yi; Castro, M. Clara; Hall, Chris M.; Gingerich, Stephen B.; Scholl, Martha A.; Warrier, Rohit B.

2017-01-01

Uneven distribution of rainfall and freshwater scarcity in populated areas in the Island of Maui, Hawaii, renders water resources management a challenge in this complex and ill-defined hydrological system. A previous study in the Galapagos Islands suggests that noble gas temperatures (NGTs) record seasonality in that fractured, rapid infiltration groundwater system rather than the commonly observed mean annual air temperature (MAAT) in sedimentary systems where infiltration is slower thus, providing information on recharge sources and potential flow paths. Here we report noble gas results from the basal aquifer, springs, and rainwater in Maui to explore the potential for noble gases in characterizing this type of complex fractured hydrologic systems. Most samples display a mass-dependent depletion pattern with respect to surface conditions consistent with previous observations both in the Galapagos Islands and Michigan rainwater. Basal aquifer and rainwater noble gas patterns are similar and suggest direct, fast recharge from precipitation to the basal aquifer. In contrast, multiple springs, representative of perched aquifers, display highly variable noble gas concentrations suggesting recharge from a variety of sources. The distinct noble gas patterns for the basal aquifer and springs suggest that basal and perched aquifers are separate entities. Maui rainwater displays high apparent NGTs, incompatible with surface conditions, pointing either to an origin at high altitudes with the presence of ice or an ice-like source of undetermined origin. Overall, noble gas signatures in Maui reflect the source of recharge rather than the expected altitude/temperature relationship commonly observed in sedimentary systems.

Untangling Basal Ganglia Network Dynamics and Function: Role of Dopamine Depletion and Inhibition Investigated in a Spiking Network Model

PubMed Central

2016-01-01

Abstract The basal ganglia are a crucial brain system for behavioral selection, and their function is disturbed in Parkinson’s disease (PD), where neurons exhibit inappropriate synchronization and oscillations. We present a spiking neural model of basal ganglia including plausible details on synaptic dynamics, connectivity patterns, neuron behavior, and dopamine effects. Recordings of neuronal activity in the subthalamic nucleus and Type A (TA; arkypallidal) and Type I (TI; prototypical) neurons in globus pallidus externa were used to validate the model. Simulation experiments predict that both local inhibition in striatum and the existence of an indirect pathway are important for basal ganglia to function properly over a large range of cortical drives. The dopamine depletion–induced increase of AMPA efficacy in corticostriatal synapses to medium spiny neurons (MSNs) with dopamine receptor D2 synapses (CTX-MSN D2) and the reduction of MSN lateral connectivity (MSN–MSN) were found to contribute significantly to the enhanced synchrony and oscillations seen in PD. Additionally, reversing the dopamine depletion–induced changes to CTX–MSN D1, CTX–MSN D2, TA–MSN, and MSN–MSN couplings could improve or restore basal ganglia action selection ability. In summary, we found multiple changes of parameters for synaptic efficacy and neural excitability that could improve action selection ability and at the same time reduce oscillations. Identification of such targets could potentially generate ideas for treatments of PD and increase our understanding of the relation between network dynamics and network function. PMID:28101525

The role of bentonite binders in single or concomitant mycotoxin contamination of chicken diets.

PubMed

Pappas, A C; Tsiplakou, E; Tsitsigiannis, D I; Georgiadou, M; Iliadi, M K; Sotirakoglou, K; Zervas, G

2016-08-01

Concomitant presence of mycotoxins is more likely to appear than a single mycotoxicosis since many mycotoxigenic fungi grow and produce their toxic metabolites under similar conditions. The present study was designed to evaluate the efficacy of 4 mycotoxin binders to protect meat-type chickens against single and concomitant administration in the feed of two mycotoxins, namely aflatoxin B1 (AFB1) and ochratoxin A (OTA) both at concentration of 0.1 mg/kg. A total of 440 as hatched, d-old, Ross 308 broilers were reared for 42 d. There were 11 dietary treatments. Chickens were fed on either an uncontaminated basal diet, basal diet and AFB1, basal with concomitant presence of AFB1 and OTA, basal diet and three binders A, B and C (1%) with or without AFB1 or basal diet and binder D (0.5%) with or without concomitant presence of AFB1 and OTA. Performance, carcass yield and several biochemical parameters were examined. Mycotoxin concentration in liver and breast muscle samples was determined. Broiler performance under concomitant mycotoxin contamination was poorer than that under single mycotoxicosis. Mycotoxin presence increased relative heart weight compared to that of broilers fed on uncontaminated diets. Only OTA and not AFB1 was detected and only in the liver. OTA concentration was four-fold lower in broilers fed on a diet with binder compared to those fed on contaminated diets without binder. In conclusion, the study revealed that binder composition and presence or not of multiple toxins may be important factors for optimum broiler performance under mycotoxicosis.

Abnormal early diastolic intraventricular flow 'kinetic energy index' assessed by vector flow mapping in patients with elevated filling pressure.

PubMed

Nogami, Yoshie; Ishizu, Tomoko; Atsumi, Akiko; Yamamoto, Masayoshi; Kawamura, Ryo; Seo, Yoshihiro; Aonuma, Kazutaka

2013-03-01

Recently developed vector flow mapping (VFM) enables evaluation of local flow dynamics without angle dependency. This study used VFM to evaluate quantitatively the index of intraventricular haemodynamic kinetic energy in patients with left ventricular (LV) diastolic dysfunction and to compare those with normal subjects. We studied 25 patients with estimated high left atrial (LA) pressure (pseudonormal: PN group) and 36 normal subjects (control group). Left ventricle was divided into basal, mid, and apical segments. Intraventricular haemodynamic energy was evaluated in the dimension of speed, and it was defined as the kinetic energy index. We calculated this index and created time-energy index curves. The time interval from electrocardiogram (ECG) R wave to peak index was measured, and time differences of the peak index between basal and other segments were defined as ΔT-mid and ΔT-apex. In both groups, early diastolic peak kinetic energy index in mid and apical segments was significantly lower than that in the basal segment. Time to peak index did not differ in apex, mid, and basal segments in the control group but was significantly longer in the apex than that in the basal segment in the PN group. ΔT-mid and ΔT-apex were significantly larger in the PN group than the control group. Multiple regression analysis showed sphericity index, E/E' to be significant independent variables determining ΔT apex. Retarded apical kinetic energy fluid dynamics were detected using VFM and were closely associated with LV spherical remodelling in patients with high LA pressure.

Delayed diagnosis of Gorlin syndrome: Learning from mistakes!

PubMed

Ramanathan, Subramaniyan; Kumar, Devendra; Al Heidous, Mahmoud; Palaniappan, Yegu

2015-01-01

Gorlin syndrome (GS) is a rare inherited multisystem disorder with predisposition to basal cell carcinomas and various other neoplasms. Characteristic features include falx calcification, multiple odontogenic keratocysts (OKCs), early onset medulloblastoma, craniofacial and skeletal malformations, cardiac and ovarian fibroma. We present a case of GS in a 9-year-old girl with recurrent dental infections which was overlooked for 8 years. Diagnosis was finally suggested by the incidental detection of multiple OKCs and ovarian fibromas on follow-up magnetic resonance imaging performed for surveillance of previous operated brain tumor.

Prostanoids and free radicals in Cl4C-induced hepatotoxicity in rats: effect of astilbin.

PubMed

Closa, D; Torres, M; Hotter, G; Bioque, G; León, O S; Gelpí, E; Rósello-Catafau, J

1997-04-01

A beneficial effect of flavonoids in Cl(4)C-induced hepatoxicity in rats has been reported. In this communication we have evaluated the protective effect of astilbin, an active flavonoid isolated from a crude extract of Hymenaea martiana, as well as its action on liver arachidonate metabolism in Cl(4)C-treated rats. The following groups of rats were studied: Group I = controls; Group II = Astilbine-treated animals (40 mg/Kg); Group III = Cl(4)C-treated at 1 ml/kg; Group IV = Astilbine + ClC4 and Group V = Vitamine E (50 mg/Kg) + Cl(4)C-treated animals. Histological findings, superoxide dismutase activity, lipoperoxides and prostanoid profiling studies revealed that the hepatoprotective effect of astilbine was higher than that of vitamin E. Astilbine was capable to restore lipoperoxides and tissue prostanoids to basal values.

Multiple non-syndromic odontogenic keratocysts in three siblings

PubMed Central

Nirwan, Amit; Wanjari, Sangeeta Panjab; Saikhedkar, Rashmi; Karun, Vinayak

2013-01-01

Occurrence of multiple cysts (MC) involving the jaw is rare. When multiple, it is usually associated with a syndrome. Occurrence of MC without syndromic association is extremely rare. Multiple odontogenic cysts mostly could be odontogenic keratocysts or dentigerous cysts. Odontogenic keratocyst shows involvement of mandible over maxilla, with peak incidence in second and third decade and it is exceedingly rare before 10 years of age. However multiple odontogenic keratocysts found in children are often reflective of nevoid basal cell carcinoma syndrome. Here is a case report which documents multiple jaw cysts involving both the jaws, in three siblings of ages 10, 13 and 17 years with negative parental history. All three reported cases were free of any systemic involvement. As odontogenic keratocyst spreads through bone marrow, destruction is more before any clinical manifestation. Therefore, early detection and intervention are essential in preventing extensive destruction. PMID:23505078

[Adherence of type 2 diabetes patients on insulin analogues application: missed dose, time imprecision and dose reduction. The results of GAPP2TM(Global Attitudes of Physicians and Patient) survey in the Czech Republic].

PubMed

Prázný, Martin

2014-11-01

Irregular insulin dose is one of the main problems associated with insulin therapy in patients with type 2 diabetes; its extent is not known precisely. The aim of survey conducted in the Czech Republic in the international project GAPP2 - Global Attitudes of Patients and Physicians was to determine the incidence and the impact of irregular use of basal insulin analogues in patients with type 2 diabetes, to point out the reasons for these irregularities and to focus on how physicians discuss irregular application of insulin with patients. The project GAPP2 is an international cross-sectional study performed on-line via the Internet using a questionnaire filled by diabetic patients treated with insulin analogues and physicians who treat these patients. The survey was conducted in two steps in 17 countries; the first step included 6 countries and was completed in the beginning of 2012, the second step involved 11 other countries including the Czech Republic with termination in 2014. The survey was designed to obtain the views of patients and physicians on certain aspects of insulin treatment and persistent issues in this field in the real daily practice. Special focus was on the incidence and management of hypoglycaemia as well as on irregularities of insulin application. In the part dedicated to adherence to basal insulin application were observed three types of irregular insulin therapy: missed dose, time imprecision of dose (± 2 hours vs. the prescribed time) and dose reduction in all cases in the past 30 days before completing the questionnaire. In addition, it was investigated the attitude and relation of patients to these issues. The results have shown that irregular insulin dose in the Czech Republic is less frequent than in other countries involved in the GAPP2 research. Nevertheless, approximately one fifth of diabetic patients using insulin analogues in basal-bolus or only basal therapy regimen is related to this problem. The last irregular insulin application was due to missed dose in 13% of cases, time imprecision in 23% and reduction of dose in 61% of cases. The most commonly reported reason was risk reduction of hypoglycaemia and the recommendations of health professionals. Fear of missed dose is present in 40% Czech patients and 35% would feel guilty if their insulin dose is missed (up to 47% in patients with intensified insulin regimen). Only 60% patients are aware of negative impact on their long-term health after missed dose of basal insulin. Questioned doctors have suspected that the patients report lower number of missed doses during regular medical check because one third of patients doesn´t admit missed dose. However, this fact conceded only 11% of patients on basal insulin and 15% of patients on intensified insulin therapy. Quarter of prescribing doctors admit that they usually don´t discuss with patients irregularities in basal insulin treatment. Although, type 2 diabetes patients in the Czech Republic follow prescribed basal insulin therapy scheme more often than patients in other countries participating in the survey GAPP2 , missed dose, time imprecision and reduction of dose is quite common and it deserves more attention from medical side during regular medical check together with appropriate education of patients.

Propagation of Southern Red Oak and Water Oak by Rooted Cuttings

Treesearch

Horace J. Duncan; Fred R. Matthews

1969-01-01

Southern red oak and water oak, needed in studies of fusiform rust of southern pines, were propagated from cuttings of rooted stump sprouts and mature tree branches placed in outdoor propagation beds in June. Root strike and root development were increased when cuttings with basal wounds were treated with both the hormone IBA and the fungicide folpet. Cuttings from...

Potential fire behavior is reduced following forest restoration treatments

Treesearch

Peter Z. Fule; Charles McHugh; Thomas A. Heinlein; W. Wallace Covington

2001-01-01

Potential fire behavior was compared under dry, windy weather conditions in 12 ponderosa pine stands treated with alternative thinning prescriptions in the wildland/urban interface of Flagstaff, Arizona. Prior to thinning, stands averaged 474 trees/ acre, 158 ft2/acre basal area, crown bulk density 0.0045 lb/ft3, and crown base height 19.2 ft. Three thinning treatments...

Influence of residual stand density on regeneration of northern hardwoods

Treesearch

W. B. Leak; Dale S. Solomon

1975-01-01

In a study of hardwood regeneration, experimental plots were treated to produce residual densities of 40, 60, 80, and 100 square feet of basal area per acre with 30, 45, and 60 percent sawtimber. After 9 years, numbers of stems and percent stocking were estimated for each species and they were rated for reproductive potential under different residual densities. Data...

Sprouting of thinned hybrid poplars on bituminous strip-mine spoils in Pennsylvania

Treesearch

Walter H. Davidson; Grant Davis

1972-01-01

Various thinning techniques were applied to 5-year old hybrid poplar stands on bituminous strip-mine spoils. Basal and stump sprays of 2, 4, 5-T in diesel oil were effective for killing the trees. There was no evidence that chemical treatments affected adjacent trees. Where trees were cut and stumps were not chemically treated, all clones sprouted prolifically....

Screening conventional fungicides...control of blister rust on sugar pine in California

Treesearch

Clarence R. Quick

1967-01-01

After 5 years, 4 of 14 fungicides tested showed varying pr of development into satisfactory direct control of blister rust. Little promise of systemic control was found. Trees treated were second-growth sugar pine in a mixed conifer forest in eastern Shasta County, California, where blister rust has been intensifying for many years. Most trees received basal-stem...

Fertilization increases diameter growth of birch-beech-maple trees in New Hampshire

Treesearch

L. O. Safford

1973-01-01

In a 60-year-old northern hardwood stand treated with lime plus NPK fertilizer, the following increases in average basal area growth rate over untreated trees were observed: sugar maple 128 percent, paper birch 69 percent, yellow birch 51 percent, and beech 20 percent. Magnitude of response was inversely related to relative growth rate of the species. Growth rate...

Promoting effects of potassium dibasic phosphate on early-stage renal carcinogenesis in unilaterally nephrectomized rats treated with N-ethyl-N-hydroxyethylnitrosamine.

PubMed

Hiasa, Y; Konishi, N; Nakaoka, S; Nakamura, T; Nishii, K; Ohshima, M

1992-07-01

The effects of potassium dibasic phosphate (PDP), potassium aluminum sulfate (PAS) and copper sulfate (CS) on early-stage renal carcinogenesis were investigated in unilaterally nephrectomized male Wistar rats after N-ethyl-N-hydroxyethylnitrosamine (EHEN) administration. After feeding 1,000 ppm EHEN, or basal diet for 2 weeks and removal of the left kidney at week 3, male Wistar rats were divided into 8 groups of 20 rats each. These groups received the following dietary treatments: 50,000 ppm PDP, 50,000 ppm PAS, 5,000 ppm CS or basal diet, respectively, for 18 weeks from weeks 3 to 20. The average numbers of adenomatous hyperplasias counted as preneoplastic lesions in the EHEN with 50,000 ppm PDP group were significantly higher than in the EHEN alone group or the EHEN followed by 50,000 ppm PAS or 5,000 ppm CS group. The treatment with 50,000 ppm PDP induced renal calcification and promoted the development of preneoplastic lesions in unilaterally nephrectomized rats treated with EHEN, but that with 50,000 ppm PAS or 5,000 ppm CS did not.

Promoting Effects of Potassium Dibasic Phosphate on Early‐stage Renal Carcinogenesis in Unilaterally Nephrectomized Rats Treated with N‐Ethyl‐N‐hydroxyethylnitrosamine

PubMed Central

Konishi, Noboru; Nakaoka, Shingo; Nakamura, Toshimitsu; Nishii, Kiyoji; Ohshima, Masato

1992-01-01

The effects of potassium dibasic phosphate (PDP), potassium aluminum sulfate (PAS) and copper sulfate (CS) on early‐stage renal carcinogenesis were investigated in unilaterally nephrectomized male Wistar rats after N‐ethyl‐N‐hydroxyethylnitrosamine (EHEN) administration. After feeding 1,000 ppm EHEN, or basal diet for 2 weeks and removal of the left kidney at week 3, male Wistar rats were divided into 8 groups of 20 rats each. These groups received the following dietary treatments: 50,000 ppm PDP, 50,000 ppm PAS, 5,000 ppm CS or basal diet, respectively, for 18 weeks from weeks 3 to 20. The average numbers of adenomatous hyperplasias counted as preneoplastic lesions in the EHEN with 50,000 ppm PDP group were significantly higher than in the EHEN alone group or the EHEN followed by 50,000 ppm PAS or 5,000 ppm CS group. The treatment with 50,000 ppm PDP induced renal calcification and promoted the development of preneoplastic lesions in unilaterally nephrectomized rats treated with EHEN, but that with 50,000 ppm PAS or 5,000 ppm CS did not. PMID:1517146

Cerebrolysin modulates pronerve growth factor/nerve growth factor ratio and ameliorates the cholinergic deficit in a transgenic model of Alzheimer's disease.

PubMed

Ubhi, Kiren; Rockenstein, Edward; Vazquez-Roque, Ruben; Mante, Michael; Inglis, Chandra; Patrick, Christina; Adame, Anthony; Fahnestock, Margaret; Doppler, Edith; Novak, Philip; Moessler, Herbert; Masliah, Eliezer

2013-02-01

Alzheimer's disease (AD) is characterized by degeneration of neocortex, limbic system, and basal forebrain, accompanied by accumulation of amyloid-β and tangle formation. Cerebrolysin (CBL), a peptide mixture with neurotrophic-like effects, is reported to improve cognition and activities of daily living in patients with AD. Likewise, CBL reduces synaptic and behavioral deficits in transgenic (tg) mice overexpressing the human amyloid precursor protein (hAPP). The neuroprotective effects of CBL may involve multiple mechanisms, including signaling regulation, control of APP metabolism, and expression of neurotrophic factors. We investigate the effects of CBL in the hAPP tg model of AD on levels of neurotrophic factors, including pro-nerve growth factor (NGF), NGF, brain-derived neurotrophic factor (BDNF), neurotropin (NT)-3, NT4, and ciliary neurotrophic factor (CNTF). Immunoblot analysis demonstrated that levels of pro-NGF were increased in saline-treated hAPP tg mice. In contrast, CBL-treated hAPP tg mice showed levels of pro-NGF comparable to control and increased levels of mature NGF. Consistently with these results, immunohistochemical analysis demonstrated increased NGF immunoreactivity in the hippocampus of CBL-treated hAPP tg mice. Protein levels of other neurotrophic factors, including BDNF, NT3, NT4, and CNTF, were unchanged. mRNA levels of NGF and other neurotrophins were also unchanged. Analysis of neurotrophin receptors showed preservation of the levels of TrKA and p75(NTR) immunoreactivity per cell in the nucleus basalis. Cholinergic cells in the nucleus basalis were reduced in the saline-treated hAPP tg mice, and treatment with CBL reduced these cholinergic deficits. These results suggest that the neurotrophic effects of CBL might involve modulation of the pro-NGF/NGF balance and a concomitant protection of cholinergic neurons. Copyright © 2012 Wiley Periodicals, Inc.

Glucagon-like peptide-1 exerts anti-inflammatory effects on mouse colon smooth muscle cells through the cyclic adenosine monophosphate/nuclear factor-κB pathway in vitro.

PubMed

Al-Dwairi, Ahmed; Alqudah, Tamara E; Al-Shboul, Othman; Alqudah, Mohammad; Mustafa, Ayman G; Alfaqih, Mahmoud A

2018-01-01

Intestinal smooth muscle cells (SMCs) undergo substantial morphological, phenotypic, and contractile changes during inflammatory bowel disease (IBD). SMCs act as a source and target for different inflammatory mediators, however their role in IBD pathogenesis is usually overlooked. Glucagon-like peptide-1 (GLP-1) is an incretin hormone reported to exert multiple anti-inflammatory effects in different tissues including the gastrointestinal tract through various mechanisms. The aim of this research is to explore the effect of GLP-1 analog exendin-4 on the expression and secretion of inflammatory markers from mouse colon smooth muscle cells (CSMCs) after stimulation with lipopolysaccharide (LPS). Freshly isolated CSMCs from male BALB/c mice were cultured in DMEM and treated with vehicle, LPS (1 μg/mL), LPS+exendin-4 (50 nM), or LPS+exendin-4 (100 nM) for 24 h. Expression of inflammatory cytokines was then evaluated by antibody array membrane. CSMCs showed basal expression of several cytokines which was enhanced with the induction of inflammation by LPS. However, exendin-4 (50 and 100 nM) significantly ( p <0.05) reduced the expression of multiple cytokines including tumor necrosis factor-α (TNF-α), interleukin-1α (IL-1α), T cell activation gene-3 (TCA-3), stromal cell-derived factor-1 (SDF-1), and macrophage colony stimulating factor (M-CSF). To confirm these results, expression of these cytokines was further assessed by enzyme-linked immunosorbent assay and real-time polymerase chain reaction and similar results were also observed. Moreover, secretion of TNF-α and IL1-α into the conditioned media was significantly downregulated by exendin-4 when compared to LPS-treated cells. Furthermore, LPS increased NF-κB phosphorylation, while exendin-4 significantly reduced levels of NF-κB phosphorylation. These data indicate that GLP-1 analogs can exert significant anti-inflammatory effects on CSMCs and can potentially be used as an adjunct treatment for inflammatory bowel conditions.

Re-irradiation of metastatic disease in the neck from xeroderma pigmentosum.

PubMed

Wei, C C; Sanfilippo, N J; Myssiorek, D

2010-06-01

Xeroderma pigmentosum, an autosomal recessive disease that occurs with a frequency of 1:250,000, is caused by a genetic defect in nucleotide excision repair enzymes. Mutation of these enzymes leads to the development of multiple basal cell and squamous cell carcinomas. We present a case of xeroderma pigmentosum in a patient with cervical and intraparotid metastatic disease from recurrent cutaneous squamous cell carcinomas of the face and scalp, treated with neck dissection and re-irradiation. With the illustrative case report, we include a literature review of diagnosis, prognostic factors, and treatment, with emphasis on surgical and radiation treatment of cervical metastatic disease from recurrent skin carcinomas. A xeroderma pigmentosum patient presented to our clinic with a 2-cm right submental and 1-cm right infra-auricular mass after resection of multiple squamous cell carcinomas of the scalp and face, and external-beam radiation therapy to the right face and neck. Fine-needle aspiration biopsy of the submental mass revealed poorly differentiated squamous cell carcinoma. The patient was brought to the operating room for a right modified radical neck dissection and excision of the right submental and intraparotid mass. Surgical pathology revealed 3 level ia and supraclavicular lymph nodes that were positive for metastatic squamous cell carcinoma. Re-irradiation to the entire right hemi-neck and left submandibular nodal region was performed using opposed oblique portals for the upper neck and a low anterior en face hemi-neck portal. The left parotid region was also included in the re-irradiation volume. Treatment was completed without delayed complications or recurrences to date. To our knowledge, this is the first case report in the literature of a patient with xeroderma pigmentosum who subsequently developed metastatic disease from recurrent cutaneous squamous cell carcinoma. Because of the rarity of xeroderma pigmentosum, this case report is also the first to describe re-irradiation to treat cervical and intraparotid metastatic disease in a xeroderma pigmentosum patient.

Rapid in vitro propagation system through shoot tip cultures of Vitex trifolia L.-an important multipurpose plant of the Pacific traditional Medicine.

PubMed

Ahmed, Rafique; Anis, Mohammad

2014-07-01

A rapid and efficient plant propagation system through shoot tip explants was established in Vitex trifolia L., a medicinally important plant belonging to the family Verbenaceae. Multiple shoots were induced directly on Murashige and Skoog (MS) medium consisting of different cytokinins, 6-benzyladenine (BA), kinetin (Kin) and 2-isopentenyl adenine (2-iP), BA at an optimal concentration of 5.0 μM was most effective in inducing multiple shoots where 90 % explants responded with an average shoot number (4.4±0.1) and shoot length (2.0±0.1 cm) after 6 weeks of culture. Inclusion of NAA in the culture medium along with the optimum concentration of BA promoted a higher rate of shoot multiplication and length of the shoot, where 19.2±0.3 well-grown healthy shoots with an average shoot length of 4.4±0.1 cm were obtained on completion of 12 weeks culture period. Ex vitro rooting was achieved best directly in soilrite when basal portion of the shoots were treated with 500 μM indole-3-butyric acid for 15 min which was the most effective in inducing roots, as 95 % of the microshoots produced roots. Plantlets went through a hardening phase in a controlled plant growth chamber, prior to ex-vitro transfer. Micropropagated plants grew well, attained maturity and flowered with 92 % survival rate. The results of this study provide the first report on in vitro plant regeneration of Vitex trifolia L. using shoot tip explants.

Bag-of-features based medical image retrieval via multiple assignment and visual words weighting.

PubMed

Wang, Jingyan; Li, Yongping; Zhang, Ying; Wang, Chao; Xie, Honglan; Chen, Guoling; Gao, Xin

2011-11-01

Bag-of-features based approaches have become prominent for image retrieval and image classification tasks in the past decade. Such methods represent an image as a collection of local features, such as image patches and key points with scale invariant feature transform (SIFT) descriptors. To improve the bag-of-features methods, we first model the assignments of local descriptors as contribution functions, and then propose a novel multiple assignment strategy. Assuming the local features can be reconstructed by their neighboring visual words in a vocabulary, reconstruction weights can be solved by quadratic programming. The weights are then used to build contribution functions, resulting in a novel assignment method, called quadratic programming (QP) assignment. We further propose a novel visual word weighting method. The discriminative power of each visual word is analyzed by the sub-similarity function in the bin that corresponds to the visual word. Each sub-similarity function is then treated as a weak classifier. A strong classifier is learned by boosting methods that combine those weak classifiers. The weighting factors of the visual words are learned accordingly. We evaluate the proposed methods on medical image retrieval tasks. The methods are tested on three well-known data sets, i.e., the ImageCLEFmed data set, the 304 CT Set, and the basal-cell carcinoma image set. Experimental results demonstrate that the proposed QP assignment outperforms the traditional nearest neighbor assignment, the multiple assignment, and the soft assignment, whereas the proposed boosting based weighting strategy outperforms the state-of-the-art weighting methods, such as the term frequency weights and the term frequency-inverse document frequency weights.

12 CFR 204.133 - Multiple savings deposits treated as a transaction account.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 12 Banks and Banking 2 2012-01-01 2012-01-01 false Multiple savings deposits treated as a transaction account. 204.133 Section 204.133 Banks and Banking FEDERAL RESERVE SYSTEM BOARD OF GOVERNORS OF...) Interpretations § 204.133 Multiple savings deposits treated as a transaction account. (a) Authority. Under section...

12 CFR 204.133 - Multiple savings deposits treated as a transaction account.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 12 Banks and Banking 2 2014-01-01 2014-01-01 false Multiple savings deposits treated as a transaction account. 204.133 Section 204.133 Banks and Banking FEDERAL RESERVE SYSTEM BOARD OF GOVERNORS OF...) Interpretations § 204.133 Multiple savings deposits treated as a transaction account. (a) Authority. Under section...

Impact of a pain protocol including hypnosis in major burns.

PubMed

Berger, Mette M; Davadant, Maryse; Marin, Christian; Wasserfallen, Jean-Blaise; Pinget, Christophe; Maravic, Philippe; Koch, Nathalie; Raffoul, Wassim; Chiolero, René L

2010-08-01

Pain is a major issue after burns even when large doses of opioids are prescribed. The study focused on the impact of a pain protocol using hypnosis on pain intensity, anxiety, clinical course, and costs. All patients admitted to the ICU, aged >18 years, with an ICU stay >24h, accepting to try hypnosis, and treated according to standardized pain protocol were included. Pain was scaled on the Visual Analog Scale (VAS) (mean of daily multiple recordings), and basal and procedural opioid doses were recorded. Clinical outcome and economical data were retrieved from hospital charts and information system, respectively. Treated patients were matched with controls for sex, age, and the burned surface area. Forty patients were admitted from 2006 to 2007: 17 met exclusion criteria, leaving 23 patients, who were matched with 23 historical controls. Altogether patients were 36+/-14 years old and burned 27+/-15%BSA. The first hypnosis session was performed after a median of 9 days. The protocol resulted in the early delivery of higher opioid doses/24h (p<0.0001) followed by a later reduction with lower pain scores (p<0.0001), less procedural related anxiety, less procedures under anaesthesia, reduced total grafting requirements (p=0.014), and lower hospital costs per patient. A pain protocol including hypnosis reduced pain intensity, improved opioid efficiency, reduced anxiety, improved wound outcome while reducing costs. The protocol guided use of opioids improved patient care without side effects, while hypnosis had significant psychological benefits.

