Localization of estrogen receptor α and progesterone receptor B in bovine cervix and vagina during the follicular and luteal phases of the sexual cycle.

PubMed

Sağsöz, H; Akbalik, M E; Saruhan, B G; Ketani, M A

2011-08-01

The localization and distribution of estrogen receptors (ERα) and progesterone receptors (PR-B) in the cervix and vagina of sexually mature bovines during the follicular and luteal phases of the sexual cycle were studied using immunohistochemistry. The estrous cycle stage of 23 Holstein bovines was assessed by gross and histological appearance of ovaries and blood steroid hormone values. Tissue samples from cervix and vagina were fixed in 10% formaldehyde for routine histological processing. Nuclear staining for ERα and PR-B was observed in the epithelial cells of the surface epithelium, stromal cells and smooth muscle cells. Generally, in the cervix, ERα immunoreactivity was more intense in the epithelial and smooth muscle cells during the follicular phase and in the epithelial cells during the luteal phase (p < 0.05). PR-B immunoreactivity was more intense in the epithelial and smooth muscle cells than in the superficial and deep stromal cells during the follicular and luteal phases (p < 0.05). In the vagina, ERα and PR-B immunoreactivities were more intense in the epithelial cells than in the connective tissue cells and smooth muscle cells during the follicular and luteal phases (p < 0.05). These results indicated that the frequency and intensity of ERα and PR-B immunoreactivity in the cervix and vagina of bovines varied according to the cervical and vaginal cell types and the phases of the sexual cycle.

[Different patterns of follicular development and luteal function].

PubMed

Gu, L; Zhang, L; Gu, F

1995-09-01

To study the relationship between luteal function and different patterns of follicular development. Different patterns of follicular development as observed under transvaginal B-ultrasound in 85 infertile patients included: (1) Ovulation from normal follicle (ONF). (2) Ovulation from two follicles at the same cycle (O2F). (3) Ovulation from small follicle (OSF). (4) Ovulation from polycystic ovaries (PCO). (5) Luteinized unruptured follicle syndrome (LUFS). (6) Anovulation with follicular atresia. The luteal function of the first 5 types was evaluated by serum and peritoneal fluid estrogen, progesterone levels, endometrial histology, estradiol receptor (ER) and progesterone receptor (PR) analyaes, and the length of luteal phase. The incidence of luteal phase deficiency (LPD): short luteal phase was 10.42%, retardation of endometrial development was 4.17% in ONF, no LPD in O2F, 21.42% in OSF, 2/3 in PCO, 3/6 in LUFS, respectively. The incidence of LPD was 14.58% in ONF, 56.52% in abnormal follicular development groups (OSF, O2F and LUFS) (P < 0.005). It was found that the retardation of endometrial development was associated either with lowered serum P level or normal serum P but lowered ER and PR concentrations. The latter condition was recognized as "pseudocorpus luteum deficiency". The different patterns of follicular development may exert a great influence over luteal function through the different production of steroid hormones and their receptors.

Effect of progesterone elevation in follicular phase of IVF-cycles on the endometrial receptivity.

PubMed

Lawrenz, B; Fatemi, H M

2017-04-01

The premature rise of progesterone during the late follicular phase in stimulated IVF cycles is a frequent event, and emerging evidence shows that premature progesterone rise does negatively affect the outcome of assisted reproductive techniques. The effect of elevated peripheral progesterone levels in the late follicular phase seems to be on the endometrium and the window of implantation, which may lead to asynchrony between the endometrium and the developing embryo. In stimulated cycles, endometrial maturation is advanced on the day of oocyte retrieval, and patients with a progesterone level above 1.5 ng/ml on the day of final oocyte maturation have different endometrial gene expression profiles. This progesterone level seems to represent the critical threshold, at which a negative effect on the ongoing pregnancy rate in fresh IVF cycles can be observed. Moreover, no association exists between progesterone elevation in the fresh cycle, and the probability of pregnancy after transfer of frozen-thawed embryos, originating from that cycle. The causes of premature progesterone elevation during ovarian stimulation are still unclear; however, recent studies point towards enhanced FSH-stimulation as a cause for progesterone elevation. Copyright © 2017 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Proteomic analysis of mare follicular fluid during late follicle development

PubMed Central

2011-01-01

Background Follicular fluid accumulates into the antrum of follicle from the early stage of follicle development. Studies on its components may contribute to a better understanding of the mechanisms underlying follicular development and oocyte quality. With this objective, we performed a proteomic analysis of mare follicular fluid. First, we hypothesized that proteins in follicular fluid may differ from those in the serum, and also may change during follicle development. Second, we used four different approaches of Immunodepletion and one enrichment method, in order to overcome the masking effect of high-abundance proteins present in the follicular fluid, and to identify those present in lower abundance. Finally, we compared our results with previous studies performed in mono-ovulant (human) and poly-ovulant (porcine and canine) species in an attempt to identify common and/or species-specific proteins. Methods Follicular fluid samples were collected from ovaries at three different stages of follicle development (early dominant, late dominant and preovulatory). Blood samples were also collected at each time. The proteomic analysis was carried out on crude, depleted and enriched follicular fluid by 2D-PAGE, 1D-PAGE and mass spectrometry. Results Total of 459 protein spots were visualized by 2D-PAGE of crude mare follicular fluid, with no difference among the three physiological stages. Thirty proteins were observed as differentially expressed between serum and follicular fluid. Enrichment method was found to be the most powerful method for detection and identification of low-abundance proteins from follicular fluid. Actually, we were able to identify 18 proteins in the crude follicular fluid, and as many as 113 in the enriched follicular fluid. Inhibins and a few other proteins involved in reproduction could only be identified after enrichment of follicular fluid, demonstrating the power of the method used. The comparison of proteins found in mare follicular fluid

Proteomic analysis of mare follicular fluid during late follicle development.

PubMed

Fahiminiya, Somayyeh; Labas, Valérie; Roche, Stéphane; Dacheux, Jean-Louis; Gérard, Nadine

2011-09-17

Follicular fluid accumulates into the antrum of follicle from the early stage of follicle development. Studies on its components may contribute to a better understanding of the mechanisms underlying follicular development and oocyte quality. With this objective, we performed a proteomic analysis of mare follicular fluid. First, we hypothesized that proteins in follicular fluid may differ from those in the serum, and also may change during follicle development. Second, we used four different approaches of Immunodepletion and one enrichment method, in order to overcome the masking effect of high-abundance proteins present in the follicular fluid, and to identify those present in lower abundance. Finally, we compared our results with previous studies performed in mono-ovulant (human) and poly-ovulant (porcine and canine) species in an attempt to identify common and/or species-specific proteins. Follicular fluid samples were collected from ovaries at three different stages of follicle development (early dominant, late dominant and preovulatory). Blood samples were also collected at each time. The proteomic analysis was carried out on crude, depleted and enriched follicular fluid by 2D-PAGE, 1D-PAGE and mass spectrometry. Total of 459 protein spots were visualized by 2D-PAGE of crude mare follicular fluid, with no difference among the three physiological stages. Thirty proteins were observed as differentially expressed between serum and follicular fluid. Enrichment method was found to be the most powerful method for detection and identification of low-abundance proteins from follicular fluid. Actually, we were able to identify 18 proteins in the crude follicular fluid, and as many as 113 in the enriched follicular fluid. Inhibins and a few other proteins involved in reproduction could only be identified after enrichment of follicular fluid, demonstrating the power of the method used. The comparison of proteins found in mare follicular fluid with proteins previously

Frequency modulation of follicle-stimulating hormone (FSH) during the luteal-follicular transition: evidence for FSH control of inhibin B in normal women.

PubMed

Welt, C K; Martin, K A; Taylor, A E; Lambert-Messerlian, G M; Crowley, W F; Smith, J A; Schoenfeld, D A; Hall, J E

1997-08-01

To isolate the impact of GnRH pulse frequency on FSH secretion and to examine the effect of differing levels of FSH on inhibin B secretion during the luteal-follicular transition, exogenous GnRH was administered to GnRH-deficient women using one of two regimens, and the results were compared to those in normal women. In the GnRH-deficient women, the GnRH pulse frequency was increased from every 4 h in the late luteal phase to every 90 min on the day of menses to mimic normal cycling women (physiological frequency transition; n = 8 studies) or the GnRH pulse frequency was kept constant at a late luteal phase frequency of every 4 h through the first 6 days of the subsequent early follicular phase of cycle 2 (slow frequency transition; n = 6 studies). The differential rise in FSH secretion induced in these studies allowed us to examine the subsequent contribution of varying levels of FSH to inhibin B secretion. A physiological regimen of GnRH during the luteal-follicular transition resulted in a rise in FSH and inhibin B levels that did not differ from that in normal cycling women and a normal follicular phase length. On the other hand, maintaining a luteal frequency of GnRH for 6 days into the subsequent early follicular phase produced FSH levels significantly lower than those in the physiological transition (P < 0.05), with the greatest difference seen on the day after menses (9.1 +/- 1.0 vs. 16.4 +/- 1.4 IU/L for the slow and physiological transition groups, respectively; P < 0.005), but no difference in LH. This slower rise of FSH secretion in the slow frequency group was associated with significantly lower inhibin B levels (43.3 +/- 21.5 vs. 140.0 +/- 24.4 pg/mL, mean days 1, 3, and 5; P < 0.02), a later doubling of estradiol from baseline (day 9.6 +/- 0.9 vs. day 5.6 +/- 0.1; P < 0.02), and a longer follicular phase length (16.0 +/- 1.4 vs. 11.6 +/- 0.9 days; P < 0.05) compared with those in the physiological transition group. In conclusion, during the luteal-follicular

Menstrual phase-related differences in the pulsatility index on the central retinal artery suggest an oestrogen vasodilatation effect that antagonizes with progesterone.

PubMed

Viana, Luiz Carlos; Faria, Marcos; Pettersen, Heverton; Sampaio, Marcos; Geber, Selmo

2011-03-01

The actual effect of steroid hormones on cerebral microcirculation is still controversial. Therefore, the aim of our study was to investigate vascular flow variations in the central retinal artery that may exist during the ovulatory menstrual cycle. A total of 34 healthy women were included in this observational, longitudinal, and prospective study. All participants were submitted to dopplerfluxometric evaluation of the eyes in order to study the pulsatility index (PI) of the central retinal arteries, during four phases of the menstrual cycle: early follicular, mid follicular, periovulatory, and mid luteal phases. Subjects' ages ranged from 14 to 47 years old (mean: 29.7 ± 10.1) and PI did not differ among age groups. The PI of the central retinal artery was different among the four phases of the menstrual cycle. PI showed a significant decrease from early follicular phase (1.72) to mid follicular phase (1.57) (p = 0.037), and was similar during periovulatory phase (1.56) and significantly increased in mid luteal phase (1.70). After that it returned to the values observed in the early follicular phase. Our results suggest the existence of an oestrogen vasodilatation effect on the central retinal artery that is menstrual phase-related and antagonized by progesterone.

Reduced Phase-Advance of Plasma Melatonin after Bright Morning Light in the Luteal, but not Follicular, Menstrual Cycle Phase in Premenstrual Dysphoric Disorder: An Extended Study

PubMed Central

Parry, Barbara L.; Meliska, Charles J.; Sorenson, Diane L.; Martínez, L. Fernando; López, Ana M.; Elliott, Jeffrey A.; Hauger, Richard L.

2011-01-01

We previously observed blunted phase-shift responses to morning bright light in women with Premenstrual Dysphoric Disorder (PMDD). The aim of this study was to determine if we could replicate these findings using a higher intensity, shorter duration light pulse and to compare these results with the effects of an evening bright light pulse. In 17 PMDD patients and 14 normal control (NC) subjects, we measured plasma melatonin at 30 minute intervals from 18:00–10:00 h in dim (< 30 lux) or dark conditions the night before (night 1) and after (night 3) a bright light pulse (administered on night 2) in both follicular and luteal menstrual cycle phases. The bright light (either 3,000 lux for 6 h or 6,000 lux for 3 h) was given either in the AM, 7 h after the Dim Light Melatonin Onset (DLMO) measured the previous month, or in the PM, 3 h after the DLMO. In the luteal, but not in the follicular, phase, AM light advanced melatonin offset between night 1 and night 3 significantly less in PMDD than in NC subjects. The effects of PM light were not significant, nor were there significant effects of the light pulse on melatonin measures of onset, duration, peak or area under the curve. These findings replicated our previous finding of a blunted phase-shift response to morning bright light in the luteal, but not the follicular, menstrual cycle phase in PMDD compared with NC women, using a brighter (6,000 vs. 3,000 lux) light pulse for a shorter duration (3 vs. 6 h). As the effect of PM bright light on melatonin phase-shift responses did not differ between groups or significantly alter other melatonin measures, these results suggest that in PMDD there is a luteal phase subsensitivity or an increased resistance to morning bright light cues which are critical in synchronizing human biological rhythms. The resulting circadian rhythm malsynchonization may contribute to the occurrence of luteal phase depressive symptoms in women with PMDD. PMID:21721857

Relationship between Numerous Mast Cells and Early Follicular Development in Neonatal MRL/MpJ Mouse Ovaries

PubMed Central

Nakamura, Teppei; Otsuka, Saori; Ichii, Osamu; Sakata, Yuko; Nagasaki, Ken-Ichi; Hashimoto, Yoshiharu; Kon, Yasuhiro

2013-01-01

In the neonatal mouse ovary, clusters of oocytes called nests break into smaller cysts and subsequently form individual follicles. During this period, we found numerous mast cells in the ovary of MRL/MpJ mice and investigated their appearance and morphology with follicular development. The ovarian mast cells, which were already present at postnatal day 0, tended to localize adjacent to the surface epithelium. Among 11 different mouse strains, MRL/MpJ mice possessed the greatest number of ovarian mast cells. Ovarian mast cells were also found in DBA/1, BALB/c, NZW, and DBA/2 mice but rarely in C57BL/6, NZB, AKR, C3H/He, CBA, and ICR mice. The ovarian mast cells expressed connective tissue mast cell markers, although mast cells around the surface epithelium also expressed a mucosal mast cell marker in MRL/MpJ mice. Some ovarian mast cells migrated into the oocyte nests and directly contacted the compressed and degenerated oocytes. In MRL/MpJ mice, the number of oocytes in the nest was significantly lower than in the other strains, and the number of oocytes showed a positive correlation with the number of ovarian mast cells. The gene expression of a mast cell marker also correlated with the expression of an oocyte nest marker, suggesting a link between the appearance of ovarian ? 4mast cells and early follicular development. Furthermore, the expression of follicle developmental markers was significantly higher in MRL/MpJ mice than in C57BL/6 mice. These results indicate that the appearance of ovarian mast cells is a unique phenotype of neonatal MRL/MpJ mice, and that ovarian mast cells participate in early follicular development, especially nest breakdown. PMID:24124609

Sex differences in acute hormonal and subjective response to naltrexone: the impact of menstrual cycle phase

PubMed Central

Roche, Daniel J.O.; King, Andrea C.

2015-01-01

Women often exhibit larger hormonal and subjective responses to opioid receptor antagonists than men, but the biological mechanisms mediating this effect remain unclear. Among women, fluctuations in estradiol (E2) and progesterone (P4) across the menstrual cycle (MC) affect the endogenous opioid system. Therefore, the goal of the current study was to compare acute naltrexone response between women in the early follicular phase of the MC (low E2 and P4), women in the luteal phase of the MC (high E2 and P4), and men. Seventy healthy controls (n = 46 women) participated in two morning sessions in which they received 50 mg naltrexone or placebo in a randomized, counterbalanced order. Women were randomized to complete both sessions in either the early follicular (n = 23) or luteal phase of the MC. Serum cortisol, prolactin, and luteinizing hormone (LH), salivary cortisol, and subjective response were assessed upon arrival to the laboratory and at regular intervals after pill administration. In luteal and early follicular women but not men, naltrexone (vs. placebo) increased serum cortisol and prolactin levels from baseline; however, the naltrexone-induced increases in these hormones were significantly greater in luteal women than early follicular women. Additionally, only luteal women demonstrated an increase from baseline in salivary cortisol levels and the severity of adverse drug effects in response to naltrexone. In sum, the results indicate that luteal phase women are more sensitive to acute hormonal and subjective effects of naltrexone than early follicular women and men. These findings may have important implications for the use of naltrexone in women. PMID:25459893

Mutational burdens and evolutionary ages of thyroid follicular adenoma are comparable to those of follicular carcinoma

PubMed Central

Jung, Seung-Hyun; Kim, Min Sung; Jung, Chan Kwon; Park, Hyun-Chun; Kim, So Youn; Liu, Jieying; Bae, Ja-Seong; Lee, Sung Hak; Kim, Tae-Min; Lee, Sug Hyung; Chung, Yeun-Jun

2016-01-01

Follicular thyroid adenoma (FTA) precedes follicular thyroid carcinoma (FTC) by definition with a favorable prognosis compared to FTC. However, the genetic mechanism of FTA to FTC progression remains unknown. For this, it is required to disclose FTA and FTC genomes in mutational and evolutionary perspectives. We performed whole-exome sequencing and copy number profiling of 14 FTAs and 13 FTCs, which exhibited previously-known gene mutations (NRAS, HRAS, BRAF, TSHR and EIF1AX) and copy number alterations (CNAs) (22q loss and 1q gain) in follicular tumors. In addition, we found eleven potential cancer-related genes with mutations (EZH1, SPOP, NF1, TCF12, IGF2BP3, KMT2C, CNOT1, BRIP1, KDM5C, STAG2 and MAP4K3) that have not been reported in thyroid follicular tumors. Of note, FTA genomes showed comparable levels of mutations to FTC in terms of the number, sequence composition and functional consequences (potential driver mutations) of mutations. Analyses of evolutionary ages using somatic mutations as molecular clocks further identified that FTA genomes were as old as FTC genomes. Whole-transcriptome sequencing did not find any gene fusions with potential significance. Our data indicate that FTA genomes may be as old as FTC genomes, thus suggesting that follicular thyroid tumor genomes during the transition from FTA to FTC may stand stable at genomic levels in contrast to the discernable changes at pathologic and clinical levels. Also, the data suggest a possibility that the mutational profiles obtained from early biopsies may be useful for the molecular diagnosis and therapeutics of follicular tumor patients. PMID:27626165

Mutational burdens and evolutionary ages of thyroid follicular adenoma are comparable to those of follicular carcinoma.

PubMed

Jung, Seung-Hyun; Kim, Min Sung; Jung, Chan Kwon; Park, Hyun-Chun; Kim, So Youn; Liu, Jieying; Bae, Ja-Seong; Lee, Sung Hak; Kim, Tae-Min; Lee, Sug Hyung; Chung, Yeun-Jun

2016-10-25

Follicular thyroid adenoma (FTA) precedes follicular thyroid carcinoma (FTC) by definition with a favorable prognosis compared to FTC. However, the genetic mechanism of FTA to FTC progression remains unknown. For this, it is required to disclose FTA and FTC genomes in mutational and evolutionary perspectives. We performed whole-exome sequencing and copy number profiling of 14 FTAs and 13 FTCs, which exhibited previously-known gene mutations (NRAS, HRAS, BRAF, TSHR and EIF1AX) and copy number alterations (CNAs) (22q loss and 1q gain) in follicular tumors. In addition, we found eleven potential cancer-related genes with mutations (EZH1, SPOP, NF1, TCF12, IGF2BP3, KMT2C, CNOT1, BRIP1, KDM5C, STAG2 and MAP4K3) that have not been reported in thyroid follicular tumors. Of note, FTA genomes showed comparable levels of mutations to FTC in terms of the number, sequence composition and functional consequences (potential driver mutations) of mutations. Analyses of evolutionary ages using somatic mutations as molecular clocks further identified that FTA genomes were as old as FTC genomes. Whole-transcriptome sequencing did not find any gene fusions with potential significance. Our data indicate that FTA genomes may be as old as FTC genomes, thus suggesting that follicular thyroid tumor genomes during the transition from FTA to FTC may stand stable at genomic levels in contrast to the discernable changes at pathologic and clinical levels. Also, the data suggest a possibility that the mutational profiles obtained from early biopsies may be useful for the molecular diagnosis and therapeutics of follicular tumor patients.

Transformation of follicular lymphoma - Why does it happen and can it be prevented?

PubMed

Link, Brian K

2018-03-01

Follicular lymphoma is a clinical disease with a multitude of presentations and behaviors. Although infrequent, transformation of follicular lymphoma to a more aggressive behaving subtype - prototypically diffuse large B-cell lymphoma - confers a substantially adverse prognosis. There is no consensus for optimal management after transformation is recognized. Historically considered a distinct clinical event, this review highlights the multiple subclinical transformational events that either variably or cumulatively result in clinical recognition of transformed follicular lymphoma. Known and suspected events include genetic and epigenetic perturbations, metabolomic changes, and alterations in the microenvironment. This diverse spectrum of pathways leads to heterogeneous clinical presentations and outcomes of transformed follicular lymphoma. Current options for prevention of transformation are limited to known strategies of managing follicular lymphoma before the transformation is recognized. Although most retrospectively analyzed studies suggest an association of lower transformation rates with early systemic therapy, specific components of therapy such as anti-CD20 antibodies, anthracyclines, or purine analogues are less strongly associated with "preventative' value. Thus, the goal of preventing transformation is of limited value among all factors that go into decisions on early management of follicular lymphoma. Future opportunities to prevent clinical evidence of transformation will benefit from early detection of markers of subclinical transformation and development of therapies to specifically target the biology implied by those markers. Copyright © 2017. Published by Elsevier Ltd.

Women with dysmenorrhoea are hypersensitive to experimentally induced forearm ischaemia during painful menstruation and during the pain-free follicular phase.

PubMed

Iacovides, S; Avidon, I; Baker, F C

2015-07-01

Monthly primary dysmenorrhoeic pain is associated with increased sensitivity to painful stimuli, particularly in deep tissue. We investigated whether women with dysmenorrhoea, compared with controls, have increased sensitivity to experimentally induced deep-tissue muscle ischaemia in a body area distant from that of referred menstrual pain. The sub-maximal effort tourniquet test was used to induce forearm ischaemia in 11 women with severe dysmenorrhoea and in nine control women both during menstruation and in the follicular phase of the menstrual cycle. Von Frey hair assessments confirmed the presence of experimental ischaemia. Women rated the intensity of menstrual and ischaemic pain on a 100-mm visual analogue scale. Women with dysmenorrhoea [mean (SD): 68 (20) mm] reported significantly greater menstrual pain compared with controls [mean (SD): 2 (6) mm; p = 0.0001] during the menstruation phase. They also rated their forearm ischaemic pain as significantly greater than the controls during the menstruation [dysmenorrhoeics vs. controls mean (SD): 58 (19) mm vs. 31 (21) mm, p < 0.01] and follicular [dysmenorrhoeics vs. controls mean (SD): 60 (18) mm vs. 40 (14) mm, p < 0.01] phases of the menstrual cycle. These data show that compared with controls, women who experience severe recurrent dysmenorrhoea have deep-tissue hyperalgesia to ischaemic pain in muscles outside of the referred area of menstrual pain both during the painful menstruation phase and pain-free follicular phase. These findings suggest the presence of long-lasting changes in muscle pain sensitivity in women with dysmenorrhoea. Our findings that dysmenorrhoeic women are hyperalgesic to a clinically relevant, deep-muscle ischaemic pain in areas outside of referred menstrual pain confirm other studies showing long-lasting changes in pain sensitivity outside of the painful period during menstruation. © 2014 European Pain Federation - EFIC®

Initiation of follicular atresia: gene networks during early atresia in pig ovaries.

PubMed

Zhang, Jinbi; Liu, Yang; Yao, Wang; Li, Qifa; Liu, Hong-Lin; Pan, Zengxiang

2018-05-09

In mammals, more than 99% of ovarian follicles undergo a degenerative process known as atresia. The molecular events involve in atresia initiation remain incompletely understood. The objective of this study was to analyze differential gene expression profiles of medium antral ovarian follicles during early atresia in pig. The transcriptome evaluation was performed on cDNA microarrays using healthy and early atretic follicle samples and was validated by quantitative PCR. Annotation analysis applying current database (sus scrofa 11.1) revealed 450 significantly differential expressed genes between healthy and early atretic follicles. Among them, 142 were significantly up-regulated in early atretic with respect to healthy group and 308 were down-regulated. Similar expression trends were observed between microarray data and qRT-PCR confirmation, which indicated the reliability of the microarray analysis. Further analysis of the differential expressed genes revealed the most significantly affected biological functions during early atresia including blood vessel development, regulation of DNA-templated transcription in response to stress and negative regulation of cell adhesion. The pathway and interaction analysis suggested that atresia initiation associates with 1) a crosstalk of cell apoptosis, autophagy, and ferroptosis rather than change of typical apoptosis markers, 2) dramatic shift of steroidogenic enzymes, 3) deficient glutathione metabolism, and 4) vascular degeneration. The novel gene candidates and pathways identified in the current study will lead to a comprehensive view of the molecular regulation of ovarian follicular atresia and a new understanding of atresia initiation.

Pulsatile luteinizing hormone patterns in the follicular phase of the menstrual cycle, polycystic ovarian disease (PCOD) and non-PCOD secondary amenorrhea.

PubMed

Burger, C W; Korsen, T; van Kessel, H; van Dop, P A; Caron, F J; Schoemaker, J

1985-12-01

To characterize the oscillations of plasma LH in normally cycling and amenorrheic women, three groups of women were studied: I, normal women during the follicular phase of the cycle (n = 9); II, women with polycystic ovarian disease (PCOD; n = 11); and III, women with non-PCOD secondary amenorrhea (n = 12). Blood samples were obtained at 10-min intervals for 6 h on 2 separate days. A pulse was defined as an increase in LH at least 20% over the preceding lowest value (nadir). Since LHRH release immediately follows the nadir of the LH levels, the nadir interval (NI) was used for analysis. For analysis, the results from 1 day were selected at random from each subject, and from each day, the same number of NIs also were randomly selected. When two NIs from each patient were selected, the median NI was 75 min in group I, 45 min in group II, and 45 min in group III. When three or four NIs were chosen, the median NI was 60 min in group I, 50 min in group II, and 40 min in group III. The differences between the groups were statistically significant. When three NIs were selected, the mean of the corresponding LH amplitudes was 2.8 U/liter in group I, 6.0 U/liter in group II, and 1.5 U/liter in group III. The differences between these groups were statistically significant. Thus, the NI in PCOD patients was shorter than that during the follicular phase of the cycle, but this short NI is not unique for PCOD, since the NI in non-PCOD secondary amenorrhea patients was even smaller. The LH amplitude was higher in PCOD and lower in non-PCOD secondary amenorrhea compared to that during the follicular phase of the cycle. The decrease in NI in PCOD and/or non-PCOD secondary amenorrhea vs. the NI of the follicular phase could be explained by either a higher frequency of LHRH pulses from the hypothalamus or an increased sensitivity of the pituitary leading to a greater response of the pituitary to LHRH pulses.

TERT promoter mutation as an early genetic event activating telomerase in follicular thyroid adenoma (FTA) and atypical FTA.

PubMed

Wang, Na; Liu, Tiantian; Sofiadis, Anastasios; Juhlin, C Christofer; Zedenius, Jan; Höög, Anders; Larsson, Catharina; Xu, Dawei

2014-10-01

The telomerase reverse transcriptase (TERT) promoter mutations C228T and C250T have been found in many malignancies, including in thyroid carcinomas. However, it is unclear how early these mutations occur in thyroid tumorigenesis. The study included primary tumors from 58 patients initially diagnosed with follicular thyroid adenoma (FTA), a benign entity, 18 with atypical FTA (AFTA) having an uncertain malignant potential, and 52 with follicular thyroid carcinoma (FTC). Sanger sequencing was used to investigate the mutational status of the TERT promoter. Telomere length and TERT messenger RNA (mRNA) expression were determined using quantitative polymerase chain reaction (PCR). Telomerase activity was assessed using a Telomerase PCR enzyme-linked immunosorbent assay kit. The C228T mutation was identified in 1 of 58 FTA (2%) and 3 of 18 AFTA (17%) samples. These 4 tumors all expressed TERT mRNA and telomerase activity, whereas the majority of C228T-negative adenomas lacked TERT expression (C228T versus wild-type, P = .008). The C228T mutation was associated with NRAS gene mutations (P = .016). The patient with C228T-mutated FTA later developed a scar recurrence and died of FTC, whereas none of the remaining 57 patients with FTA had recurrence. No recurrence occurred in 3 patients with AFTA who carried C228T during the follow-up period (36-285 months). Nine of the 52 FTCs (17%) exhibited the TERT mutation (8 of 9 C228T and 1 of 9 C250T), and the presence of the mutation was associated with shorter patient survival. TERT promoter mutations may occur as an early genetic event in thyroid follicular tumors that have not developed malignant features on routine histopathological workup. © 2014 American Cancer Society.

Follicular contact dermatitis revisited: A review emphasizing neomycin-associated follicular contact dermatitis

PubMed Central

Cohen, Philip R

2014-01-01

Follicular contact dermatitis clinically presents as individual papules that include a central hair follicle. Pathologic features involve the follicle and the surrounding dermis: spongiosis and vesicle formation of the follicular epithelium associated with perifollicular and perivascular lymphocytic inflammation. Using the PubMed database, an extensive literature search was performed on follicular contact dermatitis and neomycin. Relevant papers were reviewed and the clinical and pathologic features, the associated chemicals (including a more detailed description of neomycin), the hypothesized pathogenesis, and the management of follicular contact dermatitis were described. Several agents-either as allergens or irritants-have been reported to elicit follicular contact dermatitis. Several hypotheses have been suggested for the selective involvement of the follicles in follicular contact dermatitis: patient allergenicity, characteristics of the agent, vehicle containing the agent, application of the agent, and external factors. The differential diagnosis of follicular contact dermatitis includes not only recurrent infundibulofolliculitis, but also drug eruption, mite infestation, viral infection, and dermatoses that affect hair follicles. The primary therapeutic intervention for follicular contact dermatitis is withdrawal of the causative agent; treatment with a topical corticosteroid preparation may also promote resolution of the dermatitis. In conclusion, follicular contact dermatitis may be secondary to allergens or irritants; topical antibiotics, including neomycin, may cause this condition. Several factors may account for the selective involvement of the hair follicle in this condition. Treatment of the dermatitis requires withdrawal of the associated topical agent; in addition, topical corticosteroids may be helpful to promote resolution of lesions. PMID:25516854

Androgens stimulate early stages of follicular growth in the primate ovary.

PubMed Central

Vendola, K A; Zhou, J; Adesanya, O O; Weil, S J; Bondy, C A

1998-01-01

The concept that androgens are atretogenic, derived from murine ovary studies, is difficult to reconcile with the fact that hyperandrogenic women have more developing follicles than normal-cycling women. To evaluate androgen's effects on primate follicular growth and survival, normal-cycling rhesus monkeys were treated with placebo-, testosterone-(T), or dihydrotestosterone-sustained release implants, and ovaries were taken for histological analysis after 3-10 d of treatment. Growing preantral and small antral follicles up to 1 mm in diameter were significantly and progressively increased in number and thecal layer thickness in T-treated monkeys from 3-10 d. Granulosa and thecal cell proliferation, as determined by immunodetection of the Ki67 antigen, were significantly increased in these follicles. Preovulatory follicles (> 1 mm), however, were not increased in number in androgen-treated animals. Follicular atresia was not increased and there were actually significantly fewer apoptotic granulosa cells in the T-treated groups. Dihydrotestosterone treatment had identical effects, indicating that these growth-promoting actions are mediated by the androgen receptor. These findings show that, over the short term at least, androgens are not atretogenic and actually enhance follicular growth and survival in the primate. These new data provide a plausible explanation for the pathogenesis of "polycystic" ovaries in hyperandrogenism. PMID:9637695

Beta endorphin in serum and follicular fluid of PCOS- and non-PCOS women.

PubMed

Jaschke, Nikolai; Lunger, Fabian; Wildt, Ludwig; Seeber, Beata

2018-07-01

To compare the concentrations of beta endorphin in serum and follicular fluid (FF) of PCOS- and non-PCOS women. Secondarily, to investigate associations between beta endorphin and other parameters. Fifty-nine women undergoing in vitro fertilization (IVF) were included in the study. Sixteen were stratified to the PCOS group using the Rotterdam criteria. The remaining 43 women served as controls. Follicular fluid was collected during oocyte retrieval and peripheral blood sampling was performed on the same day. Beta endorphin concentrations in serum and follicular fluid, serum levels of insulin, glucose, LH, estradiol and progesterone were measured. Additionally, testosterone was measured before starting the stimulation protocol. There was no difference in beta endorphin levels between PCOS- and non-PCOS women. The concentration of the peptide was higher in serum than in FF, likely due to collection of FF after ovulation induction and corresponding to the early luteal phase. We found a significant correlation between the number of mature Metaphase II (MII) oocytes retrieved and beta endorphin concentration in FF. In women with biochemical hyperandrogenemia, beta endorphin levels in FF correlated with testosterone levels. Beta Endorphin concentrations in serum and FF do not differ between PCOS- and non PCOS-women undergoing IVF. However, together with sex hormones, beta endorphin might play a key role in oocyte maturation.

High frequency of luteal phase deficiency and anovulation in recreational women runners: blunted elevation in follicle-stimulating hormone observed during luteal-follicular transition.

PubMed

De Souza, M J; Miller, B E; Loucks, A B; Luciano, A A; Pescatello, L S; Campbell, C G; Lasley, B L

1998-12-01

The purposes of this investigation were to evaluate the characteristics of three consecutive menstrual cycles and to determine the frequency ofluteal phase deficiency (LPD) and anovulation in a sample of sedentary and moderately exercising, regularly menstruating women. For three consecutive menstrual cycles, subjects collected daily urine samples for analysis of FSH, estrone conjugates (E1C), pregnanediol-3-glucuronide (PdG), and creatinine (Cr). Sedentary (n=11) and exercising (n=24) groups were similar in age (27.0+/-1.3 yr), weight (60.3+/-3.1 kg), gynecological age (13.8+/-1.2 yr), and menstrual cycle length (28.3+/-0.8 days). Menstrual cycles were classified by endocrine data as ovulatory, LPD, or anovulatory. No sedentary women (0%) had inconsistent menstrual cycle classifications from cycle to cycle, but 46% of the exercising women were inconsistent. The sample prevalence of LPD in the exercising women was 48%, and the 3-month sample incidence was 79%. In the sedentary women, 90% of all menstrual cycles were ovulatory (SedOvul; n=28), whereas in the exercising women only 45% were ovulatory (ExOvul; n=30); 43% were LPD (ExLPD; n=28), and 12% were anovulatory (ExAnov; n=8). In ExLPD cycles, the follicular phase was significantly longer (17.9+/-0.7 days), and the luteal phase was significantly shorter (8.2+/-0.5 days) compared to ExOvul (14.8+/-0.9 and 12.9+/-0.3 days) and SedOvul (15.9+/-0.6 and 12.9+/-0.4 days) cycles. Luteal phase PdG excretion was lower (P < 0.001) in ExLPD (2.9+/-0.3 microg/mg Cr) and ExAnov (0.8+/-0.1 microg/mg Cr) cycles compared to SedOvul cycles (5.0+/-0.4 microg/mg Cr). ExOvul cycles also had less (P < 0.01) PdG excretion during the luteal phase (3.7+/-0.3 microg/mg Cr) than the SedOvul cycles. E1C excretion during follicular phase days 2-5 was lower (P=0.05) in ExOvul, ExLPD, and ExAnov cycles compared to SedOvul cycles and remained lower (P < 0.02) in the ExLPD and ExAnov cycles during days 6-12. The elevation in FSH during the

Giant Follicular Cyst of Ovary in an Adolescent Girl

PubMed Central

Gedam, Jaya; Bhalerao, Minal; Nadar, Ponambalaganpathi A

2014-01-01

Cystic abdominal lesions are extremely common in adolescent girls and are now diagnosed more frequently due to the availability of better imaging modalities. Presentations as huge cysts have become rare as most of them are diagnosed and treated early. Adolescent girls presenting with huge benign abdominal cysts is not uncommon, most of them due to serious cystadenomas of the ovary, but large follicular cysts are rare. We present a 13-year-old girl who presented with a large abdominal mass which was subsequently diagnosed as juvenile follicular cyst of the ovary. PMID:25177606

Suppression of follicular rupture with meloxicam, a cyclooxygenase-2 inhibitor: potential for emergency contraception.

PubMed

Jesam, Cristián; Salvatierra, Ana María; Schwartz, Jill L; Croxatto, Horacio B

2010-02-01

There is evidence that cyclooxygenase-2 (COX-2) inhibitors can prevent or delay follicular rupture. COX-2 inhibitors, such as meloxicam, may offer advantages over emergency contraception with levonorgestrel, such as extending the therapeutic window for up to 24 h. We assessed the effect of meloxicam administered in the late follicular phase upon ovulation in women. This was a single center, double blind, crossover study designed to assess the effects in 27 eligible women (18-40 years old, surgically sterilized with regular menstrual cycles) of meloxicam, 15 or 30 mg/day, administered orally for five consecutive days during the late follicular phase, starting when the leading follicle reached 18 mm diameter. Volunteers underwent two treatment cycles separated by one resting cycle, with randomization to dose sequence. Main outcomes were follicular rupture; serum LH, progesterone and estradiol (E2) levels; and incidence of adverse events. Twenty-two volunteers completed the study. There were no differences between meloxicam doses in menstrual cycle length. Dysfunctional ovulation was observed in 11/22 (50%) cycles treated with 15 mg/day and 20/22 (90.9%) cycles with 30 mg/day (P = 0.0068). All women had normal luteal phase progesterone levels; mean maximal values +/- SEM were 42 +/- 4.1 and 46.8 +/- 2.6 nmol/l for 15 and 30 mg/day groups, respectively. There were no serious adverse events, and no changes in LH and E2 levels or in cycle length. Meloxicam 30 mg given for five consecutive days in the late follicular phase is safe, effective and may be an alternative form of emergency contraception.

Uterine and systemic inflammation influences ovarian follicular function in postpartum dairy cows

PubMed Central

Sá Filho, Ocilon G.; Absalon-Medina, Victor A.; Schneider, Augusto; Butler, W. R.; Gilbert, Robert O.

2017-01-01

The objective of this study was to determine the effects of uterine and systemic inflammatory responses to uterine bacterial contamination at calving in dairy cows on the growth and ovulatory outcomes of the first dominant follicle postpartum. Ovulatory capability of the first dominant follicle postpartum was predicted in 53 multiparous cows by using a combination of follicle growth characteristics and circulating estradiol concentrations. Endotoxin levels were assayed in follicular fluid samples that were aspirated the day after ovulatory outcome prediction. Plasma levels of haptoglobin, a proinflammatory acute phase protein, and paraoxonase, a negative acute phase protein were determined. Uterine bacteria and inflammation were evaluated in three uterine fluid samples from each cow collected on the day of calving, the day after follicle aspiration, and at 35 days postpartum. Cows that had a strong initial uterine inflammatory response (robust recruitment of polymorphonuclear leukocytes of ≥ 35% and cows with uterine pH < 8.5 on the day of calving) were more likely to have an ovulatory first dominant follicle. Follicular fluid endotoxin levels were higher in non-ovulatory cows compared with ovulatory cows. Endotoxin levels in circulation were not different between ovulatory groups but were higher prepartum than on day 7 and 14 postpartum. Systemic inflammation characterized by elevated haptoglobin concentrations was higher in non-ovulatory cows despite similar bacterial contamination and circulating endotoxin levels. Paraoxonase activity in follicular fluid was significantly associated with the paraoxonase activity in plasma, however, plasma paraoxonase concentrations were not different between non-ovulatory and ovulatory cows. Cows with a higher uterine bacterial load on the day of calving had slower ovarian follicle growth. In summary, a robust uterine inflammatory response on the day of calving was positively associated with ovarian function while elevated

Comparison of low-intensity blood flow-restricted training-induced muscular hypertrophy in eumenorrheic women in the follicular phase and luteal phase and age-matched men.

PubMed

Sakamaki, Mikako; Yasuda, Tomohiro; Abe, Takashi

2012-05-01

The purpose of this study was to compare the muscle hypertrophic response in women during both the follicular (FP) and the luteal phase (LP) of their menstrual cycles following short-term, low-intensity resistance training combined with blood flow restriction (BFR). Eight eumenorrheic women and five men, all previously untrained, performed unilateral low-intensity (30% of 1 repetition maximum) dumbbell curl training with BFR once a day for 6 days. The opposite arm served as an untrained control. This 6-day training programme was conducted during both menstrual cycle phases: the early FP and the mid LP. MRI-measured biceps muscle volume (MV) and isometric elbow flexion strength were measured in both arms before and 2 days after the final training bout. Significantly (P<0.05) greater muscle hypertrophy was observed in the LP (5·7%) than in the FP (3·7%). The absolute and relative changes in serum hormone concentrations between the two phases did not correlate (P>0.05) with the percentage change in MV between the LP and FP. There was no change in MV in the control arm for both cycle phases. Following training, isometric strength increased (P<0.01) in the LP, but not in the FP (P = 0.17). Relative strength (strength per unit MV) was similar pre- and post-training in both phases. The percentage changes in MV and strength were similar between the women (average of LP and FP) and men. Our results indicate that muscle hypertrophy and strength gain are higher in the LP than in the FP following 6 days of BFR training, although the sex difference in the training response is non-existent. © 2011 The Authors. Clinical Physiology and Functional Imaging © 2011 Scandinavian Society of Clinical Physiology and Nuclear Medicine.

MicroRNA Expression Profile in Bovine Granulosa Cells of Preovulatory Dominant and Subordinate Follicles during the Late Follicular Phase of the Estrous Cycle.

PubMed

Gebremedhn, Samuel; Salilew-Wondim, Dessie; Ahmad, Ijaz; Sahadevan, Sudeep; Hossain, Md Munir; Hoelker, Michael; Rings, Franca; Neuhoff, Christiane; Tholen, Ernst; Looft, Christian; Schellander, Karl; Tesfaye, Dawit

2015-01-01

In bovine, ovarian follicles grow in a wave-like fashion with commonly 2 or 3 follicular waves emerging per estrous cycle. The dominant follicle of the follicular wave which coincides with the LH-surge becomes ovulatory, leaving the subordinate follicles to undergo atresia. These physiological processes are controlled by timely and spatially expressed genes and gene products, which in turn are regulated by post-transcriptional regulators. MicroRNAs, a class of short non-coding RNA molecules, are one of the important posttranscriptional regulators of genes associated with various cellular processes. Here we investigated the expression pattern of miRNAs in granulosa cells of bovine preovulatory dominant and subordinate follicles during the late follicular phase of bovine estrous cycle using Illumina miRNA deep sequencing. In addition to 11 putative novel miRNAs, a total of 315 and 323 known miRNAs were detected in preovulatory dominant and subordinate follicles, respectively. Moreover, in comparison with the subordinate follicles, a total of 64 miRNAs were found to be differentially expressed in preovulatory dominant follicles, of which 34 miRNAs including the miR-132 and miR-183 clusters were significantly enriched, and 30 miRNAs including the miR-17-92 cluster, bta-miR-409a and bta-miR-378 were significantly down regulated in preovulatory dominant follicles. In-silico pathway analysis revealed that canonical pathways related to oncogenesis, cell adhesion, cell proliferation, apoptosis and metabolism were significantly enriched by the predicted target genes of differentially expressed miRNAs. Furthermore, Luciferase reporter assay analysis showed that one of the differentially regulated miRNAs, the miR-183 cluster miRNAs, were validated to target the 3'-UTR of FOXO1 gene. Moreover FOXO1 was highly enriched in granulosa cells of subordinate follicles in comparison with the preovulatory dominant follicles demonstrating reciprocal expression pattern with miR-183

Improving the luteal phase after ovarian stimulation: reviewing new options.

PubMed

Yding Andersen, C; Vilbour Andersen, K

2014-05-01

The human chorionic gonadotrophin (HCG) trigger used for final follicular maturation in connection with assisted reproduction treatment combines ovulation induction and early luteal-phase stimulation of the corpora lutea. The use of a gonadotrophin-releasing hormone agonist (GnRHa) for final follicular maturation has, however, for the first time allowed a separation of the ovulatory signal from the early luteal-phase support. This has generated new information that may improve the currently employed luteal-phase support. Thus, combined results from a number of randomized controlled trials using the GnRHa trigger suggest an association between the reproductive outcome after IVF treatment and the mid-luteal-phase serum progesterone concentration. It appears that a minimum mid-luteal progesterone threshold of approximately 80-100 nmol/l exists, which, when surpassed, results in reduced early pregnancy loss and an increased live birth rate. Further, the trade off between the HCG bolus and the subsequent risk of ovarian hyperstimulation syndrome has resulted in a trend to reduce the HCG bolus from 10,000 IU to 6500-5000 IU, which augments the HCG/LH deficiency during the early/mid-luteal phase. The mid-luteal HCG/LH shortage results in an altered progesterone profile, showing the highest concentration during the early luteal phase, contrasting with the mid-luteal peak seen in the natural menstrual cycle. Copyright © 2014 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Enhanced response to ozone exposure during the follicular phase of the menstrual cycle

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

Fox, S.D.; Adams, W.C.; Brookes, K.A.

Exposure to ozone (O[sub 3]), a toxic component of photochemical smog, results in significant airway inflammation, respiratory discomfort, and pulmonary function impairment. These effects can be reduced via pretreatment with anti-inflammatory agents. Progesterone, a gonadal steroid, is known to reduce general inflammation in the uterine endometrium. However, it is not known whether fluctuation in blood levels of progesterone, which are experienced during the normal female menstrual cycle, could alter O[sub 3] inflammatory-induced pulmonary responses. In this study, we tested the hypothesis that young, adult females are more responsive to O[sub 3] inhalation with respect to pulmonary function impairment during theirmore » follicular (F) menstrual phase when progesterone levels are lowest that during their mid-luteal (ML) phase when progesterone levels are highest. Nine subjects with normal ovarian function were exposed in random order for 1 hour each to filtered air and to 0.30 ppm O[sub 3] in their F and ML menstrual phases. Ozone responsiveness was measured by percent change in pulmonary function from pre- to postexposure. Significant gas concentration effects (filtered air versus O[sub 3]) were observed for forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV[sub 1]), and forced expiratory flow between 25 and 75% of FVC (FEF[sub 25-75]), showed a significant menstrual phase and gas concentration interaction effect, with larger decrements observed in the F menstrual phase when progesterone concentrations were significantly lower. We conclude that young, adult females appear to be more responsive to acute O[sub 3] exposure during the F phase than during the ML phase of their menstrual cycles. This difference in pulmonary function response could be related to the anti-inflammatory effects of increased progesterone concentrations during the luteal phase.« less

Adrenal hormones in human follicular fluid.

PubMed

Jimena, P; Castilla, J A; Peran, F; Ramirez, J P; Vergara, F; Molina, R; Vergara, F; Herruzo, A

1992-11-01

Considerable evidence indicates that adrenal hormones may affect gonadal function. To assess the role of some adrenal hormones in human follicular fluid and their relationship with the ability of the oocyte to be fertilized and then to cleave in vitro, cortisol and dehydroepiandrosterone sulfate were measured in follicular fluid obtained at the time of oocyte recovery for in vitro fertilization from cycles stimulated by clomiphene citrate, human menopausal gonadotropin and human chorionic gonadotropin. Thirty-six follicular fluid containing mature oocyte-corona-cumulus complexes and free of visible blood contamination were included in this study. There was no significant difference in follicular fluid dehydroepiandrosterone sulfate concentration between follicles with oocytes which did or did not fertilize (5.1 +/- 1.1 vs 5.8 +/- 2.0 mumol/l). However, follicular fluid from follicles whose oocytes were not fertilized had levels of cortisol significantly higher than those in follicular fluid from follicles containing successfully fertilized oocytes (406.0 +/- 75.9 vs 339.2 +/- 37.0 nmol/l; p < 0.005). No significant correlations were found between rates of embryo cleavage and cortisol and dehydroepiandrosterone levels in follicular fluid. We conclude that cortisol levels in follicular fluid may provide an index of fertilization outcome, at least in stimulated cycles by clomiphene citrate, human menopausal gonadotropin and human chorionic gonadotropin.

[Efficacy of acupuncture-moxibustion periodic therapy on follicular maldevelopment differentiated as spleen and kidney yang deficiency].

PubMed

Yan, Yuxuan; Pan, Chang; Wu, Jie; Yang, Lijie

2017-01-12

To observe the clinical efficacy of acupuncture and moxibustion periodic therapy on folli-cular maldevelopment differentiated as spleen and kidney yang deficiency. Sixty patients of follicular maldevelopment differentiated as spleen and kidney yang deficiency were randomized as an observation group and a control group, 30 cases in each one. The conventional acupuncture-moxibustion therapy was used in the control group and the acupuncture-moxibustion periodic therapy was applied to the observation group. In the control group, the acupoints were selected in terms of spleen and kidney yang deficiency, such as Guanyuan (CV 4), Qihai (CV 6), Zusanli (ST 36), Sanyinjiao (SP 6), Taixi (KI 3), Xuehai (SP 10) and Zigong (EX-CA 1). In the observation group, the acupoints were selected in terms of the physiological characteristics of follicular phase, ovulatory phase, luteal phase and menstrual phase. The main acupoints were Zusanli (ST 36), Sanyinjiao (SP 6), Taixi (KI 3) and Xuehai (SP 10). The acupoints for benefiting kidney yin were added in the follicular phase, such as Guanyuan (CV 4) and Dahe (KI 12), etc. The acupoints for regulating qi and activating blood circulation were added in the ovulatory phase, such as Hegu (LI 4) and Taichong (LR 3), etc. The moxibustion was added for tonifying kidney yang in the luteal phase, such as Qihai (CV 6) and Guanyuan (CV 4). The treatment was discontinued during the menstrual phase in the two groups. In the rest phases, acupuncture and moxibustion were given once every two days, 30 min each time. The overall efficacy, basal body temperature (BBT), follicular development, the average endometrial thickness and morphology as well as TCM syndrome score of spleen and kidney yang deficiency were observed in the patients after 3-month menstrual periods. The adverse reactions were recorded in the two groups. In the observation group, one case gave up the treatment due to the personal reason and another one stopped the treatment due to

Triennial Reproduction Symposium: influence of follicular characteristics at ovulation on early embryonic survival.