Brain-derived neurotrophic factor levels under chronic natalizumab treatment in multiple sclerosis. A preliminary report.

PubMed

Văcăraş, Vitalie; Major, Zoltán Zsigmond; Buzoianu, Anca Dana

Our main purpose was to investigate if the chronic treatment with the disease-modifying drug natalizumab shows quantifiable effect on BDNF levels in multiple sclerosis patients. BDNF plasma concentration was evaluated using enzyme-linked immunosorbent assay in healthy individuals, not treated multiple sclerosis patients and patients treated with natalizumab. Multiple sclerosis patients have a significantly lower amount of peripheral BDNF than healthy individuals. Patients treated with natalizumab have significantly higher BDNF levels than not treated patients. Chronic natalizumab treatment is associated with significantly increased plasma BDNF concentration in multiple sclerosis. Copyright © 2017 Polish Neurological Society. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Insights into Parkinson's disease from computational models of the basal ganglia.

PubMed

Humphries, Mark D; Obeso, Jose Angel; Dreyer, Jakob Kisbye

2018-04-17

Movement disorders arise from the complex interplay of multiple changes to neural circuits. Successful treatments for these disorders could interact with these complex changes in myriad ways, and as a consequence their mechanisms of action and their amelioration of symptoms are incompletely understood. Using Parkinson's disease as a case study, we review here how computational models are a crucial tool for taming this complexity, across causative mechanisms, consequent neural dynamics and treatments. For mechanisms, we review models that capture the effects of losing dopamine on basal ganglia function; for dynamics, we discuss models that have transformed our understanding of how beta-band (15-30 Hz) oscillations arise in the parkinsonian basal ganglia. For treatments, we touch on the breadth of computational modelling work trying to understand the therapeutic actions of deep brain stimulation. Collectively, models from across all levels of description are providing a compelling account of the causes, symptoms and treatments for Parkinson's disease. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Distinct roles of dopamine and subthalamic nucleus in learning and probabilistic decision making.

PubMed

Coulthard, Elizabeth J; Bogacz, Rafal; Javed, Shazia; Mooney, Lucy K; Murphy, Gillian; Keeley, Sophie; Whone, Alan L

2012-12-01

Even simple behaviour requires us to make decisions based on combining multiple pieces of learned and new information. Making such decisions requires both learning the optimal response to each given stimulus as well as combining probabilistic information from multiple stimuli before selecting a response. Computational theories of decision making predict that learning individual stimulus-response associations and rapid combination of information from multiple stimuli are dependent on different components of basal ganglia circuitry. In particular, learning and retention of memory, required for optimal response choice, are significantly reliant on dopamine, whereas integrating information probabilistically is critically dependent upon functioning of the glutamatergic subthalamic nucleus (computing the 'normalization term' in Bayes' theorem). Here, we test these theories by investigating 22 patients with Parkinson's disease either treated with deep brain stimulation to the subthalamic nucleus and dopaminergic therapy or managed with dopaminergic therapy alone. We use computerized tasks that probe three cognitive functions-information acquisition (learning), memory over a delay and information integration when multiple pieces of sequentially presented information have to be combined. Patients performed the tasks ON or OFF deep brain stimulation and/or ON or OFF dopaminergic therapy. Consistent with the computational theories, we show that stopping dopaminergic therapy impairs memory for probabilistic information over a delay, whereas deep brain stimulation to the region of the subthalamic nucleus disrupts decision making when multiple pieces of acquired information must be combined. Furthermore, we found that when participants needed to update their decision on the basis of the last piece of information presented in the decision-making task, patients with deep brain stimulation of the subthalamic nucleus region did not slow down appropriately to revise their plan, a pattern of behaviour that mirrors the impulsivity described clinically in some patients with subthalamic nucleus deep brain stimulation. Thus, we demonstrate distinct mechanisms for two important facets of human decision making: first, a role for dopamine in memory consolidation, and second, the critical importance of the subthalamic nucleus in successful decision making when multiple pieces of information must be combined.

Multiple garlic (Allium sativum L.) microRNAs regulate the immunity against the basal rot fungus Fusarium oxysporum f. sp. Cepae.

PubMed

Chand, Subodh Kumar; Nanda, Satyabrata; Mishra, Rukmini; Joshi, Raj Kumar

2017-04-01

The basal plate rot fungus, Fusarium oxysporum f. sp. cepae (FOC), is the most devastating pathogen posing a serious threat to garlic (Allium sativum L.) production worldwide. MicroRNAs (miRNAs) are key modulators of gene expression related to development and defense responses in eukaryotes. However, the miRNA species associated with garlic immunity against FOC are yet to be explored. In the present study, a small RNA library developed from FOC infected resistant garlic line was sequenced to identify immune responsive miRNAs. Forty-five miRNAs representing 39 conserved and six novel sequences responsive to FOC were detected. qRT-PCR analyses further classified them into three classes based on their expression patterns in susceptible line CBT-As11 and in the resistant line CBT-As153. North-blot analyses of six selective miRNAs confirmed the qRT-PCR results. Expression studies on a selective set of target genes revealed a negative correlation with the complementary miRNAs. Furthermore, transgenic garlic plant overexpresing miR164a, miR168a and miR393 showed enhanced resistance to FOC, as revealed by decreased fungal growth and up-regulated expression of defense-responsive genes. These results indicate that multiple miRNAs are involved in garlic immunity against FOC and that the overexpression of miR164a, miR168a and miR393 can augment garlic resistance to Fusarium basal rot infection. Copyright © 2017 Elsevier B.V. All rights reserved.

Hepatocyte Polarity

PubMed Central

Treyer, Aleksandr; Müsch, Anne

2013-01-01

Hepatocytes, like other epithelia, are situated at the interface between the organism’s exterior and the underlying internal milieu and organize the vectorial exchange of macromolecules between these two spaces. To mediate this function, epithelial cells, including hepatocytes, are polarized with distinct luminal domains that are separated by tight junctions from lateral domains engaged in cell-cell adhesion and from basal domains that interact with the underlying extracellular matrix. Despite these universal principles, hepatocytes distinguish themselves from other nonstriated epithelia by their multipolar organization. Each hepatocyte participates in multiple, narrow lumina, the bile canaliculi, and has multiple basal surfaces that face the endothelial lining. Hepatocytes also differ in the mechanism of luminal protein trafficking from other epithelia studied. They lack polarized protein secretion to the luminal domain and target single-spanning and glycosylphosphatidylinositol-anchored bile canalicular membrane proteins via transcytosis from the basolateral domain. We compare this unique hepatic polarity phenotype with that of the more common columnar epithelial organization and review our current knowledge of the signaling mechanisms and the organization of polarized protein trafficking that govern the establishment and maintenance of hepatic polarity. The serine/threonine kinase LKB1, which is activated by the bile acid taurocholate and, in turn, activates adenosine monophosphate kinase-related kinases including AMPK1/2 and Par1 paralogues has emerged as a key determinant of hepatic polarity. We propose that the absence of a hepatocyte basal lamina and differences in cell-cell adhesion signaling that determine the positioning of tight junctions are two crucial determinants for the distinct hepatic and columnar polarity phenotypes. PMID:23720287

Repression of TFIIH Transcriptional Activity and TFIIH-Associated cdk7 Kinase Activity at Mitosis

PubMed Central

Long, John J.; Leresche, Anne; Kriwacki, Richard W.; Gottesfeld, Joel M.

1998-01-01

Nuclear transcription is repressed when eukaryotic cells enter mitosis. Mitotic repression of transcription of various cellular and viral gene promoters by RNA polymerase II can be reproduced in vitro either with extracts prepared from cells arrested at mitosis with the microtubule polymerization inhibitor nocodazole or with nuclear extracts prepared from asynchronous cells and the mitotic protein kinase cdc2/cyclin B. Purified cdc2/cyclin B kinase is also sufficient to inhibit transcription in reconstituted transcription reactions with biochemically purified and recombinant basal transcription factors and RNA polymerase II. The cyclin-dependent kinase inhibitor p21Waf1/Cip1/Sdi1 can reverse the effect of cdc2/cyclin B kinase, indicating that repression of transcription is due to protein phosphorylation. Transcription rescue and inhibition experiments with each of the basal factors and the polymerase suggest that multiple components of the transcription machinery are inactivated by cdc2/cyclin B kinase. For an activated promoter, targets of repression are TFIID and TFIIH, while for a basal promoter, TFIIH is the major target for mitotic inactivation of transcription. Protein labeling experiments indicate that the p62 and p36 subunits of TFIIH are in vitro substrates for mitotic phosphorylation. Using the carboxy-terminal domain of the large subunit of RNA polymerase II as a test substrate for phosphorylation, the TFIIH-associated kinase, cdk7/cyclin H, is inhibited concomitant with inhibition of transcription activity. Our results suggest that there exist multiple phosphorylation targets for the global shutdown of transcription at mitosis. PMID:9488463

Basal ganglia, thalamus and neocortical atrophy predicting slowed cognitive processing in multiple sclerosis.

PubMed

Batista, Sonia; Zivadinov, Robert; Hoogs, Marietta; Bergsland, Niels; Heininen-Brown, Mari; Dwyer, Michael G; Weinstock-Guttman, Bianca; Benedict, Ralph H B

2012-01-01

Information-processing speed (IPS) slowing is a primary cognitive deficit in multiple sclerosis (MS). Basal ganglia, thalamus and neocortex are thought to have a key role for efficient information-processing, yet the specific relative contribution of these structures for MS-related IPS impairment is poorly understood. To determine if basal ganglia and thalamus atrophy independently contribute to visual and auditory IPS impairment in MS, after controlling for the influence of neocortical volume, we enrolled 86 consecutive MS patients and 25 normal controls undergoing 3T brain MRI and neuropsychological testing. Using Sienax and FIRST software, neocortical and deep gray matter (DGM) volumes were calculated. Neuropsychological testing contributed measures of auditory and visual IPS using the Paced Auditory Serial Addition Test (PASAT) and the Symbol Digit Modalities Test (SDMT), respectively. MS patients exhibited significantly slower IPS relative to controls and showed reduction in neocortex, caudate, putamen, globus pallidus, thalamus and nucleus accumbens volume. SDMT and PASAT were significantly correlated with all DGM regions. These effects were mitigated by controlling for the effects of neocortical volume, but all DGM volumes remained significantly correlated with SDMT, putamen (r = 0.409, p < 0.001) and thalamus (r = 0.362, p < 0.001) having the strongest effects, whereas for PASAT, the correlation was significant for putamen (r = 0.313, p < 0.01) but not for thalamus. We confirm the significant role of thalamus atrophy in MS-related IPS slowing and find that putamen atrophy is also a significant contributor to this disorder. These DGM structures have independent, significant roles, after controlling for the influence of neocortex atrophy.

Basal deposits and drusen in eyes with age-related maculopathy: evidence for solid lipid particles.

PubMed

Curcio, Christine A; Presley, J Brett; Millican, C Leigh; Medeiros, Nancy E

2005-06-01

Neutral lipid, including esterified cholesterol, and apolipoproteins B and E are abundant in basal deposits and drusen of aged and age-related maculopathy (ARM) eyes. The principal component of basal linear deposit (BlinD), a specific ARM lesion, is membranous debris, which if actually derived from membranes cannot account for extracellular neutral lipid. We therefore used a lipid-preserving ultrastructural method to obtain improved images of membranous debris. Maculas from 44 human donors (71-96 yr) were preserved <7.5 hr after death. Blocks were post-fixed in 2% osmium or osmium-tannic acid-paraphenylenediamine (OTAP) to preserve neutral lipid for thin-section transmission electron microscopic (TEM) examination. Solid particles identified by OTAP were considered closest to the in vivo state of extracellular lipids. Micrographs were examined for intermediate forms, with greatest weight given to comparable images from different preparations of same or fellow eyes. Twenty eyes of older adults (12 with ARM including fellows treated with photodynamic and radiation therapies) had adequately preserved extracellular lipid. The exterior surface of membranous debris was thicker and more electron-dense than basal infoldings of retinal pigment epithelium (RPE) cells. By OTAP, individual membranous debris profiles were solid (diameters, 80-200 nm) and formed tracks across or aggregations within basal laminar deposits. Solid particles and/or pools of neutral lipid were visible in BlinD and drusen. When processed to preserve lipid, membranous debris resembles neither membranes of surrounding cells nor vesicles possessing aqueous interiors but rather solid particles. These results are consistent with recent evidence implicating lipoprotein particles of intra-ocular origin as a potential source of neutral lipids, including esterified cholesterol, in the specific lesions of ARM.

Comparison of an Electronic Glycemic Management System Versus Provider-Managed Subcutaneous Basal Bolus Insulin Therapy in the Hospital Setting.

PubMed

Aloi, Joseph; Bode, Bruce W; Ullal, Jagdeesh; Chidester, Paul; McFarland, Raymie S; Bedingfield, Amy E; Mabrey, Melanie; Booth, Robby; Mumpower, April; Wallia, Amisha

2017-01-01

American Diabetes Association (ADA) guidelines recommend a basal bolus correction insulin regimen as the preferred method of treatment for non-critically ill hospitalized patients. However, achieving ADA glucose targets safely, without hypoglycemia, is challenging. In this study we evaluated the safety and efficacy of basal bolus subcutaneous (SubQ) insulin therapy managed by providers compared to a nurse-directed Electronic Glycemic Management System (eGMS). This retrospective crossover study evaluated 993 non-ICU patients treated with subcutaneous basal bolus insulin therapy managed by a provider compared to an eGMS. Analysis compared therapy outcomes before Glucommander (BGM), during Glucommander (DGM), and after Glucommander (AGM) for all patients. The blood glucose (BG) target was set at 140-180 mg/dL for all groups. The safety of each was evaluated by the following: (1) BG averages, (2) hypoglycemic events <40 and <70 mg/dL, and (3) percentage of BG in target. Percentage of BG in target was BGM 47%, DGM 62%, and AGM 36%. Patients' BGM BG average was 195 mg/dL, DGM BG average was 169 mg/dL, and AGM BG average was 174 mg/dL. Percentage of hypoglycemic events <70 mg/dL was 2.6% BGM, 1.9% DGM, and 2.8% AGM treatment. Patients using eGMS in the DGM group achieved improved glycemic control with lower incidence of hypoglycemia (<40 mg/dL and <70 mg/dl) compared to both BGM and AGM management with standard treatment. These results suggest that an eGMS can safely maintain glucose control with less hypoglycemia than basal bolus treatment managed by a provider.

Basal expression of insulin-like growth factor 1 receptor determines intrinsic resistance of cancer cells to a phosphatidylinositol 3-kinase inhibitor ZSTK474

PubMed Central

Isoyama, Sho; Kajiwara, Gensei; Tamaki, Naomi; Okamura, Mutsumi; Yoshimi, Hisashi; Nakamura, Naoki; Kawamura, Kento; Nishimura, Yumiko; Namatame, Nachi; Yamori, Takao; Dan, Shingo

2015-01-01

Drug resistance often critically limits the efficacy of molecular targeted drugs. Although pharmacological inhibition of phosphatidylinositol 3-kinase (PI3K) is an attractive therapeutic strategy for cancer therapy, molecular determinants for efficacy of PI3K inhibitors (PI3Kis) remain unclear. We previously identified that overexpression of insulin-like growth factor 1 receptor (IGF1R) contributed to the development of drug resistance after long-term exposure to PI3Kis. In this study, we examined the involvement of basal IGF1R expression in intrinsic resistance of drug-naïve cancer cells to PI3Kis and whether inhibition of IGF1R overcomes the resistance. We found that cancer cells highly expressing IGF1R showed resistance to dephosphorylation of Akt and subsequent antitumor effect by ZSTK474 treatment. Knockdown of IGF1R by siRNAs facilitated the dephosphorylation and enhanced the drug efficacy. These cells expressed tyrosine-phosphorylated insulin receptor substrate 1 at high levels, which was dependent on basal IGF1R expression. In these cells, the efficacy of ZSTK474 in vitro and in vivo was improved by its combination with the IGF1R inhibitor OSI-906. Finally, we found a significant correlation between the basal expression level of IGF1R and the inefficacy of ZSTK474 in an in vivo human cancer panel, as well as in vitro. These results suggest that basal IGF1R expression affects intrinsic resistance of cancer cells to ZSTK474, and IGF1R is a promising target to improve the therapeutic efficacy. The current results provide evidence of combination therapy of PI3Kis with IGF1R inhibitors for treating IGF1R-positive human cancers. PMID:25483727

Gorlin-Goltz syndrome.

PubMed

Jawa, Deepti Singh; Sircar, Keya; Somani, Rani; Grover, Neeraj; Jaidka, Shipra; Singh, Sanjeet

2009-07-01

Gorlin-Goltz syndrome is an autosomal dominant inherited disorder characterized by the presence of multiple odontogenic keratocysts along with various cutaneous, dental, osseous, ophthalmic, neurological, and sex organ abnormalities. Early diagnosis is essential as it may progress to aggressive basal cell carcinomas and neoplasias. Gorlin-Goltz syndrome has rarely been reported from India. We report here one such patient, diagnosed at a rural hospital.

Nearest neighbor imputation of species-level, plot-scale forest structure attributes from LiDAR data

Treesearch

Andrew T. Hudak; Nicholas L. Crookston; Jeffrey S. Evans; David E. Hall; Michael J. Falkowski

2008-01-01

Meaningful relationships between forest structure attributes measured in representative field plots on the ground and remotely sensed data measured comprehensively across the same forested landscape facilitate the production of maps of forest attributes such as basal area (BA) and tree density (TD). Because imputation methods can efficiently predict multiple response...

Structural Changes in the Somatosensory System Correlate with Tic Severity in Gilles de la Tourette Syndrome

ERIC Educational Resources Information Center

Thomalla, Gotz; Siebner, Hartwig R.; Jonas, Melanie; Baumer, Tobias; Biermann-Ruben, Katja; Hummel, Friedhelm; Gerloff, Christian; Muller-Vahl, Kirsten; Schnitzler, Alfons; Orth, Michael; Munchau, Alexander

2009-01-01

Gilles de la Tourette syndrome (GTS) is a neuropsychiatric disorder characterized by multiple motor and vocal tics. Previous structural MRI studies have identified regional abnormalities in grey matter, especially in the basal ganglia. These findings are consistent with the assumption of alterations in cortico-striato-thalamo-cortical circuits and…

Identification and quantification of the basal and inducible Nrf2-dependent proteomes in mouse liver: Biochemical, pharmacological and toxicological implications

PubMed Central

Walsh, Joanne; Jenkins, Rosalind E.; Wong, Michael; Olayanju, Adedamola; Powell, Helen; Copple, Ian; O’Neill, Paul M.; Goldring, Christopher E.P.; Kitteringham, Neil R.; Park, B. Kevin

2014-01-01

The transcription factor Nrf2 is a master regulator of cellular defence: Nrf2 null mice (Nrf2(−/−)) are highly susceptible to chemically induced toxicities. We report a comparative iTRAQ-based study in Nrf2(−/−) mice treated with a potent inducer, methyl-2-cyano-3,12-dioxooleana-1,9(11)dien-28-oate (CDDO-me; bardoxolone -methyl), to define both the Nrf2-dependent basal and inducible hepatoproteomes. One thousand five hundred twenty-one proteins were fully quantified (FDR < 1%). One hundred sixty-one were significantly different (P < 0.05) between WT and Nrf2(−/−) mice, confirming extensive constitutive regulation by Nrf2. Treatment with CDDO-me (3 mg/kg; i.p.) resulted in significantly altered expression of 43 proteins at 24 h in WT animals. Six proteins were regulated at both basal and inducible levels exhibiting the largest dynamic range of Nrf2 regulation: cytochrome P4502A5 (CYP2A5; 17.2-fold), glutathione-S-transferase-Mu 3 (GSTM3; 6.4-fold), glutathione-S-transferase Mu 1 (GSTM1; 5.9-fold), ectonucleoside-triphosphate diphosphohydrolase (ENTPD5; 4.6-fold), UDP-glucose-6-dehydrogenase (UDPGDH; 4.1-fold) and epoxide hydrolase (EPHX1; 3.0-fold). These proteins, or their products, thus provide a potential source of biomarkers for Nrf2 activity. ENTPD5 is of interest due to its emerging role in AKT signalling and, to our knowledge, this protein has not been previously shown to be Nrf2-dependent. Only two proteins altered by CDDO-me in WT animals were similarly affected in Nrf2(−/−) mice, demonstrating the high degree of selectivity of CDDO-me for the Nrf2:Keap1 signalling pathway. Biological significance The Nrf2:Keap1 signalling pathway is attracting considerable interest as a therapeutic target for different disease conditions. For example, CDDO-me (bardoxolone methyl) was investigated in clinical trials for the treatment of acute kidney disease, and dimethyl fumarate, recently approved for reducing relapse rate in multiple sclerosis, is a potent Nrf2 inducer. Such compounds have been suggested to act through multiple mechanisms; therefore, it is important to define the selectivity of Nrf2 inducers to assess the potential for off-target effects that may lead to adverse drug reactions, and to provide biomarkers with which to assess therapeutic efficacy. Whilst there is considerable information on the global action of such inducers at the mRNA level, this is the first study to catalogue the hepatic protein expression profile following acute exposure to CDDO-me in mice. At a dose shown to evoke maximal Nrf2 induction in the liver, CDDO-me appeared highly selective for known Nrf2-regulated proteins. Using the transgenic Nrf2(−/−) mouse model, it could be shown that 97% of proteins induced in wild type mice were associated with a functioning Nrf2 signalling pathway. This analysis allowed us to identify a panel of proteins that were regulated both basally and following Nrf2 induction. Identification of these proteins, which display a large magnitude of variation in their expression, provides a rich source of potential biomarkers for Nrf2 activity for use in experimental animals, and which may be translatable to man to define individual susceptibility to chemical stress, including that associated with drugs, and also to monitor the pharmacological response to Nrf2 inducers. PMID:24859727

Identification and quantification of the basal and inducible Nrf2-dependent proteomes in mouse liver: biochemical, pharmacological and toxicological implications.

PubMed

Walsh, Joanne; Jenkins, Rosalind E; Wong, Michael; Olayanju, Adedamola; Powell, Helen; Copple, Ian; O'Neill, Paul M; Goldring, Christopher E P; Kitteringham, Neil R; Park, B Kevin

2014-08-28

The transcription factor Nrf2 is a master regulator of cellular defence: Nrf2 null mice (Nrf2((-/-))) are highly susceptible to chemically induced toxicities. We report a comparative iTRAQ-based study in Nrf2((-/-)) mice treated with a potent inducer, methyl-2-cyano-3,12-dioxooleana-1,9(11)dien-28-oate (CDDO-me; bardoxolone -methyl), to define both the Nrf2-dependent basal and inducible hepatoproteomes. One thousand five hundred twenty-one proteins were fully quantified (FDR <1%). One hundred sixty-one were significantly different (P<0.05) between WT and Nrf2((-/-)) mice, confirming extensive constitutive regulation by Nrf2. Treatment with CDDO-me (3mg/kg; i.p.) resulted in significantly altered expression of 43 proteins at 24h in WT animals. Six proteins were regulated at both basal and inducible levels exhibiting the largest dynamic range of Nrf2 regulation: cytochrome P4502A5 (CYP2A5; 17.2-fold), glutathione-S-transferase-Mu 3 (GSTM3; 6.4-fold), glutathione-S-transferase Mu 1 (GSTM1; 5.9-fold), ectonucleoside-triphosphate diphosphohydrolase (ENTPD5; 4.6-fold), UDP-glucose-6-dehydrogenase (UDPGDH; 4.1-fold) and epoxide hydrolase (EPHX1; 3.0-fold). These proteins, or their products, thus provide a potential source of biomarkers for Nrf2 activity. ENTPD5 is of interest due to its emerging role in AKT signalling and, to our knowledge, this protein has not been previously shown to be Nrf2-dependent. Only two proteins altered by CDDO-me in WT animals were similarly affected in Nrf2((-/-)) mice, demonstrating the high degree of selectivity of CDDO-me for the Nrf2:Keap1 signalling pathway. The Nrf2:Keap1 signalling pathway is attracting considerable interest as a therapeutic target for different disease conditions. For example, CDDO-me (bardoxolone methyl) was investigated in clinical trials for the treatment of acute kidney disease, and dimethyl fumarate, recently approved for reducing relapse rate in multiple sclerosis, is a potent Nrf2 inducer. Such compounds have been suggested to act through multiple mechanisms; therefore, it is important to define the selectivity of Nrf2 inducers to assess the potential for off-target effects that may lead to adverse drug reactions, and to provide biomarkers with which to assess therapeutic efficacy. Whilst there is considerable information on the global action of such inducers at the mRNA level, this is the first study to catalogue the hepatic protein expression profile following acute exposure to CDDO-me in mice. At a dose shown to evoke maximal Nrf2 induction in the liver, CDDO-me appeared highly selective for known Nrf2-regulated proteins. Using the transgenic Nrf2((-/-)) mouse model, it could be shown that 97% of proteins induced in wild type mice were associated with a functioning Nrf2 signalling pathway. This analysis allowed us to identify a panel of proteins that were regulated both basally and following Nrf2 induction. Identification of these proteins, which display a large magnitude of variation in their expression, provides a rich source of potential biomarkers for Nrf2 activity for use in experimental animals, and which may be translatable to man to define individual susceptibility to chemical stress, including that associated with drugs, and also to monitor the pharmacological response to Nrf2 inducers. Copyright © 2014. Published by Elsevier B.V.

Using an AMACR (P504S)/34betaE12/p63 cocktail for the detection of small focal prostate carcinoma in needle biopsy specimens.

PubMed

Jiang, Zhong; Li, Cuizhen; Fischer, Andrew; Dresser, Karen; Woda, Bruce A

2005-02-01

We assessed the usefulness of immunohistochemical analysis with a 3-antibody cocktail (alpha-methylacyl coenzyme A racemase [AMACR, or P504S], 34betaE12, p63) and a double-chromogen reaction for detection of limited prostate cancer in 138 needle biopsy specimens, including 82 with small foci of prostatic adenocarcinoma and 56 benign prostates. When carcinoma was present, red cytoplasmic granular staining (AMACR) in the malignant glands and cells and dark brown nuclear (p63) and cytoplasmic (34betaE12) staining in basal cells of adjacent nonmalignant glands were found. Of 82 cases of small foci of prostatic adenocarcinoma, 78 (95%) expressed AMACR; all malignant glands were negative for basal cell staining. All benign glands adjacent to malignant glands were recognized easily by basal cell marker positivity and little or no AMACR expression. No benign glands were simultaneously positive for AMACR and negative for basal cell markers (specificity, 100%). There were no differences in intensity and numbers of positive glands with double-chromogen staining compared with using 1-color staining. Our results indicate that immunohistochemistry with a 3-antibody cocktail and double chromogen is a simple and easy assay that can be used as a routine test, which overcomes the problems of studying small lesions in prostate needle biopsies with multiple immunohistochemical stains.

The role of the basal ganglia in learning and memory: insight from Parkinson's disease.

PubMed

Foerde, Karin; Shohamy, Daphna

2011-11-01

It has long been known that memory is not a single process. Rather, there are different kinds of memory that are supported by distinct neural systems. This idea stemmed from early findings of dissociable patterns of memory impairments in patients with selective damage to different brain regions. These studies highlighted the role of the basal ganglia in non-declarative memory, such as procedural or habit learning, contrasting it with the known role of the medial temporal lobes in declarative memory. In recent years, major advances across multiple areas of neuroscience have revealed an important role for the basal ganglia in motivation and decision making. These findings have led to new discoveries about the role of the basal ganglia in learning and highlighted the essential role of dopamine in specific forms of learning. Here we review these recent advances with an emphasis on novel discoveries from studies of learning in patients with Parkinson's disease. We discuss how these findings promote the development of current theories away from accounts that emphasize the verbalizability of the contents of memory and towards a focus on the specific computations carried out by distinct brain regions. Finally, we discuss new challenges that arise in the face of accumulating evidence for dynamic and interconnected memory systems that jointly contribute to learning. Copyright © 2011 Elsevier Inc. All rights reserved.

Nitric oxide regulates stretch-induced proliferation in C2C12 myoblasts.

PubMed

Soltow, Quinlyn A; Lira, Vitor A; Betters, Jenna L; Long, Jodi H D; Sellman, Jeff E; Zeanah, Elizabeth H; Criswell, David S

2010-09-01

Mechanical stretch of skeletal muscle activates nitric oxide (NO) production and is an important stimulator of satellite cell proliferation. Further, cyclooxygenase (COX) activity has been shown to promote satellite cell proliferation in response to stretch. Since COX-2 expression in skeletal muscle can be regulated by NO we sought to determine if NO is required for stretch-induced myoblast proliferation and whether supplemental NO can counter the effects of COX-2 and NF-kappaB inhibitors. C2C12 myoblasts were cultured for 24 h, then switched to medium containing either the NOS inhibitor, L-NAME (200 microM), the COX-2 specific inhibitor NS-398 (100 microM), the NF-kappaB inhibiting antioxidant, PDTC (5 mM), the nitric oxide donor, DETA-NONOate (10-100 microM) or no supplement (control) for 24 h. Subgroups of each treatment were exposed to 1 h of 15% cyclic stretch (1 Hz), and were then allowed to proliferate for 24 h before fixing. Proliferation was measured by BrdU incorporation during the last hour before fixing, and DAPI stain. Stretch induced a twofold increase in nuclear number compared to control, and this effect was completely inhibited by L-NAME, NS-398 or PDTC (P < 0.05). Although DETA-NONOate (10 microM) did not affect basal proliferation, the NO-donor augmented the stretch-induced increase in proliferation and rescued stretch-induced proliferation in NS-398-treated cells, but not in PDTC-treated cells. In conclusion, NO, COX-2, and NF-kappaB are necessary for stretch-induced proliferation of myoblasts. Although COX-2 and NF-kappaB are both involved in basal proliferation, NO does not affect basal growth. Thus, NO requires the synergistic effect of stretch in order to induce muscle cell proliferation.