PubMed

Geary, T W; Smith, M F; MacNeil, M D; Day, M L; Bridges, G A; Perry, G A; Abreu, F M; Atkins, J A; Pohler, K G; Jinks, E M; Madsen, C A

2013-07-01

Reproductive failure in livestock can result from failure to fertilize the oocyte or embryonic loss during gestation. Although fertilization failure occurs, embryonic mortality represents a greater contribution to reproductive failure. Reproductive success varies among species and production goals but is measured as a binomial trait (i.e., pregnancy), derived by the success or failure of multiple biological steps. This review focuses primarily on follicular characteristics affecting oocyte quality, fertilization, and embryonic health that lead to pregnancy establishment in beef cattle. When estrous cycles are manipulated with assisted reproductive technologies and ovulation is induced, duration of proestrus (i.e., interval from induced luteolysis to induced ovulation), ovulatory follicle growth rate, and ovulatory follicle size are factors that affect the maturation of the follicle and oocyte at induced ovulation. The most critical maturational component of the ovulatory follicle is the production of sufficient estradiol to prepare follicular cells for luteinization and progesterone synthesis and prepare the uterus for pregnancy. The exact roles of estradiol in oocyte maturation remain unclear, but cows that have lesser serum concentrations of estradiol have decreased fertilization rates and decreased embryo survival on d 7 after induced ovulation. When length of proestrus is held constant, perhaps the most practical follicular measure of fertility is ovulatory follicle size because it is an easily measured attribute of the follicle that is highly associated with its ability to produce estradiol.

Characterization of ovarian follicular dynamics in dromedary camels (Camelus dromedarius).

PubMed

Manjunatha, B M; Pratap, N; Al-Bulushi, Samir; Hago, B E

2012-09-15

Ovarian follicular dynamics was monitored by transrectal ultrasonography, for a period of 60 to 90 days, and its correlation with plasma estradiol-17β (E2) and progesterone (P4) were studied in seventeen, multiparous, non-lactating, 12 to 20-year-old dromedary camels. The average number of follicles recruited (12.77 ± 0.93) in each wave between animals varied (P < 0.001). The number of follicles recruited during different follicular waves was highly repeatable (0.95) within individual animals. The growth and mature phase periods of the dominant follicle (DF) were 6.10 ± 0.15 and 10.20 ± 0.47 days, respectively with a linear growth rate of 1.17 ± 0.02 mm/day between Day 0 and 10 of the follicular wave. There was an inverse relationship between the diameter of the largest DF and number of follicles (r = -0.95, P < 0.001). The DF development did not regularly alternate between the ovaries and the incidence of codominance was 45%. The mean maximum diameter of DF during its mature phase was 27.30 ± 0.78 mm and oversized follicle was 38.43 ± 1.41 mm. In 73.3% waves, the DF continued its growth for a period of 10.64 ± 1.53 days even after losing its dominance and developed into oversized follicle. The duration of the regression phase of DF and oversized follicle were 24.71 ± 3.79 and 18.50 ± 2.23 days. The mean duration of a complete follicular wave was 47.11 ± 2.94 days with an interwave interval (IWI) of 16.36 ± 0.37 days. The IWI within an individual was repeatable (0.88) and between the animals was variable (P < 0.001). Plasma E2 concentration profiles showed a wave like pattern. The peak plasma E2 concentrations were attained approximately 12 days after beginning of the growth phase, when the largest DF grew to a diameter of 18.7 mm. Plasma concentration of P4 was below 1.0 ng/mL in 85% of waves and above 1.0 ng/mL in 15% of the waves for a period of 3 to 6 days in the absence of spontaneous ovulation. It is concluded that ovarian follicular development

Intraovarian markers of follicular and oocyte maturation.

PubMed

Pellicer, A; Diamond, M P; DeCherney, A H; Naftolin, F

1987-08-01

The use of ovulation induction for multiple follicular growth in in vitro fertilization (IVF) has introduced the problem of follicular asynchrony. As a consequence of the asynchrony, the parameters most commonly used by IVF groups to assess follicular and oocyte quality within those follicles are not sufficiently sensitive or specific. Thus, each follicle must be considered separately, and specific markers of follicular and/or oocyte maturation must be sought from within the follicle. In this review we analyze previous reports of potential markers of follicular and oocyte maturation. In regards to the follicular fluid constituents, the level of estradiol in follicular fluid correlates with fertilization and pregnancy in stimulated cycles. Other steroids are only helpful when specific stimulation protocols are used. The level of some follicular proteins such as alpha-1-antitrypsin and fibrinogen also correlates with fertilization and pregnancy outcome. Cyclic AMP levels in follicular fluid are significantly reduced in follicles leading to conception. Regulators of oocyte maturation, such as the Oocyte Maturation Inhibitor (OMI) or the Meiosis Inducing Substance (MIS) have also been correlated with IVF outcome, but their exact structure remains still unknown. In addition, other sophisticated parameters, such as chemotactic activity of human leukocytes, or simple methods, such as the presence of intrafollicular echoes, have also been used as successful markers in predicting IVF outcome.

Xenotransplantation in immunodeficient mice to study ovarian follicular development in domestic animals.

PubMed

Bols, P E J; Aerts, J M J; Langbeen, A; Goovaerts, I G F; Leroy, J L M R

2010-04-01

Nowadays, in vitro study of follicular dynamics of primordial and primary follicular stages is limited because in vitro culture systems for these follicles are lacking, both in domestic animal species and in human. Therefore, additional insights might be generated by grafting ovarian tissue into immunodeficient mice to study activation and maturation of early follicular stages. A considerable amount of data has already been gathered in laboratory animals and through clinical application of human assisted reproduction technologies where live births were reported recently after the use of (cryopreserved) ovarian grafts. However, given that human preantral follicles are difficult to obtain and that there are many similarities between the bovine and human species with regard to ovarian physiology, the bovine model offers exciting additional prospects and is therefore discussed in more detail. This review will focus on recent developments related to preantral follicle and (repeated) ovarian tissue retrieval and xenotransplantation of (bovine) ovarian tissue strips to immunodeficient mice as a model to study preantral follicular dynamics. Different grafting strategies will be discussed as well as the consequences of this procedure on the viability and dynamic behavior of the grafted tissue and follicles. 2010 Elsevier Inc. All rights reserved.

Evaluation of Follicular Synchronization Caused by Estrogen Administration and Its Reproductive Outcome

PubMed Central

Wu, Bi; Shi, Yan; Gong, Xia; Yu, Lin; Chen, Qiuju; Wang, Jian; Sun, Zhaogui

2015-01-01

To evaluate multiple follicular development synchronization after estrogen stimulation in prepubertal mice, follicular responsiveness to gonadotropin superovulation, the prospective reproductive potential and ovarian polycystic ovary syndrome (PCOS)-like symptoms at adulthood, prepubertal mice were intraperitoneally injected with estrogen to establish an animal model with solvent as control. When synchronized tertiary follicles in ovaries, in vitro oocyte maturation and fertilization rates, blastocyst formation rate, developmental potential into offspring by embryo transfer, adult fertility and PCOS-like symptoms, and involved molecular mechanisms were focused, it was found that estrogen stimulation (10μg/gBW) leads to follicular development synchronization at the early tertiary stage in prepubertal mice; reproduction from oocytes to offspring could be realized by means of the artificial reproductive technology though the model mice lost their natural fertility when they were reared to adulthood; and typical symptoms of PCOS, except changes in inflammatory pathways, were not remained up to adulthood. So in conclusion, estrogen can lead to synchronization in follicular development in prepubertal mice, but does not affect reproductive outcome of oocytes, and no typical symptoms of PCOS remained at adulthood despite changes related to inflammation. PMID:26010950

Comparison of Follicular and Luteal Phase Mucosal Markers of HIV Susceptibility in Healthy Women

PubMed Central

Chandra, Neelima; Yousefieh, Nazita; Zalenskaya, Irina; Kimble, Thomas; Asin, Susana; Rollenhagen, Christiane; Anderson, Sharon M.; Herold, Betsy; Mesquita, Pedro M.M.; Richardson-Harman, Nicola; Cunningham, Tina; Schwartz, Jill L.; Doncel, Gustavo F.

2016-01-01

Abstract The purpose of this study was to evaluate differences in vaginal immune cell populations, vaginal tissue gene expression, antimicrobial activity of the cervicovaginal (CV) lavage (CVL), vaginal flora, and p24 antigen production from CV tissues after ex vivo human immunodeficiency virus (HIV) infection between follicular (FOL) and luteal (LUT) phases of the menstrual cycle. CV tissue biopsies, CV secretions, and blood samples were obtained as part of two longitudinal clinical trials of healthy women (CONRAD D11-119 and A12-124 studies). Participants (n = 39) were HIV-seronegative women not using exogenous hormone supplementation, with normal menstrual cycles, who were screened to exclude sexually transmitted and reproductive tract infections. Serum levels of estradiol and progesterone were significantly higher in the LUT versus the FOL phase of the menstrual cycle. Controlling for race, reported contraceptive use/sexual practices, and clinical trial, we found no differences in vaginal tissue immune cell populations and activation status, transcriptomes, inhibition of HIV, herpes simplex virus type 2 and Escherichia coli by the CVL, vaginal pH or Nugent score, or production of p24 antigen after ex vivo infection by HIV-1BaL between CV samples obtained in the FOL phase versus the LUT phase of the menstrual cycle. There were no significant correlations between serum estradiol and progesterone levels and CV endpoints. The hypothesis that the LUT phase of the menstrual cycle represents a more vulnerable stage for mucosal infection with HIV was not supported by data from samples obtained from the lower genital tract (ectocervix and vagina) from these two clinical trials. PMID:26750085

Frontline strategy for follicular lymphoma: are we ready to abandon chemotherapy?

PubMed

Fowler, Nathan

2016-12-02

Chemotherapy combinations have been the backbone of therapy for follicular lymphoma, and are associated with high initial response rates. Unfortunately, toxicity and secondary malignancies remain concerns, and most advanced-stage patients still relapse within 5 years, regardless of the regimen. Advances in the understanding of lymphoma biology have resulted in a new generation of noncytotoxic therapeutics with significant activity in follicular lymphoma. Recent studies exploring biological and targeted combinations in the frontline have shown promise, with response rates similar to chemotherapy. However, these regimens are also associated with significant cost as well as a unique toxicity profile. Large randomized studies are underway to compare noncytotoxic regimens with chemotherapy in the frontline, and several new combinations are being tested in the phase 2 setting. Ongoing work to identify predictive biomarkers and investment in mechanistic studies will ultimately lead to the personalization of therapy in the frontline setting for follicular lymphoma. © 2016 by The American Society of Hematology. All rights reserved.

Melatonin in human preovulatory follicular fluid

NASA Technical Reports Server (NTRS)

Brzezinski, Amnon; Seibel, Machelle M.; Lynch, Harry J.; Deng, Mei-Hua; Wurtman, Richard J.

1987-01-01

Melatonin, the major hormone of the pineal gland, has antigonadotrophic activity in many mammals and may also be involved in human reproduction. Melatonin suppresses steroidogenesis by ovarian granulosa and luteal cells in vitro. To determine if melatonin is present in the human ovary, preovulatory follicular fluids (n = 32) from 15 women were assayed for melatonin by RIA after solvent extraction. The fluids were obtained by laparoscopy or sonographically controlled follicular puncture from infertile women undergoing in vitro fertilization and embryo transfer. All patients had received clomiphene citrate, human menopausal gonadotropin, and hCG to stimulate follicle formation. Blood samples were obtained by venipuncture 30 rain or less after follicular aspiration. All of the follicular fluids contained melatonim, in concentrations substantially higher than those in the corresponding serum. A positive correlation was found between follicular fluid and serum melatonin levels in each woman; these observations indicate that preovulatory follicles contain substantial amounts of melatonin that may affect ovarian steroidogenesis.

Evaluation of the ultrasound image attributes of developing ovarian follicles in the four follicular waves of the interovulatory interval in ewes

PubMed Central

Toosi, B.M.; Seekallu, S.V.; Pierson, R.A.; Rawlings, N.C.

2010-01-01

Computer-assisted quantitative echotextural analysis was applied to ultrasound images of antral follicles in the follicular waves of an interovulatory interval in sheep. The ewe has three or four waves per cycle. Seven healthy, cyclic Western White Face ewes (Ovis aris) underwent daily, transrectal, ovarian ultrasonography for an interovulatory interval. Follicles in the third wave of the ovulatory interval had a longer static phase than that of those in Waves 1 and 2 (P < 0.05). The numeric pixel value for the wall of anovulatory follicles emerging in the third wave of the cycle was significantly higher than that for Waves 1 and 2 at the time of emergence (156.7 ± 8.09, 101.6 ± 3.72, and 116.5 ± 13.93, respectively), and it decreased as follicles in Wave 3 reached maximum follicular diameter (P < 0.05). The numeric pixel value of the antrum in the ovulatory follicles decreased as follicular diameter increased to ≥5 mm in diameter (P < 0.05). The pixel heterogeneity of the follicular antrum in Wave 1 increased from the end of the growth phase to the end of the regression phase for follicles in that wave (P < 0.05). The total area for the wall and antrum of the follicles studied were correlated with follicular diameter in all follicular waves (r = 0.938, P < 0.01 and r = 0.941, P < 0.01 for the wall and antrum, respectively). Changes in image attributes of the follicular wall and antrum indicate potential morphologic and functional differences among antral follicles emerging at different stages of the interovulatory interval in cyclic ewes. PMID:19665782

Microorganisms within Human Follicular Fluid: Effects on IVF

PubMed Central

Pelzer, Elise S.; Allan, John A.; Waterhouse, Mary A.; Ross, Tara; Beagley, Kenneth W.; Knox, Christine L.

2013-01-01

Our previous study reported microorganisms in human follicular fluid. The objective of this study was to test human follicular fluid for the presence of microorganisms and to correlate these findings with the in vitro fertilization (IVF) outcomes. In this study, 263 paired follicular fluids and vaginal swabs were collected from women undergoing IVF cycles, with various causes for infertility, and were cultured to detect microorganisms. The cause of infertility and the IVF outcomes for each woman were correlated with the microorganisms detected within follicular fluid collected at the time of trans-vaginal oocyte retrieval. Microorganisms isolated from follicular fluids were classified as: (1) ‘colonizers’ if microorganisms were detected within the follicular fluid, but not within the vaginal swab (at the time of oocyte retrieval); or (2) ‘contaminants’ if microorganisms detected in the vagina at the time of oocyte retrieval were also detected within the follicular fluid. The presence of Lactobacillus spp. in ovarian follicular fluids was associated with embryo maturation and transfer. This study revealed microorganisms in follicular fluid itself and that the presence of particular microorganisms has an adverse affect on IVF outcomes as seen by an overall decrease in embryo transfer rates and pregnancy rates in both fertile and infertile women, and live birth rates in women with idiopathic infertility. Follicular fluid microorganisms are a potential cause of adverse pregnancy outcomes in IVF in both infertile women and in fertile women with infertile male partners. PMID:23554970

Preconception folic acid use modulates estradiol and follicular responses to ovarian stimulation.

PubMed

Twigt, John M; Hammiche, Fatima; Sinclair, Kevin D; Beckers, Nicole G; Visser, Jenny A; Lindemans, Jan; de Jong, Frank H; Laven, Joop S E; Steegers-Theunissen, Régine P

2011-02-01

Folate is a methyl donor. Availability of folate affects DNA methylation profiles and thereby gene expression profiles. We investigated the effects of low-dose folic acid use (0.4 mg/d) on the ovarian response to mild and conventional ovarian stimulation in women. In a randomized trial among subfertile women, 24 and 26 subjects received conventional and mild ovarian stimulation, respectively. Blood samples were taken during the early follicular phase of the cycle prior to treatment and on the day of human chorionic gonadotropin administration for determination of serum total homocysteine, anti-Müllerian hormone (AMH), estradiol, and folate. Folic acid use was validated by questionnaire and serum folate levels. Preovulatory follicles were visualized, counted, and diameters recorded using transvaginal ultrasound. The relation between folic acid use and ovarian response was assessed using linear regression analysis. Folic acid use modified the ovarian response to ovarian stimulation treatment. The estradiol response was higher in nonfolic acid users receiving conventional treatment [β(interaction) = 0.52 (0.07-0.97); P = 0.03], and this effect was independent of serum AMH levels and the preovulatory follicle count. In the conventional treatment, the mean follicle number was also greater in nonusers compared with the users group (14.1 vs. 8.9, P = 0.03). Low-dose folic acid use attenuates follicular and endocrine responses to conventional stimulation, independent of AMH and follicle count. The nature of this observation suggests that the effect of folic acid is most prominent during early follicle development, affecting immature follicles. Deleterious effects of folate deficiency, like DNA hypomethylation and oxidative stress, can help to explain our observations.

Association between follicular tracheitis and gastroesophageal reflux.

PubMed

Duval, Melanie; Meier, Jeremy; Asfour, Fadi; Jackson, Daniel; Grimmer, J Fredrik; Muntz, Harlan R; Park, Albert H

2016-03-01

Follicular tracheitis (also known as tracheal cobblestoning) is an entity that is poorly described and of unclear significance. The objective of this study was to better define follicular tracheitis and determine the association between the clinical finding of follicular tracheitis on bronchoscopy and objective evidence of gastroesophageal reflux disease. Retrospective chart review of children with recurrent croup having undergone a rigid bronchoscopy and an investigation for gastroesophageal reflux between 2001 and 2013. 117 children with recurrent croup children age 6-144 months were included in the study. Follicular tracheitis was noted on 41% of all bronchoscopies. Fifty-nine percent of all children who underwent bronchoscopy were diagnosed with gastroesophageal reflux on at least one investigation. Forty-nine of 117 children underwent a pH probe study, and 51% were found to have evidence of reflux on this study. Nine children were diagnosed with eosinophilic esophagitis. Three patients underwent a biopsy of the follicular tracheitis lesions, which revealed chronic inflammation. There was no evidence of an association between findings of follicular tracheitis and a positive test for gastroesophageal reflux (p=0.52) or a positive pH probe study (p=0.64). There was no association between follicular tracheitis and subglottic stenosis (p=0.33) or an history of asthma and/or atopy (p=0.19). In children with recurrent croup, follicular tracheitis remains an unspecific finding associated with an inflammatory disorder of unknown etiology. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

An integrated view on the luteal phase: diagnosis and treatment in subfertility.

PubMed

Sonntag, Barbara; Ludwig, Michael

2012-10-01

The term 'luteal phase deficiency' was first coined more than 60 years ago, and, since then, it has been suggested as a clinical entity per se and an aetiological factor for subfertility, implantation failure and recurrent miscarriage. Despite the existing recommendations for rational work-up in subfertility, luteal phase evaluation and progesterone therapy alone is still common in daily practice. This review comprises results from a Pubmed literature search with the terms 'luteal phase' and 'subfertility', focussing on clinical situations not primarily related to assisted reproduction techniques. Additional data from the experimental studies published in the past 10 years on follicular maturation, oocyte developmental competence and the ovulatory cascade are integrated into the clinical continuum of dysfunctional ovulation, menstrual cycle irregularity and impaired corpus luteum function. As reliable diagnostic tools for adequate luteal function are missing, the presence of clinical symptoms such as cycle irregularity or premenstrual spotting is indicative and should initiate early follicular phase diagnostic work-up. New evidence on the interdependence of oocyte and follicular maturation and resulting developmental competence of the embryo further support the use of ovarian stimulation as the first-line therapeutic option in different subsets of patients with subfertility including luteal phase deficiency. © 2012 Blackwell Publishing Ltd.

Triennial Reproduction Symposium: The ovarian follicular reserve in cattle: What regulates its formation and size?1,2

PubMed Central

Fortune, J. E.; Yang, M. Y.; Allen, J. J.; Herrick, S. L.

2017-01-01

The ovarian follicular reserve has been linked to fertility in cattle. Young adult cattle with low vs. high numbers of antral follicles ≥ 3 mm in diameter in follicular waves also have fewer preantral follicles and decreased fertility. This underscores the importance of understanding the factors that regulate early follicular development and establish the ovarian follicular reserve, but little is known about how the follicular reserve is first established. In ruminants and humans, follicles form during fetal life, but there is a gap (about 50 d in cattle) between the appearance of the first primordial follicles and the first growing, primary follicles. In this review we present evidence that in cattle, fetal ovarian steroids (i.e., estradiol and progesterone) are negative regulators of both follicle formation and of the acquisition by newly formed follicles of the capacity to activate (i.e., initiate growth). The results indicate that capacity to activate is linked to the completion of meiotic prophase I by the oocyte. The inhibitory effects of estradiol on follicle activation were found to be reversible and correlated with inhibition of the progression of meiotic prophase I. Fetal bovine ovaries produce steroid hormones and production varies considerably during gestation and in a pattern consistent with the hypothesis that they inhibit follicle formation and capacity of newly formed follicles to activate in vivo. However, little was known about how steroid production is regulated. In our studies, both LH and FSH stimulated progesterone and estradiol production by ovarian pieces in vitro. The addition of testosterone to the culture medium enhanced estradiol production, especially when FSH was also present, but inhibited progesterone production, even in the presence of gonadotropins. Evidence is also presented for effects of maternal nutrition and health and for potential effects of estrogenic endocrine-disrupting chemicals on the size of the ovarian follicular

Melatonin in human preovulatory follicular fluid

NASA Technical Reports Server (NTRS)

Brzezinski, Amnon; Seibel, Machelle M.; Lynch, Harry J.; Deng, Mei-Hua; Wurtman, Richard J.

1987-01-01

Melatonin, the major hormone of the pineal gland, has antigonadotrophic activity in many mammals and may also be involved in human reproduction. Melatonin suppresses steroidogenesis by ovarian granulosa and luteal cells in vitro. To determine if melatonin is present in the human ovary, preovulatory follicular fluids (n = 32) from 15 women were assayed for melatonin by RIA after solvent extraction. The fluids were obtained by laparoscopy or sonographically controlled follicular puncture from infertile women undergoing in vitro fertilization and embryo transfer. All patients had received clomiphene citrate, human menopausal gonadotropin, and hCG to stimulate follicle formation. Blood samples were obtained by venipuncture 30 min or less after follicular aspiration. All of the follicular fluids contained melatonin, in concentrations (35.6 plus or minus 4.8 (plus or minus SEM) pg/mL) substantially higher than those in the corresponding serum (10.0 plus or minus 1.4 pg/mL). A positive correlation was found between follicular fluid and serum melatonin levels in each woman (r = 0.770; P less than 0.001). These observations indicate that preovulatory follicles contain substantial amounts of melatonin that may affect ovarian steroidogenesis.

TERT, HRAS, and EIF1AX Mutations in a Patient with Follicular Adenoma.

PubMed

Topf, Michael C; Wang, Zi-Xuan; Tuluc, Madalina; Pribitkin, Edmund A

2018-06-01

Molecular markers are increasingly used as diagnostic tools in the management of thyroid nodules. There is a paucity of studies evaluating the prevalence of molecular markers in benign lesions. A 68-year-old woman with hypothyroidism presented with a right thyroid nodule, which was atypia of undetermined significance on cytology. The fine-needle aspirate of the nodule was examined with next-generation sequencing and found to harbor a C228T mutation in the TERT gene, a Q61R mutation in the HRAS gene, and an A113_splice mutation in the EIF1AX gene. Right thyroid lobectomy was performed, with final pathology showing follicular adenoma. All three mutations detected in the original fine-needle aspirate specimen were detected in the final surgical specimen as well. A rare case of TERT, HRAS, and EIF1AX mutations is reported in a patient with follicular adenoma. TERT promoter mutations may be an early genetic event in the molecular pathogenesis of follicular thyroid carcinoma.

[Follicular thyroid tumor as a diagnostic and therapeutic problem].

PubMed

Król, Robert; Heitzman, Marek; Pawlicki, Jacek; Ziaja, Jacek; Cierpka, Lech

2004-01-01

Although the appearance of follicular thyroid tumors in the population is high, only a small part of them are malignant. Follicular tumors are built of follicular epithelial cells and are encapsulated. Cell atypia differentiates follicular adenoma from cancer. Follicular cancer is characterized by vascular invasion and causes metastases through blood vessels, mainly to lungs and bones. In the diagnosis of follicular thyroid neoplasm, pathological examination of postoperative material plays a leading role. In diagnosis before surgical treatment, physical examination, ultrasound (USG), and fine needle aspiration biopsy (FNAB) are of great importance. The choice of treatment in patients in which follicular neoplasm has been diagnosed by FNAB awakes controversies. In practice it is impossible to determine reliably before surgery whether the lesion is malignant or not. Because of the rare incidence of thyroid cancer in the general population, more and more authors tend to decide on partial resection of the thyroid gland and possible radicalization if cancer is diagnosed on paraffin specimen examination.

Altered Memory Circulating T Follicular Helper-B Cell Interaction in Early Acute HIV Infection

PubMed Central

Muir, Roshell; Metcalf, Talibah; Tardif, Virginie; Takata, Hiroshi; Phanuphak, Nittaya; Kroon, Eugene; Colby, Donn J.; Trichavaroj, Rapee; Valcour, Victor; Robb, Merlin L.; Michael, Nelson L.; Ananworanich, Jintanat; Trautmann, Lydie; Haddad, Elias K.