Frequency of blood glucose testing among insulin-treated diabetes mellitus patients in the United Kingdom.

PubMed

Lee, Won Chan; Smith, Elise; Chubb, Barrie; Wolden, Michael Lyng

2014-03-01

Through a retrospective database analysis, this study seeks to provide an understanding of the utilization of SMBG by insulin therapy and diabetes type and to estimate healthcare costs of blood glucose monitoring in the UK diabetes population. Data were obtained from the IMS LifeLink Electronic Medical Record-Europe (EMR-EU) Database, a longitudinal database containing anonymized patient records from physician-practice data systems of office-based physicians in the UK. Depending on the insulin types used for type 1 and type 2 diabetes, patients were sub-categorized into one of four insulin regimen groups (basal, bolus, pre-mixed, or basal-bolus). Frequency of blood glucose testing was assessed descriptively throughout the 12-month post-index period, and generalized linear models were used to evaluate the effect of baseline characteristics, including insulin type, on the likelihood of blood glucose test utilization. Healthcare resource utilization and costs for all-cause services were assessed by insulin type. This study identified 8322 type 1 and type 2 diabetes patients with two insulin pharmacy records between January 1, 2009 and December 31, 2010. After applying study inclusion and exclusion criteria, a total of 2676 (32.2%) insulin-treated diabetes mellitus patients in the UK were identified, with the number of pharmacy blood glucose test strips averaging 771.1 (median 600). The glucose testing frequency was lowest among basal-only insulin patients and pre-mixed insulin patients (mean=576.2 [median=450] and mean=599.5 [median=500], respectively; non-significantly different) compared to other insulin types. Although the data did not capture the glucose frequency comprehensively, it varied significantly by insulin types, and was higher than what is recommended in the guidelines for patients with type 2 diabetes.

Glioblastoma recurrence correlates with NLGN3 levels.

PubMed

Liu, Rui; Qin, Xing-Ping; Zhuang, Yang; Zhang, Ya; Liao, Hua-Bao; Tang, Jun-Chun; Pan, Meng-Xian; Zeng, Fei-Fei; Lei, Yang; Lei, Rui-Xue; Wang, Shu; Liu, An-Chun; Chen, Juan; Zhang, Zhi-Feng; Zhao, Dan; Wu, Song-Lin; Liu, Ren-Zhong; Wang, Ze-Fen; Wan, Qi

2018-05-18

Glioblastoma (GBM) is the most aggressive glioma in the brain. Recurrence of GBM is almost inevitable within a short term after tumor resection. In a retrospective study of 386 cases of GBM collected between 2013 and 2016, we found that recurrence of GBM mainly occurs in the deep brain regions, including the basal ganglia, thalamus, and corpus callosum. But the mechanism underlying this phenomenon is not clear. Previous studies suggest that neuroligin-3 (NLGN3) is necessary for GBM growth. Our results show that the levels of NLGN3 in the cortex are higher than those in the deep regions in a normal human brain, and similar patterns are also found in a normal mouse brain. In contrast, NLGN3 levels in the deep brain regions of GBM patients are high. We also show that an increase in NLGN3 concentration promotes the growth of U251 cells and U87-MG cells. Respective use of the cortex neuron culture medium (C-NCM) and basal ganglia neuron culture medium (BG-NCM) with DMEM to cultivate U251, U87-MG and GBM cells isolated from patients, we found that these cells grew faster after treatment with C-NCM and BG-NCM in which the cells treated with C-NCM grew faster than the ones treated with BG-NCM group. Inhibition of NLGN3 release by ADAM10i prevents NCM-induced cell growth. Together, this study suggests that increased levels of NLGN3 in the deep brain region under the GBM pathological circumstances may contribute to GBM recurrence in the basal ganglia, thalamus, and corpus callosum. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Nitric oxide synthase gene transfer for erectile dysfunction in a rat model.

PubMed

Chancellor, M B; Tirney, S; Mattes, C E; Tzeng, E; Birder, L A; Kanai, A J; de Groat, W C; Huard, J; Yoshimura, N

2003-05-01

To determine whether over-expression of nitric oxide synthase (NOS) in the corpus cavernosum of the penis improves erectile function, as NO is an important transmitter for genitourinary tract function, mediating smooth muscle relaxation and being essential for penile erection. The inducible form of the enzyme NOS (iNOS) was introduced into the corpus cavernosum of adult Sprague-Dawley rats (250-300 g) by injecting a solution of plasmid, adenovirus or adenovirus-transduced myoblast cells (adeno-myoblasts). Plasmid, adenovirus and adeno-myoblasts encoding the expression of the beta-galactosidase reporter gene were also injected into rats. Throughout the corpora cavernosum there was expression of beta-galactosidase after injecting each of the three solutions. Maximum staining was greatest for adeno-myoblast, then adenovirus and then plasmid. The mean (sd) basal intracavernosal pressure (ICP) of iNOS-treated animals (adenovirus and adeno-myoblast) increased to 55 (23) cmH2O, compared with naive animals with a basal ICP of 5 (6) cmH2O (P = 0.001). Stimulating the cavernosal nerve (15 Hz, 1.5 ms, 10-40 V, 1 min) resulted in a doubling of the ICP (adenovirus and adeno-myoblast) from the basal level of the iNOS-treated animals. Direct in situ measurement of NO showed the release of 1-1.3 micro mol/L in the adeno-myoblast penis. Myoblast-mediated gene therapy was more successful for delivering iNOS into the corpus cavernosum than direct adenovirus injection or plasmid transfection. Surprisingly, implanting muscle cells into the penis is not only feasible but also beneficial. Gene therapy for NOS may open new avenues of treatment for erectile dysfunction. Control of NOS expression would be necessary to prevent priapism.

Dietary grape seed polyphenols repress neuron and glia activation in trigeminal ganglion and trigeminal nucleus caudalis

PubMed Central

2010-01-01

Background Inflammation and pain associated with temporomandibular joint disorder, a chronic disease that affects 15% of the adult population, involves activation of trigeminal ganglion nerves and development of peripheral and central sensitization. Natural products represent an underutilized resource in the pursuit of safe and effective ways to treat chronic inflammatory diseases. The goal of this study was to investigate effects of grape seed extract on neurons and glia in trigeminal ganglia and trigeminal nucleus caudalis in response to persistent temporomandibular joint inflammation. Sprague Dawley rats were pretreated with 200 mg/kg/d MegaNatural-BP grape seed extract for 14 days prior to bilateral injections of complete Freund's adjuvant into the temporomandibular joint capsule. Results In response to grape seed extract, basal expression of mitogen-activated protein kinase phosphatase 1 was elevated in neurons and glia in trigeminal ganglia and trigeminal nucleus caudalis, and expression of the glutamate aspartate transporter was increased in spinal glia. Rats on a normal diet injected with adjuvant exhibited greater basal levels of phosphorylated-p38 in trigeminal ganglia neurons and spinal neurons and microglia. Similarly, immunoreactive levels of OX-42 in microglia and glial fibrillary acidic protein in astrocytes were greatly increased in response to adjuvant. However, adjuvant-stimulated levels of phosphorylated-p38, OX-42, and glial fibrillary acidic protein were significantly repressed in extract treated animals. Furthermore, grape seed extract suppressed basal expression of the neuropeptide calcitonin gene-related peptide in spinal neurons. Conclusions Results from our study provide evidence that grape seed extract may be beneficial as a natural therapeutic option for temporomandibular joint disorders by suppressing development of peripheral and central sensitization. PMID:21143976

Lewis lung carcinoma regulation of mechanical stretch-induced protein synthesis in cultured myotubes.

PubMed

Gao, Song; Carson, James A

2016-01-01

Mechanical stretch can activate muscle and myotube protein synthesis through mammalian target of rapamycin complex 1 (mTORC1) signaling. While it has been established that tumor-derived cachectic factors can induce myotube wasting, the effect of this catabolic environment on myotube mechanical signaling has not been determined. We investigated whether media containing cachectic factors derived from Lewis lung carcinoma (LLC) can regulate the stretch induction of myotube protein synthesis. C2C12 myotubes preincubated in control or LLC-derived media were chronically stretched. Protein synthesis regulation by anabolic and catabolic signaling was then examined. In the control condition, stretch increased mTORC1 activity and protein synthesis. The LLC treatment decreased basal mTORC1 activity and protein synthesis and attenuated the stretch induction of protein synthesis. LLC media increased STAT3 and AMP-activated protein kinase phosphorylation in myotubes, independent of stretch. Both stretch and LLC independently increased ERK1/2, p38, and NF-κB phosphorylation. In LLC-treated myotubes, the inhibition of ERK1/2 and p38 rescued the stretch induction of protein synthesis. Interestingly, either leukemia inhibitory factor or glycoprotein 130 antibody administration caused further inhibition of mTORC1 signaling and protein synthesis in stretched myotubes. AMP-activated protein kinase inhibition increased basal mTORC1 signaling activity and protein synthesis in LLC-treated myotubes, but did not restore the stretch induction of protein synthesis. These results demonstrate that LLC-derived cachectic factors can dissociate stretch-induced signaling from protein synthesis through ERK1/2 and p38 signaling, and that glycoprotein 130 signaling is associated with the basal stretch response in myotubes. Copyright © 2016 the American Physiological Society.

New data from basal Australian songbird lineages show that complex structure of MHC class II β genes has early evolutionary origins within passerines.

PubMed

Balasubramaniam, Shandiya; Bray, Rebecca D; Mulder, Raoul A; Sunnucks, Paul; Pavlova, Alexandra; Melville, Jane

2016-05-21

The major histocompatibility complex (MHC) plays a crucial role in the adaptive immune system and has been extensively studied across vertebrate taxa. Although the function of MHC genes appears to be conserved across taxa, there is great variation in the number and organisation of these genes. Among avian species, for instance, there are notable differences in MHC structure between passerine and non-passerine lineages: passerines typically have a high number of highly polymorphic MHC paralogs whereas non-passerines have fewer loci and lower levels of polymorphism. Although the occurrence of highly polymorphic MHC paralogs in passerines is well documented, their evolutionary origins are relatively unexplored. The majority of studies have focussed on the more derived passerine lineages and there is very little empirical information on the diversity of the MHC in basal passerine lineages. We undertook a study of MHC diversity and evolutionary relationships across seven species from four families (Climacteridae, Maluridae, Pardalotidae, Meliphagidae) that comprise a prominent component of the basal passerine lineages. We aimed to determine if highly polymorphic MHC paralogs have an early evolutionary origin within passerines or are a more derived feature of the infraorder Passerida. We identified 177 alleles of the MHC class II β exon 2 in seven basal passerine species, with variation in numbers of alleles across individuals and species. Overall, we found evidence of multiple gene loci, pseudoalleles, trans-species polymorphism and high allelic diversity in these basal lineages. Phylogenetic reconstruction of avian lineages based on MHC class II β exon 2 sequences strongly supported the monophyletic grouping of basal and derived passerine species. Our study provides evidence of a large number of highly polymorphic MHC paralogs in seven basal passerine species, with strong similarities to the MHC described in more derived passerine lineages rather than the simpler MHC in non-passerine lineages. These findings indicate an early evolutionary origin of highly polymorphic MHC paralogs in passerines and shed light on the evolutionary forces shaping the avian MHC.

Basal insulin persistence, associated factors, and outcomes after treatment initiation among people with type 2 diabetes mellitus in the US.

PubMed

Perez-Nieves, Magaly; Kabul, Samaneh; Desai, Urvi; Ivanova, Jasmina I; Kirson, Noam Y; Cummings, Alice Kate; Birnbaum, Howard G; Duan, Ran; Cao, Dachuang; Hadjiyianni, Irene

2016-01-01

To assess basal insulin persistence, associated factors, and economic outcomes for insulin-naïve people with type 2 diabetes mellitus (T2DM) in the US. People aged ≥18 years diagnosed with T2DM initiating basal insulin between April 2006 and March 2012 (index date), no prior insulin use, and continuous insurance coverage for 6 months before (baseline) and 24 months after index date (follow-up period) were selected using de-identified administrative claims data in the US. Based on whether there were ≥30 day gaps in basal insulin use in the first year post-index, patients were classified as continuers (no gap), interrupters (≥1 prescription after gap), and discontinuers (no prescription after gap). Factors associated with persistence - assessed using multinomial logistic regression model; annual healthcare resource use and costs during follow-up period - compared separately between continuers and interrupters, and continuers and discontinuers. Of the 19,110 people included in the sample (mean age: 59 years, ∼60% male), 20% continued to use basal insulin, 62% had ≥1 interruption, and 18% discontinued therapy in the year after initiation. Older age, multiple antihyperglycemic drug use, and injectable antihyperglycemic use during baseline were associated with significantly higher likelihoods of continuing basal insulin. Relative to interrupters and discontinuers, continuers had fewer emergency department visits, shorter hospital stays, and lower medical costs (continuers: $10,890, interrupters: $13,674, discontinuers: $13,021), but higher pharmacy costs (continuers: $7449, interrupters: $5239, discontinuers: $4857) in the first year post-index (p < 0.05 for all comparisons). Total healthcare costs were similar across the three cohorts. Findings for the second year post-index were similar. The majority of people in this study interrupted or discontinued basal insulin treatment in the year after initiation; and incurred higher medical resource use and costs than continuers. The findings are limited to the commercially insured population in the US. In addition, persistence patterns were assessed using administrative claims as opposed to actual medication-taking behavior and did not account for measures of glycemic control. Further research is needed to understand the reasons behind basal insulin persistence and the implications thereof, to help clinicians manage care for T2DM more effectively.

Safely Converting an Entire Academic Medical Center From Sliding Scale to Basal Bolus Insulin via Implementation of the eGlycemic Management System.

PubMed

Newsom, Rosalina; Patty, Christopher; Camarena, Emma; Sawyer, Regina; McFarland, Raymie; Gray, Thomas; Mabrey, Melanie

2018-01-01

Hyperglycemia is common in the inpatient setting and providers frequently rely on sliding scale insulin. This case study reviews the experience of one hospital moving from high utilization of sliding scale to basal bolus insulin therapy. This Retrospective Quality Improvement Study describes the journey of clinicians at a 580-bed hospital to convert from high usage of SSI to BBI. Hyperglycemic adult patients prescribed insulin, with/without a diagnosis of diabetes, were included. Data over the first year showed that patients treated with Glucommander (GM) spent more time in the target range of 70-180 mg/dL than patients treated with non-Glucommander (non-GM), with 2,434 fewer hypoglycemic events and 40,589 fewer hyperglycemic events. Prior to implementation of GM, SSI was close to 95%, BBI at 5%. Within the first month of use, 96% usage of BBI was achieved. Reduction of hypoglycemic events (% of BG < 70 mg/dL) by 21% with 2.16% non-GM compared to GM at 1.74% and severe Hypoglycemia (% of BG < 50 mg/dL) by 50% in the ICU 3% non-GM compared to GM at 1.5%. In addition, patients treated with GM had a shorter LOS than patients treated with non-GM by 3.18 days and used 47.4% less point of care tests per patient. Glycemic management improved with use of eGMS. The conversion from SSI to BBI enhanced overall patient safety, eliminated the time and effort otherwise required when manually titrating insulin and reduced overall cost of care for patients on insulin therapy.

Vismodegib, an antagonist of hedgehog signaling, directly alters taste molecular signaling in taste buds.

PubMed

Yang, Hyekyung; Cong, Wei-Na; Yoon, Jeong Seon; Egan, Josephine M

2015-02-01

Vismodegib, a highly selective inhibitor of hedgehog (Hh) pathway, is an approved treatment for basal-cell carcinoma. Patients on treatment with vismodegib often report profound alterations in taste sensation. The cellular mechanisms underlying the alterations have not been studied. Sonic Hh (Shh) signaling is required for cell growth and differentiation. In taste buds, Shh is exclusively expressed in type IV taste cells, which are undifferentiated basal cells and the precursors of the three types of taste sensing cells. Thus, we investigated if vismodegib has an inhibitory effect on taste cell turnover because of its known effects on Hh signaling. We gavaged C57BL/6J male mice daily with either vehicle or 30 mg/kg vismodegib for 15 weeks. The gustatory behavior and immunohistochemical profile of taste cells were examined. Vismodegib-treated mice showed decreased growth rate and behavioral responsivity to sweet and bitter stimuli, compared to vehicle-treated mice. We found that vismodegib-treated mice had significant reductions in taste bud size and numbers of taste cells per taste bud. Additionally, vismodegib treatment resulted in decreased numbers of Ki67- and Shh-expressing cells in taste buds. The numbers of phospholipase Cβ2- and α-gustducin-expressing cells, which contain biochemical machinery for sweet and bitter sensing, were reduced in vismodegib-treated mice. Furthermore, vismodegib treatment resulted in reduction in numbers of T1R3, glucagon-like peptide-1, and glucagon-expressing cells, which are known to modulate sweet taste sensitivity. These results suggest that inhibition of Shh signaling by vismodegib treatment directly results in alteration of taste due to local effects in taste buds. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

Vismodegib, an antagonist of hedgehog signaling, directly alters taste molecular signaling in taste buds

PubMed Central

Yang, Hyekyung; Cong, Wei-na; Yoon, Jeong Seon; Egan, Josephine M

2015-01-01

Vismodegib, a highly selective inhibitor of hedgehog (Hh) pathway, is an approved treatment for basal-cell carcinoma. Patients on treatment with vismodegib often report profound alterations in taste sensation. The cellular mechanisms underlying the alterations have not been studied. Sonic Hh (Shh) signaling is required for cell growth and differentiation. In taste buds, Shh is exclusively expressed in type IV taste cells, which are undifferentiated basal cells and the precursors of the three types of taste sensing cells. Thus, we investigated if vismodegib has an inhibitory effect on taste cell turnover because of its known effects on Hh signaling. We gavaged C57BL/6J male mice daily with either vehicle or 30 mg/kg vismodegib for 15 weeks. The gustatory behavior and immunohistochemical profile of taste cells were examined. Vismodegib-treated mice showed decreased growth rate and behavioral responsivity to sweet and bitter stimuli, compared to vehicle-treated mice. We found that vismodegib-treated mice had significant reductions in taste bud size and numbers of taste cells per taste bud. Additionally, vismodegib treatment resulted in decreased numbers of Ki67- and Shh-expressing cells in taste buds. The numbers of phospholipase Cβ2- and α-gustducin-expressing cells, which contain biochemical machinery for sweet and bitter sensing, were reduced in vismodegib-treated mice. Furthermore, vismodegib treatment resulted in reduction in numbers of T1R3, glucagon-like peptide-1, and glucagon-expressing cells, which are known to modulate sweet taste sensitivity. These results suggest that inhibition of Shh signaling by vismodegib treatment directly results in alteration of taste due to local effects in taste buds. PMID:25354792

A Comparison of Inpatient Cost Per Day in General Surgery Patients with Type 2 Diabetes Treated with Basal-Bolus versus Sliding Scale Insulin Regimens.

PubMed

Phillips, Victoria L; Byrd, Anwar L; Adeel, Saira; Peng, Limin; Smiley, Dawn D; Umpierrez, Guillermo E

2017-01-01

The identification of cost-effective glycaemic management strategies is critical to hospitals. Treatment with a basal-bolus insulin (BBI) regimen has been shown to result in better glycaemic control and fewer complications than sliding scale regular insulin (SSI) in general surgery patients with type 2 diabetes mellitus (T2DM), but the effect on costs is unknown. We conducted a post hoc analysis of the RABBIT Surgery trial to examine whether total inpatient costs per day for general surgery patients with T2DM treated with BBI ( n  = 103) differed from those for patients with T2DM treated with SSI ( n  = 99) regimens. Data were collected from patient clinical and hospital billing records. Charges were adjusted to reflect hospital costs. General linearized models were used to estimate the risk-adjusted effects of BBI versus SSI treatment on average total inpatient costs per day. Risk-adjusted average total inpatient costs per day were $US5404. Treatment with BBI compared with SSI reduced average total inpatient costs per day by $US751 (14%; 95% confidence interval [CI] 20-4). Being treated in a university medical centre, being African American or having a bowel procedure or higher-volume pharmacy use significantly reduced costs per day. In general surgery patients with T2DM, a BBI regimen significantly reduced average total hospital costs per day compared with an SSI regimen. BBI has been shown to improve outcomes in a randomized controlled trial. Those results, combined with our findings regarding savings, suggest that hospitals should consider adopting BBI regimens in patients with T2DM undergoing surgery.

Binge-Like Ethanol Consumption Increases Corticosterone Levels and Neurodegneration whereas occupancy of Type II Glucocorticoid Receptors with Mifepristone is Neuroprotective

PubMed Central

Cippitelli, Andrea; Damadzic, Ruslan; Hamelink, Carol; Brunnquell, Michael; Thorsell, Annika; Heilig, Markus; Eskay, Robert L

2012-01-01

Excessive ethanol (EtOH) use leads to impaired memory and cognition. Using a rat model of binge-like intoxication, we tested whether elevated corticosterone (Cort) levels contribute to the neurotoxic consequences of EtOH exposure. Rats were adrenalectomized (Adx) and implanted with cholesterol pellets, or cholesterol pellets containing basal, medium or high Cort. Intragastric EtOH or an isocaloric control solution was given 3 times daily for 4 days to achieve blood alcohol levels (BALs) ranging between 200-350 mg/dl. Mean 24 hour (24-hr) plasma Cort levels were ~110 ng/ml and ~40 ng/ml in intact EtOH treated and intact control, respectively. Basal Cort replacement in EtOH-treated Adx animals animals did not exacerbate alcohol-induced neurodegeneration in the hippocampal dentate gyrus (DG) or the entorhinal cortex (EC) as observed by amino-cupric silver staining. In contrast, Cort replacement resulting in levels 2-fold higher (medium) than normal, or higher (high) in Adx-Cort-EtOH animals increased neurodegeneration. In separate experiments, pharmacological blockade of the Type II glucocortocoid (GC) receptor was initiated with mifepristone (RU38486; 0, 5, 15 mg/kg/day, i.p.). At the higher dose, mifepristone decreased the number of degenerating hippocampal DG cells in binge-EtOH treated intact animals, whereas, only a trend for reduction was observed in 15 mg/kg/day mifepristone treated animals in the EC, as determined by Fluoro Jade B staining. These results suggest that Cort in part mediates EtOH-induced neurotoxicity in the brain through activation of Type II GC receptors. PMID:22500955

Characterization of Cardiovascular Alterations Induced by Different Chronic Cisplatin Treatments

PubMed Central

Herradón, Esperanza; González, Cristina; Uranga, José A.; Abalo, Raquel; Martín, Ma I.; López-Miranda, Visitacion

2017-01-01

In the last years, many clinical studies have revealed that some cisplatin-treated cancer survivors have a significantly increased risk of cardiovascular events, being cisplatin-induced cardiovascular toxicity an increasing concern. The aim of the present work was to evaluate the cardiovascular alterations induced by different chronic cisplatin treatments, and to identify some of the mechanisms involved. Direct blood pressure, basal cardiac (left ventricle and coronary arteries) and vascular (aortic and mesenteric) functions were evaluated in chronic (5 weeks) saline- or cisplatin-treated male Wistar rats. Three different doses of cisplatin were tested (1, 2, and 3 mg/kg/week). Alterations in cardiac and vascular tissues were also investigated by immunohistochemistry, Western Blot, and or quantitative RT-PCR analysis. Cisplatin treatment provoked a significant modification of arterial blood pressure, heart rate, and basal cardiac function at the maximum dose tested. However, vascular endothelial dysfunction occurred at lower doses. The expression of collagen fibers and conexin-43 were increased in cardiac tissue in cisplatin-treated rats with doses of 2 and 3 mg/kg/week. The expression of endothelial nitric oxide synthase was also modified in cardiac and vascular tissues after cisplatin treatment. In conclusion, chronic cisplatin treatment provokes cardiac and vascular toxicity in a dose-dependent manner. Besides, vascular endothelial dysfunction occurs at lower doses than cardiac and systemic cardiovascular toxicity. Moreover, some structural changes in cardiac and vascular tissues are also patent even before any systemic cardiovascular alterations. PMID:28533750

Characterization of Cardiovascular Alterations Induced by Different Chronic Cisplatin Treatments.

PubMed

Herradón, Esperanza; González, Cristina; Uranga, José A; Abalo, Raquel; Martín, Ma I; López-Miranda, Visitacion

2017-01-01

In the last years, many clinical studies have revealed that some cisplatin-treated cancer survivors have a significantly increased risk of cardiovascular events, being cisplatin-induced cardiovascular toxicity an increasing concern. The aim of the present work was to evaluate the cardiovascular alterations induced by different chronic cisplatin treatments, and to identify some of the mechanisms involved. Direct blood pressure, basal cardiac (left ventricle and coronary arteries) and vascular (aortic and mesenteric) functions were evaluated in chronic (5 weeks) saline- or cisplatin-treated male Wistar rats. Three different doses of cisplatin were tested (1, 2, and 3 mg/kg/week). Alterations in cardiac and vascular tissues were also investigated by immunohistochemistry, Western Blot, and or quantitative RT-PCR analysis. Cisplatin treatment provoked a significant modification of arterial blood pressure, heart rate, and basal cardiac function at the maximum dose tested. However, vascular endothelial dysfunction occurred at lower doses. The expression of collagen fibers and conexin-43 were increased in cardiac tissue in cisplatin-treated rats with doses of 2 and 3 mg/kg/week. The expression of endothelial nitric oxide synthase was also modified in cardiac and vascular tissues after cisplatin treatment. In conclusion, chronic cisplatin treatment provokes cardiac and vascular toxicity in a dose-dependent manner. Besides, vascular endothelial dysfunction occurs at lower doses than cardiac and systemic cardiovascular toxicity. Moreover, some structural changes in cardiac and vascular tissues are also patent even before any systemic cardiovascular alterations.

Cimetidine (Tagamet) is a reproductive toxicant in male rats affecting peritubular cells.

PubMed

França, L R; Leal, M C; Sasso-Cerri, E; Vasconcelos, A; Debeljuk, L; Russell, L D

2000-11-01

Cimetidine (Tagamet) is a potent histaminic H2-receptor antagonist, extensively prescribed for ulcers and now available without prescription. Cimetidine is a known testicular toxicant, but its mechanism of action remains uncertain. Rats were treated i.p. with cimetidine either at 50 mg/kg or 250 mg/kg body weight for 59 days. Accessory sex organ weights, but not testis weight, were significantly reduced in the high dose treated groups. FSH levels were significantly elevated in both treated groups, but testosterone levels were unchanged. A high degree of variability characterized testis histology, with most tubules appearing normal and some tubules (15-17%) partially lacking or devoid of germ cells. Morphometry showed that although seminiferous tubule volume was not significantly changed, the volume of peritubular tissue was reduced in the high dose group. There was extensive duplication of the basal lamina, lamina densa in both apparently normal spermatogenic tubules and severely damaged tubules. Apoptotic peritubular myoid cells were also found. TUNEL labeling confirmed extensive apoptotic cell death in peritubular cells, but revealed apoptosis of vascular smooth muscle. Given that 1) peritubular myoid cell apoptosis occurs in apparently normal tubules, that 2) basal lamina disorders are found, and that 3) peritubular cells are lost from the testis, it is suggested that the primary event in cimetidine-related damage is targeted to testicular smooth muscle cells. This is the first in vivo-administered toxicant to be described that targets myoid cells, resulting in abnormal spermatogenesis.

Fetal bovine serum and human constitutive androstane receptor: Evidence for activation of the SV23 splice variant by artemisinin, artemether, and arteether in a serum-free cell culture system

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lau, Aik Jiang; Chang, Thomas K.H., E-mail: thomas.chang@ubc.ca

The naturally occurring SV23 splice variant of human constitutive androstane receptor (hCAR-SV23) is activated by di-(2-ethylhexyl)phthalate (DEHP), which is detected as a contaminant in fetal bovine serum (FBS). In our initial experiment, we compared the effect of dialyzed FBS, charcoal-stripped, dextran-treated FBS (CS-FBS), and regular FBS on the basal activity and ligand-activation of hCAR-SV23 in a cell-based reporter gene assay. In transfected HepG2 cells cultured in medium supplemented with 10% FBS, basal hCAR-SV23 activity varied with the type of FBS (regular > dialyzed > CS). DEHP increased hCAR-SV23 activity when 10% CS-FBS, but not regular FBS or dialyzed FBS, wasmore » used. With increasing concentrations (1–10%) of regular FBS or CS-FBS, hCAR-SV23 basal activity increased, whereas in DEHP-treated cells, hCAR-SV23 activity remained similar (regular FBS) or slightly increased (CS-FBS). Subsequent experiments identified a serum-free culture condition to detect DEHP activation of hCAR-SV23. Under this condition, artemisinin, artemether, and arteether increased hCAR-SV23 activity, whereas they decreased it in cells cultured in medium supplemented with 10% regular FBS. By comparison, FBS increased the basal activity of the wild-type isoform of hCAR (hCAR-WT), whereas it did not affect the basal activity of the SV24 splice variant (hCAR-SV24) or ligand activation of hCAR-SV24 and hCAR-WT by 6-(4-chlorophenyl)imidazo[2,1-b][1,3]thiazole-5-carbaldehyde O-(3,4-dichlorobenzyl)oxime (CITCO). The use of serum-free culture condition was suitable for detecting CITCO activation of hCAR-WT and hCAR-SV24. In conclusion, FBS leads to erroneous classification of pharmacological ligands of hCAR-SV23 in cell-based assays, but investigations on functional ligands of hCAR isoforms can be conducted in serum-free culture condition. - Highlights: • FBS leads to erroneous pharmacological classification of hCAR-SV23 ligands. • Artemisinin, artemether, and arteether activate hCAR-SV23 in the absence of FBS. • Serum-free culture condition can be used for identifying ligands of hCAR isoforms.« less

The Lack of a Long-Term Growth Effect of Annosus Control in Southeastern United States

Treesearch

F. H. Tainter; J. G. Williams; N. J. Hess; S. W. Oak; D. A. Starkey

1989-01-01

An evaluation of basal area increment was made in 1988 of six pine plantations located across the southeastern United States. These plantations had been thinned in 1969-1970 and stumps treated with borax to measure long-term efficacy of annosus root rot control. In the present study, no long-term growth effects were identified. There were neither negative growth...