2016-01-01

The RV254 cohort of HIV-infected very early acute (4thG stage 1 and 2) (stage 1/2) and late acute (4thG stage 3) (stage 3) individuals was used to study T helper- B cell responses in acute HIV infection and the impact of early antiretroviral treatment (ART) on T and B cell function. To investigate this, the function of circulating T follicular helper cells (cTfh) from this cohort was examined, and cTfh and memory B cell populations were phenotyped. Impaired cTfh cell function was observed in individuals treated in stage 3 when compared to stage 1/2. The cTfh/B cell cocultures showed lower B cell survival and IgG secretion at stage 3 compared to stage 1/2. This coincided with lower IL-10 and increased RANTES and TNF-α suggesting a role for inflammation in altering cTfh and B cell responses. Elevated plasma viral load in stage 3 was found to correlate with decreased cTfh-mediated B cell IgG production indicating a role for increased viremia in cTfh impairment and dysfunctional humoral response. Phenotypic perturbations were also evident in the mature B cell compartment, most notably a decrease in resting memory B cells in stage 3 compared to stage 1/2, coinciding with higher viremia. Our coculture assay also suggested that intrinsic memory B cell defects could contribute to the impaired response despite at a lower level. Overall, cTfh-mediated B cell responses are significantly altered in stage 3 compared to stage 1/2, coinciding with increased inflammation and a reduction in memory B cells. These data suggest that early ART for acutely HIV infected individuals could prevent immune dysregulation while preserving cTfh function and B cell memory. PMID:27463374

A Rare Case of Retroperitoneal Follicular Dendritic Cell Sarcoma Identified by 99mTc-HYNIC-TOC SPECT/CT.

PubMed

Li, Yi; Xu, Xiaoping; Xu, Junyan; Huang, Dan

2018-05-31

Follicular dendritic cell sarcoma is a very rare neoplasm, which is not lymphoma, but originates from a type of immune cells called follicular dendritic cells. We presented a 37-year-old woman who has suffered from obstructive jaundice, weight loss and right upper abdominal pain for 2 months. The contrast CT revealed masses located in the region of pancreatic head and lots of enlarged retroperitoneal lymph nodes, both of which were enhanced on the artery phase of CT images. Meanwhile, Tc-HYNIC-TOC SPECT/CT revealed high activity in the corresponding lesions. After biopsy, the masses were pathologically confirmed as retroperitoneal follicular dendritic cell sarcoma.

Primary conjunctival follicular lymphoma mimicking chronic conjunctivitis.

PubMed

Labrador Velandia, S; García Lagarto, E; Saornil, M A; García Álvarez, C; Cuello, R; Diezhandino, P

2016-02-01

The case is presented of a 43 year-old male patient with chronic follicular conjunctivitis, negative bacterial serology, and refractory to local treatment. The incisional biopsy performed showed to be consistent with reactive lymphoid hyperplasia. A year later, a new incisional biopsy showed follicular lymphoma, with no systemic involvement, and he was treated with local radiotherapy. When a chronic follicular conjunctivitis is refractory to treatment, it is essential to perform an incisional biopsy to establish the histopathological diagnosis that can range from chronic inflammation, reactive lymphoid hyperplasia to lymphoma. Follicular lymphoma is rare among conjunctival lymphomas, and the staging is indispensable for the correct therapeutic approach. Copyright © 2014 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

The mare model for follicular maturation and reproductive aging in the woman.

PubMed

Carnevale, E M

2008-01-01

Reproductive aging and assisted reproduction are becoming progressively more relevant in human medicine. Research with human subjects is limited in many aspects, and consequently animal models may have considerable utility. Such models have provided insight into follicular function, oocyte maturation, and reproductive aging. However, models are often selected based on factors other than physiological or functional similarities. Although the mare has received limited attention as a model for reproduction in women, comparisons between these species indicate that the mare has many attributes of a good model. As the mare ages, cyclic and hormonal changes parallel those of older women. The initial sign of reproductive aging in both species is a shortening of the reproductive cycle with elevated concentrations of FSH. Subsequently, cycles become longer with intermittent ovulations and elevated concentrations of FSH and LH. Reproduction ceases with failure of follicular growth and elevated gonadotropins, apparently because of ovarian failure. In the older woman and mare, oocytes have been maintained in meiotic arrest for decades -- approximately four to five for the woman and two to three for the mare; in both species, reduced oocyte quality is the end factor identified in age-associated infertility. After induction of oocyte maturation in vivo, the timeline to ovulation is the same for the mare and woman, suggesting a comparable sequence of events. The mare's anatomy, long follicular phase and single dominant follicle provide a foundation for studies in oocyte and follicular development. The aim of this review is to evaluate the mare as an animal model to study age-associated changes in reproduction and to improve our understanding of oocyte and follicular maturation in vivo.

Abnormal patterns of pulsatile luteinizing hormone in women with luteal phase deficiency.

PubMed

Soules, M R; Steiner, R A; Clifton, D K; Bremner, W J

1984-05-01

Luteal phase deficiency is usually a problem of inadequate progesterone production associated with inadequate ovarian follicular development. The hypothesis that luteal phase deficiency results from an abnormal secretion pattern of luteinizing hormone (LH) was tested in these women. To this end, the early follicular LH secretion pattern in four women with luteal phase deficiency was characterized and compared with patterns in normal women. Blood samples were obtained through indwelling catheters every ten minutes for eight hours (10 AM to 6 PM), and plasma levels of LH and FSH were measured. Luteinizing hormone and FSH secretion profiles were analyzed for pulse frequency, amplitude, and mean plasma level. A significantly greater LH pulse frequency in women with luteal phase deficiency was observed when compared with the frequency in normal controls (luteal phase deficiency, 10.5 pulses/eight hours; normal, 5.2 pulses/eight hours; P less than or equal to .05). The mean FSH concentration was less in the women with luteal phase deficiency, but the level was not significant. These data suggest that the abnormal LH secretion pattern observed in women with luteal phase deficiency is responsible for their inadequate luteal phase progesterone secretion and their infertility.

Developmental programming: Prenatal BPA treatment disrupts timing of LH surge and ovarian follicular wave dynamics in adult sheep

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

Veiga-Lopez, A.; Beckett, E.M.; Abi Salloum, B.

Developmental exposure to BPA adversely affects reproductive function. In sheep, prenatal BPA treatment induces reproductive neuroendocrine defects, manifested as LH excess and dampened LH surge and perturbs early ovarian gene expression. In this study we hypothesized that prenatal BPA treatment will also disrupt ovarian follicular dynamics. Pregnant sheep were treated from days 30 to 90 of gestation with 3 different BPA doses (0.05, 0.5, or 5 mg/kg BW/day). All female offspring were estrus synchronized and transrectal ultrasonography was performed daily for 22 days to monitor ovarian follicular and corpora lutea dynamics. Blood samples were collected to assess preovulatory hormonal changesmore » and luteal progesterone dynamics. Statistical analysis revealed that the time interval between the estradiol rise and the preovulatory LH surge was shortened in the BPA-treated females. None of the three BPA doses had an effect on corpora lutea, progestogenic cycles, and mean number or duration of ovulatory and non-ovulatory follicles. However, differences in follicular count trajectories were evident in all three follicular size classes (2–3 mm, 4–5 mm, and ≥ 6 mm) of prenatal BPA-treated animals compared to controls. Number of follicular waves tended also to be more variable in the prenatal BPA-treated groups ranging from 2 to 5 follicular waves per cycle, while this was restricted to 3 to 4 waves in control females. These changes in ovarian follicular dynamics coupled with defects in time interval between estradiol rise and preovulatory LH release are likely to lead to subfertility in prenatal BPA-treated females. - Highlights: • Prenatal BPA shortens interval between estradiol rise and preovulatory LH surge. • Prenatal BPA affects follicular count trajectory and follicular wave occurrence. • Prenatal BPA does not affect ovulatory rate and progesterone dynamics.« less

The Expression Pattern of microRNAs in Granulosa Cells of Subordinate and Dominant Follicles during the Early Luteal Phase of the Bovine Estrous Cycle

PubMed Central

Gebremedhn, Samuel; Sahadevan, Sudeep; Hossain, MD Munir; Rings, Franca; Hoelker, Michael; Tholen, Ernst; Neuhoff, Christiane; Looft, Christian; Schellander, Karl; Tesfaye, Dawit

2014-01-01

This study aimed to investigate the miRNA expression patterns in granulosa cells of subordinate (SF) and dominant follicle (DF) during the early luteal phase of the bovine estrous cycle. For this, miRNA enriched total RNA isolated from granulosa cells of SF and DF obtained from heifers slaughtered at day 3 and day 7 of the estrous cycle was used for miRNAs deep sequencing. The results revealed that including 17 candidate novel miRNAs, several known miRNAs (n = 291–318) were detected in SF and DF at days 3 and 7 of the estrous cycle of which 244 miRNAs were common to all follicle groups. The let-7 families, bta-miR-10b, bta-miR-26a, bta-miR-99b and bta-miR-27b were among abundantly expressed miRNAs in both SF and DF at both days of the estrous cycle. Further analysis revealed that the expression patterns of 16 miRNAs including bta-miR-449a, bta-miR-449c and bta-miR-222 were differentially expressed between the granulosa cells of SF and DF at day 3 of the estrous cycle. However, at day 7 of the estrous cycle, 108 miRNAs including bta-miR-409a, bta-miR-383 and bta-miR-184 were differentially expressed between the two groups of granulosa cell revealing the presence of distinct miRNA expression profile changes between the two follicular stages at day 7 than day 3 of the estrous cycle. In addition, unlike the SF, marked temporal miRNA expression dynamics was observed in DF groups between day 3 and 7 of the estrous cycle. Target gene prediction and pathway analysis revealed that major signaling associated with follicular development including Wnt signaling, TGF-beta signaling, oocyte meiosis and GnRH signaling were affected by differentially expressed miRNAs. Thus, this study highlights the miRNA expression patterns of granulosa cells in subordinate and dominant follicles that could be associated with follicular recruitment, selection and dominance during the early luteal phase of the bovine estrous cycle. PMID:25192015

Melanins as biomarkers of ovarian follicular atresia in the catfish Heteropneustes fossilis: biochemical and histochemical characterization, seasonal variation and hormone effects.

PubMed

Kumar, Ravi; Joy, Keerikkattil P

2015-06-01

Follicular atresia is a common feature of the vertebrate ovary that occurs at different stages of folliculogenesis and ovarian regression. It has physiological significance to maintain homeostasis and control fecundity, and ensure removal of post-ovulatory follicular remnants for preparing the ovary for the next cycle. Pigments appear late in the atretic process as indigestible waste formed out of the degradation of the oocytes, follicle wall and granulocytes. In the present study, pigment accumulation was demonstrated by Schmorl's and Perls' staining methods in the atretic ovarian follicles of Heteropneustes fossilis during follicular development and regression. Melanins were characterized spectrophotometrically for the first time in fish ovary. The predominant form is eumelanin, followed by pheomelanin and alkali-soluble melanin. Melanins showed significant seasonal variations with levels low in gonad resting phase, increasing to the peak in the post-spawning phase. The concentration of melanins increased time-dependently in post-ovulated ovary after human chorionic gonadotropin treatment. In the spawning phase, in vitro incubation of ovary slices with estradiol-17β or dexamethasone for 8 or 16 h decreased both eumelanin and pheomelanin levels time-dependently. The alkali-soluble melanin showed a significant decrease only in the dexamethasone group at 16 h. The results show that melanin assay can be used as a biomarker of follicular atresia in fish ovary, natural or induced by environmental toxicants.

Developmental programming: Prenatal BPA treatment disrupts timing of LH surge and ovarian follicular wave dynamics in adult sheep

PubMed Central

Veiga-Lopez, A; Beckett, EM; Abi Salloum, B; Ye, W; Padmanabhan, V

2014-01-01

Developmental exposure to BPA adversely affects reproductive function. In sheep, prenatal BPA treatment induces reproductive neuroendocrine defects, manifested as LH excess and dampened LH surge and perturbs early ovarian gene expression. In this study we hypothesized that prenatal BPA treatment will also disrupt ovarian follicular dynamics. Pregnant sheep were treated from days 30 to 90 of gestation with 3 different BPA doses (0.05, 0.5, or 5 mg/kg BW/day). All female offspring were estrus synchronized and transrectal ultrasonography was performed daily for 22 days to monitor ovarian follicular and corpora lutea dynamics. Blood samples were collected to assess hormonal preovulatory changes and luteal progesterone dynamics. Statistical analysis revealed that the time interval between the estradiol rise and the preovulatory LH surge was shortened in the BPA-treated females. None of the three BPA doses had an effect on corpora lutea, progestogenic cycles, and mean or duration of ovulatory and non-ovulatory follicles. However, differences in follicular count trajectories were evident in all three follicular size classes (2–3 mm, 4–5 mm, and ≥ 6 mm) of prenatal BPA-treated animals compared to controls. Number of follicular waves tended also to be more variable in the prenatal BPA-treated groups ranging from 2 to 5 follicular waves per cycle, while this was restricted to 3 to 4 waves in control females. These changes in ovarian follicular dynamics coupled with defects in time interval between estradiol rise and preovulatory LH release are likely to lead to subfertility in prenatal BPA-treated females. PMID:24923655

Temperature-Enhanced Follicular Penetration of Thermoresponsive Nanogels

NASA Astrophysics Data System (ADS)

Jung, Sora; Nagel, Gregor; Giulbudagian, Michael; Calderón, Marcelo; Patzelt, Alexa; Knorr, Fanny; Lademann, Jürgen

2018-05-01

Hair follicles can serve as an effective reservoir for dermal drug delivery upon the topical application of particulate substances. Here, the follicular penetration of an indodicarbocyanine-labelled thermoresponsive nanogel (189 nm) having a cloud point temperature of 34°C and linked via an acid-labile linker to the model drug indocarbocyanine was investigated. In total, 227 hair follicles of porcine ear skin were examined after topical application of the thermoresponsive nanogels at room temperature (21°C), physiological skin surface temperature (32°C) and core body temperature (37°C) for the follicular penetration depths of indodicarbocyanine and indocarbocyanine using confocal laser scanning microscopy. The results showed a significantly increased mean follicular penetration of the carrier to a depth of 298.8±85.8 μm after incubation at 37°C compared to samples incubated at 21°C and 32°C with mean follicular penetration depths of 202.7±81.7 μm and 219.4±52.9 μm, respectively (p<0.001). Possibly structural changes in the thermoresponsive nanogel induced by the increased incubation temperature led to an enhancement of follicular penetration. Therefore, thermoresponsive nanogels may be suitable for the temperature-enhanced penetration into the hair follicles under physiological conditions.

Cardiovascular response to short-term fasting in menstrual phases in young women: an observational study.

PubMed

Ohara, Kumiko; Okita, Yoshimitsu; Kouda, Katsuyasu; Mase, Tomoki; Miyawaki, Chiemi; Nakamura, Harunobu

2015-08-28

Menstrual cycle-related symptoms are an important health issue for many women, and some may affect cardiac autonomic regulation. In the present study, we evaluated the cardiovascular and physiological stress response to 12-h short-term fasting in the menstrual phases of healthy young women. We performed a randomized crossover study. Subjects were seven female university students (age: 22.3 ± 1.0 years). The experiments comprised four sessions: meal intake in the follicular phase, meal intake in the luteal phase, fasting in the follicular phase, and fasting in the luteal phase. All subjects participated in a total of four experimental sessions during two successive phases (follicular and luteal phase in the same menstrual cycle, or luteal phase and follicular phase in the next menstrual cycle) according to a randomized crossover design. R-R intervals were continuously recorded before and after meals, and power spectral analysis of heart rate variability was performed. Other physiological data were obtained before and 20, 40, 60, and 80 min after meal intake or after the corresponding time point of meal intake (fasting in the follicular or luteal phase). Heart rate decreased during fasting in the follicular and luteal phases. High frequency power increased during fasting in the follicular and luteal phases. In addition, salivary cortisol concentrations decreased during fasting in the luteal phase. In the present study, short-term fasting resulted in higher parasympathetic activity and lower cortisol levels in the luteal phase in these young women. These results indicate a possibility to produce an anti-stress effect in the luteal phase, which may reduce menstrual symptoms.

Expression of inhibitor of apoptosis proteins (IAPs) in rat granulosa cells during ovarian follicular development and atresia.

PubMed

Li, J; Kim, J M; Liston, P; Li, M; Miyazaki, T; Mackenzie, A E; Korneluk, R G; Tsang, B K

1998-03-01

The inhibitor of apoptosis proteins (IAPs) constitute a family of highly conserved apoptosis suppressor proteins that was originally identified in baculoviruses. Although IAP homologs have been recently identified and demonstrated to suppress apoptosis in mammalian cells, their expression and role during follicular development and atresia are unknown. The present study was conducted to address these questions. Using established in vivo models for the induction of follicular development and atresia in immature rats, it was possible to compare the immunolocalization of X-link inhibitor of apoptosis protein (Xiap) and human inhibitor of apoptosis protein-2 (Hiap-2), two members of the IAP family, at defined stages of follicular maturation and to relate the differences observed with those of follicular cell proliferation and apoptosis [as determined by proliferating cell nuclear antigen (PCNA) immunohistochemistry and in situ terminal deoxynucleotidyl transferase-mediated dUTP-biotin end labeling (TUNEL), respectively]. In addition, granulosa cell DNA and proteins were assessed for apoptotic fragmentation by 3'-end labeling/agarose gel electrophoresis (DNA ladder) and Hiap-2 and Xiap protein content by Western blot analysis, respectively. Hiap-2 and Xiap expression in both granulosa and theca cells increased with follicular maturation, reaching maximal levels at the antral stage of development. The immunoreactivity for PCNA, Xiap, and Hiap-2 decreased markedly in atretic (TUNEL-positive) follicles at the small to medium sized antral stage of development, suggesting follicular atresia may be associated with decreased granulosa cell IAP protein content and decreased proliferation. Atresia was also associated with a change in the intracellular distribution of IAPs in granulosa cells. Biochemical analysis of DNA fragmentation (DNA ladder) in granulosa cells from preantral and early antral follicles indicates extensive apoptosis that was associated with minimal IAP protein

Luteal activity and effect of dietary energy restriction on follicular development in lactating cows.

PubMed

Comin, A; Peric, T; Montillo, M; Cappa, A; Marchi, V; Veronesi, M C; Prandi, A

2017-08-01

The aim of this research has been to evaluate the presence of anomalies in the ovarian cycle activity during postpartum and to verify whether 72-hr dietary fasting during the dominance phase, the phase before ovulation, might modify the ovarian follicle population. The presence of anomalies in ovarian cycle activity has been evaluated in 30 Italian Friesian cows starting from 20 days postpartum until 211 days of lactation. Long oestrus and brief dioestrus or scarce luteal activity have been the main anomalies found through measuring progesterone concentrations in the whey. Until 100 days of lactation, the BCS values of the problematic animals have been significantly lower than those in animals with normal ovarian activity. After 100 days of lactation, the ovarian anomalies continued to appear despite the fact that all the animals have reached comparable BCS values. Starting from the results of this trial, the effect of 72-hr dietary fasting on dominant follicles has been studied in six cows. Ultrasonography revealed that the diameter of the follicles at 71 days postpartum has been significantly lower than at 181 days. A 72-hr dietary restriction at 101 and 211 days postpartum did not affect the size of the dominant follicle. However, at 101 days postpartum, half of the animals presented follicular cysts. The effect of fasting differed if the animal has been in early postpartum or 211 days of lactation. Further researches are necessary to understand how different metabolic conditions can modify the follicular population but on the other hand the study shows the utility for farmers and field veterinarians of monitoring the resumption of the ovarian cycle postpartum through the whey progesterone concentrations. © 2017 Blackwell Verlag GmbH.

Follicular thyroglobulin induces cathepsin H expression and activity in thyrocytes

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

Oda, Kenzaburo; Laboratory of Molecular Diagnostics, Department of Mycobacteriology, Leprosy Research Center, National Institute of Infectious Diseases, 4-2-1 Aoba-cho, Higashimurayama, Tokyo 189-0002; Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, Toho University, 5-21-16 Omorinishi, Ota, Tokyo 143-8540

Thyroglobulin (Tg) stored in thyroid follicles exerts a potent negative-feedback effect on each step of pre-hormone biosynthesis, including Tg gene transcription and iodine uptake and organification, by suppressing the expression of specific transcription factors that regulate these steps. Pre-hormones are stored in the follicular colloid before being reabsorbed. Following lysosomal proteolysis of its precursor, thyroid hormone (TH) is released from thyroid follicles. Although the suppressive effects of follicular Tg on each step of pre-hormone biosynthesis have been extensively characterized, whether follicular Tg accumulation also affects hormone reabsorption, proteolysis, and secretion is unclear. In this study we explored whether follicular Tgmore » can regulate the expression and function of the lysosomal endopeptidases cathepsins. We found that in the rat thyroid cell line FRTL-5 follicular Tg induced cathepsin H mRNA and protein expression, as well as cathepsin H enzyme activity. Double immunofluorescence staining showed that Tg endocytosis promoted cathepsin H translocalization into lysosomes where it co-localized with internalized Tg. These results suggest that cathepsin H is an active participant in lysosome-mediated pre-hormone degradation, and that follicular Tg stimulates mobilization of pre-hormones by activating cathepsin H-associated proteolysis pathways. - Highlights: • Follicular Tg increases cathepsin H mRNA and protein levels in rat thyroid cells. • Follicular Tg increases cathepsin H enzyme activity in rat thyroid cells. • After Tg stimulation cathepsin H co-localizes to lysosomes with follicular Tg. • Cathepsin H promotes hormone secretion by lysosome-mediated mechanisms.« less

Development of the ovarian follicular epithelium.

PubMed

Rodgers, R J; Lavranos, T C; van Wezel, I L; Irving-Rodgers, H F

1999-05-25

A lot is known about the endocrine control of the development of ovarian follicles, but a key question now facing researchers is which molecular and cellular processes take part in control of follicular growth and development. The growth and development of ovarian follicles occurs postnatally and throughout adult life. In this review, we focus on the follicular epithelium (membrana granulosa) and its basal lamina. We discuss a model of how granulosa cells arise from a population of stem cells and then enter different lineages before differentiation. The structure of the epithelium at the antral stage of development is presented, and the effects that follicle growth has on the behavior of the granulosa cells are discussed. Finally, we discuss the evidence that during follicle development the follicular basal lamina changes in composition. This would be expected if the behavior of the granulosa cells changes, or if the permeability of the basal lamina changes. It will be evident that the follicular epithelium has similarities to other epithelia in the body, but that it is more dynamic, as gross changes occur during the course of follicle development. This basic information will be important for the development of future reproductive technologies in both humans and animals, and possibly for understanding polycystic ovarian syndrome in women.

Phase III of Early Restoration | NOAA Gulf Spill Restoration

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information about this phase of Early Restoration, including fact sheets on each project. The final Phase III 44 projects are documented in a final Record of Decision. Information about Phase III of Early Archive Home Phase III of Early Restoration Phase III of Early Restoration Beach habitat would be restored

Follicular unit transplantation: 2005.

PubMed

Bernstein, Robert M; Rassman, William R

2005-07-01

The recognition that the follicular unit is a discrete, anatomic and physiologic entity, and that preserving it through stereomicroscopic dissection is the best way to ensure the naturalness of the restoration, has brought hair transplantation into the twenty-first century. Issues yet to be resolved include determining the maximum density and number of grafts that can be used safely in a single session, deciding whether it is preferable to premake recipient sites or immediately place grafts into sites as they are made, and defining the precise role of follicular unit extraction. The essence of providing the best care for patients rests on proper patient selection, establishing realistic expectations, and using nonsurgical management for young persons who are just starting to thin.

Rituximab With or Without Yttrium Y-90 Ibritumomab Tiuxetan in Treating Patients With Untreated Follicular Lymphoma

ClinicalTrials.gov

2018-02-05

Stage I Grade 1 Follicular Lymphoma; Stage I Grade 2 Follicular Lymphoma; Stage II Grade 1 Contiguous Follicular Lymphoma; Stage II Grade 1 Non-Contiguous Follicular Lymphoma; Stage II Grade 2 Contiguous Follicular Lymphoma; Stage II Grade 2 Non-Contiguous Follicular Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma

Cortisol and hypothalamic–pituitary–gonadal axis hormones in follicular-phase women with fibromyalgia and chronic fatigue syndrome and effect of depressive symptoms on these hormones

PubMed Central

Gur, Ali; Cevik, Remzi; Nas, Kemal; Colpan, Leyla; Sarac, Serdar

2004-01-01

We investigated abnormalities of the hypothalamic–pituitary–gonadal axis and cortisol concentrations in women with fibromyalgia and chronic fatigue syndrome (CFS) who were in the follicular phase of their menstrual cycle, and whether their scores for depressive symptoms were related to levels of these hormones. A total of 176 subjects participated – 46 healthy volunteers, 68 patients with fibromyalgia, and 62 patients with CFS. We examined concentrations of follicle-stimulating hormone, luteinizing hormone (LH), estradiol, progesterone, prolactin, and cortisol. Depressive symptoms were assessed using the Beck Depression Inventory (BDI). Cortisol levels were significantly lower in patients with fibromyalgia or CFS than in healthy controls (P < 0.05); there were no significant differences in other hormone levels between the three groups. Fibromyalgia patients with high BDI scores had significantly lower cortisol levels than controls (P < 0.05), and so did CFS patients, regardless of their BDI scores (P < 0.05). Among patients without depressive symptoms, cortisol levels were lower in CFS than in fibromyalgia (P < 0.05). Our study suggests that in spite of low morning cortisol concentrations, the only abnormalities in hypothalamic–pituitary–gonadal axis hormones among follicular-phase women with fibromyalgia or CFS are those of LH levels in fibromyalgia patients with a low BDI score. Depression may lower cortisol and LH levels, or, alternatively, low morning cortisol may be a biological factor that contributes to depressive symptoms in fibromyalgia. These parameters therefore must be taken into account in future investigations. PMID:15142269

Induction of Fas-Mediated Apoptosis by Interferon-γ is Dependent on Granulosa Cell Differentiation and Follicular Maturation in the Rat Ovary.