Early diagnosis of Gorlin-Goltz syndrome: case report.

PubMed

Casaroto, Ana R; Loures, Daniela C N Rocha; Moreschi, Eduardo; Veltrini, Vanessa C; Trento, Cleverson L; Gottardo, Vilmar D; Lara, Vanessa S

2011-01-25

The Gorlin-Goltz syndrome, also known as nevoid basal cell carcinoma syndrome (NBCCS), is an infrequent multisystemic disease inherited in a dominant autosomal way, which shows a high level of penetrance and variable expressiveness. It is characterized by keratocystic odontogenic tumors (KCOT) in the jaw, multiple basal cell nevi carcinomas and skeletal abnormities. This syndrome may be diagnosed early by a dentist by routine radiographic exams in the first decade of life, since the KCOTs are usually one of the first manifestations of the syndrome. This article paper reports the case of a patient, a 10-year-old boy with NBCCS, emphasizing its clinical and radiographic manifestations. This study highlights the importance of health professionals in the early diagnosis of NBCCS and in a preventive multidisciplinary approach to provide a better prognosis for the patient.

Energetic cost of standard activities in Gurkha and British soldiers.

PubMed

Strickland, S S; Ulijaszek, S J

1990-01-01

Measurements of basal metabolic rate and energy expenditure at lying, sitting, standing, and performing a step test at four levels of exercise, were made on Gurkha soldiers stationed in Britain and on British controls matched by body weight and occupational background. There was no significant difference in basal metabolic rate (BMR), nor in the energy cost of lying, sitting and standing between the two groups. Gurhas showed significantly lower gross and net energy expenditure, and so significantly greater net mechanical efficiency, at the lower levels of step exercise. The ratio of gross energy expenditure to BMR was lower in Gurkhas at the lowest rates of stepping compared with the British controls. These results suggest that the energy cost of some physical activities expressed as multiples of BMR may not be constant across populations.

Learning to Select Actions with Spiking Neurons in the Basal Ganglia

PubMed Central

Stewart, Terrence C.; Bekolay, Trevor; Eliasmith, Chris

2012-01-01

We expand our existing spiking neuron model of decision making in the cortex and basal ganglia to include local learning on the synaptic connections between the cortex and striatum, modulated by a dopaminergic reward signal. We then compare this model to animal data in the bandit task, which is used to test rodent learning in conditions involving forced choice under rewards. Our results indicate a good match in terms of both behavioral learning results and spike patterns in the ventral striatum. The model successfully generalizes to learning the utilities of multiple actions, and can learn to choose different actions in different states. The purpose of our model is to provide both high-level behavioral predictions and low-level spike timing predictions while respecting known neurophysiology and neuroanatomy. PMID:22319465

The In Vivo Effect of Ytterbium-Doped Fiber Laser on Rat Buccal Mucosa as a Simulation of Its Effect on the Urinary Tract: A Preclinical Histopathological Evaluation.

PubMed

Piao, Songzhe; Wang, Yue; Lee, Young Ju; Hong, Seungsoo; Jeong, Yoonchan; Oh, Seung-June

2017-04-01

The aim of this study was to perform a histological analysis of the effect of a ytterbium-doped fiber (YDF) laser on oral buccal mucosa tissue in vivo to simulate its effect on the mucosa of the lower urinary tract. A total of 90 8-week-old Sprague-Dawley rats were anesthetized with urethrane (1.2 g/kg intraperitoneally). A prespecified inner buccal mucosal site was irradiated with a YDF master-oscillator power amplifier (MOPA) system for 60 seconds, with output power settings of 0.5, 1, and 2 W, respectively, in 3 treatment groups. Specimens of irradiated tissue were harvested at 2 hours, 24 hours, 2 weeks, and 4 weeks after irradiation. The tissue specimens were stained with hematoxylin and eosin for histological analysis. In the group treated with 0.5 W, basal cell elongation and vacuolization were observed at 2 hours and 24 hours after treatment, respectively. No evident injury was observed after 2 or 4 weeks. The group treated with 1 W presented partial basal layer separation, and even complete epidermal ablation, within 2 hours. At 24 hours after laser treatment, new capillaries on an edematous background of fibroblasts and myofibroblasts, as well as profuse infiltration of the neutrophils to the basal layer, were observed. Collagen deposition and reepithelization were observed in specimens taken 2 weeks and 4 weeks after treatment. The group treated with 2 W presented bigger and deeper injuries at 2 hours after irradiation. Meanwhile, subepidermal bullae with full-thickness epidermal necrosis and underlying inflammatory infiltrate were observed 24 hours after treatment. The presence of fibrous connective tissue and collagen deposition were observed 2 weeks and 4 weeks after the treatment. To our knowledge, this is the first report regarding the effect of a YDF laser on living tissue. Our study demonstrated that the typical histological findings of the tissue reaction to the YDF MOPA apparatus were very similar to those associated with thermal injuries. The extent and degree of tissue damage increased proportionally to the output power.

Topically applied NO-releasing nanoparticles can increase intracorporal pressure and elicit spontaneous erections in a rat model of radical prostatectomy

PubMed Central

Tar, Moses; Cabrales, Pedro; Mahantesh, Navarti; Adler, Brandon; Nacharaju, Parimala; Friedman, Adam; Friedman, Joel; Davies, Kelvin P.

2014-01-01

Introduction Patients undergoing radical prostatectomy (RP) suffer from erectile dysfunction (ED) refractory to PDE5 inhibitors, which act downstream of CN-mediated release of nitric oxide (NO). Direct delivery of NO to the penis could potentially circumvent this limitation. Aim To determine if topically applied NO-releasing nanoparticles (NO-np) can elicit erections in a rat model of RP and demonstrate that the mechanism is through increased blood flow. Methods 26 Sprague–Dawley rats underwent bilateral transection of the CN. One week later NO-np were applied topically to the penile shaft in DMSO-gel (10 animals) or coconut oil (6 animals). Control animals were treated with empty-np. Erectile function was determined through the intracorporal pressure/blood pressure ratio (ICP/BP). The effect of the NO-np on blood flow was determined using a hamster dorsal window chamber. Main Outcome Measures Animals were investigated for spontaneous erections, onset and duration of erectile response and basal ICP/BP ratio. Microcirculatory blood-flow was determined through arteriolar and venular diameter and blood flow. Results Eight of ten animals treated with NO-np suspended in DMSO-gel had significant increases in basal ICP/BP, and six out of these ten animals demonstrated spontaneous erections of approximately one minute duration. Onset of spontaneous erections ranged from 5–37 minutes and occurred for at least 45 minutes. Similar results were observed with NO-np applied in coconut oil. No erectile response was observed in control animal models treated with empty-np. The hamster dorsal window chamber demonstrated NO-np applied as a suspension in coconut oil caused a significant increase in the microcirculatory blood flow, sustained over 90 minutes. Conclusions Topically applied NO-np induced spontaneous erections and increased basal ICP in an animal model of RP. These effects are most likely due to increased microcirculatory blood flow. These characteristics suggest that the NO-np would be useful in penile rehabilitation of patients following RP. PMID:25302850

Topically applied NO-releasing nanoparticles can increase intracorporal pressure and elicit spontaneous erections in a rat model of radical prostatectomy.

PubMed

Tar, Moses; Cabrales, Pedro; Navati, Mahantesh; Adler, Brandon; Nacharaju, Parimala; Friedman, Adam J; Friedman, Joel; Davies, Kelvin P

2014-12-01

Patients undergoing radical prostatectomy (RP) suffer from erectile dysfunction (ED) refractory to phosphodiesterase 5 inhibitors, which act downstream of cavernous nerve (CN)-mediated release of nitric oxide (NO). Direct delivery of NO to the penis could potentially circumvent this limitation. This study aimed to determine if topically applied NO-releasing nanoparticles (NO-NPs) could elicit erections in a rat model of RP through increased blood flow. Twenty-six Sprague Dawley rats underwent bilateral transection of the CN. One week later, NO-NPs were applied topically to the penile shaft in dimethylsulfoxide (DMSO) gel (10 animals) or coconut oil (6 animals). Control animals were treated with empty NPs. Erectile function was determined through the intracorporal pressure/blood pressure ratio (ICP/BP). The effect of the NO-NPs on blood flow was determined using a hamster dorsal window chamber. Animals were investigated for spontaneous erections, onset and duration of erectile response, and basal ICP/BP ratio. Microcirculatory blood flow was determined through measurements of arteriolar and venular diameter and red blood cell velocity. Eight of 10 animals treated with NO-NPs suspended in DMSO gel had significant increases in basal ICP/BP, and 6 out of these 10 animals demonstrated spontaneous erections of approximately 1 minute in duration. Time to onset of spontaneous erections ranged from 5 to 37 minutes, and they occurred for at least 45 minutes. Similar results were observed with NO-NPs applied in coconut oil. No erectile response was observed in control animal models treated with empty NPs. The hamster dorsal window chamber experiment demonstrated that NO-NPs applied as a suspension in coconut oil caused a significant increase in the microcirculatory blood flow, sustained over 90 minutes. Topically applied NO-NPs induced spontaneous erections and increased basal ICP in an animal model of RP. These effects are most likely due to increased microcirculatory blood flow. These characteristics suggest that NO-NPs would be useful in penile rehabilitation of patients following RP. © 2014 International Society for Sexual Medicine.

Energy value of paraquat-treated and resin-soaked lobolly pine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kossuth, S.V.; Roberts, D.R.; Huffman, J.B.

1984-07-01

With a basal injector, loblolly pines were treated with 5% paraquat cation (weight/weight basis) and harvested after 18 months. The resin acid, turpentine, moisture content (MC) and energy value were measured in three bolts of the stem. In bolt 1, the first 152 cm above the injection site, the increase in resin acids was 392% and in turpentine, 564%. Within the whole stem (the first two 152 cm bolts and the third bolt to a 7.6 cm inside-bark diameter) resin acids and turpentine increased 203 and 296% respectively. Moisture content was reduced 9%, 8%, and 8% in bolts 1, 2more » and 3, respectively. Turpentine from treated and untreated trees had an average heating value of 19,369 cal/g. When weighted for volume, net energy content was 7.8% greater for treated than control trees because of the increase in resin, including turpentine and the lowered MC.« less

Evaluation of ferrihydrite as amendment to restore an arsenic-polluted mine soil.

PubMed

Abad-Valle, P; Álvarez-Ayuso, E; Murciego, A

2015-05-01

The effectiveness of ferrihydrite as amendment to restore the soil habitat functioning of a soil polluted with As by mining activities was evaluated. Its influence on As mobility and phytoavailability was also assessed. Soil treated with increasing amendment doses (0, 1, 2, and 5 %) were analyzed for soil microbiological parameters such as basal soil respiration and dehydrogenase, β-glucosidase, urease, acid and alkaline phosphatase, and arylsulfatase activities. Batch leaching tests and plant growth experiments using ryegrass and alfalfa plants were performed. The treatment with ferrihydrite was effective to reduce As mobility and plant As uptake, translocation, and accumulation. Likewise, the soil microbiological status was generally improved as derived from basal soil respiration and dehydrogenase and acid and alkaline phosphatase activities, which showed increases up to 85, 45, 11, and 47 %, respectively, at a ferrihydrite addition rate of 5 %.

MELK is an oncogenic kinase essential for mitotic progression in basal-like breast cancer cells

PubMed Central

Wang, Yubao; Lee, Young-Mi; Baitsch, Lukas; Huang, Alan; Xiang, Yi; Tong, Haoxuan; Lako, Ana; Von, Thanh; Choi, Christine; Lim, Elgene; Min, Junxia; Li, Li; Stegmeier, Frank; Schlegel, Robert; Eck, Michael J; Gray, Nathanael S; Mitchison, Timothy J; Zhao, Jean J

2014-01-01

Despite marked advances in breast cancer therapy, basal-like breast cancer (BBC), an aggressive subtype of breast cancer usually lacking estrogen and progesterone receptors, remains difficult to treat. In this study, we report the identification of MELK as a novel oncogenic kinase from an in vivo tumorigenesis screen using a kinome-wide open reading frames (ORFs) library. Analysis of clinical data reveals a high level of MELK overexpression in BBC, a feature that is largely dependent on FoxM1, a master mitotic transcription factor that is also found to be highly overexpressed in BBC. Ablation of MELK selectively impairs proliferation of basal-like, but not luminal breast cancer cells both in vitro and in vivo. Mechanistically, depletion of MELK in BBC cells induces caspase-dependent cell death, preceded by defective mitosis. Finally, we find that Melk is not required for mouse development and physiology. Together, these data indicate that MELK is a normally non-essential kinase, but is critical for BBC and thus represents a promising selective therapeutic target for the most aggressive subtype of breast cancer. DOI: http://dx.doi.org/10.7554/eLife.01763.001 PMID:24844244

Undermining plastic surgery as a possible option for treating basal cell carcinoma of the forehead.

PubMed

Tchernev, Georgi; Pidakev, Ivan; Lozev, Ilia; Lotti, Torello; Cardoso, Jose Carlos; Patterson, James W

2017-04-01

Basal cell carcinoma (BCC) is the most common cutaneous cancer. Although most cases can be cured with simple surgical procedures and are associated with a good prognosis, a minority of BCCs may pose significant therapeutic challenges. This occurs mostly in cases of so-called advanced BCC, which a loosely defined term that encompasses locally advanced lesions and tumors with metastatic spread. Treatment of these cases is often complex and sometimes may need combinations of therapeutic modalities, including surgery, radiotherapy and/or targeted therapy directed towards sonic hedgehog (SHH) signaling pathways, such as vismodegib. We herein present the case of a 74-year-old man presenting with a large basal cell of the forehead evolving for more than 7 years. The patient underwent excision of the lesion with clear surgical margins. Reconstruction of the defect was performed after extensive undermining of the skin allowing subsequent direct closure with a simple suture, which resulted in an acceptable cosmetic outcome. We discuss the potential advantages, disadvantages, and applicability of this relatively simple surgical maneuver in the reconstruction of defects resulting from excision of considerably large cutaneous tumors.

Mechanisms and time course of impaired skeletal muscle glucose transport activity in streptozocin diabetic rats.

PubMed Central

Napoli, R; Hirshman, M F; Horton, E S

1995-01-01

Skeletal muscle glucose transport is altered in diabetes in humans, as well as in rats. To investigate the mechanisms of this abnormality, we measured glucose transport Vmax, the total transporter number, their average intrinsic activity, GLUT4 and GLUT1 contents in skeletal muscle plasma membrane vesicles from basal or insulin-stimulated streptozocin diabetic rats with different duration of diabetes, treated or not with phlorizin. The glucose transport Vmax progressively decreased with the duration of diabetes. In the basal state, this decrease was primarily associated with the reduction of transporter intrinsic activity, which appeared earlier than any change in transporter number or GLUT4 and GLUT1 content. In the insulin-stimulated state, the decrease of transport was mainly associated with severe defects in transporter translocation. Phlorizin treatment partially increased the insulin-stimulated glucose transport by improving the transporter translocation defects. In conclusion, in streptozocin diabetes (a) reduction of intrinsic activity plays a major and early role in the impairment of basal glucose transport; (b) a defect in transporter translocation is the mechanism responsible for the decrease in insulin-stimulated glucose transport; and (c) hyperglycemia per se affects the insulin-stimulated glucose transport by altering the transporter translocation. PMID:7615815

Erythropoietin during hypoglycaemia in type 1 diabetes: relation to basal renin-angiotensin system activity and cognitive function.

PubMed

Kristensen, Peter Lommer; Høi-Hansen, Thomas; Olsen, Niels Vidiendal; Pedersen-Bjergaard, Ulrik; Thorsteinsson, Birger

2009-07-01

Preservation of cognitive function during hypoglycaemic episodes is crucial for patients with insulin-treated diabetes to avoid severe hypoglycaemic events. Erythropoietin has neuroprotective potential. However, the role of erythropoietin during hypoglycaemia is unclear. The aim of the study was to explore plasma erythropoietin response to hypoglycaemia and the relationship to basal renin-angiotensin system (RAS) activity and cognitive function. We performed a single-blinded, controlled, cross-over study with induced hypoglycaemia or maintained glycaemic level. Nine patients with type 1 diabetes with high and nine with low activity in RAS were studied. Hypoglycaemia was induced using a standardized insulin-infusion. Overall, erythropoietin concentrations increased during hypoglycaemia. In the high RAS group erythropoietin rose 29% (p=0.032) whereas no significant response was observed in the low RAS group (7% increment; p=0.43). Independently, both hypoglycaemia and high RAS activity were associated with higher levels of erythropoietin (p=0.02 and 0.04, respectively). Low plasma erythropoietin at baseline was associated with poorer cognitive performance during hypoglycaemia. Hypoglycaemia triggers a rise in plasma erythropoietin in patients with type 1 diabetes. The response is influenced by basal RAS activity. Erythropoietin may carry a neuroprotective potential during hypoglycaemia.

Systemic Injections of Cannabidiol Enhance Acetylcholine Levels from Basal Forebrain in Rats.

PubMed

Murillo-Rodríguez, Eric; Arankowsky-Sandoval, Gloria; Rocha, Nuno Barbosa; Peniche-Amante, Rodrigo; Veras, André Barciela; Machado, Sérgio; Budde, Henning

2018-06-06

Cannabis sativa is a plant that contains more than 500 components, of which the most studied are Δ 9 -tetrahydrocannabinol (Δ 9 -THC) and cannabidiol (CBD). Several studies have indicated that CBD displays neurobiological effects, including wake promotion. Moreover, experimental evidence has shown that injections of CBD enhance wake-related compounds, such as monoamines (dopamine, serotonin, epinephrine, and norepinephrine). However, no clear evidence is available regarding the effects of CBD on additional wake-related neurochemicals such as acetylcholine (ACh). Here, we demonstrate that systemic injections of CBD (0, 5, 10 or 30 mg/kg, i.p.) at the beginning of the lights-on period, increase the extracellular levels of ACh collected from the basal forebrain and measured by microdialysis and HPLC means. Moreover, the time course effects on the contents of ACh were present 5 h post-injection of CBD. Altogether, these data demonstrate that CBD increases ACh levels in a brain region related to wake control. This study is the first to show the effects of ACh levels in CBD-treated rats and suggests that the basal forebrain might be a site of action of CBD for wakefulness modulation.

The use of the Artelon CMC Spacer for osteoarthritis of the basal joint of the thumb.

PubMed

Richard, Marc J; Lunich, Julie A; Correll, Gretchen R

2014-01-01

Favorable clinical outcomes have been reported with the Artelon CMC Spacer, however, several studies have documented complications with the device. The purpose of this study is to review a single surgeon's experience with the Artelon CMC Spacer for the treatment of basal joint arthritis of the thumb. Five thumbs in 6 patients with symptomatic osteoarthritis of the thumb carpometacarpal (CMC) joint were treated with the Artelon CMC Spacer. The mean age of the patients was 60.8 years old. Patients were followed for a mean of 39.3 months (6-63) post-operatively. Complications occurred in 4 of the 6 thumbs and half of the thumbs required at least one secondary operative procedure. A documented foreign-body reaction was present in 2 of the 6 thumbs. The Artelon CMC Spacer is an interposition material that acts as a biologic spacer for arthritic joints while maintaining mechanical strength. Due to an unacceptably high complication rate, we no longer use the Artelon CMC Spacer for the management of basal joint arthritis of the thumb. 4. Copyright © 2014 Hanley & Belfus. Published by Elsevier Inc. All rights reserved.

Source of a micro-nutrient in a semi-synthetic basal diet as a causative factor in inducing urinary calculi in rats and its inhibition by PSC 833, a potent inhibitor of P-glycoprotein.

PubMed

Kankesan, Janarthanan; Vanama, Ramesh; Renlund, Richard; Thiessen, Jake J; Ling, Victor; Rao, Prema M; Rajalakshmi, Srinivasan; Sarma, Dittakavi S R

2003-08-01

We report a serendipitous finding of urinary calculi in rats fed a semi-synthetic basal diet. This observation was made during ongoing studies to evaluate the inhibitory effect of PSC 833, a potent inhibitor of P-glycoprotein, on development of tumors in rodent tumor model systems. A large number of specific-pathogen-free (SPF) female Sprague-Dawley and SPF male Fischer 344 rats being fed the diet were euthanized when it became evident clinically that they were uremic. At necropsy, the renal pelvis, ureters, and urinary bladder contained numerous calculi. The presence of urinary calculi was determined to be related to the source of a Food Chemical Codex grade of choline bitartrate. Rats being fed the same basal diet containing the United States Pharmacopia grade of choline bitartrate failed to develop urinary calculi. Interestingly, rats treated with the P-glycoprotein inhibitor were at significantly reduced risk of developing urinary calculi. This finding highlights how something seemingly innocuous as a minor dietary constituent can have a profound impact and, thereby, affect experimental outcome.

Plasticity of the dense hydrous magnesium silicate phase A at subduction zones conditions

DOE PAGES

Gouriet, K.; Hilairet, N.; Amiguet, E.; ...

2015-09-12

The plasticity of the dense hydrous magnesium silicate (DHMS) phase A, a key hydrous mineral within cold subduction zones, was investigated by two complementary approaches: high-pressure deformation experiments and computational methods. The deformation experiments were carried out at 11 GPa, 400 and 580 °C, with in situ measurements of stress, strain and lattice preferred orientations (LPO). Based on viscoplastic self-consistent modeling (VPSC) of the observed LPO, the deformation mechanisms at 580 °C are consistent with glide on the (0 0 0 1) basal and prismatic planes. At 400 °C the deformation mechanisms involve glide on prismatic, (0 0 0 1)more » basal and pyramidal planes. Both give flow stresses of 2.5–3 GPa at strain rates of 2–4 × 10-5 s-1. We use the Peierls–Nabarro–Galerkin (PNG) approach, relying on first-principles calculations of generalized stacking fault (γ-surface), and model the core structure of potential dislocations in basal and prismatic planes. The computations show multiple dissociations of the and dislocations (⟨a⟩ and ⟨b⟩ dislocations) in the basal plane, which is compatible with the ubiquity of basal slip in the experiments. The γ-surface calculations also suggest and dislocations (⟨a+c⟩ or ⟨c-b⟩ directions) in prismatic and pyramidal planes, which is also consistent with the experimental data. Phase A has a higher flow strength than olivine. When forming at depths from the dehydration of weak and highly anisotropic hydrated ultramafic rocks, phase A may not maintain the mechanical softening antigorite can provide. The seismic properties calculated for moderately deformed aggregates suggest that S-wave seismic anisotropy of phase A-bearing rocks is lower than hydrous subduction zone lithologies such as serpentinites and blueschists.« less

Regulation of basal and reserve cardiac pacemaker function by interactions of cAMP mediated PKA-dependent Ca2+ cycling with surface membrane channels

PubMed Central

Vinogradova, Tatiana M.; Lakatta, Edward G.

2009-01-01

Decades of intensive research of primary cardiac pacemaker, the sinoatrial node, have established potential roles of specific membrane channels in the generation of the diastolic depolarization, the major mechanism allowing sinoatrial node cells generate spontaneous beating. During the last three decades, multiple studies made either in the isolated sinoatrial node or sinoatrial node cells have demonstrated a pivotal role of Ca2+ and, specifically Ca2+-release from sarcoplasmic reticulum, for spontaneous beating of cardiac pacemaker. Recently, spontaneous, rhythmic local subsarcolemmal Ca2+ releases from ryanodine receptors during late half of the diastolic depolarization have been implicated as a vital factor in the generation of sinoatrial node cells spontaneous firing. Local Ca2+ releases are driven by a unique combination of high basal cAMP production by adenylyl cyclases, high basal cAMP degradation by phosphodiesterases and a high level of cAMP-mediated PKA-dependent phosphorylation. These local Ca2+ releases activate an inward Na+-Ca2+ exchange current which accelerates the terminal diastolic depolarization rate and, thus, controls the spontaneous pacemaker firing. Both the basal primary pacemaker beating rate and its modulation via β-adrenergic receptor stimulation appear to be critically dependent upon intact RyR function and local subsarcolemmal sarcoplasmic reticulum generated Ca2+ releases. This review aspires to integrate the traditional viewpoint that has emphasized the supremacy of the ensemble of surface membrane ion channels in spontaneous firing of the primary cardiac pacemaker, and these novel perspectives of cAMP-mediated PKA-dependent Ca2+ cycling in regulation of the heart pacemaker clock, both in the basal state and during β-adrenergic receptor stimulation. PMID:19573534

Simulating the roles of crevasse routing of surface water and basal friction on the surge evolution of Basin 3, Austfonna ice cap

NASA Astrophysics Data System (ADS)

Gong, Yongmei; Zwinger, Thomas; Åström, Jan; Altena, Bas; Schellenberger, Thomas; Gladstone, Rupert; Moore, John C.

2018-05-01

The marine-terminating outlet in Basin 3, Austfonna ice cap, has been accelerating since the mid-1990s. Stepwise multi-annual acceleration associated with seasonal summer speed-up events was observed before the outlet entered the basin-wide surge in autumn 2012. We used multiple numerical models to explore hydrologic activation mechanisms for the surge behaviour. A continuum ice dynamic model was used to invert basal friction coefficient distributions using the control method and observed surface velocity data between April 2012 and July 2014. This has provided input to a discrete element model capable of simulating individual crevasses, with the aim of finding locations where meltwater entered the glacier during the summer and reached the bed. The possible flow paths of surface meltwater reaching the glacier bed as well as those of meltwater produced at the bed were calculated according to the gradient of the hydraulic potential. The inverted friction coefficients show the unplugging of the stagnant ice front and expansion of low-friction regions before the surge reached its peak velocity in January 2013. Crevasse distribution reflects the basal friction pattern to a high degree. The meltwater reaches the bed through the crevasses located above the margins of the subglacial valley and the basal melt that is generated mainly by frictional heating flows either to the fast-flowing units or potentially accumulates in an overdeepened region. Based on these results, the mechanisms facilitated by basal meltwater production, crevasse opening and the routing of meltwater to the bed are discussed for the surge in Basin 3.

Effect of somatostatin-14 on duodenal mucosal bicarbonate secretion in guinea pigs.

PubMed

Odes, H S; Muallem, R; Reimer, R; Ioffe, S; Beil, W; Schwenk, M; Sewing, K F

1995-03-01

The role of somatostatin-14 in duodenal mucosal HCO3- secretion was investigated in anesthetized, indomethacin-treated guinea pigs. Net HCO3- output from the isolated, perfused (24 mM NaHCO3 + 130 mM NaCl) proximal duodenum was measured during intravenous infusion (alone or in combination) of somatostatin-14, carbachol, vasoactive intestinal peptide (VIP), and prostaglandin E2 (PGE2). In homogenates of duodenal enterocytes, the effect of these agents on adenylate cyclase activity was studied. Basal duodenal HCO3- secretion (3.5 +/- 0.2 mumol/cm/10 min) was reduced dose dependently by somatostatin-14 (10(-11) mol/kg, 10(-9) mol/kg, and 10(-7) mol/kg). Carbachol, VIP, and PGE2 (all 10(-8) mol/kg) increased basal duodenal HCO3- secretion two- to threefold. Somatostatin-14 (10(-7) mol/kg) abolished the stimulatory effect of carbachol and VIP, but not that of PGE2. Basal adenylate cyclase activity in isolated duodenal enterocytes (9.4 +/- 1.0 pmol cAMP/mg protein/min) was unaltered by somatostatin (10(-6) mol/liter) or carbachol (10(-3) mol/liter). VIP (10(-8) mol/liter) and PGE2 (10(-7) mol/liter) increased adenylate cyclase activity two- to threefold, and these effects were unchanged by somatostatin-14 (10(-6) mol/liter). In conclusion, somatostatin-14 inhibits basal and carbachol- and VIP-stimulated duodenal HCO3- secretion, and its mechanism of action is not via inhibition of adenylate cyclase activity in duodenal enterocytes.

Surgery Versus 5% Imiquimod for Nodular and Superficial Basal Cell Carcinoma: 5-Year Results of the SINS Randomized Controlled Trial.