PubMed

Lee, Hye-Jeong; Kim, Ji Young; Park, Ji Eun; Yoon, Yong-Dal; Tsang, Benjamin K; Kim, Jong-Min

2016-12-01

Fas ligand (FasL) and its receptor Fas have been implicated in granulosa cell apoptosis during follicular atresia. Although interferon-gamma (IFN-γ) is believed to be involved in the regulation Fas expression in differentiated granulosa or granulosa-luteal cells, the expression of this cytokine and its role in the regulation of the granulosa cell Fas/FasL system and apoptosis during follicular maturation have not been thoroughly investigated. In the present study, we have examined the presence of IFN-γ in ovarian follicles at different stage of development by immunohistochemistry and related their relative intensities with follicular expression of Fas and FasL, and with differences in granulosa cell sensitivity to Fas activation by exogenous agonistic Anti-Fas monoclonal antibody (Fas mAb). Although IFN-γ immunostaining was detectable in oocyte and granulosa cells in antral follicles, most intense immunoreactivity for the cytokine was observed in these cells of preantral follicles. Intense immunoreactivity for IFN-γ was most evident in granulosa cells of atretic early antral follicles where increased Fas and FasL expression and apoptosis were also observed. Whereas low concentrations of IFN-γ (10-100 U/mL) significantly increased Fas expression in undifferentiated granulosa cells (from preantral or very early antral follicles) in vitro , very higher concentrations (≥ 1,000 U/mL) were required to up-regulate of Fas in differentiated cells isolated from eCG-primed (antral) follicles. Addition of agonistic Fas mAb to cultures of granulosa cells at the two stages of differentiation and pretreated with IFN-γ (100 U/mL) elicited morphological and biochemical apoptotic features which were more prominent in cells not previously exposed to the gonadotropin in vivo . These findings suggested that IFN-γ is an important physiologic intra-ovarian regulator of follicular atresia and plays a pivotal role in regulation of expression of Fas receptor and subsequent

Induction of Fas-Mediated Apoptosis by Interferon-γ is Dependent on Granulosa Cell Differentiation and Follicular Maturation in the Rat Ovary

PubMed Central

Lee, Hye-Jeong; Kim, Ji Young; Park, Ji Eun; Yoon, Yong-Dal; Tsang, Benjamin K.; Kim, Jong-Min

2016-01-01

ABSTRACT Fas ligand (FasL) and its receptor Fas have been implicated in granulosa cell apoptosis during follicular atresia. Although interferon-gamma (IFN-γ) is believed to be involved in the regulation Fas expression in differentiated granulosa or granulosa-luteal cells, the expression of this cytokine and its role in the regulation of the granulosa cell Fas/FasL system and apoptosis during follicular maturation have not been thoroughly investigated. In the present study, we have examined the presence of IFN-γ in ovarian follicles at different stage of development by immunohistochemistry and related their relative intensities with follicular expression of Fas and FasL, and with differences in granulosa cell sensitivity to Fas activation by exogenous agonistic Anti-Fas monoclonal antibody (Fas mAb). Although IFN-γ immunostaining was detectable in oocyte and granulosa cells in antral follicles, most intense immunoreactivity for the cytokine was observed in these cells of preantral follicles. Intense immunoreactivity for IFN-γ was most evident in granulosa cells of atretic early antral follicles where increased Fas and FasL expression and apoptosis were also observed. Whereas low concentrations of IFN-γ (10-100 U/mL) significantly increased Fas expression in undifferentiated granulosa cells (from preantral or very early antral follicles) in vitro, very higher concentrations (≥ 1,000 U/mL) were required to up-regulate of Fas in differentiated cells isolated from eCG-primed (antral) follicles. Addition of agonistic Fas mAb to cultures of granulosa cells at the two stages of differentiation and pretreated with IFN-γ (100 U/mL) elicited morphological and biochemical apoptotic features which were more prominent in cells not previously exposed to the gonadotropin in vivo. These findings suggested that IFN-γ is an important physiologic intra-ovarian regulator of follicular atresia and plays a pivotal role in regulation of expression of Fas receptor and subsequent

Artificial neural network model to distinguish follicular adenoma from follicular carcinoma on fine needle aspiration of thyroid.

PubMed

Savala, Rajiv; Dey, Pranab; Gupta, Nalini

2018-03-01

To distinguish follicular adenoma (FA) and follicular carcinoma (FC) of thyroid in fine needle aspiration cytology (FNAC) is a challenging problem. In this article, we attempted to build an artificial neural network (ANN) model from the cytological and morphometric features of the FNAC smears of thyroid to distinguish FA from FC. The cytological features and morphometric analysis were done on the FNAC smears of histology proven cases of FA (26) and FC (31). The cytological features were analysed semi-quantitatively by two independent observers (RS and PD). These data were used to make an ANN model to differentiate FA versus FC on FNAC material. The performance of this ANN model was assessed by analysing the confusion matrix and receiving operator curve. There were 39 cases in training set, 9 cases each in validation and test sets. In the test group, ANN model successfully distinguished all cases (9/9) of FA and FC. The area under receiver operating curve was 1. The present ANN model is efficient to diagnose follicular adenoma and carcinoma cases on cytology smears without any error. In future, this ANN model will be able to diagnose follicular adenoma and carcinoma cases on thyroid aspirate. This study has immense potential in future. This is an open ended ANN model and more parameters and more cases can be included to make the model much stronger. © 2017 Wiley Periodicals, Inc.

Processing emotions: Effects of menstrual cycle phase and premenstrual symptoms on the startle reflex, facial EMG and heart rate.

PubMed

Armbruster, Diana; Grage, Tobias; Kirschbaum, Clemens; Strobel, Alexander

2018-10-01

Emotional reactivity varies across the menstrual cycle although physiological findings are not entirely consistent. We assessed facial EMG and heart rate (HR) changes in healthy free cycling women (N = 45) with an emotional startle paradigm both during the early follicular and the late luteal phase, verified by repeated salivary 17β-estradiol, progesterone and testosterone assessments. Cycle phase impacted startle responses with larger magnitudes during the luteal phase. Notably, this effect was only present when premenstrual symptoms and sequence of lab sessions were included as co-variates. At rest, participants showed a tendency towards higher HR and reduced high frequency (HF) power during the luteal phase indicating reduced parasympathetic tone. HF power was also negatively associated with startle magnitudes. HR changes in response to emotional images differed between the two cycle phases. Initial HR deceleration was more marked during the follicular phase particularly when viewing negative pictures. However, cycle phase did not significantly impact corrugator and zygomaticus activity in response to emotional pictures. Among the three gonadal steroids, correlation patterns were most consistent for testosterone. During the follicular phase, testosterone was associated with zygomaticus activity while viewing neutral or positive pictures and with less pronounced HR deceleration in response to negative images. During the luteal phase, testosterone was negatively associated with fear potentiated startle. The findings underscore the importance of considering menstrual cycle phase when investigating physiological indicators of emotion. However, the modulating effect of premenstrual symptoms also emphasizes potential inter-individual differences. Copyright © 2018 Elsevier B.V. All rights reserved.

Androgens as double-edged swords: Induction and suppression of follicular development.

PubMed

Pan, Jie-Xue; Zhang, Jun-Yu; Ke, Zhang-Hong; Wang, Fang-Fang; Barry, John A; Hardiman, Paul J; Qu, Fan

2015-01-01

Androgens, which are mediated via the androgen receptor (AR), play important roles in normal follicular development and female fertility. However, just like a double-edged sword, besides the positive effects of androgen on follicular development, abnormal androgen levels, especially as in hyperandrogenism, seriously suppress normal follicular development. A crucial balance exists between the importance of androgens in follicular development and their negative effects when in excess. As the first meiotic division and epigenetic reprogramming are two critical events in oogenesis, abnormal androgen levels or deficiency in androgen/AR signaling in the ovary may affect these vital events. Oocytes have a tendency to develop genomic instability, thus resulting in an increasing incidence of unpredictable adult diseases. Although many studies have explored the effects of androgens and AR on follicular development, the conclusions are controversial and there has been no thorough review of this topic. This review focuses on the roles of androgens in the physiological process of follicular development, summarizes new insights into the roles of androgens in the arrested development of follicles, and discusses the potential risk of adult diseases originating from abnormal follicular androgen levels or androgen receptor signals, which may determine areas for future studies.

Phase III Early Restoration Public Meetings | NOAA Gulf Spill Restoration

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Archive Home Phase III Early Restoration Public Meetings Phase III Early Restoration Public Meetings share Posted on December 6, 2013 | Assessment and Early Restoration Restoration Area Title: Phase III Early on the draft plan for the third phase of Early Restoration, which proposes more than $625 million in

Phase V of Early Restoration | NOAA Gulf Spill Restoration

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Phase V Early Restoration Plan and Environmental Assessment. The project will acquire land along Florida million. Phase V Early Restoration Plan and Environmental Assessment (pdf, 10 MB) Draft Phase V Early Restoration Plan and Environmental Assessment (Executive Summary) (2 MB) Phase V Fact Sheet (pdf, 2 MB) Gulf

[Explore microcosmic connection between autophagy mechanism and follicular development based on "kidney governing reproduction" theory].

PubMed

Bai, Jun; Wu, Ke-Ming; Gao, Ran-Ran

2018-03-01

In the theory of traditional Chinese medicine(TCM) that "kidney storing essence and governing reproduction", reproductive essence is an important part of the kidney essence and acts as the original material of offspring embryos. Sperm, oocyte and zygote should be all included in the range of reproductive essence. Ovum is the essence of reproduction from inborn. The follicles maturation depends on the quality of oocyte and the vigor of kidney essence. Meanwhile, discharge of mature ovum relies on the stimulation and promotion by kidney Qi. Autophagy almost exists in different cells stages and all various of mammalian cells. Many studies have found that autophagy not only participates in the formation of follicles, but also in every phase of the follicles development, and is involved in the occurrence and development of ovarian diseases. Recently, more and more scholars believe that autophagy is a new field to explore the microcosmic relationship between autophagy and TCM. Kidney-nourishing TCM could promote follicular growth and improve variety clinical symptoms by inhibiting the apoptosis of ovarian granulosa cells and reducing follicular atresia. Meanwhile, apoptosis of ovarian granulosa cells is closely related to autophagy of ovarian granulosa cells. In order to provide some theoretical foundation for kidney-nourishing therapy's promoting effect on follicular growth and improving effect on ovarian function, also to further explore the molecular mechanism of kidney-nourishing medicine in promoting follicular development, this paper would explain the microcosmic relationship between autophagy and follicular development based on the theory of "kidney governing reproduction". All of these would be of great significance to prevent and intervene the diseases of reproductive system timely and effectively. Copyright© by the Chinese Pharmaceutical Association.

Primary follicular lymphoma of the cervix uteri: a review.

PubMed

Korcum, Aylin Fidan; Karadogan, Ihsan; Aksu, Gamze; Aralasmak, Ayse; Erdogan, Gulgun

2007-09-01

Primary non-Hodgkin's lymphoma of the cervix is a rare disease, of which a subgroup of follicular lymphoma constitutes only 8.5%. There is not an established treatment protocol neither for primary cervical lymphoma nor for its follicular subgroup. We presented a case with Ann Arbor stage IEA (Extra-nodal involvement and absence of weight loss, fever, night sweat) primary follicular lymphoma of the cervix. She was treated with chemotherapy followed by pelvic radiotherapy. Upon relapse with a nodal neck mass, she was treated with rituximab alone. She remained well for 23 months after rituximab. In the 39 months of follow-up, there was no evidence of disease. In the light of our case, we reviewed the reported cases of primary follicular lymphoma of the cervix while discussing their treatment protocols and the cases of primary cervix lymphoma treated with rituximab.

Follicular vitiligo: A report of 8 cases.

PubMed

Gan, Emily Yiping; Cario-André, Muriel; Pain, Catherine; Goussot, Jean-Francois; Taïeb, Alain; Seneschal, Julien; Ezzedine, Khaled

2016-06-01

Follicular vitiligo, a recently proposed new subtype of vitiligo, has primary involvement of the hair follicle melanocytic reservoir. We sought to characterize follicular vitiligo through a case series of 8 patients. Patients with features of follicular vitiligo who were seen at the vitiligo clinic in the National Center for Rare Skin Disorders in Bordeaux, France, were recruited. A retrospective review of case records and clinical photographs was carried out. There were 8 male patients with a mean age of 48 years. All patients reported significant whitening of their body and, in some, scalp hairs before cutaneous depigmentation. Examination revealed classic generalized depigmented lesions of vitiligo and an impressive presence of leukotrichia, not only in the vitiliginous areas, but also in areas with clinically normal-appearing skin. Punch biopsy specimen of the leukotrichia and vitiligo lesions demonstrated loss of melanocytes and precursors in the basal epidermis and hair follicle. This was a cross-sectional study based on a single-center experience. Follicular vitiligo is a distinct entity within the spectrum of vitiligo. This entity may serve as the missing link between alopecia areata and vitiligo, with probable physiopathological similarities between these conditions. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Follicular dysplasia in five Weimaraners.

PubMed

Laffort-Dassot, Catherine; Beco, Luc; Carlotti, Didier Noel

2002-10-01

This study evaluated the clinical and histopathological features and results of light and electron scanning microscopy assessments of follicular dysplasia in five Weimar Pointers. The data were compared with those obtained in three normal Weimaraners. In our study, this dermatosis affected young adults that showed progressive alopecia of the trunk (head and limbs were spared) associated with recurrent folliculitis/furunculosis. Exclusion of other dermatoses and the presence of histopathological lesions and hair shafts abnormalities seen in light and/or scanning electron microscopy similar to colour dilution alopecia led to the diagnosis of follicular dysplasia. The lesions we observed are the same as those described previously in colour dilution alopecia, but they were less pronounced in all our samples.

Mammalian follicular development and atresia: role of apoptosis.

PubMed

Asselin, E; Xiao, C W; Wang, Y F; Tsang, B K

2000-01-01

The regulation of follicular development and atresia is a complex process and involves interactions between endocrine factors (gonadotropins) and intraovarian regulators (sex steroids, growth factors and cytokines) in the control of follicular cell fate (i.e. proliferation, differentiation and programmed cell death). Granulosa and theca cells are key players in this fascinating process. As atresia is the fate of most follicles, understanding of how these physiological regulators participate in determining the destiny of the follicle (to degenerate or to ovulate) at cellular and subcellular levels is fundamental. This short review summarizes the role of intraovarian modulators of programmed cell death in the induction of atresia during follicular development. Copyright 2000 S. Karger AG, Basel

T follicular helper and T follicular regulatory cells have different TCR specificity

PubMed Central

Maceiras, Ana Raquel; Almeida, Silvia Cristina Paiva; Mariotti-Ferrandiz, Encarnita; Chaara, Wahiba; Jebbawi, Fadi; Six, Adrien; Hori, Shohei; Klatzmann, David; Faro, Jose; Graca, Luis

2017-01-01

Immunization leads to the formation of germinal centres (GCs) that contain both T follicular helper (Tfh) and T follicular regulatory (Tfr) cells. Whether T-cell receptor (TCR) specificity defines the differential functions of Tfh and Tfr cells is unclear. Here we show that antigen-specific T cells after immunization are preferentially recruited to the GC to become Tfh cells, but not Tfr cells. Tfh cells, but not Tfr cells, also proliferate efficiently on restimulation with the same immunizing antigen in vitro. Ex vivo TCR repertoire analysis shows that immunization induces oligoclonal expansion of Tfh cells. By contrast, the Tfr pool has a TCR repertoire that more closely resembles that of regulatory T (Treg) cells. Our data thus indicate that the GC Tfh and Tfr pools are generated from distinct TCR repertoires, with Tfh cells expressing antigen-responsive TCRs to promote antibody responses, and Tfr cells expressing potentially autoreactive TCRs to suppress autoimmunity. PMID:28429709

Women in the midluteal phase of the menstrual cycle have difficulty suppressing the processing of negative emotional stimuli: An event-related potential study.

PubMed

Lusk, Bethany R; Carr, Andrea R; Ranson, Valerie A; Felmingham, Kim L

2017-08-01

Emotion regulation deficits have been implicated in anxiety and depressive disorders, and these internalising disorders are more prevalent in women than men. Few electrophysiological studies have investigated sex differences in emotional reactivity and emotion regulation controlling for menstrual phase. Event-related potentials (ERPs) were recorded from 28 early follicular women, 29 midluteal women, and 27 men who completed an emotion regulation task. A novel finding of increased N2 amplitude during suppression was found for midluteal women compared with men. These findings suggest midluteal women may be significantly less able to suppress cortical processing of negative stimuli compared to men. This ERP finding was complemented by behavioral ratings data which revealed that while both early follicular and midluteal women reported more distress than men, midluteal women also reported greater effort when suppressing their responses than men. P1 and N1 components were increased in midluteal women compared to men regardless of instructional set, suggesting greater early attentional processing. No sex or menstrual phase differences were apparent in P3 or LPP. This study underscores the importance of considering menstrual phase when examining sex differences in the cortical processing of emotion regulation and demonstrates that midluteal women may have deficits in down-regulating their neural and behavioural responses.

Pattern of CD14+ follicular dendritic cells and PD1+ T cells independently predicts time to transformation in follicular lymphoma.

PubMed

Smeltzer, Jacob P; Jones, Jason M; Ziesmer, Steven C; Grote, Deanna M; Xiu, Bing; Ristow, Kay M; Yang, Zhi Zhang; Nowakowski, Grzegorz S; Feldman, Andrew L; Cerhan, James R; Novak, Anne J; Ansell, Stephen M

2014-06-01

Transformation of follicular lymphoma is a critical event associated with a poor prognosis. The role of the tumor microenvironment in previous transformation studies has yielded conflicting results. To define cell subtypes associated with transformation, we examined tissue specimens at diagnosis from patients with follicular lymphoma that later transformed and, using immunohistochemistry (IHC), stained for CD68, CD11c, CD21, CXCL13, FOXP3, PD1, and CD14. Cell content and the pattern of expression were evaluated. Those identified as significantly associated with time to transformation (TTT) and overall survival (OS) were further characterized by flow cytometry and multicolor IHC. Of note, 58 patients were analyzed with median TTT of 4.7 years. The pattern of PD1(+) and CD14(+) cells rather than the quantity of cells was predictive of clinical outcomes. On multivariate analysis, including the follicular lymphoma international prognostic index score, CD14(+) cells localized in the follicle were associated with a shorter TTT (HR, 3.0; P = 0.004). PD1(+) cells with diffuse staining were associated with a shorter TTT (HR, 1.9; P = 0.045) and inferior OS (HR, 2.5; P = 0.012). Multicolor IHC and flow cytometry identified CD14(+) cells as follicular dendritic cells (FDC), whereas PD1(+) cells represented two separate populations, TFH and exhausted T cells. These results identify the presence of PD1(+) T cells and CD14(+) FDC as independent predictors of transformation in follicular lymphoma. Clin Cancer Res; 20(11); 2862-72. ©2014 AACR. ©2014 American Association for Cancer Research.

Novel Drugs in Follicular Lymphoma.

PubMed

Anastasia, Antonella; Rossi, Giuseppe

2016-01-01

Follicular lymphoma(FL) is the most common indolent non-Hodgkin lymphoma and constitutes 15% to 30% of lymphoma diagnoses. The natural history of the disease is characterized by recurrent relapses and progressively shorter remissions with a median survival of 10yrs. The impossibility of achieving a definite cure, have prompted investigations into the possible role of more active and less toxic strategies with innovative therapeutic agents. Recently Casulo et al. demonstrated that approximately 20% of patients with FL relapse within two years after achieving remission with R-CHOP and have a poor prognosis. It is conceivable that this particularly chemoresistant population would benefit from specifically targeting the biologic and genetic factors that likely contribute to their poor prognosis. Evolving strategies for difficult to treat FL patients have recently considered immunomodulatory agents, new monoclonal antibodies as well as drugs targeting selective intracellular pathways. The importance of targeting the microenvironment together with the malignant FL cell has been particularly underscored. We review the most promising approaches, such as combining anti-CD20 antibodies with immunomodulatory drugs (Lenalidomide), mAbs directed against other surface antigens such as CD22 and CD23 (Epratuzumab, Lumiliximab), immunomodulatory antibodies such as PD-1, or inhibitors of key steps in the B-cell receptor pathway signaling such as PI3K inhibitors (Idelalisib, Duvelisib). Another highly attractive approach is the application of the bi-specific T-cell engaging (BiTE) antibody blinatumomab which targets both CD19 and CD3 antigens. Moreover, we highlight the potential of these therapies, taking into account their toxicity. Of course, we must wait for Phase III trials results to confirm the benefit of these new treatment strategies toward a new era of chemotherapy-free treatment for follicular lymphoma.

Novel Drugs in Follicular Lymphoma

PubMed Central

Anastasia, Antonella; Rossi, Giuseppe

2016-01-01

Follicular lymphoma(FL) is the most common indolent non-Hodgkin lymphoma and constitutes 15% to 30% of lymphoma diagnoses. The natural history of the disease is characterized by recurrent relapses and progressively shorter remissions with a median survival of 10yrs. The impossibility of achieving a definite cure, have prompted investigations into the possible role of more active and less toxic strategies with innovative therapeutic agents. Recently Casulo et al. demonstrated that approximately 20% of patients with FL relapse within two years after achieving remission with R-CHOP and have a poor prognosis. It is conceivable that this particularly chemoresistant population would benefit from specifically targeting the biologic and genetic factors that likely contribute to their poor prognosis. Evolving strategies for difficult to treat FL patients have recently considered immunomodulatory agents, new monoclonal antibodies as well as drugs targeting selective intracellular pathways. The importance of targeting the microenvironment together with the malignant FL cell has been particularly underscored. We review the most promising approaches, such as combining anti-CD20 antibodies with immunomodulatory drugs (Lenalidomide), mAbs directed against other surface antigens such as CD22 and CD23 (Epratuzumab, Lumiliximab), immunomodulatory antibodies such as PD-1, or inhibitors of key steps in the B-cell receptor pathway signaling such as PI3K inhibitors (Idelalisib, Duvelisib). Another highly attractive approach is the application of the bi-specific T-cell engaging (BiTE) antibody blinatumomab which targets both CD19 and CD3 antigens. Moreover, we highlight the potential of these therapies, taking into account their toxicity. Of course, we must wait for Phase III trials results to confirm the benefit of these new treatment strategies toward a new era of chemotherapy-free treatment for follicular lymphoma. PMID:27872741

Immunotherapy with Rituximab in Follicular Lymphomas

PubMed Central

SAGUNA, Carmen; MUT, Ileana Delia; LUPU, Anca Roxana; TEVET, Mihaela; BUMBEA, Horia; DRAGAN, Cornel

2011-01-01

ABSTRACT Background: Non-Hodgkin Lymphomas (NHL) represent a recent and fascinating domain of hemato-oncology, in which remarkable progress has been made. The conventional treatments of indolent lymphomas do not extend the survival rate, nor do they cure. Recent directions are centered on using several new drugs that are capable of overcoming the mechanisms that are resistant to recovery. The initiation of immunotherapy (Rituximab in 1997) seems to have changed the natural evolution of follicular lymphomas (FL). It is possible that resistance to healing in follicular lymphomas may be neutralized with Rituximab by suppressing STAT-1 positive macrophages that are present in the cellular microenvironment.Thereinafter, the re-evaluation of recent models of prognostic and therapeutic paradigmas that were used in FL became compulsory. The purpose of the paper is to compare the evolution of patients with follicular lymphoma and the period of response, according to the treatments. Material and method: The study group consisted of the 71 patients diagnosed with follicular lymphoma, out of a total of 767 malignant lymphatic proliferations with B cells, for a period of 7 years (2002-2008), at the Hematology Department, Hospital Coltea, Bucharest and Hematology Department, Universitary Hospital, Bucharest Results and conclusions: Combining chemotherapy with Rituximab had better results compared to the same chemotherapy, administered alone, both in induction and in case of relapse. The overall response rate in our study group was 74.7%, out of which 42.3% complete remissions. The overall response rate was 84.61% in the Rituximab group, compared to 68.88% in patients without Rituximab. PMID:22205891

Immunotherapy with rituximab in follicular lymphomas.