PubMed

Williams, Hywel C; Bath-Hextall, Fiona; Ozolins, Mara; Armstrong, Sarah J; Colver, Graham B; Perkins, William; Miller, Paul S J

2017-03-01

We previously reported modest clinical 3-year benefit for topical imiquimod compared with surgery for superficial or nodular basal cell carcinoma at low-risk sites in our noninferiority randomized controlled SINS trial. Here we report 5-year data. Participants were randomized to imiquimod 5% cream once daily (superficial basal cell carcinoma, 6 weeks; nodular basal cell carcinoma, 12 weeks) or excisional surgery (4-mm margin). The primary outcome was clinical absence of initial failure or signs of recurrence at the 3-year dermatology review. Five-year success was defined as 3-year success plus absence of recurrences identified through hospital, histopathology, and general practitioner records. Of 501 participants randomized, 401 contributed to the modified intention-to-treat analyses at year 3 (primary outcome), 383 (96%) of whom had data at year 5. Five-year success rates for imiquimod were 82.5% (170/206) compared with 97.7% (173/177) for surgery (relative risk of imiquimod success = 0.84, 95% confidence interval = 0.77-0.91, P < 0.001). These were comparable to year 3 success rates of 83.6% (178/213) and 98.4% (185/188) for imiquimod and surgery, respectively. Most imiquimod treatment failures occurred in year 1. Although surgery is clearly superior to imiquimod, this study shows sustained benefit for lesions that respond early to topical imiquimod. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Listening to Rhythmic Music Reduces Connectivity within the Basal Ganglia and the Reward System.

PubMed

Brodal, Hans P; Osnes, Berge; Specht, Karsten

2017-01-01

Music can trigger emotional responses in a more direct way than any other stimulus. In particular, music-evoked pleasure involves brain networks that are part of the reward system. Furthermore, rhythmic music stimulates the basal ganglia and may trigger involuntary movements to the beat. In the present study, we created a continuously playing rhythmic, dance floor-like composition where the ambient noise from the MR scanner was incorporated as an additional instrument of rhythm. By treating this continuous stimulation paradigm as a variant of resting-state, the data was analyzed with stochastic dynamic causal modeling (sDCM), which was used for exploring functional dependencies and interactions between core areas of auditory perception, rhythm processing, and reward processing. The sDCM model was a fully connected model with the following areas: auditory cortex, putamen/pallidum, and ventral striatum/nucleus accumbens of both hemispheres. The resulting estimated parameters were compared to ordinary resting-state data, without an additional continuous stimulation. Besides reduced connectivity within the basal ganglia, the results indicated a reduced functional connectivity of the reward system, namely the right ventral striatum/nucleus accumbens from and to the basal ganglia and auditory network while listening to rhythmic music. In addition, the right ventral striatum/nucleus accumbens demonstrated also a change in its hemodynamic parameter, reflecting an increased level of activation. These converging results may indicate that the dopaminergic reward system reduces its functional connectivity and relinquishing its constraints on other areas when we listen to rhythmic music.

Listening to Rhythmic Music Reduces Connectivity within the Basal Ganglia and the Reward System

PubMed Central

Brodal, Hans P.; Osnes, Berge; Specht, Karsten

2017-01-01

Music can trigger emotional responses in a more direct way than any other stimulus. In particular, music-evoked pleasure involves brain networks that are part of the reward system. Furthermore, rhythmic music stimulates the basal ganglia and may trigger involuntary movements to the beat. In the present study, we created a continuously playing rhythmic, dance floor-like composition where the ambient noise from the MR scanner was incorporated as an additional instrument of rhythm. By treating this continuous stimulation paradigm as a variant of resting-state, the data was analyzed with stochastic dynamic causal modeling (sDCM), which was used for exploring functional dependencies and interactions between core areas of auditory perception, rhythm processing, and reward processing. The sDCM model was a fully connected model with the following areas: auditory cortex, putamen/pallidum, and ventral striatum/nucleus accumbens of both hemispheres. The resulting estimated parameters were compared to ordinary resting-state data, without an additional continuous stimulation. Besides reduced connectivity within the basal ganglia, the results indicated a reduced functional connectivity of the reward system, namely the right ventral striatum/nucleus accumbens from and to the basal ganglia and auditory network while listening to rhythmic music. In addition, the right ventral striatum/nucleus accumbens demonstrated also a change in its hemodynamic parameter, reflecting an increased level of activation. These converging results may indicate that the dopaminergic reward system reduces its functional connectivity and relinquishing its constraints on other areas when we listen to rhythmic music. PMID:28400717

Effect of platelet-rich plasma on patients after blepharoplasty surgery.

PubMed

Parra, Fidelina; Morales-Rome, David Enrique; Campos-Rodríguez, Rafael; Cruz-Hernández, Teresita Rocío; Drago-Serrano, Maria Elisa

2018-04-01

To evaluate the effect of platelet-rich plasma (PRP) treatment on patients after blepharoplasty surgery. After undergoing blepharoplasty, 20 patients were randomly divided into two groups (n = 10 each). One was treated with autologous PRP and the other was not given any post-surgery treatment (basal group). Autologous PRP application was performed intradermically 24 h, 1 month, and 2 months post-surgery, and the outcome of the applications was assessed 1, 2, and 3 months post-surgery. The postoperative wound was assessed on a patient and observer scar assessment scale (POSAS) by patients and by an unblinded clinical observer. Statistical comparison between the two groups was analyzed by using the Mann-Whitney unpaired, two-tailed test. Significant differences were considered with P ≤ 0.05. Patient-reported data indicate that compared to the basal group, the PRP group showed no significant differences regarding pain, itching, or color, but had better values for stiffness and thickness (months 1 and 2) as well as scar irregularity (month 1). Data reported by the clinical observer showed that in comparison with the basal group, the PRP group showed no differences in vascularization or pigmentation, but had lower (better) scores regarding thickness, relief, and pliability (at all assessment times). The total assessment values from patients and the observer were significantly better for the PRP than the basal group. Autologous PRP treatment enhanced some parameters associated with healing properties, suggesting a potential therapeutic value after blepharoplasty surgery.

Regional differences in insulin therapy regimens in five European countries
.

PubMed

Rathmann, Wolfgang; Czech, Marcin; Franek, Edward; Kostev, Karel

2017-05-01

The purpose of this study was to investigate differences of insulin therapy regimens in five European countries. Proportions of basal bolus therapy (intensified insulin therapy (ICT), basal insulin supported oral therapy (BOT), conventional therapy (CT), and short-acting prandial insulin (SIT) among insulin-treated diabetes patients in Germany (n = 64,055), the UK (n = 6,740), and France (n = 4,779) were estimated using representative general medicine practice databases (Disease Analyzer: 2014). Insulin regimens in Hungary (n = 40,769) and Poland (n = 68,136) were analyzed based on nationwide prescription databases (LRx: 2014). ICT was the most frequent insulin regimen (46 - 81%) in all countries except France (BOT > ICT). SIT showed the lowest use, ranging from 2.5% in the UK to 11.2% in Germany. BOT was more frequently used than CT in Germany and Hungary, which was just the opposite in the UK and Poland. The share of insulin analogs among all prescriptions was higher in Germany, the UK, and France (short-acting insulins: 59 - 98%; basal insulins: 70 - 93%) than in Hungary and Poland (short-acting insulins: 41 - 57%; basal insulins: 23 - 46%) (all p < 0.001). Despite national and international guidelines, insulin regimens differ substantially between European countries. Our results most likely reflect differences in regulations and reimbursement systems, national diabetes care systems as well as patient characteristics and expectations.
.

Protective effect of caspase inhibition on compression-induced muscle damage

PubMed Central

Teng, Bee T; Tam, Eric W; Benzie, Iris F; Siu, Parco M

2011-01-01

Abstract There are currently no effective therapies for treating pressure-induced deep tissue injury. This study tested the efficacy of pharmacological inhibition of caspase in preventing muscle damage following sustained moderate compression. Adult Sprague–Dawley rats were subjected to prolonged moderate compression. Static pressure of 100 mmHg compression was applied to an area of 1.5 cm2 in the tibialis region of the right limb of the rats for 6 h each day for two consecutive days. The left uncompressed limb served as intra-animal control. Rats were randomized to receive either vehicle (DMSO) as control treatment (n = 8) or 6 mg kg−1 of caspase inhibitor (z-VAD-fmk; n = 8) prior to the 6 h compression on the two consecutive days. Muscle tissues directly underneath the compression region of the compressed limb and the same region of control limb were harvested after the compression procedure. Histological examination and biochemical/molecular measurement of apoptosis and autophagy were performed. Caspase inhibition was effective in alleviating the compression-induced pathohistology of muscle. The increases in caspase-3 protease activity, TUNEL index, apoptotic DNA fragmentation and pro-apoptotic factors (Bax, p53 and EndoG) and the decreases in anti-apoptotic factors (XIAP and HSP70) observed in compressed muscle of DMSO-treated animals were not found in animals treated with caspase inhibitor. The mRNA content of autophagic factors (Beclin-1, Atg5 and Atg12) and the protein content of LC3, FoxO3 and phospho-FoxO3 that were down-regulated in compressed muscle of DMSO-treated animals were all maintained at their basal level in the caspase inhibitor treated animals. Our data provide evidence that caspase inhibition attenuates compression-induced muscle apoptosis and maintains the basal autophagy level. These findings demonstrate that pharmacological inhibition of caspase/apoptosis is effective in alleviating muscle damage as induced by prolonged compression. PMID:21540338

[Efficacy and tolerance of aniracetam in elderly patients with primary or secondary mental deterioration].

PubMed

Canonico, V; Forgione, L; Paoletti, C; Casini, A; Colonna, C V; Bertini, M; Acito, R; Rengo, F

1991-01-01

The study was carried out on 60 patients (mean age 69.9 +/- 10.3 years) suffering from slight-moderate brain pathology primary or secondary to vascular forms. Patients were treated with 1500 mg/day per os of Aniracetam or placebo. Drug efficiency evaluation was performed utilizing the following psychometric tests: Blessed Scale, figures repetition test, Benton test, Corsi test, Rey test, Pieron test, phrases construction test, verbal fluency test. They were carried out during basal visit after two and four month treatment. In Aniracetam treated group the score showed a significant improving during the first and second control. In placebo treated group no change statistically considerable happened in any test. Aniracetam has proved to be a useful drug in slight-moderate brain decay treatment of the elderly.

Odontogenic Keratocysts in Gorlin-Goltz Syndrome: A Case Report.

PubMed

Chandran, Satheesh; Marudhamuthu, Karthikeyan; Riaz, R; Balasubramaniam, Saravanan

2015-01-01

Gorlin-Goltz syndrome is an autosomal dominant inherited condition comprising the principle triad of basal cell carcinomas, multiple jaw keratocysts, and skeletal anomalies. The presence of jaw cysts are the early diagnostic feature of this syndrome, and this can be incidentally identified by routine radiographs. A patient presented with signs and symptoms of Gorlin-Goltz syndrome to us in her early stages.

Skeletal stigmata as keys to access to the composite and ancient Gorlin-Goltz syndrome history: The Egypt, Pompeii and Herculaneum lessons.

PubMed

Ponti, Giovanni; Pellacani, Giovanni; Tomasi, Aldo; Sammaria, Giuliano; Manfredini, Marco

2016-09-10

There are several genetic diseases with a wide spectrum of congenital bone stigmata in association to cutaneous and visceral benign and malignant neoplasms. Gorlin-Goltz syndrome, also named nevoid basal cell carcinoma syndrome, is an autosomal dominant systemic disease with almost complete penetrance and high intra-familial phenotypic variability, caused by germline mutations of the gene PTCH1. The syndrome is characterized by unusual skeletal changes and high predisposition to the development of multiple basal cell carcinomas, odontogenic keratocysts tumors and other visceral tumors. The Gorlin syndrome, clinically defined as distinct syndrome in 1963, existed during Dynastic Egyptian times, as revealed by a costellation of skeletal findings compatible with the syndrome in mummies dating back to 3000years ago and, most likely, in the ancient population of Pompeii. These paleogenetic and historical evidences, together with the clinical and biomolecular modern evidences, confirm the quite benign behavior of the syndrome and the critical value of the multiple and synchronous skeletal anomalies in the recognition of these rare and complex genetic disease. Copyright © 2016 Elsevier B.V. All rights reserved.

A case of multiple system atrophy-parkinsonian type with stuttering- and palilalia-like dysfluencies and putaminal atrophy.

PubMed

Kikuchi, Yoshikazu; Umezaki, Toshiro; Uehara, Taira; Yamaguchi, Hiroo; Yamashita, Koji; Hiwatashi, Akio; Sawatsubashi, Motohiro; Adachi, Kazuo; Yamaguchi, Yumi; Murakami, Daisuke; Kira, Jun-Ichi; Nakagawa, Takashi

2017-11-14

Both developmental and acquired stuttering are related to the function of the basal ganglia-thalamocortical loop, which includes the putamen. Here, we present a case of stuttering- and palilalia-like dysfluencies that manifested as an early symptom of multiple system atrophy-parkinsonian type (MSA-P) and bilateral atrophy of the putamen. The patient was a 72-year-old man with no history of developmental stuttering who presented with a stutter for consultation with our otorhinolaryngology department. The patient was diagnosed with MSA-P based on parkinsonism, autonomic dysfunction, and bilateral putaminal atrophy revealed by T2-weighted magnetic resonance imaging. Treatment with levodopa improved both the motor functional deficits related to MSA-P and stuttering-like dysfluencies while reading; however, the palilalia-like dysfluencies were much less responsive to levodopa therapy. The patient died of aspiration pneumonia two years after his first consultation at our hospital. In conclusion, adult-onset stuttering- and palilalia-like dysfluencies warrant careful examination of the basal ganglia-thalamocortical loop, and especially the putamen, using neuroimaging techniques. Acquired stuttering may be related to deficits in dopaminergic function. Copyright © 2017 Elsevier Inc. All rights reserved.

Carbonized Micro- and Nanostructures: Can Downsizing Really Help?

PubMed Central

Naraghi, Mohammad; Chawla, Sneha

2014-01-01

In this manuscript, we discuss relationships between morphology and mechanical strength of carbonized structures, obtained via pyrolysis of polymeric precursors, across multiple length scales, from carbon fibers (CFs) with diameters of 5–10 μm to submicron thick carbon nanofibers (CNFs). Our research points to radial inhomogeneity, skin–core structure, as a size-dependent feature of polyacrylonitrile-based CFs. This inhomogeneity is a surface effect, caused by suppressed diffusion of oxygen and stabilization byproducts during stabilization through skin. Hence, reducing the precursor diameters from tens of microns to submicron appears as an effective strategy to develop homogeneous carbonized structures. Our research establishes the significance of this downsizing in developing lightweight structural materials by comparing intrinsic strength of radially inhomogeneous CFs with that of radially homogeneous CNF. While experimental studies on the strength of CNFs have targeted randomly oriented turbostratic domains, via continuum modeling, we have estimated that strength of CNFs can reach 14 GPa, when the basal planes of graphitic domains are parallel to nanofiber axis. The CNFs in our model are treated as composites of amorphous carbon (matrix), reinforced with turbostratic domains, and their strength is predicted using Tsai–Hill criterion. The model was calibrated with existing experimental data. PMID:28788651

Prognostic value of CtIP/RBBP8 expression in breast cancer

PubMed Central

Soria-Bretones, Isabel; Sáez, Carmen; Ruíz-Borrego, Manuel; Japón, Miguel A; Huertas, Pablo

2013-01-01

CtIP/RBBP8 is a multifunctional protein involved in transcription, DNA replication, DNA repair by homologous recombination and the G1 and G2 checkpoints. Its multiple roles are controlled by its interaction with several specific factors, including the tumor suppressor proteins BRCA1 and retinoblastoma. Both its functions and interactors point to a putative oncogenic potential of CtIP/RBBP8 loss. However, CtIP/RBBP8 relevance in breast tumor appearance, development, and prognosis has yet to be established. We performed a retrospective analysis of CtIP/RBBP8 and RB1 levels by immunohistochemistry using 384 paraffin-embedded breast cancer biopsies obtained during tumor removal surgery. We have observed that low or no expression of CtIP/RBBP8 correlates with high-grade breast cancer and with nodal metastasis. Reduction on CtIP/RBBP8 is most common in hormone receptor (HR)-negative, HER2-positive, and basal-like tumors. We observed lower levels of RB1 on those tumors with reduced CtIP/RBBP8 levels. On luminal tumors, decreased but not absence of CtIP/RBBP8 levels correlate with increased disease-free survival when treated with a combination of hormone, radio, and chemo therapies. PMID:24403251

Establishment of a Novel Lingual Organoid Culture System: Generation of Organoids Having Mature Keratinized Epithelium from Adult Epithelial Stem Cells

NASA Astrophysics Data System (ADS)

Hisha, Hiroko; Tanaka, Toshihiro; Kanno, Shohei; Tokuyama, Yoko; Komai, Yoshihiro; Ohe, Shuichi; Yanai, Hirotsugu; Omachi, Taichi; Ueno, Hiroo

2013-11-01

Despite the strong need for the establishment of a lingual epithelial cell culture system, a simple and convenient culture method has not yet been established. Here, we report the establishment of a novel lingual epithelium organoid culture system using a three-dimensional matrix and growth factors. Histological analyses showed that the generated organoids had both a stratified squamous epithelial cell layer and a stratum corneum. Very recently, we showed via a multicolor lineage tracing method that Bmi1-positive stem cells exist at the base of the epithelial basal layer in the interpapillary pit. Using our new culture system, we found that organoids could be generated by single Bmi1-positive stem cells and that in the established organoids, multiple Bmi1-positive stem cells were generated at the outermost layer. Moreover, we observed that organoids harvested at an early point in culture could be engrafted and maturate in the tongue of recipient mice and that the organoids generated from carcinogen-treated mice had an abnormal morphology. Thus, this culture system presents valuable settings for studying not only the regulatory mechanisms of lingual epithelium but also lingual regeneration and carcinogenesis.

Multiple orthokeratinized odontogenic cysts: a case report.

PubMed

Cheng, Yi-Shing Lisa; Liang, Hui; Wright, John; Teenier, Tom

2015-03-01

The purpose of this report is to document the clinical, radiographic, pathological and molecular findings of the first case of multiple orthokeratinized odontogenic cysts (OOCs). Multiple odontogenic keratocysts are one of the major features of nevoid basal cell carcinoma syndrome (NBCCS), and loss of heterozygosity in the PTCH gene, the culprit gene for NBCCS, has recently been found in sporadic OOC cases. Therefore, in this presenting case, we also investigated the possibility that this patient might also have NBCCS, by comparing the available clinical information and the molecular findings of this case to the diagnostic criteria for NBCCS (as proposed by the First International Colloquium on NBCCS in 2011). However, this patient with multiple OOCs showed no evidence of having NBCCS. This conclusion supports the findings from previous case series based on sporadic cases that OOC does not appear to be associated with NBCCS.

Fortune favours the bold: a higher predator reduces the impact of a native but not an invasive intermediate predator.

PubMed

Barrios-O'Neill, Daniel; Dick, Jaimie T A; Emmerson, Mark C; Ricciardi, Anthony; MacIsaac, Hugh J; Alexander, Mhairi E; Bovy, Helene C

2014-05-01

Emergent multiple predator effects (MPEs) might radically alter predictions of predatory impact that are based solely on the impact of individuals. In the context of biological invasions, determining if and how the individual-level impacts of invasive predators relates to their impacts in multiple-individual situations will inform understanding of how such impacts might propagate through recipient communities. Here, we use functional responses (the relationship between prey consumption rate and prey density) to compare the impacts of the invasive freshwater mysid crustacean Hemimysis anomala with a native counterpart Mysis salemaai when feeding on basal cladoceran prey (i) as individuals, (ii) in conspecific groups and (iii) in conspecific groups in the presence of a higher fish predator, Gasterosteus aculeatus. In the absence of the higher predator, the invader consumed significantly more basal prey than the native, and consumption was additive for both mysid species - that is, group consumption was predictable from individual-level consumption. Invaders and natives were themselves equally susceptible to predation when feeding with the higher fish predator, but an MPE occurred only between the natives and higher predator, where consumption of basal prey was significantly reduced. In contrast, consumption by the invaders and higher predator remained additive. The presence of a higher predator serves to exacerbate the existing difference in individual-level consumption between invasive and native mysids. We attribute the mechanism responsible for the MPE associated with the native to a trait-mediated indirect interaction, and further suggest that the relative indifference to predator threat on the part of the invader contributes to its success and impacts within invaded communities. © 2013 The Authors. Journal of Animal Ecology © 2013 British Ecological Society.

Long-term development of regeneration under longleaf pine seedtree and shelterwood stands

Treesearch

William D. Boyer

1993-01-01

Well-stocked mature longleaf pine (Pinus palustris Mill.) stands were cut tofive residual basal areas in 1957, namely 9,18,2 7.36, and 45 ft2 per ac, to observe the effect of stand density on seed production and seedling establishment. Seedlings, mainly from the 195.5 or 1961 seed crops, were established in treated stands. All pines on net 0.9 ac...

Engineering Devices to Treat Epilepsy: A Clinical Perspective

DTIC Science & Technology

2001-10-25

Research over the next three decades reinforced the idea that seizures likely spread through discrete, functional neuronal networks [2]. Over the last...15 years, researchers have demonstrated that it is possible to modulate the activity of functional neuronal networks in animal models of epilepsy by...hypothalamus [5], mamillary bodies [6], cerebellum [7], basal ganglia [8], locus ceruleus [9] and the substantia nigra [10]. At the same time some

Current trend in drug delivery considerations for subcutaneous insulin depots to treat diabetes.

PubMed

P V, Jayakrishnapillai; Nair, Shantikumar V; Kamalasanan, Kaladhar

2017-05-01

Diabetes mellitus (DM) is a metabolic disorder due to irregularities in glucose metabolism, as a result of insulin disregulation. Chronic DM (Type 1) is treated by daily insulin injections by subcutaneous route. Daily injections cause serious patient non-compliance and medication non-adherence. Insulin Depots (ID) are parenteral formulations designed to release the insulin over a specified period of time, to control the plasma blood glucose level for intended duration. Physiologically, pancreas produces and secretes insulin in basal and pulsatile mode into the blood. Delivery systems mimicking basal release profiles are known as open-loop systems and current marketed products are open-loop systems. Future trend in open-loop systems is to reduce the number of injections per week by enhancing duration of action, by modifying the depot properties. The next generation technologies are closed-loop systems that mimic the pulsatile mode of delivery by pancreas. In closed-loop systems insulin will be released in response to plasma glucose. This review focuses on future trend in open-loop systems; by understanding (a) the secretion of insulin from pancreas, (b) the insulin regulation normal and in DM, (c) insulin depots and (d) the recent progress in open-loop depot technology particularly with respect to nanosystems. Copyright © 2017 Elsevier B.V. All rights reserved.

Chlamydia trahomatis in cell culture. I. Comparison of efficiencies of infection in several chemically defined media, at various pH and temperature values, and after exposure to diethylaminoethyl-dextran

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rota, T.R.; Nichols, R.L.

1973-10-01

Three chemically defined cell culture media, Eagle minimum essential medium (MEM) with Earle basal salt solution, Eagle MEM with Hanks basal salt solution, and a modified Eagle MEM, were tested and found capable of supporting the development of Chlamydia trachomatis in /sup 60/Co-treated McCoy cells. The enhancement of trachoma infection by diethylaminoethyl-dextran (DEAE-D) was greater at pH values closer to neutrality than at and other pH values measured at the start of the experiments. Centrifugation of the trachoma inoculum onto cell monolayers at 33 C increased the number of inclusions when compared to centrifugation at 20 C. When the inoculummore » was centrifuged onto cell monolayers and subsequent incubation was at temperatures ranging from 34 to 39 C, the greatest number of inclusions was observed after incubation from 35 through 37 C. Enhancement of the trachoma infection by DEAE-D was tested at temperatures ranging from 35 to 37 C. These cultures had three- to fivefold increases in inclusions when compared to previously reported experiments in which DEAE-D- treated cultures were incubated at 34 C. (auth)« less

Basal cell nevus syndrome (Gorlin syndrome): genetic insights, diagnostic challenges, and unmet milestones.

PubMed

Akbari, Maryam; Chen, Harold; Guo, Grace; Legan, Zachary; Ghali, Ghali

2018-01-31

In this article, we present three clinical case reports on Basal Cell Nevus Syndrome (Gorlin Syndrome). Gorlin syndrome is an inherited medical condition with challenges that manifest in multiple body systems and complicate early diagnosis. We examine the epidemiology of the disease and benefits of genetic testing, molecular pathophysiology, and advancement in the molecular-based therapy of Basal Cell Nevus syndrome. The goal of this paper is to shed light on both unmet challenges and advancements in the management of Gorlin syndrome and to provide a new clinical perspective and guidance for future research. Furthermore, the FDA approved Hedgehog pathway inhibitors Vismodegib and Sonidegib designed for advanced basal cell carcinoma have opened a new door for treatment that may ultimately decrease the number of surgeries for a patient with Gorlin syndrome. The role of these agents in syndromic odontogenic keratocyst has not been studied extensively, but one study found that hedgehog pathway inhibitors decrease the size of syndromic odontogenic keratocyst. Ideal surgical treatment that balances low recurrence rates with low impact on one's quality of life for syndromic odontogenic keratocyst is another unanswered question for oral and maxillofacial surgeons. Per survey studies, treatment options practiced for syndromic odontogenic keratocyst range from marsupialization to segmental osteotomy. Future studies performed should take a comprehensive long-term approach with at least three years of follow-up in order to determine the most appropriate treatment. Copyright © 2018 Elsevier B.V. All rights reserved.

The transcription factor MTF-1 is essential for basal and heavy metal-induced metallothionein gene expression.

PubMed

Heuchel, R; Radtke, F; Georgiev, O; Stark, G; Aguet, M; Schaffner, W

1994-06-15

We have described and cloned previously a factor (MTF-1) that binds specifically to heavy metal-responsive DNA sequence elements in the enhancer/promoter region of metallothionein genes. MTF-1 is a protein of 72.5 kDa that contains six zinc fingers and multiple domains for transcriptional activation. Here we report the disruption of both alleles of the MTF-1 gene in mouse embryonic stem cells by homologous recombination. The resulting null mutant cell line fails to produce detectable amounts of MTF-1. Moreover, due to the loss of MTF-1, the endogenous metallothionein I and II genes are silent, indicating that MTF-1 is required for both their basal and zinc-induced transcription. In addition to zinc, other heavy metals, including cadmium, copper, nickel and lead, also fail to activate metal-responsive promoters in null mutant cells. However, cotransfection of an MTF-1 expression vector and metal-responsive reporter genes yields strong basal transcription that can be further boosted by zinc treatment of cells. These results demonstrate that MTF-1 is essential for metallothionein gene regulation. Finally, we present evidence that MTF-1 itself is a zinc sensor, which exhibits increased DNA binding activity upon zinc treatment.

Harvesting in delayed food web model with omnivory

NASA Astrophysics Data System (ADS)

Collera, Juancho A.

2016-02-01

We consider a tri-trophic community module called intraguild predation (IGP) that includes a prey and its predator which share a common basal resource for their sustenance. The growth of the basal resource in the absence of predation follows the Hutchinson's equation where the delay parameter arises, while functional responses in our model are of Lotka-Volterra type. Moreover, the basal resource is harvested for its economic value with a constant harvesting rate. This work generalizes the previous works on the same model with no harvesting and no time delay. We show that the harvesting rate has to be small enough in order for the equilibria to exist. Moreover, we show that by increasing the delay parameter the stability of the equilibrium solutions may change, and periodic solutions may emerge through Hopf bifurcations. In the case of the positive equilibrium solution, multiple stability switches are obtained, and numerical continuation shows that a stable branch of periodic solutions emerges once the positive equilibrium loses its stability at the first Hopf bifurcation point. This result is important because it gives an alternative for the coexistence of all three species, avoiding extinction of one or more species when the positive equilibrium becomes unstable.

The Work Softening Behavior of Pure Mg Wire during Cold Drawing.

PubMed

Sun, Liuxia; Bai, Jing; Xue, Feng; Chu, Chenglin; Meng, Jiao

2018-04-13

We performed multiple-pass cold drawing for pure Mg wire which showed excellent formability (~138% accumulative true strain) at room temperature. Different from the continuous work hardening occurring during cold drawing of Mg alloy wires, for pure Mg, an initially rapid increase in hardness and strength was followed by significant work softening and finally reached a steady-state level, approximately 40~45 HV. The work softening can be attributed to the dynamic recovery and recrystallization of pure Mg at room temperature. Meanwhile, an abrupt change in texture component also was detected with the transition from work hardening to softening in the strain range of 28~34%. During the whole drawing, the strongest texture component gradually transformed from as-extruded basal to <10 1 ¯ 0> fiber (~28% accumulative true strain), and then rapidly returned to the weak basal texture.

I2 basal stacking fault as a degradation mechanism in reverse gate-biased AlGaN/GaN HEMTs

NASA Astrophysics Data System (ADS)

Lang, A. C.; Hart, J. L.; Wen, J. G.; Miller, D. J.; Meyer, D. J.; Taheri, M. L.

2016-09-01

Here, we present the observation of a bias-induced, degradation-enhancing defect process in plasma-assisted molecular beam epitaxy grown reverse gate-biased AlGaN/GaN high electron mobility transistors (HEMTs), which is compatible with the current theoretical framework of HEMT degradation. Specifically, we utilize both conventional transmission electron microscopy and aberration-corrected transmission electron microscopy to analyze microstructural changes in not only high strained regions in degraded AlGaN/GaN HEMTs but also the extended gate-drain access region. We find a complex defect structure containing an I2 basal stacking fault and offer a potential mechanism for device degradation based on this defect structure. This work supports the reality of multiple failure mechanisms during device operation and identifies a defect potentially involved with device degradation.

[Lichen planus, a T-lymphocyte mediated reaction involving the skin and mucous membranes].

PubMed

van den Akker, T W

2001-10-06

Lichen planus concerns a benign skin disorder without involvement of other organ systems. Its course is generally limited to less than a year. Classic lichen planus is characterized by pruritic, violaceous, plane papules which occur most commonly on the inside of the wrists, the lower back, the lower legs and the perimalleolar region of adults aged between 30-60 years. Frequently, oral and genital mucous membrane lesions are involved. Erosive mucosal lesions are particularly painful and long-lasting. Many clinical variants have been described ranging from lichenoid drug eruptions to associations with graft-versus-host disease. The cause of lichen planus is unknown. An immunopathological pathogenesis with T-lymphocytes directed against basal keratinocytes or the basal membrane zone is assumed. Multiple therapeutic options exist: local and systemic corticosteroids, psoralens with ultraviolet A light (PUVA), retinoids, cyclosporin.

Reduced cortical innervation of the subthalamic nucleus in MPTP-treated parkinsonian monkeys

PubMed Central

Mathai, Abraham; Ma, Yuxian; Paré, Jean-Francois; Villalba, Rosa M.; Wichmann, Thomas

2015-01-01

The striatum and the subthalamic nucleus are the main entry points for cortical information to the basal ganglia. Parkinson’s disease affects not only the function, but also the morphological integrity of some of these inputs and their synaptic targets in the basal ganglia. Significant morphological changes in the cortico-striatal system have already been recognized in patients with Parkinson’s disease and in animal models of the disease. To find out whether the primate cortico-subthalamic system is also subject to functionally relevant morphological alterations in parkinsonism, we used a combination of light and electron microscopy anatomical approaches and in vivo electrophysiological methods in monkeys rendered parkinsonian following chronic exposure to low doses of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). At the light microscopic level, the density of vesicular glutamate transporter 1-positive (i.e. cortico-subthalamic) profiles in the dorsolateral part of the subthalamic nucleus (i.e. its sensorimotor territory) was 26.1% lower in MPTP-treated parkinsonian monkeys than in controls. These results were confirmed by electron microscopy studies showing that the number of vesicular glutamate transporter 1-positive terminals and of axon terminals forming asymmetric synapses in the dorsolateral subthalamic nucleus was reduced by 55.1% and 27.9%, respectively, compared with controls. These anatomical findings were in line with in vivo electrophysiology data showing a 60% reduction in the proportion of pallidal neurons that responded to electrical stimulation of the cortico-subthalamic system in parkinsonian monkeys. These findings provide strong evidence for a partial loss of the hyperdirect cortico-subthalamic projection in MPTP-treated parkinsonian monkeys. PMID:25681412

Targeting monoamine oxidase A in advanced prostate cancer.

PubMed

Flamand, Vincent; Zhao, Hongjuan; Peehl, Donna M

2010-11-01

Inhibitors of monoamine oxidase A (MAOA), a mitochondrial enzyme that degrades neurotransmitters including serotonin and norepinephrine, are commonly used to treat neurological conditions including depression. Recently, we and others identified high expression of MAOA in normal basal prostatic epithelium and high-grade primary prostate cancer (PCa). In contrast, MAOA is low in normal secretory prostatic epithelium and low-grade PCa. An irreversible inhibitor of MAOA, clorgyline, induced secretory differentiation in primary cultures of normal basal epithelial cells and high-grade PCa. Furthermore, clorgyline inhibited several oncogenic pathways in PCa cells, suggesting clinical value of MAOA inhibitors as a pro-differentiation and anti-oncogenic therapy for high-risk PCa. Here, we extended our studies to a model of advanced PCa, VCaP cells, which were derived from castration-resistant metastatic PCa and express a high level of MAOA. Growth of VCaP cells in the presence or absence of clorgyline was evaluated in vitro and in vivo. Gene expression changes in response to clorgyline were determined by microarray and validated by quantitative real-time polymerase chain reaction. Treatment with clorgyline in vitro inhibited growth and altered the transcriptional pattern of VCaP cells in a manner consistent with the pro-differentiation and anti-oncogenic effects seen in treated primary PCa cells. Src, beta-catenin, and MAPK oncogenic pathways, implicated in androgen-independent growth and metastasis, were significantly downregulated. Clorgyline treatment of mice bearing VCaP xenografts slowed tumor growth and induced transcriptome changes similar to those noted in vitro. Our results support the possibility that anti-depressant drugs that target MAOA might find a new application in treating PCa.

Diet Restriction Inhibits Apoptosis and HMGB1 Oxidation and Promotes Inflammatory Cell Recruitment during Acetaminophen Hepatotoxicity

PubMed Central

Antoine, Daniel James; Williams, Dominic P; Kipar, Anja; Laverty, Hugh; Park, B Kevin

2010-01-01

Acetaminophen (APAP) overdose is a major cause of acute liver failure and serves as a paradigm to elucidate mechanisms, predisposing factors and therapeutic interventions. The roles of apoptosis and inflammation during APAP hepatotoxicity remain controversial. We investigated whether fasting of mice for 24 h can inhibit APAP-induced caspase activation and apoptosis through the depletion of basal ATP. We also investigated in fasted mice the critical role played by inhibition of caspase-dependent cysteine 106 oxidation within high mobility group box-1 protein (HMGB1) released by ATP depletion in dying cells as a mechanism of immune activation. In fed mice treated with APAP, necrosis was the dominant form of hepatocyte death. However, apoptosis was also observed, indicated by K18 cleavage, DNA laddering and procaspase-3 processing. In fasted mice treated with APAP, only necrosis was observed. Inflammatory cell recruitment as a consequence of hepatocyte death was observed only in fasted mice treated with APAP or fed mice cotreated with a caspase inhibitor. Hepatic inflammation was also associated with loss in detection of serum oxidized-HMGB1. A significant role of HMGB1 in the induction of inflammation was confirmed with an HMGB1-neutralizing antibody. The differential response between fasted and fed mice was a consequence of a significant reduction in basal hepatic ATP, which prevented caspase processing, rather than glutathione depletion or altered APAP metabolism. Thus, the inhibition of caspase-driven apoptosis and HMGB1 oxidation by ATP depletion from fasting promotes an inflammatory response during drug-induced hepatotoxicity/liver pathology. PMID:20811657

Basal-topographic control of stationary ponds on a continuously moving landslide

USGS Publications Warehouse

Coe, J.A.; McKenna, J.P.; Godt, J.W.; Baum, R.L.

2009-01-01

The Slumgullion landslide in the San Juan Mountains of southwestern Colorado has been moving for at least the last few hundred years and has multiple ponds on its surface. We have studied eight ponds during 30 trips to the landslide between July 1998 and July 2007. During each trip, we have made observations on the variability in pond locations and water levels, taken ground-based photographs to document pond water with respect to moving landslide material and vegetation, conducted Global Positioning System surveys of the elevations of water levels and mapped pond sediments on the landslide surface. Additionally, we have used stereo aerial photographs taken in October 1939, October 1940 and July 2000 to measure topographic profiles of the eight pond locations, as well as a longitudinal profile along the approximate centerline of the landslide, to examine topographic changes over a 60- to 61-year period of time. Results from field observations, analyses of photographs, mapping and measurements indicate that all pond locations have remained spatially stationary for 60-300 years while landslide material moves through these locations. Water levels during the observation period were sensitive to changes in the local, spring-fed, stream network, and to periodic filling of pond locations by sediment from floods, hyperconcentrated flows, mud flows and debris flows. For pond locations to remain stationary, the locations must mimic depressions along the basal surface of the landslide. The existence of such depressions indicates that the topography of the basal landslide surface is irregular. These results suggest that, for translational landslides that have moved distances larger than the dimensions of the largest basal topographic irregularities (about 200 m at Slumgullion), landslide surface morphology can be used as a guide to the morphology of the basal slip surface. Because basal slip surface morphology can affect landslide stability, kinematic models and stability analyses of translational landslides should attempt to incorporate irregular basal surface topography. Additional implications for moving landslides where basal topography controls surface morphology include the following: dateable sediments or organic material from basal layers of stationary ponds will yield ages that are younger than the date of landslide initiation, and it is probable that other landslide surface features such as faults, streams, springs and sinks are also controlled by basal topography. The longitudinal topographic profile indicated that the upper part of the Slumgullion landslide was depleted at a mean vertical lowering rate of 5.6 cm/yr between 1939 and 2000, while the toe advanced at an average rate of 1.5 m/yr during the same period. Therefore, during this 61-year period, neither the depletion of material at the head of the landslide nor continued growth of the landslide toe has decreased the overall movement rate of the landslide. Continued depletion of the upper part of the landslide, and growth of the toe, should eventually result in stabilization of the landslide. Copyright ?? 2008 John Wiley & Sons, Ltd.

Dermatocosmetologic aspects of treatment of basal-cell skin cancer

NASA Astrophysics Data System (ADS)

Geinitz, A. V.; Stranadko, Ye. F.; Yusupova, Zh. M.; Tkachenko, S. B.

2005-08-01

The obtained clinical findings demonstrate excellent results after surgical MSC treatment with the application of modem laser surgical technologies. All the operated patients were under oncologist"s control during 1.5-2.5 years. In 6 cases we observed topical recurrences which needed a repeated intervention. Thus, our experience of applying LPh for surgical treatment of basal-cell carcinomas of the head and neck dem- onstrate that in the analysed cases it is more reasonable to use two models of laser devices different in their physical parameters. These devices are used at different surgical stages so as to provide a precise effect in laser tumour va- porization within the borders of the healthy tissue, to make better vascular coagulation and laser smoothing of wound surface. Immediate, direct and long-term results of modern surgical lasers" application for treating skin BSC almost in all cases give good and excellent cosmetic effect after such intenventions.

Matrix metalloproteinase 9 (MMP-9) is indispensable for long term potentiation in the central and basal but not in the lateral nucleus of the amygdala.

PubMed

Gorkiewicz, Tomasz; Balcerzyk, Marcin; Kaczmarek, Leszek; Knapska, Ewelina

2015-01-01

It has been shown that matrix metalloproteinase 9 (MMP-9) is required for synaptic plasticity, learning and memory. In particular, MMP-9 involvement in long-term potentiation (LTP, the model of synaptic plasticity) in the hippocampus and prefrontal cortex has previously been demonstrated. Recent data suggest the role of MMP-9 in amygdala-dependent learning and memory. Nothing is known, however, about its physiological correlates in the specific pathways in the amygdala. In the present study we show that LTP in the basal and central but not lateral amygdala (LA) is affected by MMP-9 knock-out. The MMP-9 dependency of LTP was confirmed in brain slices treated with a specific MMP-9 inhibitor. The results suggest that MMP-9 plays different roles in synaptic plasticity in different nuclei of the amygdala.

Odontogenic Keratocysts in Gorlin–Goltz Syndrome: A Case Report

PubMed Central

Chandran, Satheesh; Marudhamuthu, Karthikeyan; Riaz, R; Balasubramaniam, Saravanan

2015-01-01

Gorlin–Goltz syndrome is an autosomal dominant inherited condition comprising the principle triad of basal cell carcinomas, multiple jaw keratocysts, and skeletal anomalies. The presence of jaw cysts are the early diagnostic feature of this syndrome, and this can be incidentally identified by routine radiographs. A patient presented with signs and symptoms of Gorlin–Goltz syndrome to us in her early stages. PMID:26225111

A nearest-neighbor imputation approach to mapping tree species over large areas using forest inventory plots and moderate resolution raster data

Treesearch

B. Tyler Wilson; Andrew J. Lister; Rachel I. Riemann

2012-01-01

The paper describes an efficient approach for mapping multiple individual tree species over large spatial domains. The method integrates vegetation phenology derived from MODIS imagery and raster data describing relevant environmental parameters with extensive field plot data of tree species basal area to create maps of tree species abundance and distribution at a 250-...

Effects of basal area on survival and growth of longleaf pine when practicing selection silviculture

Treesearch

Ferhat Kara; Edward F. Loewenstein; Dale G. Brockway

2017-01-01

Aim of study: Uneven-aged (UEA) management systems can achieve multiple-use objectives, however, use of UEA techniques to manage longleaf pine (Pinus palustris Mill.) forests are still open to question, because of the species’ intolerance of competition. It was our aim to examine the influence of different levels (9.2, 13.8 and...

Basal fire wounds on some southern Appalachian hardwoods

Treesearch

RM Nelson; IH Sims; MS. Abell

1933-01-01

Data from 317 oaks and yellow poplars wounded by a spring fire in Virginia were analyzed by means of multiple linear correlation. A method was obtained whereby the size of wound can be predicted provided the areas of discolored bark and diameters of injured trees are known. The method of prediction so far is safely applicable only to groups of trees similar to those...

TASK Channels on Basal Forebrain Cholinergic Neurons Modulate Electrocortical Signatures of Arousal by Histamine

PubMed Central

Vu, Michael T.; Du, Guizhi; Bayliss, Douglas A.

2015-01-01

Basal forebrain cholinergic neurons are the main source of cortical acetylcholine, and their activation by histamine elicits cortical arousal. TWIK-like acid-sensitive K+ (TASK) channels modulate neuronal excitability and are expressed on basal forebrain cholinergic neurons, but the role of TASK channels in the histamine-basal forebrain cholinergic arousal circuit is unknown. We first expressed TASK channel subunits and histamine Type 1 receptors in HEK cells. Application of histamine in vitro inhibited the acid-sensitive K+ current, indicating a functionally coupled signaling mechanism. We then studied the role of TASK channels in modulating electrocortical activity in vivo using freely behaving wild-type (n = 12) and ChAT-Cre:TASKf/f mice (n = 12), the latter lacking TASK-1/3 channels on cholinergic neurons. TASK channel deletion on cholinergic neurons significantly altered endogenous electroencephalogram oscillations in multiple frequency bands. We then identified the effect of TASK channel deletion during microperfusion of histamine into the basal forebrain. In non-rapid eye movement sleep, TASK channel deletion on cholinergic neurons significantly attenuated the histamine-induced increase in 30–50 Hz activity, consistent with TASK channels contributing to histamine action on basal forebrain cholinergic neurons. In contrast, during active wakefulness, histamine significantly increased 30–50 Hz activity in ChAT-Cre:TASKf/f mice but not wild-type mice, showing that the histamine response depended upon the prevailing cortical arousal state. In summary, we identify TASK channel modulation in response to histamine receptor activation in vitro, as well as a role of TASK channels on cholinergic neurons in modulating endogenous oscillations in the electroencephalogram and the electrocortical response to histamine at the basal forebrain in vivo. SIGNIFICANCE STATEMENT Attentive states and cognitive function are associated with the generation of γ EEG activity. Basal forebrain cholinergic neurons are important modulators of cortical arousal and γ activity, and in this study we investigated the mechanism by which these neurons are activated by the wake-active neurotransmitter histamine. We found that histamine inhibited a class of K+ leak channels called TASK channels and that deletion of TASK channels selectively on cholinergic neurons modulated baseline EEG activity as well as histamine-induced changes in γ activity. By identifying a discrete brain circuit where TASK channels can influence γ activity, these results represent new knowledge that enhances our understanding of how subcortical arousal systems may contribute to the generation of attentive states. PMID:26446210

Species-environment relationships and vegetation patterns: Effects of spatial scale and tree life-stage

USGS Publications Warehouse

Stohlgren, T.J.; Bachand, R.R.; Onami, Y.; Binkley, Dan

1998-01-01

Do relationships between species and environmental gradients strengthen or weaken with tree life-stage (i.e., small seedlings, large seedlings, saplings, and mature trees)? Strengthened relationships may lead to distinct forest type boundaries, or weakening connections could lead to gradual ecotones and heterogeneous forest landscapes. We quantified the changes in forest dominance (basal area of tree species by life-stage) and environmental factors (elevation, slope, aspect, intercepted photosynthetically active radiation (PAR), summer soil moisture, and soil depth and texture) across 14 forest ecotones (n = 584, 10 m x 10 m plots) in Rocky Mountain National Park, Colorado, U.S.A. Local, ecotone-specific species-environment relationships, based on multiple regression techniques, generally strengthened from the small seedling stage (multiple R2 ranged from 0.00 to 0.26) to the tree stage (multiple R2 ranged from 0.20 to 0.61). At the landscape scale, combined canonical correspondence analysis (CCA) among species and for all tree life-stages suggested that the seedlings of most species became established in lower-elevation, drier sites than where mature trees of the same species dominated. However, conflicting evidence showed that species-environment relationships may weaken with tree life-stage. Seedlings were only found in a subset of plots (habitats) occupied by mature trees of the same species. At the landscape scale, CCA results showed that species-environment relationships weakened somewhat from the small seedling stage (86.4% of the variance explained by the first two axes) to the tree stage (76.6% of variance explained). The basal area of tree species co-occurring with Pinus contorta Doug. ex. Loud declined more gradually than P. contorta basal area declined across ecotones, resulting in less-distinct forest type boundaries. We conclude that broad, gradual ecotones and heterogeneous forest landscapes are created and maintained by: (1) sporadic establishment of seedlings in sub-optimal habitats; (2) survivorship of saplings and mature trees in a wider range of environmental conditions than seedlings presently endure; and (3) the longevity of trees and persistence of tree species in a broad range of soils, climates, and disturbance regimes.

Patient awareness and sun protection behaviour following excision of basal cell carcinoma.

PubMed

de Blacam, Catherine; Dermott, Clodagh Mc; Sugrue, Conor; Kilmartin, Darren; Kelly, Jack

2017-02-01

Limited information is available regarding disease awareness and sun protection behaviour in patients previously treated for non-melanoma skin cancer. Using a telephone-administered questionnaire, we investigated these characteristics in 250 patients in the west of Ireland who had undergone excision of basal cell carcinomas between January 2011 and December 2012. Only 28.8% of respondents knew that the lesion they had excised was a BCC and understood that there was a significant chance of developing another similar lesion in the next 3 years. Women and patients under age 65 were significantly better informed about their diagnosis than men (p = 0.021 and 0.000 respectively). The majority of patients (71.2%) knew that the overall effect of UV radiation on the skin was harmful and did employ some form of sun protection (avoid midday sun 72%; stay in shade 74%; wear hat 73.6%; wear sunscreen 72.8%). Females were statistically more likely to exercise better sun-protection behaviour (p = 0.002). While 76.8% of patients undertook some form of outdoor activity every day, only 22.8% wore sunscreen every day. Greater efforts should be made to communicate disease details and sun protection implications associated with basal cell carcinoma, especially to male patients. Improved population specific skin cancer awareness may lead to earlier detection and thus decrease both the patient morbidity and economic burden associated with locally advanced basal cell carcinoma. Copyright © 2015 Royal College of Surgeons of Edinburgh (Scottish charity number SC005317) and Royal College of Surgeons in Ireland. Published by Elsevier Ltd. All rights reserved.

Enhanced basal activation of mitogen-activated protein kinases in adipocytes from type 2 diabetes: potential role of p38 in the downregulation of GLUT4 expression.

PubMed

Carlson, Christian J; Koterski, Sandra; Sciotti, Richard J; Poccard, German Braillard; Rondinone, Cristina M

2003-03-01

Serine and threonine kinases may contribute to insulin resistance and the development of type 2 diabetes. To test the potential for members of the mitogen-activated protein (MAP) kinase family to contribute to type 2 diabetes, we examined basal and insulin-stimulated Erk 1/2, JNK, and p38 phosphorylation in adipocytes isolated from healthy and type 2 diabetic individuals. Maximal insulin stimulation increased the phosphorylation of Erk 1/2 and JNK in healthy control subjects but not type 2 diabetic patients. Insulin stimulation did not increase p38 phosphorylation in either healthy control subjects or type 2 diabetic patients. In type 2 diabetic adipocytes, the basal phosphorylation status of these MAP kinases was significantly elevated and was associated with decreased IRS-1 and GLUT4 in these fat cells. To determine whether MAP kinases were involved in the downregulation of IRS-1 and GLUT4 protein levels, selective inhibitors were used to inhibit these MAP kinases in 3T3-L1 adipocytes treated chronically with insulin. Inhibition of Erk 1/2, JNK, or p38 had no effect on insulin-stimulated reduction of IRS-1 protein levels. However, inhibition of the p38 pathway prevented the insulin-stimulated decrease in GLUT4 protein levels. In summary, type 2 diabetes is associated with an increased basal activation of the MAP kinase family. Furthermore, upregulation of the p38 pathway might contribute to the loss of GLUT4 expression observed in adipose tissue from type 2 diabetic patients.

Ex vivo-expanded bone marrow CD34(+) for acute myocardial infarction treatment: in vitro and in vivo studies.

PubMed

Gunetti, Monica; Noghero, Alessio; Molla, Fabiola; Staszewsky, Lidia Irene; de Angelis, Noeleen; Soldo, Annarita; Russo, Ilaria; Errichiello, Edoardo; Frasson, Chiara; Rustichelli, Deborah; Ferrero, Ivana; Gualandris, Anna; Berger, Massimo; Geuna, Massimo; Scacciatella, Paolo; Basso, Giuseppe; Marra, Sebastiano; Bussolino, Federico; Latini, Roberto; Fagioli, Franca

2011-10-01

Bone marrow (BM)-derived cells appear to be a promising therapeutic source for the treatment of acute myocardial infarction (AMI). However, the quantity and quality of the cells to be used, along with the appropriate time of administration, still need to be defined. We thus investigated the use of BM CD34(+)-derived cells as cells suitable for a cell therapy protocol (CTP) in the treatment of experimental AMI. The need for a large number of cells was satisfied by the use of a previously established protocol allowing the expansion of human CD34(+) cells isolated from neonatal and adult hematopoietic tissues. We evaluated gene expression, endothelial differentiation potential and cytokine release by BM-derived cells during in vitro culture. Basal and expanded CD34(+) cells were used as a delivery product in a murine AMI model consisting of a coronary artery ligation (CAL). Cardiac function recovery was evaluated after injecting basal or expanded cells. Gene expression analysis of in vitro-expanded cells revealed that endothelial markers were up-regulated during culture. Moreover, expanded cells generated a CD14(+) subpopulation able to differentiate efficiently into VE-cadherin-expressing cells. In vivo, we observed a cardiac function recovery in mice sequentially treated with basal and expanded cells injected 4 h and 7 days after CAL, respectively. Our data suggest that combining basal and expanded BM-derived CD34(+) cells in a specific temporal pattern of administration might represent a promising strategy for a successful cell-based therapy.

The Birmingham pituitary database: auditing the outcome of the treatment of acromegaly.

PubMed

Jenkins, D; O'Brien, I; Johnson, A; Shakespear, R; Sheppard, M C; Stewart, P M

1995-11-01

Reduction of GH concentrations in acromegalic subjects may improve the increased mortality associated with the condition. Audit of the biochemical outcome of the management of acromegaly is, therefore, important. (1) To audit the biochemical 'cure' rate of acromegalic patients treated by surgery and/or radiotherapy under the care of the South Birmingham Endocrine Clinic. (2) To assess the correlation between random or basal GH with IGF-I and nadir GH during an oral glucose tolerance test. Ascertainment of acromegalic patients from a pituitary database. Mode of therapy, pretreatment GH, pretreatment tumour size, post-treatment GH, post-treatment IGF-I and post-treatment nadir GH were recorded. Biochemical cure was defined as a most recent random or basal GH < 5 mU/l. Cure rates were determined. Eighty-nine acromegalic patients were identified as having received surgery and/or radiotherapy. In 35/89 (39%) the most recent GH was < 5 mU/l. The cure rate following surgery was 26/78 (33%). This was not significantly associated with tumour size, but was associated with pretreatment GH concentration (chi 2 = 7.1, 2d.f., P < 0.05). Random/basal GH showed a log-linear association with IGF-I, r = 0.72, and a linear association with nadir GH, r = 0.93. Biochemical cure of acromegaly was more strongly associated with pretreatment GH than with tumour size. Random/basal GH measurements are useful and convenient for the audit of treatment outcome in acromegaly. Ways of improving the biochemical outcome of acromegaly should be sought.

Targeted Metabolomics Reveals a Protective Role for Basal PPARα in Cholestasis Induced by α-Naphthylisothiocyanate.

PubMed

Dai, Manyun; Hua, Huiying; Lin, Hante; Xu, Gangming; Hu, Xiaowei; Li, Fei; Gonzalez, Frank J; Liu, Aiming; Yang, Julin

2018-04-06

α-Naphthylisothiocyanate (ANIT) is an experimental agent used to induce intrahepatic cholestasis. The Ppara-null mouse line is widely employed to explore the physiological and pathological roles of PPARα. However, little is known about how PPARα influences the hepatotoxicity of ANIT. In the present study, wild-type and Ppara-null mice were orally treated with ANIT to induce cholestasis. The serum metabolome of wild-type mice segregated from that of the Ppara-null mice, driven by changes of bile acid (BA) metabolites. Alkaline phosphatase and total BAs were elevated preferentially in Ppara-null mice, which correlated with changes in Cyp7a1, Cyp8b1, Mrp3, Cyp3a11, Cyp2b10, Ugt1a2, and Ugt1a5 genes and showed cross-talk between basal PPARα and potentially adaptive pathways. Il6, Tnfa, and target genes in the STAT3 pathway ( Socs3, Fga, Fgb, and Fgg) were up-regulated in Ppara-null mice but not in wild-type mice. The JNK pathway was activated in both mouse lines, while NF-κB and STAT3 were activated only in Ppara-null mice. These data suggest protection against cholestasis by basal PPARα involves regulation of BA metabolism and inhibition of NF-κB/STAT3 signaling. Considering studies on the protective effects of both basal and activated PPARα, caution should be exercised when one attempts to draw conclusions in which the PPARα is modified by genetic manipulation, fasting, or activation in pharmacological and toxicological studies.

The effect of temperature on basal tension and thyroarytenoid muscle contraction in an isolated rat glottis model.

PubMed

Wang, Hsing-Won; Chu, Yueng-Hsiang; Chao, Pin-Zhir; Lee, Fei-Peng

2014-10-01

The pitch of voice is closely related to the vocal fold tension, which is the end result of coordinated movement of the intralaryngeal muscles, and especially the thyroarytenoid muscle. It is known that vocal quality may be affected by surrounding temperature; however, the effect of temperature on vocal fold tension is mostly unknown. Thus, the aim of this study was to evaluate the effect of temperature on isolated rat glottis and thyroarytenoid muscle contraction induced by electrical field stimulation. In vitro isometric tension of the glottis ring from 30 Sprague-Dawley rats was continuously recorded by the tissue bath method. Electrical field stimulation was applied to the glottis ring with two wire electrodes placed parallel to the glottis and connected to a direct-current stimulator. The tension changes of the rat glottis rings that were either untreated or treated with electrical field stimulation were recorded continuously at temperatures from 37 to 7 °C or from 7 to 37 °C. Warming from 7 to 37 °C increased the basal tension of the glottis rings and decreased the electrical field stimulation-induced glottis ring contraction, which was chiefly due to thyroarytenoid muscle contraction. In comparison, cooling from 37 to 7 °C decreased the basal tension and enhanced glottis ring contraction by electrical field stimulation. We concluded that warming increased the basal tension of the glottis in vitro and decreased the amplitude of electrical field stimulation-induced thyroarytenoid muscle contraction. Thus, vocal pitch and the fine tuning of vocal fold tension might be affected by temperature in vivo.

Recovery of microtubules on the blepharoplast of Ceratopteris spermatogenous cells after oryzalin treatment.

PubMed

Vaughn, Kevin C; Bowling, Andrew J

2008-11-01

Most land plants have ill-defined microtubule-organizing centers (MTOCs), consisting of sites on the nuclear envelope or even along microtubules (MTs). In contrast, the spermatogenous cells of the pteridophyte Ceratopteris richardii have a well-defined MTOC, the blepharoplast, which organizes MTs through the last two division cycles. This allows a rare opportunity to study the organization and workings of a structurally well-defined plant MTOC. In this study, antheridial plants were treated with levels of oryzalin that cause complete MT loss from the cells containing blepharoplasts. The oryzalin was then washed out and plants were allowed to recover for varying amounts of time. If the spermatogenous cells were fixed prior to washing out, the blepharoplasts had an unusual appearance. In the matrix (pericentriolar) material where MT ends are normally found, clear areas of about the diameter of MTs were seen embedded in a much deeper matrix, made more obvious in stereo pairs. Occasionally, the matrix material was highly distended, although the basal body template cylinder morphology appeared to be unaltered. The blepharoplasts often occurred as clusters of 2 or 4, indicating that blepharoplast reproduction is not affected by the lack of MTs, but that their movement to the poles is. Gamma (gamma) tubulin antibodies labeled the edge of the blepharoplast in areas where the pits are located, indicating that these might be sites for MT nucleation. After wash out, the new MTs always re-appeared on the blepharoplast and the recovery occurred within an hour of washout. MT lengths increased with increasing washout time and were indistinguishable from untreated blepharoplasts after 24 h of recovery. After washout, arrays formed in new sperm cells such as the spline and basal bodies were often malformed or present in multiple copies, as were the blepharoplasts in these cells prior to wash out. These data indicate that the blepharoplast serves as the site of MT nucleation and organization even after complete MT de-polymerization.