PubMed

Saguna, Carmen; Mut, Ileana Delia; Lupu, Anca Roxana; Tevet, Mihaela; Bumbea, Horia; Dragan, Cornel

2011-04-01

Non-Hodgkin Lymphomas (NHL) represent a recent and fascinating domain of hemato-oncology, in which remarkable progress has been made. The conventional treatments of indolent lymphomas do not extend the survival rate, nor do they cure. Recent directions are centered on using several new drugs that are capable of overcoming the mechanisms that are resistant to recovery. The initiation of immunotherapy (Rituximab in 1997) seems to have changed the natural evolution of follicular lymphomas (FL). It is possible that resistance to healing in follicular lymphomas may be neutralized with Rituximab by suppressing STAT-1 positive macrophages that are present in the cellular microenvironment.Thereinafter, the re-evaluation of recent models of prognostic and therapeutic paradigmas that were used in FL became compulsory.The purpose of the paper is to compare the evolution of patients with follicular lymphoma and the period of response, according to the treatments. The study group consisted of the 71 patients diagnosed with follicular lymphoma, out of a total of 767 malignant lymphatic proliferations with B cells, for a period of 7 years (2002-2008), at the Hematology Department, Hospital Coltea, Bucharest and Hematology Department, Universitary Hospital, BucharestResults and conclusions: Combining chemotherapy with Rituximab had better results compared to the same chemotherapy, administered alone, both in induction and in case of relapse. The overall response rate in our study group was 74.7%, out of which 42.3% complete remissions. The overall response rate was 84.61% in the Rituximab group, compared to 68.88% in patients without Rituximab.

Phase IV of Early Restoration | NOAA Gulf Spill Restoration

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Trustees published the Final Phase IV Early Restoration Plan and Environmental Assessments. The plan habitats. Useful Links: Final Phase IV Early Restoration Plan and Environmental Assessments (pdf, 4.8 MB ) Final Phase IV Early Restoration Plan and Environmental Assessments Executive Summary (pdf, 729 KB

Estrus behavior, ovarian dynamics, and progesterone secretion in Criollo cattle during estrous cycles with two and three follicular waves.

PubMed

Quezada-Casasola, Andrés; Avendaño-Reyes, Leonel; Macías-Cruz, Ulises; Ramírez-Godínez, José Alejandro; Correa-Calderón, Abelardo

2014-04-01

In beef and dairy cattle, the number of follicular waves affects endocrine, ovarian, and behavioral events during a normal estrous cycle. However, in Mexican-native Criollo cattle, a shortly and recently domesticated breed, the association between wave patterns and follicular development has not been studied. The objective of this study was to evaluate the effect of number of follicular waves in an estrous cycle on development of anovulatory and ovulatory follicles, corpus luteum (CL) development and functionality, as well as estrual behavior in Criollo cows. Ovarian follicular activities of 22 cycling multiparous Criollo cows were recorded daily by transrectal ultrasound examinations during a complete estrous cycle. Additionally, blood samples were collected daily to determine serum progesterone concentrations. Only two- (n = 17, 77.3%) and three-wave follicular (n = 5, 22.7%) patterns were observed. Duration of estrus, length of estrous cycle, and length of follicular and luteal phases were similar (P > 0.05) between cycles of two and three waves. Two-wave cows ovulated earlier (P < 0.05) after detection of estrus than three-wave cows. Detected day and maximum diameter of first anovulatory follicle were not affected (P > 0.05) by number of waves. Growth rate of first dominant follicle was higher (P < 0.05) in three-wave cycles. Onset of regression of the first dominant follicle was earlier (P < 0.01) in cycles with three waves than in those with two waves. In two-wave cycles, ovulatory follicles were detected earlier (P < 0.01) and had lower (P < 0.01) growth rate than in three-wave cycles. Development (i.e., maximum diameter and volume) and functionality (minimum and maximum progesterone concentration) of CL were similar (P > 0.05) between two- and three-wave patterns. In conclusion, Criollo cows have two or three follicular waves per estrous cycle, which alters partially ovulatory follicle development and ovulation time after detection of estrus. Length of

Follicular morphological characteristics may be associated with invasion in follicular thyroid neoplasms with papillary-like nuclear features.

PubMed

Can, Nuray; Celik, Mehmet; Sezer, Yavuz Atakan; Ozyilmaz, Filiz; Ayturk, Semra; Tastekin, Ebru; Sut, Necdet; Gurkan, Hakan; Ustun, Funda; Bulbul, Buket Yilmaz; Guldiken, Sibel; Puyan, Fulya Oz

2017-08-20

The newly proposed nomenclature and diagnostic criteria for encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC), the noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), could improve the consistency and accuracy of diagnosing this entity. Diagnosis of NIFTP requires evaluation of the complete tumor border or capsule. The presence of tumor invasion in follicular thyroid neoplasms with papillary-like nuclear features has been recently discussed by many authors. In this study, we examined the predictive value and association of follicular morphological characteristics with the tumor invasion. In addition, we analyzed the association between tumor encapsulation and molecular profile in EFVPTC/NIFTP cases. A total of 106 cases of FVPTC were included in the study. The tumors were grouped based on the presence of tumor capsule and characteristics of tumor border, as 1) completely encapsulated tumors without invasion, 2) encapsulated tumors with invasion, 3) infiltrative tumors without a capsule. Clinicopathological features, histomorphological features [nuclear criteria, minor diagnostic features, follicles oriented perpendicular to tumor border/capsule (FOPBC)] and molecular alterations in BRAF, NRAS, and KRAS genes were evaluated. FOPBC were significantly more frequently seen in encapsulated tumors with invasion (p = 0.008). The nuclear features were not associated with the presence of encapsulation and characteristics of tumor border. BRAF mutation was more frequent in infiltrative tumors, while NRAS mutation was more frequent in encapsulated tumors, but the results were not statistically significant (p = 0.917). In conclusion, FOPBC histomorphological feature may be associated with tumor invasion in EFVPTC/NIFTP. Additionally, BRAF/KRAS/NRAS mutation analysis may prevent inadequate treatment in these patients.

Follicular aspiration versus coasting for ovarian hyper-stimulation syndrome prevention

PubMed Central

Bushaqer, Nayla J.; Dayoub, Nawal M.; AlHattali, Khalsa K.; Ayyoub, Hisham A.; AlFaraj, Samaher S.; Hassan, Samar N.

2018-01-01

Objectives: To compare follicular reduction prior to human chorionic gonadotropin (HCG) trigger and coasting in terms of ovarian hyper-stimulation syndrome (OHSS) reduction, pregnancy, and cancellation rates in in vitro fertilization/ intracytoplasmic sperm injection (IVF/ICSI) cycles. Methods: This study was designed as a prospective study. The setting was the IVF unit at King Abdulaziz Medical City, Riyadh, Kingdom of Saudi Arabia. A total of 39 patients undergoing IVF/ICSI cycles, who were at risk of OHSS, 20 were put into a coasting group and 19 had follicular reduction instead. This occurred between October 2010 and January 2011. Our main outcome was OHSS reduction. Results: Six (30%) women developed OHSS in the coasting group and 2 (10.5%) women developed OHSS in the follicular group (p-value=0.235). The pregnancy rates in the cycles were similar for both groups: 4/20 (20%) in the coasting group and 3/19 (15.8%) in the follicular group (p-value=1.000). The cancellation rate of the cycles was similar for both groups, 6/20 (30%) in the coasting group and 1/19 (5.3%) in the follicular group (p-value=0.09). The median number of punctured follicles was significantly lower in the follicular group (16 follicles, interquartile range (IQR)=21-12) compared to the coasting group (29 follicles, IQR=37.8-19.8, p-value=0.001). The retrieved, fertilized, and cleaved oocytes, as well as the number of embryos transferred, were similar amongst both groups. Conclusion: There was no difference between follicular reduction prior to HCG and coasting, in terms of OHSS reduction, pregnancy, and cancellation rates in both the IVF and ICSI cycles. PMID:29543308

Ofatumumab and Bendamustine Hydrochloride With or Without Bortezomib in Treating Patients With Untreated Follicular Non-Hodgkin Lymphoma

ClinicalTrials.gov

2018-04-17

Ann Arbor Stage III Grade 1 Follicular Lymphoma; Ann Arbor Stage III Grade 2 Follicular Lymphoma; Ann Arbor Stage III Grade 3 Follicular Lymphoma; Ann Arbor Stage IV Grade 1 Follicular Lymphoma; Ann Arbor Stage IV Grade 2 Follicular Lymphoma; Ann Arbor Stage IV Grade 3 Follicular Lymphoma; Grade 3a Follicular Lymphoma

Origin of estradiol fatty acid esters in human ovarian follicular fluid.

PubMed

Pahuja, S L; Kim, A H; Lee, G; Hochberg, R B

1995-03-01

The estradiol fatty acid esters are the most potent of the naturally occurring steroidal estrogens. These esters are present predominantly in fat, where they are sequestered until they are hydrolyzed by esterases. Thus they act as a preformed reservoir of estradiol. We have previously shown that ovarian follicular fluid from patients undergoing gonadotropin stimulation contains very high amounts of estradiol fatty acid esters (approximately 10(-7) M). The source of these esters is unknown. They can be formed by esterification of estradiol in the follicular fluid by lecithin:cholesterol acyltransferase (LCAT), or in the ovary by an acyl coenzyme A:acyltransferase. In order to determine which of these enzymatic processes is the source of the estradiol esters in the follicular fluid, we incubated [3H]estradiol with follicular fluid and cells isolated from human ovarian follicular fluid and characterized the fatty acid composition of the [3H]estradiol esters biosynthesized in each. In addition, we characterized the endogenous estradiol fatty acid esters in the follicular fluid and compared them to the biosynthetic esters. The fatty acid composition of the endogenous esters was different than those synthesized by the cellular acyl coenzyme A:acyltransferase, and the same as the esters synthesized by LCAT, demonstrating that the esters are produced in situ in the follicular fluid. Although the role of these estradiol esters in the ovary is not known, given their remarkable estrogenic potency it is highly probable that they have an important physiological role.

Gene expression profiles of Vibrio parahaemolyticus in the early stationary phase.

PubMed

Meng, L; Alter, T; Aho, T; Huehn, S

2015-09-01

Vibrio (V.) parahaemolyticus is an aquatic bacterium capable of causing foodborne gastroenteritis. In the environment or the food chain, V. parahaemolyticus cells are usually forced into the stationary phase, the common phase for bacterial survival in the environment. So far, little is known about whole genomic expression of V. parahaemolyticus in the early stationary phase compared with the exponential growth phase. We performed whole transcriptomic profiling of V. parahaemolyticus cells in both phases (exponential and early stationary phase). Our data showed in total that 172 genes were induced in early stationary phase, while 61 genes were repressed in early stationary phase compared with the exponential phase. Three functional categories showed stable gene expression in the early stationary phase. Eleven functional categories showed that up-regulation of genes was dominant over down-regulation in the early stationary phase. Although genes related to endogenous metabolism were repressed in the early stationary phase, massive regulation of gene expression occurred in the early stationary phase, indicating the expressed gene set of V. parahaemolyticus in the early stationary phase impacts environmental survival. Vibrio (V.) parahaemolyticus is one of the main bacterial causes of foodborne intestinal infections. This bacterium usually is forced into stationary phase in the environment, which includes, e.g. seafood. When bacteria are in stationary phase, physiological changes can lead to a resistance to many stresses, including physical and chemical challenges during food processing. To the best of our knowledge, highlighting the whole genome expression changes in the early stationary phase compared with exponential phase, as well as the investigation of physiological changes of V. parahaemolyticus such as the survival mechanism in the stationary phase has been the very first study in this field. © 2015 The Society for Applied Microbiology.

The mediation effect of menstrual phase on negative emotion processing: evidence from N2.

PubMed

Wu, Haiyan; Chen, Chunping; Cheng, Dazhi; Yang, Suyong; Huang, Ruiwang; Cacioppo, Stephanie; Luo, Yue-Jia

2014-01-01

Numerous studies have shown a 'negativity bias' in emotion processing and effect of menstrual phase on emotion processing. Most of these results, however, did not match the arousal of different types of stimuli. The present study examined the time course of negative emotion processing across different menstrual phases (e.g., late luteal/premenstrual phase and follicular phase) when the arousal level of negative and neutral stimuli was equal. Following previous studies, an oddball paradigm was utilized in present study. Participants viewed neutral and negative (highly (HN) and moderately negative (MN)) stimuli with matched arousal and were asked to make deviant vs. standard judgments. The behavioral results showed a higher accuracy for HN stimuli than neutral stimuli, and the other comparisons were not significant. The major event-related potential (ERP) finding was that N2 amplitude was larger for MN than neutral in the late luteal phase, whereas such difference was absent during the follicular phase. Moreover, The N2 for HN stimuli was larger in late luteal phase than in follicular phase. Therefore, female may be with higher sensitivity to MN stimuli during late luteal phase than during follicular phase when the arousal of stimuli was well controlled. These results provide additional insight to premenstrual affective syndrome and affective disorder.

Follicular neoplasms of the thyroid: importance of clinical and cytological correlation.

PubMed

Granados-García, Martín; Cortés-Flores, Ana Olivia; del Carmen González-Ramírez, Imelda; Cano-Valdez, Ana María; Flores-Hernández, Lorena; Aguilar-Ponce, José Luis

2010-01-01

Thyroid cancer presents as nodules. Thyroid nodules are frequent, but only 5-30% are malignant. Fine needle aspiration biopsy (FNAB) is useful for initial evaluation; nevertheless, malignancy is uncertain when follicular neoplasm is reported. Some factors can be associated with malignancy. Therefore, we analyzed our follicular neoplasms in order to identify those factors associated with a higher risk of malignancy. We analyzed the clinical files of consecutive patients with cytological diagnoses of follicular neoplasm. From 1,005 cases of thyroid nodules, 121 were follicular neoplasms according to cytology. Of these, 75 were surgically treated. Definitive report showed 45 benign (60%) and 30 malignant (40%) cases. Benign cases included 29 goiters, 11 follicular adenomas, and 5 cases of thyroiditis. Malignant cases were comprised of 12 papillary carcinomas, 4 follicular carcinomas, 3 papillary carcinomas-follicular variant, 1 lymphoma, 1 teratoma, 5 medullary carcinomas, 2 insular carcinomas, 1 anaplastic carcinoma and 1 metastatic breast carcinoma. Tumor size of benign lesions was 3.43 ± 2.04 cm, and 4.67 ± 2.78 (p = 0.049) for malignant lesions. Age was 46.95 ± 15.39 years for benign lesions and 48.67 ± 17.28 for malignant lesions (p = 0.66). Fifty percent of males showed malignancy vs. 37.7% of females (p < 0.005). Our results suggest that size and gender, but not age, are associated with cytological pattern. Ultrasonographic characteristics may be useful discriminating patients with a higher risk of malignancy. FNAB is a useful tool for initial evaluation of thyroid nodules, but clinical evaluation can enhance predictive value.

Rituximab and Oblimersen in Treating Patients With Stage II, Stage III, or Stage IV Follicular Non-Hodgkin's Lymphoma

ClinicalTrials.gov

2013-01-04

Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma

Resting state alpha frequency is associated with menstrual cycle phase, estradiol and use of oral contraceptives.

PubMed

Brötzner, Christina P; Klimesch, Wolfgang; Doppelmayr, Michael; Zauner, Andrea; Kerschbaum, Hubert H

2014-08-19

Ongoing intrinsic brain activity in resting, but awake humans is dominated by alpha oscillations. In human, individual alpha frequency (IAF) is associated with cognitive performance. Noticeable, performance in cognitive and emotional tasks in women is associated with menstrual cycle phase and sex hormone levels, respectively. In the present study, we correlated frequency of alpha oscillation in resting women with menstrual cycle phase, sex hormone level, or use of oral contraceptives. Electroencephalogram (EEG) was recorded from 57 women (aged 24.07 ± 3.67 years) having a natural menstrual cycle as well as from 57 women (aged 22.37 ± 2.20 years) using oral contraceptives while they sat in an armchair with eyes closed. Alpha frequency was related to the menstrual cycle phase. Luteal women showed highest and late follicular women showed lowest IAF or center frequency. Furthermore, IAF as well as center frequency correlated negatively with endogenous estradiol level, but did not reveal an association with endogenous progesterone. Women using oral contraceptives showed an alpha frequency similar to women in the early follicular phase. We suggest that endogenous estradiol modulate resting alpha frequency. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

Extending the Impact of RAC1b Overexpression to Follicular Thyroid Carcinomas

PubMed Central

Faria, Márcia; Capinha, Liliana; Simões-Pereira, Joana; Bugalho, Maria João; Silva, Ana Luísa

2016-01-01

RAC1b is a hyperactive variant of the small GTPase RAC1 known to be a relevant molecular player in different cancers. Previous studies from our group lead to the evidence that its overexpression in papillary thyroid carcinoma (PTC) is associated with an unfavorable prognosis. In the present study, we intended to extend the analysis of RAC1b expression to thyroid follicular neoplasms and to seek for clinical correlations. RAC1b expression levels were determined by RT-qPCR in thyroid follicular tumor samples comprising 23 follicular thyroid carcinomas (FTCs) and 33 follicular thyroid adenomas (FTAs). RAC1b was found to be overexpressed in 33% of carcinomas while no RAC1b overexpression was documented among follicular adenomas. Patients with a diagnosis of FTC were divided into two groups based on longitudinal evolution and final outcome. RAC1b overexpression was significantly associated with both the presence of distant metastases (P = 0.01) and poorer clinical outcome (P = 0.01) suggesting that, similarly to that previously found in PTCs, RAC1b overexpression in FTCs is also associated with worse outcomes. Furthermore, the absence of RAC1b overexpression in follicular adenomas hints its potential as a molecular marker likely to contribute, in conjunction with other putative markers, to the preoperative differential diagnosis of thyroid follicular lesions. PMID:27127508

Association of menstrual phase with smoking behavior, mood and menstrual phase-associated symptoms among young Japanese women smokers.

PubMed

Sakai, Hiroko; Ohashi, Kazutomo

2013-03-02

Previous studies of the relationship between the menstrual phases and smoking behavior have been problematic, so the association of menstrual phases with smoking behavior and correlations among smoking, psychological and physical conditions in each phase of the menstrual cycle are unclear. To accurately examine the association between menstrual phases and the amount of smoking (number of cigarettes smoked and breath CO concentration), craving of smoking on visual analogue scale (VAS), depression in the Center for Epidemiologic Studies Depression (CES-D) Scale, and menstrual phase-associated symptoms in the Menstrual Distress Questionnaire (MDQ), we improved various methodological issues, specifically, 1) Ovulation was confirmed by measuring the basal body temperature and identifying a urinary luteinizing hormone (LH) surge in two cycles; 2) The menstrual, follicular, and luteal phases were clearly defined for subjects with different menstrual cycles; 3) The breath CO concentration was measured every day. A notice was posted on public bulletin boards to recruit research subjects and twenty-nine young Japanese women smokers aged 19 to 25 years old were analyzed. The number of cigarettes smoked was greater and the CO concentration was higher in the luteal phase than in the follicular phase. The levels of craving for smoking (VAS), depressiveness (CES-D), and menstrual phase-associated symptoms (MDQ) in the menstrual and luteal phases were higher than those in the follicular phase. The mean score for CES-D was 16 points (the cut-off value in screening for depression) or higher in the menstrual (16.9 ± 8.2) and luteal phases (17.2 ± 8.4).The number of cigarettes smoked and CO concentration were significantly correlated with the levels of craving for smoking, depressiveness, and menstrual phase-associated symptoms in all phases except for MDQ scores in follicular phase. The amount of smoking in the luteal phase was most strongly correlated with these symptoms

“Nodule in Nodule” on Thyroid Ultrasonography: Possibility of Follicular Carcinoma Transformed from Benign Thyroid Tumor

PubMed Central

Kobayashi, Kaoru; Ota, Hisashi; Hirokawa, Mitsuyoshi; Yabuta, Tomonori; Fukushima, Mitsuhiro; Masuoka, Hiroo; Higashiyama, Takuya; Kihara, Minoru; Ito, Yasuhiro; Miya, Akihiro; Miyauchi, Akira

2017-01-01

Background It is generally considered impossible to differentiate follicular carcinomas from follicular adenomas by means of ultrasonography or cytology before surgery. Therefore, follicular carcinoma is histopathologically diagnosed by verifying capsular and/or vascular invasion after surgery. However, ultrasonography may play an important role in diagnosing follicular carcinoma preoperatively in a small number of cases. Case Description Four cases of follicular carcinoma or follicular neoplasm that transformed from a benign thyroid tumor and demonstrated a “nodule in nodule” appearance on ultrasonography are presented in this report. Characteristic ultrasound features of such patients are: (1) a “nodule in nodule” appearance, (2) a well-defined boundary line between the nodules, and (3) separate distribution of blood signals within each nodule. Conclusion A small number of patients with follicular carcinomas or follicular neoplasms may present with a “nodule in nodule” appearance on ultrasonography. It was suggested a long time ago that follicular carcinomas may develop from benign thyroid tumors. The fact that follicular carcinomas appear within benign tumors may be evidence of thyroid tumorigenesis. PMID:28589092

Similarities of prosurvival signals in Bcl-2-positive and Bcl-2-negative follicular lymphomas identified by reverse phase protein microarray.

PubMed

Zha, Hongbin; Raffeld, Mark; Charboneau, Lu; Pittaluga, Stefania; Kwak, Larry W; Petricoin, Emanuel; Liotta, Lance A; Jaffe, Elaine S

2004-02-01

Overexpression of Bcl-2 protein has been known to play a role in the pathogenesis of follicular lymphoma (FL). However, 10-15% of FLs are negative for Bcl-2 by immunohistochemistry, raising the possibility that another gene product(s) may provide prosurvival signal(s). We used reverse phase protein microarray to analyze lysates of follicle center cells isolated by laser capture microdissection from: Bcl-2+ FL, Bcl-2- FL and reactive follicular hyperplasia (FH) (nine cases each group). TUNEL assay confirmed similar and reduced levels of apoptosis in Bcl-2+ FL and Bcl-2- FL, indicating the likelihood of Bcl-2-independent inhibition of apoptosis. Arrays were quantitatively analyzed with antibodies to proteins involved in the apoptotic pathway. As expected, Bcl-2 levels were up to eight-fold higher in Bcl-2+ FL than in FH and Bcl-2- FL. However, there was no difference in levels of Mcl-1 and survivin among these three groups. Bcl-X(L) showed a trend for increased expression in Bcl-2- FL as compared with Bcl-2+ FL, although the differences did not reach statistical significance (P>0.1). The increase in Bcl-X(L) may provide an alternative antiapoptotic signal in FL negative for Bcl-2 protein. Interestingly, Bax expression was higher in FL (Bcl-2+ or -) than in FH (P=0.001). Notably, phospho-Akt (Ser-473) was increased in FL (Bcl-2+ or -) (P<0.03) with increased phospho-Bad (Ser-136), as compared with levels in FH. The activation of the Akt/Bad pathway provides further evidence of prosurvival signals in FL, independent of Bcl-2 alone. These data suggest that nodal FL represents a single disease with a final common biochemical pathway.

Protein concentration in pre-ovulatory follicular fluid related to ovarian stimulation.

PubMed

Suchanek, E; Mujkic-Klaric, A; Grizelj, V; Simunic, V; Kopjar, B

1990-05-01

Sixty follicular fluids obtained from 26 women with either clomiphene citrate and human menopausal gonadotropins (hMG) or hMG-induced ovulation were analyzed for the contents of total proteins, fibrinogen, plasminogen, antithrombin III, ceruloplasmin, alpha-2 macroglobulin, alpha-1 antitrypsin and immunoglobulins (IgG, IgA, IgM). Concentrations of these proteins was correlated to the type of ovarian follicle growth induction. Follicular fluids from patients stimulated with clomiphene citrate-hMG contained significantly higher concentrations of ceruloplasmin than those treated with hMG alone. No significant differences in the concentrations of other proteins were noted between the two types of ovarian induction. A multivariate data analysis resulted in three Varimax factors (VRX I) suggesting that proteins with antiprotease activity in the follicular fluid may play a role in human follicle maturation. Follicular fluid Ig may reflect the degree of follicular wall permeability under hMG treatment. Accordingly, it may be assumed that a combination of different proteins described by VRX factors could be used for evaluation of ovarian stimulation.

Interconnected subsets of memory follicular helper T cells have different effector functions.

PubMed

Asrir, Assia; Aloulou, Meryem; Gador, Mylène; Pérals, Corine; Fazilleau, Nicolas

2017-10-10

Follicular helper T cells regulate high-affinity antibody production. Memory follicular helper T cells can be local in draining lymphoid organs and circulate in the blood, but the underlying mechanisms of this subdivision are unresolved. Here we show that both memory follicular helper T subsets sustain B-cell responses after reactivation. Local cells promote more plasma cell differentiation, whereas circulating cells promote more secondary germinal centers. In parallel, local memory B cells are homogeneous and programmed to become plasma cells, whereas circulating memory B cells are able to rediversify. Local memory follicular helper T cells have higher affinity T-cell receptors, which correlates with expression of peptide MHC-II at the surface of local memory B cells only. Blocking T-cell receptor-peptide MHC-II interactions induces the release of local memory follicular helper T cells in the circulating compartment. Our studies show that memory follicular helper T localization is highly intertwined with memory B cells, a finding that has important implications for vaccine design.Tfh cells can differentiate into memory cells. Here the authors describe distinct functional and phenotypic profiles of these memory Tfh cells dependent on their anatomical localization to the lymphoid organs or to the circulation.

Follicular lymphoma in the palate with clinical appearance similar to salivary gland tumors.