A monograph of Otidea (Pyronemataceae, Pezizomycetes).

PubMed

Olariaga, I; Van Vooren, N; Carbone, M; Hansen, K

2015-12-01

The easily recognised genus Otidea is subjected to numerous problems in species identification. A number of old names have undergone various interpretations, materials from different continents have not been compared and misidentifications occur commonly. In this context, Otidea is monographed, based on our multiple gene phylogenies assessing species boundaries and comparative morphological characters (see Hansen & Olariaga 2015). All names combined in or synonymised with Otidea are dealt with. Thirty-three species are treated, with full descriptions and colour illustrations provided for 25 of these. Five new species are described, viz. O. borealis, O. brunneoparva, O. oregonensis, O. pseudoleporina and O. subformicarum. Otidea cantharella var. minor and O. onotica var. brevispora are elevated to species rank. Otideopsis kaushalii is combined in the genus Otidea. A key to the species of Otidea is given. An LSU dataset containing 167 sequences (with 44 newly generated in this study) is analysed to place collections and determine whether the named Otidea sequences in GenBank were identified correctly. Fourty-nine new ITS sequences were generated in this study. The ITS region is too variable to align across Otidea, but had low intraspecific variation and it aided in species identifications. Thirty type collections were studied, and ITS and LSU sequences are provided for 12 of these. A neotype is designated for O. cantharella and epitypes for O. concinna, O. leporina and O. onotica, along with several lectotypifications. The apothecial colour and shape, and spore characters are important for species identification. We conclude that to distinguish closely related or morphologically similar species, a combination of additional features are needed, i.e. the shape of the paraphyses, ectal excipulum structure, types of ectal excipulum resinous exudates and their reactions in Melzer's reagent and KOH, tomentum and basal mycelium colours and exudates. The KOH reaction of excipular resinous exudates and basal mycelium are introduced as novel taxonomic characters.

Hemolytic Uremic Syndrome-associated Encephalopathy Successfully Treated with Corticosteroids.

PubMed

Hosaka, Takashi; Nakamagoe, Kiyotaka; Tamaoka, Akira

2017-11-01

The encephalopathy that occurs in association with hemolytic uremic syndrome (HUS), which is caused by enterohemorrhagic Escherichia coli (E. coli), has a high mortality rate and patients sometimes present sequelae. We herein describe the case of a 20-year-old woman who developed encephalopathy during the convalescent stage of HUS caused by E.coli O26. Hyperintense lesions were detected in the pons, basal ganglia, and cortex on diffusion-weighted brain MRI. From the onset of HUS encephalopathy, we treated the patient with methylprednisolone (mPSL) pulse therapy alone. Her condition improved, and she did not present sequelae. Our study shows that corticosteroids appear to be effective for the treatment of some patients with HUS encephalopathy.

Photodynamic therapy effective for the treatment of actinic keratosis and basal cell carcinoma in bullous pemphigoid patients.

PubMed

Canavan, Theresa N; de la Feld, Salma Faghri; Huang, Conway; Sami, Naveed

2017-06-01

Treating skin cancers and extensive actinic keratosis in patients with bullous pemphigoid (BP) can be challenging. Treatment options pose unique risks in these patients as surgical wounds can have delayed wound healing and photodynamic therapy (PDT) may exacerbate their blistering disease. We report the successful use of PDT to treat actinic keratosis and skin cancers in two patients with BP, both of whom had excellent response to PDT and tolerated treatment without any bullous disease flares. Carefully selected patients with skin cancers and stable, well controlled BP can be safely considered for treatment using PDT. Copyright © 2017 Elsevier B.V. All rights reserved.

Management of type 2 diabetes with Fixed-Ratio combination insulin degludec/liraglutide (IDEGLIRA) versus Basal-Bolus therapy (INSULIN GLARGINE U100 PLUS INSULIN ASPART): A Short-Term Cost-Effectiveness analysis in the UK setting.

PubMed

Drummond, R S; Malkin, Sjp; Du Preez, M; Lee, X Y; Hunt, B

2018-05-24

Insulin degludec/liraglutide (IDegLira) is a once-daily, single-injection, fixed-ratio combination of insulin degludec, a basal insulin with a half-life of more than 24 hours, and GLP-1 receptor agonist liraglutide. The present analysis evaluated the cost-effectiveness of IDegLira versus basal-bolus therapy (BBT) with insulin glargine U100 plus up to four times daily insulin aspart for management of type 2 diabetes in the UK. A Microsoft Excel model was used to evaluate the cost-utility of IDegLira versus BBT over a 1-year time horizon. Clinical input data were taken from the treat-to-target DUAL VII trial, conducted in patients unable to achieve adequate glycaemic control (Hb A1c <7.0%) with basal insulin, with IDegLira associated with lower rates of hypoglycaemia and reduced body mass index (BMI) in comparison with BBT, with similar Hb A1c reductions. Costs (GBP) and event-related disutilities were taken from published sources. Extensive sensitivity analyses were performed. IDegLira was associated with an improvement of 0.05 quality-adjusted life years (QALYs) versus BBT, due to reductions in non-severe hypoglycaemic episodes and BMI with IDegLira. Costs were higher with IDegLira by GBP 303 per patient, leading to an incremental cost-effectiveness ratio (ICER) of GBP 5,924 per QALY gained for IDegLira versus BBT. ICERs remained below GBP 20,000 per QALY gained across a range of sensitivity analyses. IDegLira is a cost-effective alternative to BBT with insulin glargine U100 plus insulin aspart, providing equivalent glycaemic control with a simpler treatment regimen for patients with type 2 diabetes inadequately controlled on basal insulin in the UK. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

A systematic review of postoperative hand therapy management of basal joint arthritis.

PubMed

Wolfe, Terri; Chu, Jennifer Y; Woods, Tammy; Lubahn, John D

2014-04-01

There are a variety of postoperative immobilization and therapy options for patients with basal joint arthritis. Although prior systematic reviews have compared surgical procedures used to treat basal joint arthritis, none to our knowledge compares therapy protocols for this condition, which are considered an important part of the treatment. (1) We sought to determine whether differences in the length and type of postoperative immobilization affect clinical results after basal joint arthritis surgery. (2) We also compared specific therapy protocols that were prescribed. (3) Finally, we evaluated published protocols to determine when patients were released to full activity to see whether these appeared to affect clinical results. A systematic review of English-language studies in the PubMed and Cochrane databases was performed. Studies were then reviewed to determine what postoperative immobilization and therapy protocols the authors used and when patients were released to full activities. A total of 19 studies were identified using the search criteria. All but one of the studies included a postoperative period of immobilization in either a cast or splint. Immobilization time varied depending on whether Kirschner wires were used for the surgery and whether an implant was placed. Postoperative therapy protocols also varied but followed three general patterns. Some therapy protocols involved teaching patients a home exercise program only, whereas some authors described routine referral to a therapist. The third group consisted of studies in which patients were only referred for therapy if the physicians determined it was necessary during followup. Many studies did not give a specific time for full return to activity and instead described a gradual transition to full activity after immobilization was discontinued. Because of the variability and small numbers, no conclusive recommendations could be made on any of the three study questions. Comparative, multicenter studies comparing different immobilization and therapy protocols after the surgical treatment of basal joint arthritis would be helpful for both surgeons and therapists looking to refine their treatment protocols.

Lubiprostone Increases Small Intestinal Smooth Muscle Contractions Through a Prostaglandin E Receptor 1 (EP1)-mediated Pathway.

PubMed

Chan, Walter W; Mashimo, Hiroshi

2013-07-01

Lubiprostone, a chloride channel type 2 (ClC-2) activator, was thought to treat constipation by enhancing intestinal secretion. It has been associated with increased intestinal transit and delayed gastric emptying. Structurally similar to prostones with up to 54% prostaglandin E2 activity on prostaglandin E receptor 1 (EP1), lubiprostone may also exert EP1-mediated procontractile effect on intestinal smooth muscles. We investigated lubiprostone's effects on intestinal smooth muscle contractions and pyloric sphincter tone. Isolated murine small intestinal (longitudinal and circular) and pyloric tissues were mounted in organ baths with modified Krebs solution for isometric recording. Basal muscle tension and response to electrical field stimulation (EFS; 2 ms pulses/10 V/6 Hz/30 sec train) were measured with lubiprostone (10(-10)-10(-5) M) ± EP1 antagonist. Significance was established using Student t test and P < 0.05. Lubiprostone had no effect on the basal tension or EFS-induced contractions of longitudinal muscles. With circular muscles, lubiprostone caused a dose-dependent increase in EFS-induced contractions (2.11 ± 0.88 to 4.43 ± 1.38 N/g, P = 0.020) that was inhibited by pretreatment with EP1 antagonist (1.69 ± 0.70 vs. 4.43 ± 1.38 N/g, P = 0.030). Lubiprostone had no effect on circular muscle basal tension, but it induced a dose-dependent increase in pyloric basal tone (1.07 ± 0.01 to 1.97 ± 0.86 fold increase, P < 0.05) that was inhibited by EP1 antagonist. In mice, lubiprostone caused a dose-dependent and EP1-mediated increase in contractility of circular but not longitudinal small intestinal smooth muscles, and in basal tone of the pylorus. These findings suggest another mechanism for lubiprostone's observed clinical effects on gastrointestinal motility.

Insulin lispro low mixture twice daily versus basal insulin glargine once daily and prandial insulin lispro once daily in patients with type 2 diabetes requiring insulin intensification: a randomized phase IV trial.

PubMed

Tinahones, F J; Gross, J L; Onaca, A; Cleall, S; Rodríguez, A

2014-10-01

To compare the efficacy and safety of two insulin intensification strategies in patients with type 2 diabetes inadequately controlled on basal insulin glargine with metformin and/or pioglitazone. A multinational, randomized, open-label trial that compared insulin lispro low mixture (LM25; n = 236) twice daily with a basal-prandial regimen of insulin glargine once daily and insulin lispro once daily (IGL; n = 240) over 24 weeks in patients with HbA1c 7.5-10.5% and fasting plasma glucose ≤ 6.7 mmol/l. The primary objective was to assess non-inferiority [per-protocol (PP) population], and then superiority [intention-to-treat (ITT) population], of LM25 versus IGL according to change in HbA1c after 24 weeks (non-inferiority margin 0.4%, two-sided significance level 0.05). Estimated change [least squares (LS) mean (95% CI)] in HbA1c after 24 weeks: -1.30 (-1.44, -1.16)% with LM25 and -1.08 (-1.22, -0.94)% with IGL. Non-inferiority was shown [LS mean (95% CI) HbA1c treatment difference -0.21 (-0.38, -0.04) (PP population)]; gated superiority assessment showed a statistically significant advantage for LM25 (p = 0.010; ITT population). Mean blood glucose, glycaemic variability, overall tolerability and hypoglycaemic episodes per patient-year did not show significant differences between treatments during the study. In patients with type 2 diabetes inadequately controlled on once-daily basal insulin glargine and metformin and/or pioglitazone, intensification with LM25 was superior to a basal-prandial approach in terms of reduction in HbA1c after 24 weeks and did not increase hypoglycaemia episodes. © 2014 The Authors. Diabetes, Obesity and Metabolism published by JohnWiley & Sons Ltd.

Adolescent binge drinking alters adult brain neurotransmitter gene expression, behavior, brain regional volumes, and neurochemistry in mice

PubMed Central

Coleman, Leon G.; He, Jun; Lee, Joohwi; Styner, Martin; Crews, Fulton T.

2013-01-01

Background Binge-drinking is common in human adolescents. The adolescent brain is undergoing structural maturation and has a unique sensitivity to alcohol neurotoxicity. Therefore, adolescent binge ethanol may have long-term effects on the adult brain that alter brain structure and behaviors that are relevant to alcohol use disorders. Methods In order to determine if adolescent ethanol binge drinking alters the adult brain, male C57BL/6 mice were treated with either water or ethanol during adolescence (5g/kg/day i.g., post-natal days P28-37) and assessed during adulthood (P60-P88). An array of neurotransmitter-specific genes, behavioral tests (i.e. reversal learning, prepulse inhibition, and open field), and post-mortem brain structure using MRI and immunohistochemistry, were employed to assess persistent alterations in adult brain. Results At P38, 24 hours after adolescent ethanol (AE) binge, many neurotransmitter genes, particularly cholinergic and dopaminergic, were reduced by ethanol treatment. Interestingly, dopamine receptor type 4 mRNA was reduced and confirmed using immunohistochemistry. Normal control maturation (P38-P88) resulted in decreased neurotransmitter mRNA, e.g. an average decrease of 56%. Following adolescent ethanol treatment, adults showed greater gene expression reductions than controls, averaging 73%. Adult spatial learning assessed in the Morris water maze was not changed by adolescent ethanol treatment, but reversal learning experiments revealed deficits. Assessment of adult brain region volumes using MRI indicated that the olfactory bulb and basal forebrain were smaller in adults following adolescent ethanol. Immunohistochemical analyses found reduced basal forebrain area and fewer basal forebrain cholinergic neurons. Conclusions Adolescent binge ethanol treatment reduces adult neurotransmitter gene expression, particularly cholinergic genes, reduces basal forebrain and olfactory bulb volumes, and causes a reduction in the density of basal forebrain acetylcholine neurons. Loss of cholinergic neurons and forebrain structure could underlie adult reversal learning deficits following adolescent binge drinking. PMID:21223304

Effect of the glucocorticoid receptor antagonist Org 34850 on basal and stress-induced corticosterone secretion.

PubMed

Spiga, F; Harrison, L R; Wood, S A; Atkinson, H C; MacSweeney, C P; Thomson, F; Craighead, M; Grassie, M; Lightman, S L

2007-11-01

The activity of the hypothalamic-pituitary-adrenal (HPA) axis is characterised both by an ultradian pulsatile pattern of glucocorticoid secretion and an endogenous diurnal rhythm. Glucocorticoid feedback plays a major role in regulating HPA axis activity and this mechanism occurs via two different receptors: mineralocorticoid (MR) and glucocorticoid receptors (GR). In the present study, the effects of both acute and subchronic treatment with the GR antagonist Org 34850 on basal and stress-induced HPA axis activity in male rats were evaluated. To investigate the effect of Org 34850 on basal diurnal corticosterone rhythm over the 24-h cycle, an automated blood sampling system collected samples every 10 min. Acute injection of Org 34850 (10 mg/kg, s.c.) did not affect basal or stress-induced corticosterone secretion, but was able to antagonise the inhibitory effect of the glucocorticoid agonist methylprednisolone on stress-induced corticosterone secretion. However, 5 days of treatment with Org 34850 (10 mg/kg, s.c., two times a day), compared to rats treated with vehicle (5% mulgofen in 0.9% saline, 1 ml/kg, s.c.), increased corticosterone secretion over the 24-h cycle and resulted in changes in the pulsatile pattern of hormone release, but had no significant effect on adrenocorticotrophic hormone secretion or on stress-induced corticosterone secretion. Subchronic treatment with Org 34850 did not alter GR mRNA expression in the hippocampus, paraventricular nucleus of the hypothalamus or anterior-pituitary, or MR mRNA expression in the hippocampus. Our data suggest that a prolonged blockade of GRs is required to increase basal HPA axis activity. The changes observed here with ORG 34850 are consistent with inhibition of GR-mediated negative feedback of the HPA axis. In light of the evidence showing an involvement of dysfunctional HPA axis in the pathophysiology of depression, Org 34850 could be a potential treatment for mood disorders.

Cortical and subcortical afferents to the nucleus reticularis tegmenti pontis and basal pontine nuclei in the macaque monkey.

PubMed

Giolli, R A; Gregory, K M; Suzuki, D A; Blanks, R H; Lui, F; Betelak, K F

2001-01-01

Anatomical findings are presented that identify cortical and subcortical sources of afferents to the nucleus reticularis tegmenti pontis (NRTP) and basal pontine nuclei. Projections from the middle temporal visual area (MT), medial superior temporal visual area (MST), lateral intraparietal area (LIP), and areas 7a and 7b to the basal pontine nuclei were studied using 3H-leucine autoradiography. The results complemented a parallel study of retrograde neuronal labeling attributable to injecting WGA-HRP into NRTP and neighboring pontine nuclei. Small 3H-leucine injections confined to MT, MST, LIP, area 7a, or area 7b, produced multiple patches of pontine terminal label distributed as follows: (1) An injection within MT produced terminal label limited to the dorsolateral and lateral pontine nuclei. (2) Injections restricted to MST or LIP showed patches of terminal label in the dorsal, dorsolateral, lateral, and peduncular pontine nuclei. (3) Area 7a targets the dorsal, dorsolateral, lateral, peduncular, and ventral pontine nuclei, whereas area 7b projects, additionally, to the dorsomedial and paramedian pontine nuclei. Notably, no projections were seen to NRTP from any of these cortical areas. In contrast, injections made by other investigators into cortical areas anterior to the central sulcus revealed cerebrocortical afferents to NRTP, in addition to nuclei of the basal pontine gray. With our pontine WGA-HRP injections, retrograde neuronal labeling was observed over a large extent of the frontal cortex continuing onto the medial surface which included the lining of the cingulate sulcus and cingulate gyrus. Significant subcortical sources for afferents to the NRTP and basal pontine nuclei were the zona incerta, ventral mesencephalic tegmentum, dorsomedial hypothalamic area, rostral interstitial nucleus of the medial longitudinal fasciculus, red nucleus, and subthalamic nucleus. The combined anterograde and retrograde labeling data indicated that visuo-motor cortico-pontine pathways arising from parietal cortices target only the basal pontine gray, whereas the NRTP, together with select pontine nuclei, is a recipient of afferents from frontal cortical areas. The present findings implicate the existence of parallel direct and indirect cortico-pontine pathways from frontal motor-related cortices to NRTP and neighboring pontine nuclei.

Primary care physician perspectives on basal insulin initiation and maintenance in patients with type 2 diabetes mellitus.

PubMed

Kalirai, Samaneh; Stephenson, Judith; Perez-Nieves, Magaly; Grabner, Michael; Hadjiyianni, Irene; Geremakis, Caroline; Pollom, Roy Daniel; Reed, Beverly; Fisher, Lawrence

2018-04-01

To describe primary care physicians' (PCPs) perceptions of patient reactions and concerns about insulin initiation and identify opportunities for increased support. Cross-sectional, online survey of PCPs prescribing basal insulin to adults with type 2 diabetes mellitus (T2DM). PCPs were identified from administrative claims of a large commercial health plan and descriptive results of PCP responses were reported. PCPs (N=100) treated an average of 17 patients receiving insulin during a typical week. More than 85% of insulin initiation recommendations originated with PCPs. Most offered glucose monitoring instructions (96%) and advice on diet, exercise, and diabetes management (96%); 35% provided insulin titration algorithms; 93% reported that patients often or always took their insulin daily within 3 months of initiation; 31% of PCPs reported monthly office contacts with patients for the first 3 months; 16% reported no outreach efforts; fewer than 20% connected patients with support groups. When starting basal insulin, PCPs reported patients feeling personal failure regarding their diabetes treatment (33% often/always) and lacking confidence in their ability to manage insulin therapy (38% often/always). Study results identify additional opportunities for assisting patients in making the transition to insulin, including more frequent direct outreach to monitor insulin usage. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Restoration of long-term potentiation in middle-aged hippocampus after induction of brain-derived neurotrophic factor.

PubMed

Rex, Christopher S; Lauterborn, Julie C; Lin, Ching-Yi; Kramár, Eniko A; Rogers, Gary A; Gall, Christine M; Lynch, Gary

2006-08-01

Restoration of neuronal viability and synaptic plasticity through increased trophic support is widely regarded as a potential therapy for the cognitive declines that characterize aging. Previous studies have shown that in the hippocampal CA1 basal dendritic field deficits in the stabilization of long-term potentiation (LTP) are evident by middle age. The present study tested whether increasing endogenous brain-derived neurotrophic factor (BDNF) could reverse this age-related change. We report here that in middle-aged (8- to 10-mo-old) rats, in vivo treatments with a positive AMPA-type glutamate receptor modulator both increase BDNF protein levels in the cortical telencephalon and restore stabilization of basal dendritic LTP as assessed in acute hippocampal slices 18 h after the last drug treatment. These effects were not attributed to enhanced synaptic transmission or to facilitation of burst responses used to induce LTP. Increasing extracellular levels of BDNF by exogenous application to slices of middle-aged rats was also sufficient to rescue the stabilization of basal dendritic LTP. Finally, otherwise stable LTP in ampakine-treated middle-aged rats can be eliminated by infusion of the extracellular BDNF scavenger TrkB-Fc. Together these results indicate that increases in endogenous BDNF signaling can offset deficits in the postinduction processes that stabilize LTP.

Photodynamic Therapy Treatment to Enhance Fracture Healing

DTIC Science & Technology

2013-06-01

applied to treat multiple types  of cancer, skin diseases and  age   related   macular   degeneration . This treatment involves the local  or systemic...treatment, which has been successfully applied to treat multiple types of cancer, skin diseases and age related macular degeneration . This treatment...minimally invasive local treatment, which has been successfully applied to treat multiple types of cancer, skin diseases and age related macular

Embryonic treatment with xenobiotics disrupts steroid hormone profiles in hatchling red-eared slider turtles (Trachemys scripta elegans).

PubMed Central

Willingham, E; Rhen, T; Sakata, J T; Crews, D

2000-01-01

Many compounds in the environment capable of acting as endocrine disruptors have been assayed for their developmental effects on morphogenesis; however, few studies have addressed how such xenobiotics affect physiology. In the current study we examine the effects of three endocrine-disrupting compounds, chlordane, trans-nonachlor, and the polychlorinated biphenyl (PCB) mixture Aroclor 1242, on the steroid hormone concentrations of red-eared slider turtle (Trachemys scripta elegans) hatchlings treated in ovo. Basal steroid concentrations and steroid concentrations in response to follicle-stimulating hormone were examined in both male and female turtles treated with each of the three compounds. Treated male turtles exposed to Aroclor 1242 or chlordane exhibited significantly lower testosterone concentrations than controls, whereas chlordane-treated females had significantly lower progesterone, testosterone, and 5[alpha]-dihydrotestosterone concentrations relative to controls. The effects of these endocrine disruptors extend beyond embryonic development, altering sex-steroid physiology in exposed animals. Images Figure 1 Figure 2 PMID:10753091

Simultaneous Activation of Multiple Memory Systems during Learning: Insights from Electrophysiology and Modeling

DTIC Science & Technology

2010-06-01

autonomic and pain functions, and facilitating/inhibiting voluntary movements. The external segment of the globus pallidus (globus pallidus externa, GPe...or less responsive to pain stimuli. 1.2.4. Other cortico-basal ganglia loops Alexander, Strick and colleagues have additionally defined a number of... orofacial loop and loops through inferotemporal and posterior parietal cortical areas have also been defined. 1.2.5. Interactions between loops Once

Quantitative High-throughput Luciferase Screening in Identifying CAR Modulators

PubMed Central

Lynch, Caitlin; Zhao, Jinghua; Wang, Hongbing; Xia, Menghang

2017-01-01

Summary The constitutive androstane receptor (CAR, NR1I3) is responsible for the transcription of multiple drug metabolizing enzymes and transporters. There are two possible methods of activation for CAR, direct ligand binding and a ligand-independent method, which makes this a unique nuclear receptor. Both of these mechanisms require translocation of CAR from the cytoplasm into the nucleus. Interestingly, CAR is constitutively active in immortalized cell lines due to the basal nuclear location of this receptor. This creates an important challenge in most in vitro assay models because immortalized cells cannot be used without inhibiting the basal activity. In this book chapter, we go into detail of how to perform quantitative high-throughput screens to identify hCAR1 modulators through the employment of a double stable cell line. Using this line, we are able to identify activators, as well as deactivators, of the challenging nuclear receptor, CAR. PMID:27518621

Quantitative High-Throughput Luciferase Screening in Identifying CAR Modulators.

PubMed

Lynch, Caitlin; Zhao, Jinghua; Wang, Hongbing; Xia, Menghang

2016-01-01

The constitutive androstane receptor (CAR, NR1I3) is responsible for the transcription of multiple drug metabolizing enzymes and transporters. There are two possible methods of activation for CAR, direct ligand binding and a ligand-independent method, which makes this a unique nuclear receptor. Both of these mechanisms require translocation of CAR from the cytoplasm into the nucleus. Interestingly, CAR is constitutively active in immortalized cell lines due to the basal nuclear location of this receptor. This creates an important challenge in most in vitro assay models because immortalized cells cannot be used without inhibiting the high basal activity. In this book chapter, we go into detail of how to perform quantitative high-throughput screens to identify hCAR1 modulators through the employment of a double stable cell line. Using this line, we are able to identify activators, as well as deactivators, of the challenging nuclear receptor, CAR.

Accelerated ice shelf rifting and retreat at Pine Island Glacier, West Antarctica

NASA Astrophysics Data System (ADS)

Jeong, Seongsu; Howat, Ian M.; Bassis, Jeremy N.

2016-11-01

Pine Island Glacier has undergone several major iceberg calving events over the past decades. These typically occurred when a rift at the heavily fractured shear margin propagated across the width of the ice shelf. This type of calving is common on polar ice shelves, with no clear connection to ocean-ice dynamic forcing. In contrast, we report on the recent development of multiple rifts initiating from basal crevasses in the center of the ice shelf, resulted in calving further upglacier than previously observed. Coincident with rift formation was the sudden disintegration of the ice mélange that filled the northern shear margin, resulting in ice sheet detachment from this margin. Examination of ice velocity suggests that this internal rifting resulted from the combination of a change in ice shelf stress regime caused by disintegration of the mélange and intensified melting within basal crevasses, both of which may be linked to ocean forcing.

Pigmented Paraaxillary Located "Complex" Basal Cell Carcinoma Imitating clinically irritated Melanocytic Lesion - Succesfull Surgical Approach in Bulgarian Patient.

PubMed

Voicu, Cristiana; Mihai, Mara; Lupu, Mihai; Patterson, James W; Koleva, Nely; Wollina, Uwe; Lotti, Torello; Lotti, Jacopo; França, Katlein; Batashki, Atanas; Gianfaldoni, Serena; Bakardzhiev, Ilko; Mangarov, Hristo; Tchernev, Georgi

2017-07-25

Basal cell carcinoma (BCC) is the most frequently encountered neoplasm worldwide. While nodular BCC is the most frequent clinical subtype, other forms of BCC, such as superficial, cystic, morpheiform, infiltrative, and pigmented may also be encountered. We present the case of a 67-year-old male with a relatively well-defined infiltrative, pigmented plaque with multiple colours and peripheral growth situated in the right axillary region. The histopathologic examination performed after complete surgical excision of the tumour revealed a complex pigmented BCC with macronodular, fibroepithelioma-like, cystic, focally infiltrative and basosquamous features. Uncommon locations of BCCs in sun-protected areas such as the axillary region require a higher degree of suspicion for diagnosis. The complex histology of the presented case, including subtypes with differing biologic attributes, emphasises the importance of histopathological examination in the diagnosis and therapeutic management of BCC.

Gorlin Syndrome.

PubMed

Palacios-Álvarez, I; González-Sarmiento, R; Fernández-López, E

2018-04-01

Gorlin syndrome is a rare autosomal dominant disease caused by mutations in the sonic hedgehog signaling pathway. Of particular importance is the PTCH1 gene. The disease is characterized by the development of multiple basal cell carcinomas at young ages. These tumors may present with other skin manifestations such as palmoplantar pits and with extracutaneous manifestations such as odontogenic keratocysts and medulloblastoma. Although the dermatologist may be key for recognizing clinical suspicion of the syndrome, a multidisciplinary team is usually necessary for diagnosis, treatment, and follow-up. Skin treatment may be complicated due to the large number of basal cell carcinomas and the extent of involvement. In recent years, new drugs that inhibit targets in the sonic hedgehog pathway have been developed. Although these agents appear promising options for patients with Gorlin syndrome, their efficacy is limited by adverse effects and the development of resistance. Copyright © 2017 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

A non-destructive selection criterion for fibre content in jute : II. Regression approach.

PubMed

Arunachalam, V; Iyer, R D

1974-01-01

An experiment with ten populations of jute, comprising varieties and mutants of the two species Corchorus olitorius and C.capsularis was conducted at two different locations with the object of evolving an effective criterion for selecting superior single plants for fibre yield. At Delhi, variation existed only between varieties as a group and mutants as a group, while at Pusa variation also existed among the mutant populations of C. capsularis.A multiple regression approach was used to find the optimum combination of characters for prediction of fibre yield. A process of successive elimination of characters based on the coefficient of determination provided by individual regression equations was employed to arrive at the optimal set of characters for predicting fibre yield. It was found that plant height, basal and mid-diameters and basal and mid-dry fibre weights would provide such an optimal set.

Hemodynamic changes after propacetamol administration in patients with febrile UTI in the ED.

PubMed

Kang, Soo; Durey, Areum; Suh, Young Ju; Kim, Ah Jin

2018-06-01

Clinical studies have indicated that transient hypotension can occur after propacetamol administration. This study aimed to analyze the hemodynamic changes after propacetamol administration in patients visiting the ED due to febrile UTI. We also examined the incidence of propacetamol-induced hypotension and compared the clinical characteristics of patients with persistent hypotension, defined as requiring additional fluids or vasopressors, to those with transient hypotension. A retrospective analysis of the electronic medical records of patients who visited the ED between June 2015 and May 2016, were diagnosed with febrile UTI, and treated with propacetamol, was conducted. We included 195 patients in this study; of these, 87 (44.6%) showed hypotension. In all patients, significant decreases in systolic blood pressure (SBP; 135.06±20.45mmHg vs 117.70±16.41mmHg), diastolic blood pressure (DBP; 79.74±12.17mmHg vs 69.69±10.96mmHg), and heart rate (97.46±17.14mmHg vs 90.72±14.90mmHg) were observed after propacetamol administration. The basal SBP and DBP were higher in the hypotension than in the non-hypotension group (basal SBP: 144.4±22.3mmHg vs 127.6±15.3mmHg; basal DBP: 83.3±12.6mmHg vs 76.9±11.0mmHg). Patients with persistent hypotension had a lower baseline BP, which was not elevated despite fever, and a higher rate of bacteremia than those with transient hypotension. Although febrile UTI patients treated with propacetamol in the ED showed hemodynamic changes, these changes did not have a large effect on their prognosis. However, in patients who showed bacteremia or a normal initial BP despite fever, the possibility of developing persistent hypotension should be considered. Copyright © 2017. Published by Elsevier Inc.

Gi proteins regulate adenylyl cyclase activity independent of receptor activation.

PubMed

Melsom, Caroline Bull; Ørstavik, Øivind; Osnes, Jan-Bjørn; Skomedal, Tor; Levy, Finn Olav; Krobert, Kurt Allen

2014-01-01

Despite the view that only β2- as opposed to β1-adrenoceptors (βARs) couple to G(i), some data indicate that the β1AR-evoked inotropic response is also influenced by the inhibition of Gi. Therefore, we wanted to determine if Gi exerts tonic receptor-independent inhibition upon basal adenylyl cyclase (AC) activity in cardiomyocytes. We used the Gs-selective (R,R)- and the Gs- and G(i)-activating (R,S)-fenoterol to selectively activate β2ARs (β1AR blockade present) in combination with Gi inactivation with pertussis toxin (PTX). We also determined the effect of PTX upon basal and forskolin-mediated responses. Contractility was measured ex vivo in left ventricular strips and cAMP accumulation was measured in isolated ventricular cardiomyocytes from adult Wistar rats. PTX amplified both the (R,R)- and (R,S)-fenoterol-evoked maximal inotropic response and concentration-dependent increases in cAMP accumulation. The EC50 values of fenoterol matched published binding affinities. The PTX enhancement of the Gs-selective (R,R)-fenoterol-mediated responses suggests that Gi regulates AC activity independent of receptor coupling to Gi protein. Consistent with this hypothesis, forskolin-evoked cAMP accumulation was increased and inotropic responses to forskolin were potentiated by PTX treatment. In non-PTX-treated tissue, phosphodiesterase (PDE) 3 and 4 inhibition or removal of either constitutive muscarinic receptor activation of Gi with atropine or removal of constitutive adenosine receptor activation with CGS 15943 had no effect upon contractility. However, in PTX-treated tissue, PDE3 and 4 inhibition alone increased basal levels of cAMP and accordingly evoked a large inotropic response. Together, these data indicate that Gi exerts intrinsic receptor-independent inhibitory activity upon AC. We propose that PTX treatment shifts the balance of intrinsic G(i) and Gs activity upon AC towards Gs, enhancing the effect of all cAMP-mediated inotropic agents.

Gi Proteins Regulate Adenylyl Cyclase Activity Independent of Receptor Activation

PubMed Central

Melsom, Caroline Bull; Ørstavik, Øivind; Osnes, Jan-Bjørn; Skomedal, Tor; Levy, Finn Olav; Krobert, Kurt Allen

2014-01-01

Background and purpose Despite the view that only β2- as opposed to β1-adrenoceptors (βARs) couple to Gi, some data indicate that the β1AR-evoked inotropic response is also influenced by the inhibition of Gi. Therefore, we wanted to determine if Gi exerts tonic receptor-independent inhibition upon basal adenylyl cyclase (AC) activity in cardiomyocytes. Experimental approach We used the Gs-selective (R,R)- and the Gs- and Gi-activating (R,S)-fenoterol to selectively activate β2ARs (β1AR blockade present) in combination with Gi inactivation with pertussis toxin (PTX). We also determined the effect of PTX upon basal and forskolin-mediated responses. Contractility was measured ex vivo in left ventricular strips and cAMP accumulation was measured in isolated ventricular cardiomyocytes from adult Wistar rats. Key results PTX amplified both the (R,R)- and (R,S)-fenoterol-evoked maximal inotropic response and concentration-dependent increases in cAMP accumulation. The EC50 values of fenoterol matched published binding affinities. The PTX enhancement of the Gs-selective (R,R)-fenoterol-mediated responses suggests that Gi regulates AC activity independent of receptor coupling to Gi protein. Consistent with this hypothesis, forskolin-evoked cAMP accumulation was increased and inotropic responses to forskolin were potentiated by PTX treatment. In non-PTX-treated tissue, phosphodiesterase (PDE) 3 and 4 inhibition or removal of either constitutive muscarinic receptor activation of Gi with atropine or removal of constitutive adenosine receptor activation with CGS 15943 had no effect upon contractility. However, in PTX-treated tissue, PDE3 and 4 inhibition alone increased basal levels of cAMP and accordingly evoked a large inotropic response. Conclusions and implications Together, these data indicate that Gi exerts intrinsic receptor-independent inhibitory activity upon AC. We propose that PTX treatment shifts the balance of intrinsic Gi and Gs activity upon AC towards Gs, enhancing the effect of all cAMP-mediated inotropic agents. PMID:25203113

Effects of selenium and zinc supplementation on nutritional status in patients with cancer of digestive tract.

PubMed

Federico, A; Iodice, P; Federico, P; Del Rio, A; Mellone, M C; Catalano, G; Federico, P

2001-04-01

To evaluate the effect of oral administration of selenium and zinc tablets in patients with cancer of the digestive tract during chemotherapy. A case-control, randomized study. Medical Oncology, II University of Naples, Naples, Italy. A total of 60 patients (median age 55 y, range 46-61 y) with diagnosis of gut cancer were randomized in 1999. Patients were treated for 60 days with chemotherapy. Trace elements were measured by atomic absorption spectroscopy. The nutritional status of the patients was assessed by biochemical and bio-impedance analysis (BIA) parameters in basal condition and after 60 days of treatment. Oral administration of selenium and zinc in oral tablet form for 50 days was Se 200 microg/day (50 microg/tablet) and Zn 21 mg/day (7 mg/tablet). Both in the basal condition and at 60 days all patients were malnourished. Selenium and zinc concentrations were significantly lower (P < 0.01) whereas copper concentration was significantly higher (P < 0.01) in cancer patients than in control subjects. However, 21/30 (70%) of those treated with Se and Zn did not showed a further worsening of nutritional status and experienced a significant decrease of asthenia with an increase of appetite. On the other hand, 24/30 (80%) untreated patients had a significant decline of all parameters studied after 60 days (prealbumin, cholesterol, transferrin, P < 0.05 vs 0 time; total proteins, albumin/globulin ratio, P < 0.01 vs 0 time; fat-free mass, fat mass, Na+/K+ ratio, body mass index P < 0.05 vs 0 time; fat free mass/fat mass, total body water, extra cellular/intra cellular water, basal metabolic rate: P < 0.01 vs 0 time). Data indicate that Se and Zn supplementation may improve the clinical course of general conditions in patients with gut cancer. These effects of Se and Zn require confirmation in an independent trial of appropriate design before new public health recommendations regarding Se and Zn supplementation can be made.

Do Perceptions of Insulin Pump Usability Impact Attitudes Toward Insulin Pump Therapy? A Pilot Study of Individuals With Type 1 and Insulin-Treated Type 2 Diabetes

PubMed Central

Gilgen, Emily

2014-01-01

Background: We assessed the impact of perceived insulin pump usability on attitudes toward insulin pump therapy in diabetic individuals currently treated with multiple daily insulin injections (MDI). Method: This comparative, single-arm study recruited 28 adults with type 1 (n = 16) and insulin-treated type 2 diabetes (n = 12) to evaluate 2 current insulin pumps: Medtronic Revel 723 (Pump 1), Asante Snap Insulin Pump (Pump 2). Participants were randomized 1:1 to 1 of 2 assessment sequences: Pump 1 followed by Pump 2; and Pump 2 followed by Pump 1. Structured observational protocols were utilized to assess participants’ ability and time required to learn/perform common tasks associated with pump setup/use. Participants used a modified version of the System Usability Scale (SUS) and investigator-developed questionnaires to rate pump usability and task difficulty; pre-post questionnaires assessed changes in attitudes toward insulin pump therapy. Results: All participants completed the study. SUS scores showed Pump 2 to be more usable than Pump 1 on all usability attributes. Participants rated Pump 2 more positively than Pump 1, overall mean SUS scores of 5.7 versus 4.1 respectively, F(1, 52) = 32.7, P < .001, and SUS scores were higher if participants used the Pump 2 last, 5.3 versus 4.4 for Pump 1 last, F(1, 52) = 10.8, P < .01. Pump 2 was preferred for all tasks: manual bolus (86%), bolus calculation (71%), managing basal rates (93%), interpreting alarms (96%), transferring settings (100%), changing insulin and infusion sets (93%), all P < .05. Conclusions: Perceptions of pump usability can directly impact acceptance and use of features that may benefit those who wear them. Simpler pump devices that decrease perceptions of complexity may encourage broader use of this technology. PMID:25269659

Abnormal neural activation patterns underlying working memory impairment in chronic phencyclidine-treated mice.

PubMed

Arime, Yosefu; Akiyama, Kazufumi

2017-01-01

Working memory impairment is a hallmark feature of schizophrenia and is thought be caused by dysfunctions in the prefrontal cortex (PFC) and associated brain regions. However, the neural circuit anomalies underlying this impairment are poorly understood. The aim of this study is to assess working memory performance in the chronic phencyclidine (PCP) mouse model of schizophrenia, and to identify the neural substrates of working memory. To address this issue, we conducted the following experiments for mice after withdrawal from chronic administration (14 days) of either saline or PCP (10 mg/kg): (1) a discrete paired-trial variable-delay task in T-maze to assess working memory, and (2) brain-wide c-Fos mapping to identify activated brain regions relevant to this task performance either 90 min or 0 min after the completion of the task, with each time point examined under working memory effort and basal conditions. Correct responses in the test phase of the task were significantly reduced across delays (5, 15, and 30 s) in chronic PCP-treated mice compared with chronic saline-treated controls, suggesting delay-independent impairments in working memory in the PCP group. In layer 2-3 of the prelimbic cortex, the number of working memory effort-elicited c-Fos+ cells was significantly higher in the chronic PCP group than in the chronic saline group. The main effect of working memory effort relative to basal conditions was to induce significantly increased c-Fos+ cells in the other layers of prelimbic cortex and the anterior cingulate and infralimbic cortex regardless of the different chronic regimens. Conversely, this working memory effort had a negative effect (fewer c-Fos+ cells) in the ventral hippocampus. These results shed light on some putative neural networks relevant to working memory impairments in mice chronically treated with PCP, and emphasize the importance of the layer 2-3 of the prelimbic cortex of the PFC.

Abnormal neural activation patterns underlying working memory impairment in chronic phencyclidine-treated mice

PubMed Central

Akiyama, Kazufumi

2017-01-01

Working memory impairment is a hallmark feature of schizophrenia and is thought be caused by dysfunctions in the prefrontal cortex (PFC) and associated brain regions. However, the neural circuit anomalies underlying this impairment are poorly understood. The aim of this study is to assess working memory performance in the chronic phencyclidine (PCP) mouse model of schizophrenia, and to identify the neural substrates of working memory. To address this issue, we conducted the following experiments for mice after withdrawal from chronic administration (14 days) of either saline or PCP (10 mg/kg): (1) a discrete paired-trial variable-delay task in T-maze to assess working memory, and (2) brain-wide c-Fos mapping to identify activated brain regions relevant to this task performance either 90 min or 0 min after the completion of the task, with each time point examined under working memory effort and basal conditions. Correct responses in the test phase of the task were significantly reduced across delays (5, 15, and 30 s) in chronic PCP-treated mice compared with chronic saline-treated controls, suggesting delay-independent impairments in working memory in the PCP group. In layer 2–3 of the prelimbic cortex, the number of working memory effort-elicited c-Fos+ cells was significantly higher in the chronic PCP group than in the chronic saline group. The main effect of working memory effort relative to basal conditions was to induce significantly increased c-Fos+ cells in the other layers of prelimbic cortex and the anterior cingulate and infralimbic cortex regardless of the different chronic regimens. Conversely, this working memory effort had a negative effect (fewer c-Fos+ cells) in the ventral hippocampus. These results shed light on some putative neural networks relevant to working memory impairments in mice chronically treated with PCP, and emphasize the importance of the layer 2–3 of the prelimbic cortex of the PFC. PMID:29253020

Immunohistochemical evidence for the involvement of gonadotropin releasing hormone in neuroleptic and cataleptic effects of haloperidol in mice.

PubMed

Fegade, Harshal A; Umathe, Sudhir N

2016-04-01

Blockade of dopamine D2 receptor by haloperidol is attributed for neuroleptic and cataleptic effects; and also for the release of gonadotropin releasing hormone (GnRH) from the hypothalamus. GnRH agonist is reported to exhibit similar behavioural effects as that of haloperidol, and pre-treatment with GnRH antagonist is shown to attenuate the effects of haloperidol, suggesting a possibility that GnRH might mediate the effects of haloperidol. To substantiate such possibility, the influence of haloperidol on GnRH immunoreactivity (GnRH-ir) in the brain was studied in vehicle/antide pre-treated mice by peroxidase-antiperoxidase method. Initially, an earlier reported antide-haloperidol interaction in rat was confirmed in mice, wherein haloperidol (250μg/kg, i.p.) exhibited suppression of conditioned avoidance response (CAR) on two-way shuttle box, and induced catalepsy in bar test; and pre-treatment with antide (50μg/kg, s.c., GnRH antagonist) attenuated both effects of haloperidol. Immunohistochemical study was carried out to identify GnRH-ir in the brain, isolated 1h after haloperidol treatment to mice pre-treated with vehicle/antide. The morphometric analysis of microphotographs of brain sections revealed that haloperidol treatment increased integrated density units of GnRH-ir in various regions of the limbic system. Considering basal GnRH-ir in vehicle treated group as 100%, the increase in GnRH-ir after haloperidol treatment was by 100.98% in the medial septum; 54.26% in the bed nucleus of the stria terminalis; 1152.85% in the anteroventral periventricular nucleus; 120.79% in the preoptic area-organum vasculosum of the lamina terminalis and 138.82% in the arcuate nucleus. Antide did not influence basal and haloperidol induced increase in GnRH-ir in any of the regions. As significant increase in GnRH-ir after haloperidol treatment was observed in such regions of the brain which are reported to directly or indirectly communicate with the hippocampus and basal ganglia, the regions respectively responsible for neuroleptic and cataleptic effects; and as GnRH antagonist eliminated the effects of haloperidol without affecting GnRH-ir, it appears that GnRH released by haloperidol mediates its neuroleptic and cataleptic effects. Copyright © 2015 Elsevier Ltd. All rights reserved.

Comparison of interleukin 10 homologs on dermal wound healing using a novel human skin ex vivo organ culture model

PubMed Central

Balaji, Swathi; Moles, Chad M.; Bhattacharya, Sukanta S.; LeSaint, Maria; Dhamija, Yashu; Le, Louis D.; King, Alice; Kidd, Mykia; Bouso, Muhammad F.; Shaaban, Aimen; Crombleholme, Timothy M.; Bollyky, Paul; Keswani, Sundeep G.

2015-01-01

Background Anti-inflammatory cytokine interleukin (IL)-10 has been shown to induce regenerative healing in postnatal wounds. A viral homolog of IL-10 produced by human cytomegalovirus (CMV IL-10) similarly generates potent immunoregulatory effects, but its effects on wound healing have not been investigated. Currently, there are limited cost-effective methods of screening vulnerary therapeutics. Taken together, we aim to develop and validate a novel human ex vivo dermal wound model and hypothesize that CMV IL-10 will enhance dermal wound healing. Methods Full-thickness circular (6-mm) explants were taken from surgical skin samples and 3-mm full-thickness wounds were created. Explants were embedded in collagen I matrix and maintained in specially formulated media with the epidermis at air–liquid interface, and treated with human IL-10 or CMV IL-10 (200 ng/mL). The viability of cultured explants was validated by histology and lactate dehydrogenase (LDH) activity. Epithelial gap, epithelial height, basal keratinocyte migration, vascular endothelial growth factor levels, and neovascularization were measured at days 3 and 7 to determine IL-10 effects on wound healing. Results Culture explants at day 7 appeared similar to fresh skin in morphology, cell, and vessel density. By day 14, the epidermis separated from the dermis and the cell density diminished. Day 7 wounds appeared viable with advancing epithelial and basal keratinocyte migration with no evidence of necrosis. Cytotoxicity analysis via the quantification of LDH revealed no differences between controls and treated groups. There was a slight increase in the quantity of LDH in media at day 3; however, this decreased at day 5 and continued to decline up to day 21. CMV IL-10 treatment resulted in a significant decrease in the epithelial gap and an increase in epithelial height. There were no differences in the rates of basal keratinocyte migration at day 7 between treated and control groups. Interestingly, human IL-10 increased vascular endothelial growth factor expression and neovascularization compared with controls. Conclusions The human ex vivo wound model provides a simple and viable design to study dermal wound healing. Both IL-10 homologs demonstrate vulnerary effects. The viral homolog demonstrates enhanced effects on wound closure compared with human IL-10. These data represent a novel tool that can be used to screen therapeutics, such as CMV IL-10, before preclinical studies. PMID:24814764

PGE2 /EP4 Signaling Controls the Transfer of the Mammary Stem Cell State by Lipid Rafts in Extracellular Vesicles.

PubMed

Lin, Meng-Chieh; Chen, Shih-Yin; Tsai, Ho-Min; He, Pei-Lin; Lin, Yen-Chun; Herschman, Harvey; Li, Hua-Jung

2017-02-01

Prostaglandin E 2 (PGE 2 )-initiated signaling contributes to stem cell homeostasis and regeneration. However, it is unclear how PGE 2 signaling controls cell stemness. This study identifies a previously unknown mechanism by which PGE 2 /prostaglandin E receptor 4 (EP 4 ) signaling regulates multiple signaling pathways (e.g., PI3K/Akt signaling, TGFβ signaling, Wnt signaling, EGFR signaling) which maintain the basal mammary stem cell phenotype. A shift of basal mammary epithelial stem cells (MaSCs) from a mesenchymal/stem cell state to a non-basal-MaSC state occurs in response to prostaglandin E receptor 4 (EP 4 ) antagonism. EP 4 antagonists elicit release of signaling components, by controlling their trafficking into extracellular vesicles/exosomes in a lipid raft/caveolae-dependent manner. Consequently, EP 4 antagonism indirectly inactivates, through induced extracellular vesicle/exosome release, pathways required for mammary epithelial stem cell homeostasis, e.g. canonical/noncanonical Wnt, TGFβ and PI3K/Akt pathways. EP 4 antagonism causes signaling receptors and signaling components to shift from non-lipid raft fractions to lipid raft fractions, and to then be released in EP 4 antagonist-induced extracellular vesicles/exosomes, resulting in the loss of the stem cell state by mammary epithelial stem cells. In contrast, luminal mammary epithelial cells can acquire basal stem cell properties following ingestion of EP 4 antagonist-induced stem cell extracellular vesicles/exosomes, and can then form mammary glands. These findings demonstrate that PGE 2 /EP 4 signaling controls homeostasis of mammary epithelial stem cells through regulating extracellular vesicle/exosome release. Reprogramming of mammary epithelial cells can result from EP 4 -mediated stem cell property transfer by extracellular vesicles/exosomes containing caveolae-associated proteins, between mammary basal and luminal epithelial cells. Stem Cells 2017;35:425-444. © 2016 The Authors STEM CELLS published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Amman, G.D.; Ryan, K.C.

The bark beetle antiaggregative pheromones, verbenone and ipsdienol, were tested in protecting heat-injured lodgepole pine (Pinus contorta Dougl. ex Loud.) from mountain pine beetle (Dendroctonus ponderosae) infestation in the Sawtooth National Recreation Area in central Idaho. Peat moss was placed around 70 percent of the basal circumference of lodgepole pines. When the peat moss was ignited, it simulated the smoldering of natural duff, generating temperatures that killed the cambium. The four treatments tested were uninjured tree, heat-injured tree, heat-injured tree treated with verbenone, and heat-injured tree treated with verbenone plus ipsdienol. Treatments were replicated 20 times. Mountain pine beetles weremore » attracted into treatment blocks by placing mountain pine beetle tree baits on metal posts 3 to 5 meters from treated trees. Fisher's Extract Test showed that treatment and beetle infestation were not independent (P < 0.015). Check treatments contained more unattacked and mass-attacked trees, whereas pheromone treatments contained more unsuccessfully attacked trees.« less

Dietary choline, betaine and lecithin mitigates endosulfan-induced stress in Labeo rohita fingerlings.

PubMed

Kumar, Neeraj; Jadhao, S B; Chandan, N K; Kumar, Kundan; Jha, A K; Bhushan, S; Kumar, Saurav; Rana, R S

2012-08-01

A five-week experiment was conducted to delineate stress-mitigating effects of three different methyl donors in Labeo rohita fingerlings subjected to endosulfan toxicity. Four iso-nitrogenous and iso-caloric feed were prepared with and without supplementation of methyl donors. The feed were basal or control diet (i.e., without methyl donor supplementation), feed supplemented with choline, feed supplemented with betaine and feed supplemented with lecithin. Two hundred and twenty-five fishes were distributed randomly in five treatment groups each with three replicates. The experimental setup were normal water (without endosulfan) and fed with control diet (control group), endosulfan-treated water and fed with control diet (T₁), endosulfan-treated water and fed with choline supplemented feed (T₂), endosulfan-treated water and fed with betaine supplemented feed (T₃) and endosulfan-treated water and fed with lecithin-supplemented feed (T₄). The level of endosulfan in endosulfan treated water was maintained at the level of 1/10 of LC₅₀, that is, 0.2 ppb. During the experiment, growth performances, metabolic enzyme activity and histological examination were done to assess the effect of treatments. The growth performance (percentage weight gain, feed conversion ratio, specific growth rate and protein efficiency ratio) and nutrient digestibility were significantly different (P<0.01) in lecithin, betaine and choline fed group when compared to endosulfan-exposed group fed with basal diet. The liver LDH and MDH activity were significantly (P<0.01) improved in the groups fed with methyl donor supplemented diet. The liver AST and ALT, brain AChE and muscle ALT did not change with supplementation in the diet, but muscle ALT and G6PDH significantly (P<0.01) changed with supplementation. The gill and liver ATPase and intestinal ALP were significantly (P<0.01) noticeably changed in supplemented group. After endosulfan exposure, histopathology alter like slight large vacuolation in hepatocyte and lipoid vacuole were observed and with supplementation normal appearance of liver were observed. The chromosome aberration (karyotype) was observed in endosulfan-exposed group. The result obtained in present study concluded that inclusion of methyl donors, particularly lecithin and betaine, in feed as nutritional supplements has a potential stress-mitigating effect in L. rohita fingerlings.

Four-year follow-up of a Wilson disease pedigree complicated with epilepsy and hypopituitarism: Case report with a literature review.

PubMed

Zhang, Qi-Jie; Xu, Liu-Qing; Wang, Chong; Hu, Wei; Wang, Ning; Chen, Wan-Jin

2016-12-01

Wilson's disease (WD) is an autosomal recessive inherited disorder of copper metabolism with excellent prognosis if treated timely. However, WD is usually prone to neglect and misdiagnosis at an early stage. We reported a rare WD pedigree, and the clinical features, laboratory tests, and gene mutations were analyzed in detail. The patient was a 17-year-old and 136-cm-tall girl who presented with limb weakness, combined with multi-organ disorders including blind eye, epilepsy, and hypopituitarism. Clinical tests showed a low serum ceruloplasmin level, high urinary copper excretion and Kayser-Fleischer (K-F) rings. She carried a compound heterozygous mutations in ATP7B gene (c.2828G>A and c.3884C>T). Her younger brother, as an asymptomatic patient, manifested with elevation of transaminases but without neurological and hepatic symptoms. They were diagnosed as WD finally. They were treated with sodium dimercaptosulphonate, supplemented with zinc gluconate, vitamin B6, vitamin C, as well as restriction of dietary copper. The urinary copper excretion and serum transaminase level decreased gradually. The abnormal signals in brainstem and basal ganglia were also remarkably decreased after 4-year of de-copper treatment. As to the patients with complicated clinical manifestations, the extrapyramidal symptom and basal ganglia signals should be concerned. The serum ceruloplasmin detection and ATP7B gene mutation screening are necessary.

Control of Basal Stem Rot Disease in Oil Palm by Supplementation of Calcium, Copper, and Salicylic Acid.

PubMed

Bivi, M Shahul Hamid Rahamah; Paiko, Adamu Saidu; Khairulmazmi, Ahmad; Akhtar, M S; Idris, Abu Seman

2016-10-01

Continuous supplementation of mineral nutrients and salicylic acid (SA) as foliar application could improve efficacy in controlling basal stem rot (BSR) disease in oil palm seedling. It is revealed from the results that the highest disease severity index (58.3%) was recorded in T8 treatments at 9 months after inoculation. The best disease control was achieved by T7 treatments (calcium/copper/SA [Ca/Cu/SA]) (5.0%) followed by T1 (5.5%), T5 (5.8%), T3 (8.3%), T6 (8.3%), T4 (13.3%), and T2 (15.8%) treatments. Continuous supplementation of Ca/Cu/SA was found to be the most effective in controlling the disease and the high performance liquid chromatography results showed the detection of ergosterol at very low concentration in the treated samples. Moreover, the transmission electron microscopy analysis results clearly indicated that T7 treatment was also enhancing lignification, which was responsible for the thickness of the secondary cell walls and middle lamella compared to untreated samples. It was therefore, concluded that continuous supplementation of minerals nutrients and SA could effectively suppress disease severity by reducing ergosterol activity and also improve the process of lignification in the treated plants. Furthermore, this treatment also managed to delay the onset of BSR symptoms and promote the growth of the seedlings and eventually suppress the BSR disease.

Adrenergic factors regulating cell division in the colonic crypt epithelium during carcinogenesis and in colonic adenoma and adenocarcinoma.

PubMed Central

Kennedy, M. F.; Tutton, P. J.; Barkla, D. H.

1985-01-01

Evidence exists implicating adrenergic factors in the control of intestinal epithelial cell proliferation in both normal and diseased states. In this report, attention is focussed on changes in the amine requirements of proliferating cells during the chemical induction of tumours in the colon of mouse. Cell proliferation rates were measured stathmokinetically. Tumours were induced by s.c. injection of dimethylhydrazine (DMH). Results with a series of adrenoceptor agonists and antagonists suggest that there is an alpha 2-adrenoceptor mediated excitatory effect in normal colon but an alpha 2 adrenoceptor mediated inhibitory effect in adenoma and carcinoma. Alpha 1 adrenoceptors, on the other hand, have an inhibitory effect in normal crypts and in adenomas, and an excitatory effect in carcinomas. Beta adrenoceptors have an inhibitory effect in the normal and DMH-treated crypt, and in adenomas, but not in carcinomas. In the crypt epithelium of DMH-treated mice, two regions on cell proliferation, with differing regulatory factors, could be identified. In the upper region of the carcinogen-exposed crypt is a zone where cell proliferation is stimulated by an alpha 2 adrenergic mechanism, thus resembling the basal region of the normal crypt. By contrast, in the basal region of these crypts, cell proliferation is stimulated by an alpha 1 mechanism, thus resembling a malignant tumour. PMID:4041364

Adrenergic factors regulating cell division in the colonic crypt epithelium during carcinogenesis and in colonic adenoma and adenocarcinoma.

PubMed

Kennedy, M F; Tutton, P J; Barkla, D H

1985-09-01

Evidence exists implicating adrenergic factors in the control of intestinal epithelial cell proliferation in both normal and diseased states. In this report, attention is focussed on changes in the amine requirements of proliferating cells during the chemical induction of tumours in the colon of mouse. Cell proliferation rates were measured stathmokinetically. Tumours were induced by s.c. injection of dimethylhydrazine (DMH). Results with a series of adrenoceptor agonists and antagonists suggest that there is an alpha 2-adrenoceptor mediated excitatory effect in normal colon but an alpha 2 adrenoceptor mediated inhibitory effect in adenoma and carcinoma. Alpha 1 adrenoceptors, on the other hand, have an inhibitory effect in normal crypts and in adenomas, and an excitatory effect in carcinomas. Beta adrenoceptors have an inhibitory effect in the normal and DMH-treated crypt, and in adenomas, but not in carcinomas. In the crypt epithelium of DMH-treated mice, two regions on cell proliferation, with differing regulatory factors, could be identified. In the upper region of the carcinogen-exposed crypt is a zone where cell proliferation is stimulated by an alpha 2 adrenergic mechanism, thus resembling the basal region of the normal crypt. By contrast, in the basal region of these crypts, cell proliferation is stimulated by an alpha 1 mechanism, thus resembling a malignant tumour.