PubMed

Lima, Marina de Deus Moura; Artico, Gabriela; Soares, Fernando Augusto; Martins, Marília Trierveiler; Alves, Fabio Abreu

2010-09-01

Intraoral presentation of follicular lymphoma is rare, and only three cases in the palate have been reported to date. The present case report describes an uncommon case of follicular lymphoma affecting the palate. The clinical aspect was similar to salivary gland neoplasm, and an incisional biopsy was important to establish the correct diagnosis and consequently to plan the treatment. Also discussed is the differential diagnosis among follicular lymphoma, mucosa-associated lymphoid tissue lymphoma, and follicular lymphoid hyperplasia with regard to the histopathologic and immunohistochemical features.

Follicular penetration of topically applied caffeine via a shampoo formulation.

PubMed

Otberg, N; Teichmann, A; Rasuljev, U; Sinkgraven, R; Sterry, W; Lademann, J

2007-01-01

Follicular drug delivery is the prerequisite for an effective treatment of androgenetic alopecia or other reasons of premature hair loss. The follicular penetration of caffeine, applied topically in a shampoo formulation for 2 min, was measured with highly sensitive surface ionization in combination with mass spectroscopy, a selective method for the detection of very small quantities of transcutaneously absorbed substances in the blood. An experimental protocol, developed to selectively block the follicular pathway within the test area, was used. Based on this principle, a clear distinction between interfollicular and follicular penetration of topically applied caffeine was feasible. After 2 min, caffeine penetrated via the hair follicles and stratum corneum. It was found that the penetration via hair follicles was faster and higher compared with the interfollicular route and that hair follicles are the only pathway for fast caffeine absorption during the first 20 min after application. Copyright 2007 S. Karger AG, Basel.

Pharmacogenomics in early-phase clinical development

PubMed Central

Burt, Tal; Dhillon, Savita

2015-01-01

Pharmacogenomics (PGx) offers the promise of utilizing genetic fingerprints to predict individual responses to drugs in terms of safety, efficacy and pharmacokinetics. Early-phase clinical trial PGx applications can identify human genome variations that are meaningful to study design, selection of participants, allocation of resources and clinical research ethics. Results can inform later-phase study design and pipeline developmental decisions. Nevertheless, our review of the clinicaltrials.gov database demonstrates that PGx is rarely used by drug developers. Of the total 323 trials that included PGx as an outcome, 80% have been conducted by academic institutions after initial regulatory approval. Barriers for the application of PGx are discussed. We propose a framework for the role of PGx in early-phase drug development and recommend PGx be universally considered in study design, result interpretation and hypothesis generation for later-phase studies, but PGx results from underpowered studies should not be used by themselves to terminate drug-development programs. PMID:23837482

Increase in endogenous estradiol in the progeny of obese rats is associated with precocious puberty and altered follicular development in adulthood.

PubMed

Ambrosetti, Valery; Guerra, Marcelo; Ramírez, Luisa A; Reyes, Aldo; Álvarez, Daniela; Olguín, Sofía; González-Mañan, Daniel; Fernandois, Daniela; Sotomayor-Zárate, Ramón; Cruz, Gonzalo

2016-07-01

Maternal obesity during pregnancy has been related with several pathological states in offspring. However, the impact of maternal obesity on reproductive system on the progeny is beginning to be elucidated. In this work, we characterize the effect of maternal obesity on puberty onset and follicular development in adult offspring in rats. We also propose that alterations in ovarian physiology observed in offspring of obese mothers are due to increased levels of estradiol during early development. Offspring of control dams and offspring of dams exposed to a high-fat diet (HF) were studied at postnatal days (PND) 1, 7, 14, 30, 60, and 120. Body weight and onset of puberty were measured. Counting of ovarian follicles was performed at PND 60 and 120. Serum estradiol, estriol, androstenedione, FSH, LH, and insulin levels were measured by ELISA. Hepatic CYP3A2 expression was determined by Western blot. HF rats had a higher weight than controls at all ages and they also had a precocious puberty. Estradiol levels were increased while CYP3A2 expression was reduced from PND 1 until PND 60 in HF rats compared to controls. Estriol was decreased at PND60 in HF rats. Ovaries from HF rats had a decrease in antral follicles at PND60 and PND120 and an increase in follicular cysts at PND60 and PND120. In this work, we demonstrated that maternal obesity in rats alters follicular development and induces follicular cysts generation in the adult offspring. We observed that maternal obesity produces an endocrine disruption through increasing endogenous estradiol in early life. A programmed failure in hepatic metabolism of estradiol is probably the cause of its increase.

Cortisol levels during prolonged exercise: the influence of menstrual phase and menstrual status.

PubMed

Kanaley, J A; Boileau, R A; Bahr, J M; Misner, J E; Nelson, R A

1992-05-01

The purpose of this study was to determine the influence of menstrual phase and menstrual status on the cortisol response during 90 minutes of treadmill running at 60% VO2max. Eight eumenhorrheic athletes were tested in the early follicular (EF) (day 3-5), late follicular (LF) (day 13-15) and mid-luteal (ML) (day 22-24) phases. Six amenorrheic athletes were tested on two separate occasions. The resting cortisol levels were similar in each menstrual phase and overall a decreasing pattern of cortisol response to exercise was observed in all menstrual phases (P greater than .05). The amenorrheic athletes had a significantly greater (P less than .01) pattern of cortisol response than was observed in eumenorrheic athletes. The net increment in cortisol levels during exercise were distinctly greater (P less than .01) in amenorrheic than eumenorrheic athletes (amenorrheic: 413.8 +/- 113.1, eumenorrheic: EF: -482.8 +/- 88.3, LF: -311.8 +/- 102.1, ML: -386.3 +/- 146.2 nmol.l-1). In conclusion the cortisol levels are independent of menstrual phase. Also a larger cortisol increment is observed in amenorrheic athletes in response to prolonged submaximal exercise. The elevated cortisol levels in amenorrheics at rest and throughout exercise provides further evidence that disturbances in the hypothalamic-pituitary-adrenal function are associated with exercise-induced amenorrhea, although the site(s) of physiological disturbance have not been identified.

MicroRNAs: New Insight in Modulating Follicular Atresia: A Review.

PubMed

Worku, Tesfaye; Rehman, Zia Ur; Talpur, Hira Sajjad; Bhattarai, Dinesh; Ullah, Farman; Malobi, Ngabu; Kebede, Tesfaye; Yang, Liguo

2017-02-09

Our understanding of the post-transcriptional mechanisms involved in follicular atresia is limited; however, an important development has been made in understanding the biological regulatory networks responsible for mediating follicular atresia. MicroRNAs have come to be seen as a key regulatory actor in determining cell fate in a wide range of tissues in normal and pathological processes. Profiling studies of miRNAs during follicular atresia and development have identified several putative miRNAs enriched in apoptosis signaling pathways. Subsequent in vitro and/or in vivo studies of granulosa cells have elucidated the functional role of some miRNAs along with their molecular pathways. In particular, the regulatory roles of some miRNAs have been consistently observed during studies of follicular cellular apoptosis. Continued work should gradually lead to better understanding of the role of miRNAs in this field. Ultimately, we expect this understanding will have substantial benefits for fertility management at both the in vivo or/and in vitro levels. The stable nature of miRNA holds remarkable promise in clinical use as a diagnostic tool and in reproductive medicine to solve the ever-increasing fertility problem. In this review, we summarize current knowledge of the involvement of miRNAs in follicular atresia, discuss the challenges for further work and pinpoint areas for future research.

MicroRNAs: New Insight in Modulating Follicular Atresia: A Review

PubMed Central

Worku, Tesfaye; Rehman, Zia Ur; Talpur, Hira Sajjad; Bhattarai, Dinesh; Ullah, Farman; Malobi, Ngabu; Kebede, Tesfaye; Yang, Liguo

2017-01-01

Our understanding of the post-transcriptional mechanisms involved in follicular atresia is limited; however, an important development has been made in understanding the biological regulatory networks responsible for mediating follicular atresia. MicroRNAs have come to be seen as a key regulatory actor in determining cell fate in a wide range of tissues in normal and pathological processes. Profiling studies of miRNAs during follicular atresia and development have identified several putative miRNAs enriched in apoptosis signaling pathways. Subsequent in vitro and/or in vivo studies of granulosa cells have elucidated the functional role of some miRNAs along with their molecular pathways. In particular, the regulatory roles of some miRNAs have been consistently observed during studies of follicular cellular apoptosis. Continued work should gradually lead to better understanding of the role of miRNAs in this field. Ultimately, we expect this understanding will have substantial benefits for fertility management at both the in vivo or/and in vitro levels. The stable nature of miRNA holds remarkable promise in clinical use as a diagnostic tool and in reproductive medicine to solve the ever-increasing fertility problem. In this review, we summarize current knowledge of the involvement of miRNAs in follicular atresia, discuss the challenges for further work and pinpoint areas for future research. PMID:28208755

Pegfilgrastim and Rituximab in Treating Patients With Untreated, Relapsed, or Refractory Follicular Lymphoma, Small Lymphocytic Lymphoma, or Marginal Zone Lymphoma

ClinicalTrials.gov

2017-09-08

Contiguous Stage II Grade 1 Follicular Lymphoma; Contiguous Stage II Grade 2 Follicular Lymphoma; Contiguous Stage II Grade 3 Follicular Lymphoma; Contiguous Stage II Marginal Zone Lymphoma; Contiguous Stage II Small Lymphocytic Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Grade 1 Follicular Lymphoma; Noncontiguous Stage II Grade 2 Follicular Lymphoma; Noncontiguous Stage II Grade 3 Follicular Lymphoma; Noncontiguous Stage II Marginal Zone Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Splenic Marginal Zone Lymphoma; Stage I Grade 1 Follicular Lymphoma; Stage I Grade 2 Follicular Lymphoma; Stage I Grade 3 Follicular Lymphoma; Stage I Marginal Zone Lymphoma; Stage I Small Lymphocytic Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Small Lymphocytic Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Small Lymphocytic Lymphoma

Follicular Dowling Degos disease: a rare variant of an evolving dermatosis.

PubMed

Singh, Saurabh; Khandpur, Sujay; Verma, Parul; Singh, Manoj

2013-01-01

Dowling Degos disease is a rare, reticulate pigmentary disorder with variable phenotypic expression that manifests as hyperpigmented macules and reticulate pigmentary anomaly of the flexures. Many variants of this condition and its overlap with other reticulate pigmentary disorders have been reported in the literature. We present here two cases of DDD with follicular localization, both clinically and histologically. It was associated with ichthyosis vulgaris in one case. Follicular DDD is an uncommon variant of this evolving dermatosis. Our report supports the possible role for disordered follicular keratinisation in its pathogenesis.

[Recovery and light microscopic evaluation of follicular oocytes of swine and relationship between the degeneration rate of oocytes and the estrus phase].

PubMed

Schnurrbusch, U; Schmette, C; Elze, K

1990-10-01

Cumulus-oocyte complexes were recovered from 25 gilts by aspiration of follicular fluid or cutting of follicles from all Graafian follicles of greater than or equal to 3 mm in diameter during diestrus, proestrus or estrus. In 5 gilts the oocytes were collected post ovulation by flushing of oviducts. The recovery rate of follicular oocytes differed between 75.5% during the late diestrus (days 13-17) and 43.5% during the proestrus (days 18-21). During the proestrus and on day 1 of the estrus the recovery of oocytes was more difficult as a result of the higher viscosity of follicular fluid and the mucification of cumulus-oocyte complexes. The degeneration rate of oocytes was high during the diestrus with a peak at the time of regression of corpora lutea. From diestrus to the estrus the degeneration rate decreased. Following degeneration rates were found in the oocytes during the cycle: days 7-12: 38.8%, days 13-17: 50.0%, days 18-21: 29.6%, day 1 of the estrus: 10.8%, day 2 of the estrus ante ovulation: 11.8%, day 2 of the estrus post ovulation: 6.2%. Signs of degeneration were: Loss of cumulus cells (during diestrus and proestrus), damaged zona pellucida, enlargement of perivitelline space, deformation of oocyte, alteration of structure of the ooplasm, diameter of vitellus less than 100 microns. It was concluded that the selection of dominant follicles takes place in pigs during a long time of the cycle, especially during the diestrus. There were not any indications of a 2-wave hypothesis of follicular growth during the cycle in pig.

Follicular flushing during oocyte retrieval: a systematic review and meta-analysis.

PubMed

Roque, Matheus; Sampaio, Marcos; Geber, Selmo

2012-11-01

The purpose of this systematic review and meta-analysis was to examine the literature and identify randomized controlled trials (RCTs), in order to answer if performing follicular flushing during the oocyte retrieval may improve the assisted reproductive technologies (ART) outcomes. An exhaustive electronic search was performed using MEDLINE and EMBASE databases. Only RCTs comparing follicular flushing to aspiration only during ART, were included. We included 5 trials, with a total of 482 patients randomized, with median ages ranging from 30.5 to 37.1. The data analyses did not show significant differences regarding live birth rate, clinical pregnancies rates, and the number of oocytes retrieved. The duration of oocyte retrieval was significantly increased in the follicular flushing group. The results from this systematic review and meta-analysis suggest that there is no advantage to use of routine follicular flushing during OR in an unselected group of patients.

Hyperfunctioning Solid/Trabecular Follicular Carcinoma of the Thyroid Gland

PubMed Central

Giovanella, Luca; Fasolini, Fabrizio; Suriano, Sergio; Mazzucchelli, Luca

2010-01-01

A 68-year-old woman with solid/trabecular follicular thyroid carcinoma inside of an autonomously functioning thyroid nodule is described in this paper. The patient was referred to our clinic for swelling of the neck and an increased pulse rate. Ultrasonography showed a slightly hypoechoic nodule in the right lobe of the thyroid. Despite suppressed TSH levels, the 99mTc-pertechnetate scan showed a hot area corresponding to the nodule with a suppressed uptake in the remaining thyroid tissue. Histopathological examination of the nodule revealed a solid/trabecular follicular thyroid carcinoma. To the best of our knowledge, this is the first case of hyperfunctioning follicular solid/trabecular carcinoma reported in the literature. Even if a hyperfunctioning thyroid carcinoma is an extremely rare malignancy, careful management is recommended so that a malignancy will not be overlooked in the hot thyroid nodules. PMID:20847957

Hyperfunctioning solid/trabecular follicular carcinoma of the thyroid gland.

PubMed

Giovanella, Luca; Fasolini, Fabrizio; Suriano, Sergio; Mazzucchelli, Luca

2010-01-01

A 68-year-old woman with solid/trabecular follicular thyroid carcinoma inside of an autonomously functioning thyroid nodule is described in this paper. The patient was referred to our clinic for swelling of the neck and an increased pulse rate. Ultrasonography showed a slightly hypoechoic nodule in the right lobe of the thyroid. Despite suppressed TSH levels, the (99m)Tc-pertechnetate scan showed a hot area corresponding to the nodule with a suppressed uptake in the remaining thyroid tissue. Histopathological examination of the nodule revealed a solid/trabecular follicular thyroid carcinoma. To the best of our knowledge, this is the first case of hyperfunctioning follicular solid/trabecular carcinoma reported in the literature. Even if a hyperfunctioning thyroid carcinoma is an extremely rare malignancy, careful management is recommended so that a malignancy will not be overlooked in the hot thyroid nodules.

MicroRNA Mediating Networks in Granulosa Cells Associated with Ovarian Follicular Development.

PubMed

Zhang, Baoyun; Chen, Long; Feng, Guangde; Xiang, Wei; Zhang, Ke; Chu, Mingxing; Wang, Pingqing

2017-01-01

Ovaries, which provide a place for follicular development and oocyte maturation, are important organs in female mammals. Follicular development is complicated physiological progress mediated by various regulatory factors including microRNAs (miRNAs). To demonstrate the role of miRNAs in follicular development, this study analyzed the expression patterns of miRNAs in granulosa cells through investigating three previous datasets generated by Illumina miRNA deep sequencing. Furthermore, via bioinformatic analyses, we dissected the associated functional networks of the observed significant miRNAs, in terms of interacting with signal pathways and transcription factors. During the growth and selection of dominant follicles, 15 dysregulated miRNAs and 139 associated pathways were screened out. In comparison of different styles of follicles, 7 commonly abundant miRNAs and 195 pathways, as well as 10 differentially expressed miRNAs and 117 pathways in dominant follicles in comparison with subordinate follicles, were collected. Furthermore, SMAD2 was identified as a hub factor in regulating follicular development. The regulation of miR-26a/b on smad2 messenger RNA has been further testified by real time PCR. In conclusion, we established functional networks which play critical roles in follicular development including pivotal miRNAs, pathways, and transcription factors, which contributed to the further investigation about miRNAs associated with mammalian follicular development.

Reactive oxygen species level in follicular fluid--embryo quality marker in IVF?

PubMed

Das, S; Chattopadhyay, R; Ghosh, S; Ghosh, S; Goswami, S K; Chakravarty, B N; Chaudhury, K

2006-09-01

The impact of oxidative stress in female reproduction is not clear. Contradictory reports on the effect of various oxidative stress markers on follicular fluid, oocytes and embryo quality and fertilization potential exist. The objectives of this study were to examine reactive oxygen species (ROS) levels in follicular fluid of women undergoing IVF and to relate these levels to embryo formation and quality. A total of 208 follicular fluid samples were obtained from 78 women undergoing controlled ovarian stimulation and analysed for ROS and lipid peroxidation (LPO). These samples were divided into groups I and II which represented follicular fluid containing grade III and grade II oocytes, respectively. These groups were further subdivided into groups IA, IB, IIA and IIB according to embryo quality. Subgroups IA and IIA consisted of follicular fluid samples corresponding to grade I/II embryo formation. Subgroups IB and IIB represented fertilization failure/pro-nucleolus (PN) arrest/grade III embryos. No significant correlation was observed in ROS levels on comparing groups I and II (P > 0.05). However, ROS levels were observed to be significantly different on comparing groups IA and IB (P < or = 0.01) and groups IIA and IIB (P < or = 0.05). LPO levels further supported our results. ROS levels in follicular fluid appear to play a significant role in embryo formation and quality.

Uterine blood flow responses to ICI 182 780 in ovariectomized oestradiol-17beta-treated, intact follicular and pregnant sheep.

PubMed

Magness, Ronald R; Phernetton, Terrance M; Gibson, Tiffini C; Chen, Dong-Bao

2005-05-15

Oestrogen dramatically increases uterine blood flow (UBF) in ovariectomized (Ovx) ewes. Both the follicular phase and pregnancy are normal physiological states with elevated levels of circulating oestrogen. ICI 182 780 is a pure steroidal oestrogen receptor (ER) antagonist that blocks oestrogenic actions in oestrogen-responsive tissue. We hypothesized that an ER-mediated mechanism is responsible for in vivo rises in UBF in physiological states of high oestrogen. The purpose of the study was to examine the effect of an ER antagonist on exogenous and endogenous oestradiol-17beta (E2beta)-mediated elevations in UBF. Sheep were surgically instrumented with bilateral uterine artery blood flow transducers, and uterine and femoral artery catheters. Ovx animals (n = 8) were infused with vehicle (35% ethanol) or ICI 182 780 (0.1-3.0 microg min(-1)) into one uterine artery for 10 min before and 50 min after E2beta was given (1 microg kg(-1) I.V. bolus) and UBF was recorded for an additional hour. Intact, cycling sheep were synchronized to the follicular phase using progesterone, prostaglandin F2alpha(PGF2alpha) and pregnant mare serum gonadotrophin (PMSG). When peri-ovulatory rises in UBF reached near peak levels, ICI 182 780 (1 or 2 microg (ml uterine blood flow)-1) was infused unilaterally (n = 4 sheep). Ewes in the last stages of pregnancy (late pregnant ewes) were also given ICI 182 780 (0.23-2.0 microg (ml uterine blood flow)-1; 60 min infusion) into one uterine artery (n = 8 sheep). In Ovx sheep, local infusion of ICI 182 780 did not alter systemic cardiovascular parameters, such as mean arterial blood pressure or heart rate; however, it maximally decreased ipsilateral, but not contralateral, UBF vasodilatory responses to exogenous E2beta by approximately 55-60% (P < 0.01). In two models of elevated endogenous E2beta, local ICI 182 780 infusion inhibited the elevated UBF seen in follicular phase and late pregnant ewes in a time-dependent manner by approximately 60% and

Keratosis Pilaris Revisited: Is It More Than Just a Follicular Keratosis?

PubMed Central

Thomas, Mary; Khopkar, Uday Sharadchandra

2012-01-01

Background: Keratosis pilaris (KP) is characterized by keratinous plugs in the follicular orifices and varying degrees of perifollicular erythema. The most accepted theory of its pathogenesis proposes defective keratinization of the follicular epithelium resulting in a keratotic infundibular plug. We decided to test this hypothesis by doing dermoscopy of patients diagnosed clinically as keratosis pilaris. Materials and Methods: Patients with a clinical diagnosis of KP seen between September 2011 and December 2011 were included in the study. A clinical history was obtained and examination and dermoscopic evaluation were performed on the lesions of KP. Results: The age of the patients ranged from 6-38 years. Sixteen patients had history of atopy. Nine had concomitant ichthyosis vulgaris. All the 25 patients were found to have coiled hair shafts within the affected follicular infundibula. The hair shafts were extracted with the help of a sterile needle and were found to retain their coiled nature. Perifollicular erythema was seen in 11 patients; perifollicular scaling in 9. Conclusion: Based on our observations and previously documented histological data of KP, we infer that KP may not be a disorder of keratinization, but caused by the circular hair shaft which ruptures the follicular epithelium leading to inflammation and abnormal follicular keratinization. PMID:23766609

Effect of calcium soaps of fatty acids and administration of somatotropin on milk production, preovulatory follicular development, and plasma and follicular fluid lipid composition in high yielding dairy cows.

PubMed

Moallem, U; Folman, Y; Bor, A; Arav, A; Sklan, D

1999-11-01

The effect of fat and bovine somatotropin (bST) on preovulatory follicular hormones and lipids was evaluated by feeding cows for 150 d from parturition a control diet, a control diet plus 0.55 kg/d of calcium soaps of fatty acids, or a control diet with 500 mg of bST injected every 14 d. Fourteen days after a synchronized or natural estrus, cows were injected with a PGF2 alpha analogue; 48 h later, follicular fluid from all ovarian follicles > 8 mm was aspirated. Cows fed fat or injected with bST produced more milk and milk solids than did control cows, and cows on the bST treatment lost more body condition after calving than did cows on the other treatments. Both treatments changed the proportion of estradiol-active follicles (> 400 ng of estradiol/ml of follicular fluid) and the correlation between follicular fluid estradiol concentration and the total number large follicles per cow. In follicles aspirated between 60 and 90 DIM the percentage of estradiol-active follicles was 67, 40, and 0 for cows on the control, calcium soaps of fatty acids, and bST treatments, respectively. After 90 DIM, no differences existed between treatments in the percentage of estradiol-active follicles. Estradiol concentration in follicular fluid was correlated with DIM at follicle aspiration (r = 0.51). The proportion of oleic acid in free fatty acids in plasma at 50 DIM was lower in control cows and was lower in follicular fluid of estradiol-active follicles. Both calcium soaps of fatty acids and bST had a considerable effect on follicular development and activity and the composition of fatty acids in follicles.

Autologous transplantation versus allogeneic transplantation in patients with follicular lymphoma experiencing early treatment failure.

PubMed

Smith, Sonali M; Godfrey, James; Ahn, Kwang Woo; DiGilio, Alyssa; Ahmed, Sairah; Agrawal, Vaibhav; Bachanova, Veronika; Bacher, Ulrike; Bashey, Asad; Bolaños-Meade, Javier; Cairo, Mitchell; Chen, Andy; Chhabra, Saurabh; Copelan, Edward; Dahi, Parastoo B; Aljurf, Mahmoud; Farooq, Umar; Ganguly, Siddhartha; Hertzberg, Mark; Holmberg, Leona; Inwards, David; Kanate, Abraham S; Karmali, Reem; Kenkre, Vaishalee P; Kharfan-Dabaja, Mohamed A; Klein, Andreas; Lazarus, Hillard M; Mei, Matthew; Mussetti, Alberto; Nishihori, Taiga; Ramakrishnan Geethakumari, Praveen; Saad, Ayman; Savani, Bipin N; Schouten, Harry C; Shah, Nirav; Urbano-Ispizua, Alvaro; Vij, Ravi; Vose, Julie; Sureda, Anna; Hamadani, Mehdi

2018-06-15

Early treatment failure (ETF) in follicular lymphoma (FL), defined as relapse or progression within 2 years of frontline chemoimmunotherapy, is a newly recognized marker of poor survival and identifies a high-risk group of patients with an expected 5-year overall survival (OS) rate of approximately 50%. Transplantation is an established option for relapsed FL, but its efficacy in this specific ETF FL population has not been previously evaluated. This study compared autologous hematopoietic stem cell transplantation (auto-HCT) with either matched sibling donor (MSD) or matched unrelated donor (MUD) allogeneic hematopoietic cell transplantation (allo-HCT) as the first transplantation approach for patients with ETF FL (age ≥ 18 years) undergoing auto-HCT or allo-HCT between 2002 and 2014. The primary endpoint was OS. The secondary endpoints were progression-free survival, relapse, and nonrelapse mortality (NRM). Four hundred forty FL patients had ETF (auto-HCT, 240; MSD hematopoietic stem cell transplantation [HCT], 105; and MUD HCT, 95). With a median follow-up of 69 to 73 months, the adjusted probability of 5-year OS was significantly higher after auto-HCT (70%) or MSD HCT (73%) versus MUD HCT (49%; P = .0008). The 5-year adjusted probability of NRM was significantly lower for auto-HCT (5%) versus MSD (17%) or MUD HCT (33%; P < .0001). The 5-year adjusted probability of disease relapse was lower with MSD (31%) or MUD HCT (23%) versus auto-HCT (58%; P < .0001). Patients with high-risk FL, as defined by ETF, undergoing auto-HCT for FL have low NRM and a promising 5-year OS rate (70%). MSD HCT has lower relapse rates than auto-HCT but similar OS. Cancer 2018;124:2541-51. © 2018 American Cancer Society. © 2018 American Cancer Society.

Regenerative hair waves in aging mice and extra-follicular modulators follistatin, dkk1, and sfrp4.

PubMed

Chen, Chih-Chiang; Murray, Philip J; Jiang, Ting Xin; Plikus, Maksim V; Chang, Yun-Ting; Lee, Oscar K; Widelitz, Randall B; Chuong, Cheng-Ming

2014-08-01

Hair cycling is modulated by factors both intrinsic and extrinsic to hair follicles. Cycling defects lead to conditions such as aging-associated alopecia. Recently, we demonstrated that mouse skin exhibits regenerative hair waves, reflecting a coordinated regenerative behavior in follicle populations. Here, we use this model to explore the regenerative behavior of aging mouse skin. Old mice (>18 months) tracked over several months show that with progressing age, hair waves slow down, wave propagation becomes restricted, and hair cycle domains fragment into smaller domains. Transplanting aged donor mouse skin to a young host can restore donor cycling within a 3 mm range of the interface, suggesting that changes are due to extracellular factors. Therefore, hair stem cells in aged skin can be reactivated. Molecular studies show that extra-follicular modulators Bmp2, Dkk1, and Sfrp4 increase in early anagen. Further, we identify follistatin as an extra-follicular modulator, which is highly expressed in late telogen and early anagen. Indeed, follistatin induces hair wave propagation and its level decreases in aging mice. We present an excitable medium model to simulate the cycling behavior in aging mice and illustrate how the interorgan macroenvironment can regulate the aging process by integrating both "activator" and "inhibitor" signals.

Luteal phase clomiphene citrate for ovulation induction in women with polycystic ovary syndrome: a systematic review and meta-analysis.

PubMed

Ding, Nan; Chang, Jianbo; Jian, Qiliang; Liang, Xuefei; Liang, Zhongzhen; Wang, Fang

2016-11-01

To assess the efficacy of late luteal phase clomiphene citrate (CC) administration relative to early follicular phase CC for ovulation induction for polycystic ovary syndrome (PCOS). Review. A complete electronic databases including PubMed, Embase, The Cochrane Library, Web of Science, and CBM were searched for relevant randomized controlled trials (RCTs). The search was not restricted by language and publication time. Two reviewers selected trials and assessed trial quality by the Cochrane Handbook 5.1.0 independently. Four eligible RCT studies involving 708 women (934 cycles) were included. The results of the Meta-analysis: Late luteal phase group was associated with a number of higher total follicles (MD 1.82; 95% CI 0.86-2.78, p < 0.00001) and significant higher endometrial thickness on the day of HCG (MD 0.88; 95% CI 0.78-0.99, p < 0.00001) compared with early follicular group. There were no significant differences in the rate of pregnancy (RR 1.29; 95% CI 0.83-2.01, p = 0.26), ovulation rate (RR 0.99; 95% CI 0.86-1.14, p = 0.87), and abortion rate (RR 1.12; 95% CI 0.38 to 3.29, p = 0.84) between the two groups. It appeared that late luteal phase CC for ovulation induction might be an effective method for ovulation induction in women with PCOS compared to conventional CC administration. Further intensive randomized-controlled studies should be warranted to define the efficacy of CC used in late luteal phase.

A phase 1, multicentre, open-label study to evaluate ovarian follicular activity and hormone levels with an extended-regimen combined oral contraceptive with low-dose ethinyl estradiol supplementation.

PubMed

Kroll, Robin; Seidman, Larry; Ricciotti, Nancy; Howard, Brandon; Weiss, Herman

2015-01-01

To evaluate the effect on ovarian follicular activity of the 91-day extended-regimen combined oral contraceptive (COC), consisting of 84 days of levonorgestrel (LNG)/ethinylestradiol (EE) 150 μg/30 μg tablets plus seven days of EE 10 μg tablets in place of placebo. This was a phase 1, open-label study. Ovarian follicular activity was classified via the Hoogland and Skouby method. Safety and tolerability as well as return to ovulation were assessed. Of the 35 subjects included in the efficacy analysis, luteinized, unruptured follicles, or ovulation were detected in 0 of 35 cycles during the first 28-day interval; 1 of 35 cycles (2.9%) in the second 28-day interval; and 2 of 35 cycles (5.7%) in the final 35-day interval. The ovarian activity rate over the entire 91-day treatment period was 2.9%. There was a low incidence of treatment-emergent adverse events. Ovulation returned in most subjects (77.1%, 27/35) within 32 days following the last dose of COC. The 91-day extended-regimen COC with low-dose EE supplementation was found to be effective in suppressing ovarian activity and inhibiting ovulation and was well tolerated. Return to ovulation was rapid, occurring within approximately one month after discontinuation of COC.

The effect of follicular wave on fertility characteristics in beef cattle

USDA-ARS?s Scientific Manuscript database

Adequate fertility of beef cattle in the US is a major economic concern. The use of luminogenic substrates to ascertain steroid metabolism in beef females bred to the dominant follicle of the first follicular wave versus the dominant follicle of the second follicular wave in this study further provi...

Effect of menstrual cycle phase on corticolimbic brain activation by visual food cues.

PubMed

Frank, Tamar C; Kim, Ginah L; Krzemien, Alicja; Van Vugt, Dean A

2010-12-02

Food intake is decreased during the late follicular phase and increased in the luteal phase of the menstrual cycle. While a changing ovarian steroid milieu is believed to be responsible for this behavior, the specific mechanisms involved are poorly understood. Brain activity in response to visual food stimuli was compared during the estrogen dominant peri-ovulatory phase and the progesterone dominant luteal phase of the menstrual cycle. Twelve women underwent functional magnetic resonance imaging during the peri-ovulatory and luteal phases of the menstrual cycle in a counterbalanced fashion. Whole brain T2* images were collected while subjects viewed pictures of high calorie (HC) foods, low calorie (LC) foods, and control (C) pictures presented in a block design. Blood oxygen level dependent (BOLD) signal in the late follicular phase and luteal phase was determined for the contrasts HC-C, LC-C, HC-LC, and LC-HC. Both HC and LC stimuli activated numerous corticolimbic brain regions in the follicular phase, whereas only HC stimuli were effective in the luteal phase. Activation of the nucleus accumbens (NAc), amygdala, and hippocampus in response to the HC-C contrast and the hippocampus in response to the LC-C contrast was significantly increased in the late follicular phase compared to the luteal phase. Activation of the orbitofrontal cortex and mid cingulum in response to the HC-LC contrast was greater during the luteal phase. These results demonstrate for the first time that brain responses to visual food cues are influenced by menstrual cycle phase. We postulate that ovarian steroid modulation of the corticolimbic brain contributes to changes in ingestive behavior during the menstrual cycle. Copyright © 2010 Elsevier B.V. All rights reserved.

Effect of menstrual cycle phase on the ventilatory response to rising body temperature during exercise.

PubMed

Hayashi, Keiji; Kawashima, Takayo; Suzuki, Yuichi

2012-07-01

To examine the effect of menstrual cycle on the ventilatory sensitivity to rising body temperature, ten healthy women exercised for ~60 min on a cycle ergometer at 50% of peak oxygen uptake during the follicular and luteal phases of their cycle. Esophageal temperature, mean skin temperature, mean body temperature, minute ventilation, and tidal volume were all significantly higher at baseline and during exercise in the luteal phase than the follicular phase. On the other hand, end-tidal partial pressure of carbon dioxide was significantly lower during exercise in the luteal phase than the follicular phase. Plotting ventilatory parameters against esophageal temperature revealed there to be no significant menstrual cycle-related differences in the slopes or intercepts of the regression lines, although minute ventilation and tidal volume did significantly differ during exercise with mild hyperthermia. To evaluate the cutaneous vasodilatory response, relative laser-Doppler flowmetry values were plotted against mean body temperature, which revealed that the mean body temperature threshold for cutaneous vasodilation was significantly higher in the luteal phase than the follicular phase, but there were no significant differences in the sensitivity or peak values. These results suggest that the menstrual cycle phase influences the cutaneous vasodilatory response during exercise and the ventilatory response at rest and during exercise with mild hyperthermia, but it does not influence ventilatory responses during exercise with moderate hyperthermia.

Follicular lymphoma: 2014 update on diagnosis and management.

PubMed

Freedman, Arnold

2014-04-01

Follicular lymphoma is generally an indolent B cell lymphoproliferative disorder of transformed follicular center B cells. Follicular lymphoma (FL) is characterized by diffuse lymphoadenopathy, bone marrow involvement, splenomegaly, and less commonly other extranodal sites of involvement. In general cytopenias can occur but constitutional symptoms of fever, nightsweats, and weight loss are uncommon. Diagnosis is based on histology of preferably a biopsy of a lymph node. Immunohistochemical staining is positive in virtually all cases for cell surface CD19, CD20, CD10, and monoclonal immunoglobulin, as well as cytoplasmic expression of bcl-2 protein. The overwhelming majority of cases have the characteristic t(14;18) translocation involving the IgH/bcl-2 genes. The Follicular Lymphoma International Prognostic Index prognostic model for FL uses five independent predictors of inferior survival: age >60 years, hemoglobin <12 g/dL, serum LDH > normal, Ann Arbor stage III/IV, number of involved nodal areas > 4. The presence of 0, 1, 2, and  ≥ 3 adverse factors defines low, intermediate, and high-risk disease. With the use of more modern therapies, outcomes have improved. Observation continues to be adequate for asymptomatic patients with low bulk disease and no cytopenias. For patients needing therapy, most patients are treated with chemotherapy plus rituximab, which has improved response rates, duration of response and overall survival. Randomized studies have shown additional benefit for maintenance rituximab both following chemotherapy-rituximab and single agent rituximab. Experimental therapies as well as stem cell transplantation (SCT) are considered for recurrent disease. Copyright © 2014 Wiley Periodicals, Inc.

Comparative Proteomic Analysis of Yak Follicular Fluid during Estrus

PubMed Central

Guo, Xian; Pei, Jie; Ding, Xuezhi; Chu, Min; Bao, Pengjia; Wu, Xiaoyun; Liang, Chunnian; Yan, Ping

2016-01-01

The breeding of yaks is highly seasonal, there are many crucial proteins involved in the reproduction control program, especially in follicular development. In order to isolate differential proteins between mature and immature follicular fluid (FF) of yak, the FF from yak follicles with different sizes were sampled respectively, and two-dimensional gel electrophoresis (2-DE) of the proteins was carried out. After silver staining, the Image Master 2D platinum software was used for protein analysis and matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS) was performed for differential protein identification. The expression level of transferrin and enolase superfamily member 1 (ENOSF1) was determined by Western blotting for verification analysis. The results showed that 2-DE obtained an electrophoresis map of proteins from mature and immature yak FF with high resolution and repeatability. A comparison of protein profiles identified 12 differently expressed proteins, out of which 10 of them were upregulated while 2 were downregulated. Western blotting showed that the expression of transferrin and ENOSF1 was enhanced with follicular development. Both the obtained protein profiles and the differently expressed proteins identified in this study provided experimental data related to follicular development during yak breeding seasons. This study also laid the foundation for understanding the microenvironment during oocyte development. PMID:26954118

[DIAGNOSTIC AND TREATMENT STRATEGY IN FOLLICULAR TUMOR OF THYROID GLAND].

PubMed

Mikhaĭlova, M V; Zubarovskiĭ, I N; Osipenko, S K

2015-01-01

The article is based on the treatment results of 44 patients with follicular tunor of thyroid gland. A staged morphological assessment of thyroid nodes was performed for all patients: in case of preoperative fine-needle biopsy, urgent intraoperative study and according to results of final histological research. The urgent histological study of surgical material was conducted for 44 patients with diagnosis "follicular tumor" according to fine-needle biopsy. The data of final histological study were matched with findings of intraoperative research. A micro-follicular adenoma was detected in 22 patients (50%) and 6 (13,6%) patients had this diagnosis combined with autoimmune thyroiditis. The general part of patients didn't changed in final study, but the rate of diagnosis "micro-follicular adenoma against the background of autoimmune thyroiditis" increased. Papillary carcinoma was revealed in 5 (11,4%) patients and follicular cancer had 4 (9,1%) patients detected in intraoperative study and 3 (6,8%) more patients according to data of final research. The histopathologic feature of colloid goiter was observed in 7 (15,9%) cases and a part of such patients reduced to 6,8% during final study. One of the patients (2,3%) had final diagnosis "oncocytoma". In case of thyroid nodules detection the needle biopsy should be carried out regardless to the size of nodule. The authors recommended performing the surgery with the urgent histological study in case of undetermined histological report. The following surgical strategy was specified by the results of the urgent histological report.

Effects of corticotropin-releasing hormone and its antagonist on the gene expression of gonadotrophin-releasing hormone (GnRH) and GnRH receptor in the hypothalamus and anterior pituitary gland of follicular phase ewes.

PubMed

Ciechanowska, Magdalena; Łapot, Magdalena; Malewski, Tadeusz; Mateusiak, Krystyna; Misztal, Tomasz; Przekop, Franciszek

2011-01-01

There is no information in the literature regarding the effect of corticotropin-releasing hormone (CRH) on genes encoding gonadotrophin-releasing hormone (GnRH) and the GnRH receptor (GnRHR) in the hypothalamus or on GnRHR gene expression in the pituitary gland in vivo. Thus, the aim of the present study was to investigate, in follicular phase ewes, the effects of prolonged, intermittent infusion of small doses of CRH or its antagonist (α-helical CRH 9-41; CRH-A) into the third cerebral ventricle on GnRH mRNA and GnRHR mRNA levels in the hypothalamo-pituitary unit and on LH secretion. Stimulation or inhibition of CRH receptors significantly decreased or increased GnRH gene expression in the hypothalamus, respectively, and led to different responses in GnRHR gene expression in discrete hypothalamic areas. For example, CRH increased GnRHR gene expression in the preoptic area, but decreased it in the hypothalamus/stalk median eminence and in the anterior pituitary gland. In addition, CRH decreased LH secretion. Blockade of CRH receptors had the opposite effect on GnRHR gene expression. The results suggest that activation of CRH receptors in the hypothalamus of follicular phase ewes can modulate the biosynthesis and release of GnRH through complex changes in the expression of GnRH and GnRHR genes in the hypothalamo-anterior pituitary unit. © CSIRO 2011 Open Access

Ovarian follicular development in the hawksbill turtle (Cheloniidae: Eretmochelys imbricata L.).

PubMed

Pérez-Bermúdez, Emir; Ruiz-Urquiola, Ariel; Lee-González, Idania; Petric, Benjamin; Almaguer-Cuenca, Nilda; Sanz-Ochotorena, Ana; Espinosa-López, Georgina

2012-12-01

Ovarian follicular development is an essential process in the determination of maturation stages associated with size. This association acquires importance when managing populations of threatened species. We histologically processed 11 prepubescent ovaries, four pubescent ovaries, and one breeding adult ovary with vitellogenic follicles using specific staining techniques to identify the follicular stages of Eretmochelys imbricata. Follicular stages were compared with maturation stages [including straight carapace length (SCL)]. The ovary presented several germinal beds and a lacunar system less histochemically and morphologically heterogeneous than that of crocodiles. During previtellogenesis (four stages), the oocyte grows rapidly due to the strong transcriptional activity of lampbrush chromosomes and numerous nucleoli, and the strong metabolism associated with lipid synthesis. The Stage III ooplasm showed a Sudan positive band. This stage was the most frequent in all ovarian sections and it was independent of maximal follicular stage. Stage IV, more frequent in pubescent and adult ovaries, presented a lipid vacuole-rich ooplasm and a broadening of the zona pellucida and the theca. The vitellogenesis begins with the penetration and accumulation of spherical glycoprotein yolk platelets and chemically neutral lipid droplets which are observed to be mixed, but spatially and chemically segregated. Both the yolk platelets and lipid droplets increase in size, density, and proximity to the periphery of the oocyte due to their coalescence. The SCL of the immature females did not determine the maximal follicular stage nor its frequency in the ovaries. Straight carapace length turned out to be an imprecise measure in identifying the presence of follicular stages in females larger than the minimum legal size limit in Cuba. Consequently, for a national conservation program to be successful, it must emphasize the critically endangered status of E. imbricata, as well as the

Altered functional brain asymmetry for mental rotation: effect of estradiol changes across the menstrual cycle.

PubMed

Zhu, Xun; Kelly, Thomas H; Curry, Thomas E; Lal, Chitra; Joseph, Jane E

2015-09-30

Mental rotation is a visuospatial task associated with pronounced sex differences. Performance is also affected by gonadal hormones such as testosterone and estradiol. To better understand hormonal modulation of the neural substrates of mental rotation, the present study examined the influence of estradiol using functional MRI. Ten premenopausal women were tested on a 3D mental rotation task during the early follicular and late follicular phases of the menstrual cycle. Change in estradiol between the two phases was confirmed by hormone assays. Brain activation patterns were similar across the two phases, but the change in estradiol had different associations with the two hemispheres. Better performance in the late follicular than the early follicular phase was associated with a pattern of reduced recruitment of the right hemisphere and increased recruitment of the left hemisphere. The increased recruitment of the left hemisphere was directly associated with greater changes in estradiol. Given that the right hemisphere is the dominant hemisphere in visuospatial processing, our results suggest that estradiol is associated with reduced functional asymmetry, consistent with recent accounts of hormonal modulation of neurocognitive function.

Early Intervention Services for Early-Phase Psychosis - Centre for integrative psychiatry in Psychiatric Hospital "Sveti Ivan", Croatia.

PubMed

Matić, Katarina; Gereš, Natko; Gerlach, Josefina; Prskalo-Čule, Diana; Zadravec Vrbanc, Tihana; Lovretić, Vanja; Librenjak, Dina; Vuk Pisk, Sandra; Ivezić, Ena; Šimunović Filipčić, Ivona; Jeleč, Vjekoslav; Filipčić, Igor

2018-06-01

There is a growing body of evidence suggesting that early and effective management in the critical early years of schizophrenia can improve long-term outcomes. The objective of this study was to evaluate time to relapse of the patients with early-phase psychosis treated in the Centre for integrative psychiatry (CIP). We performed a retrospective cohort study on the sample of 373 early-phase psychosis patients admitted to Psychiatric Hospital "Sveti Ivan", Zagreb Croatia: from January 1, 2015 to December 31, 2017. The primary outcome was time to relapse. Patients who were admitted to group psychotherapeutic program after the end of acute treatment had 70% lower hazard for relapse (HR=0.30; 95% CI 0.16-0.58). Patients who were included first in the psychotherapeutic program and then treated and controlled in the daily hospital had 74% lower hazard for relapse (HR=0.26; 95% CI 0.10-0.67). In early-phase psychosis, integrative early intervention service has relevant beneficial effects compare to treatment as usual. These results justified the implementation of multimodal early intervention services in treatment of patients with early-phase psychosis.

Pembrolizumab and Vorinostat in Treating Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma, Follicular Lymphoma, or Hodgkin Lymphoma

ClinicalTrials.gov

2018-04-23

Grade 3a Follicular Lymphoma; Grade 3b Follicular Lymphoma; Recurrent Classical Hodgkin Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Follicular Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Mediastinal (Thymic) Large B-Cell Cell Lymphoma; Refractory Classical Hodgkin Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Follicular Lymphoma; Refractory Mediastinal (Thymic) Large B-Cell Cell Lymphoma

Advances in the management of follicular lymphoma.

PubMed

Seiler, Till M; Hiddemann, Wolfgang

2012-11-01

Antibody-based therapy has revolutionized treatment strategies in follicular lymphoma. This review focuses on current standards and recent innovations in the management of the disease. Understanding the mechanism of action of antibodies led to the development of next generation CD20 antibodies, antibodies targeting other molecules and bispecific antibodies. With obinutuzumab, a promising next generation of CD20 antibodies has entered phase III of clinical trials. The bispecific T-cell engager blinatumomab combines targeted therapy with immunologic activation of T cells exerting cytotoxic activity on the target cells. Apart from antibodies, small molecules targeting key pathways in lymphoma have shown promising activity in vitro and are currently in clinical development. A wealth of new substances has entered various stages of clinical trials and has yet to show superiority over rituximab-based immunochemotherapy. Intelligent therapeutic regimens containing these drugs have to be developed. Large randomized trials comparing promising treatment options are urgently needed.

Response of thyroid follicular cells to gamma irradiation compared to proton irradiation: II. The role of connexin 32

NASA Technical Reports Server (NTRS)

Green, L. M.; Tran, D. T.; Murray, D. K.; Rightnar, S. S.; Todd, S.; Nelson, G. A.

2002-01-01

The objective of this study was to determine whether connexin 32-type gap junctions contribute to the "contact effect" in follicular thyrocytes and whether the response is influenced by radiation quality. Our previous studies demonstrated that early-passage follicular cultures of Fischer rat thyroid cells express functional connexin 32 gap junctions, with later-passage cultures expressing a truncated nonfunctional form of the protein. This model allowed us to assess the role of connexin 32 in radiation responsiveness without relying solely on chemical manipulation of gap junctions. The survival curves generated after gamma irradiation revealed that early-passage follicular cultures had significantly lower values of alpha (0.04 Gy(-1)) than later-passage cultures (0.11 Gy(-1)) (P < 0.0001, n = 12). As an additional way to determine whether connexin 32 was contributing to the difference in survival, cultures were treated with heptanol, resulting in higher alpha values, with early-passage cultures (0.10 Gy(-1)) nearly equivalent to untreated late-passage cultures (0.11 Gy(-1)) (P > 0.1, n = 9). This strongly suggests that the presence of functional connexin 32-type gap junctions was contributing to radiation resistance in gamma-irradiated thyroid follicles. Survival curves from proton-irradiated cultures had alpha values that were not significantly different whether cells expressed functional connexin 32 (0.10 Gy(-1)), did not express connexin 32 (0.09 Gy(-1)), or were down-regulated (early-passage plus heptanol, 0.09 Gy(-1); late-passage plus heptanol, 0.12 Gy(-1)) (P > 0.1, n = 19). Thus, for proton irradiation, the presence of connexin 32-type gap junctional channels did not influence their radiosensitivity. Collectively, the data support the following conclusions. (1) The lower alpha values from the gamma-ray survival curves of the early-passage cultures suggest greater repair efficiency and/or enhanced resistance to radiation-induced damage, coincident with the

ISOLATION OF CHICKEN FOLLICULAR DENDRITIC CELLS

USDA-ARS?s Scientific Manuscript database

The aim of the present study was to isolate chicken follicular dendritic cells (FDC). A combination of methods involving panning, iodixanol density gradient centrifugation, and magnetic cell separation technology made it possible to obtain functional FDC from the cecal tonsils from chickens, which h...

Metabolomics analysis of follicular fluid in women with ovarian endometriosis undergoing in vitro fertilization.

PubMed

Karaer, Abdullah; Tuncay, Gorkem; Mumcu, Akın; Dogan, Berat

2018-05-28

The purpose of this study was to investigate whether a change in the follicular fluid metabolomics profile due to endometrioma is identifiable. Twelve women with ovarian endometriosis (aged<40 years, with a body mass index [BMI] of <30 kg/m 2 ) and 12 age- and BMI-matched controls (women with infertility purely due to a male factor) underwent ovarian stimulation for intracytoplasmic sperm injection (ICSI). Follicular fluid samples were collected from both of groups at the time of oocyte retrieval for ICSI. Next, nuclear magnetic resonance (NMR) spectroscopy was performed for the collected follicular fluids. The metabolic compositions of the follicular fluids were then compared using univariate and multivariate statistical analyses of NMR data. Univariate and multivariate statistical analyses of NMR data showed that the metabolomic profiles of the follicular fluids obtained from the women with ovarian endometriosis were distinctly different from those obtained from the control group. In comparison with the controls, the follicular fluids of the women with ovarian endometriosis had statistically significant elevated levels of lactate, β-glucose, pyruvate, and valine. We conclude that the levels of lactate, β-glucose, pyruvate, and valine in the follicular fluid of the women with endometrioma were higher than those of the controls. ASRM: American Society for Reproductive Medicine; BMI: body mass index; CPMG: Carr-Purcell-Meiboom-Gill; E 2 : estradiol; ESHRE: European Society of Human Reproduction and Embryology; ERETIC: electronic to access in vivo concentration; FF: follicular fluid; FSH: follicle-stimulating hormone; hCG: human chorionic gonadotropin; HEPES: 2-hydroxyethyl-1-piperazineethanesulfonic acid; ICSI: intracytoplasmic sperm injection; IVF: in vitro fertilization; NMR: nuclear magnetic resonance spectroscopy; PCA: principal component analysis; PCOS: polycystic ovary syndrome; PLS-DA: partial least squares discriminant analysis; ppm: parts per million

The role of menstrual cycle phase and anxiety sensitivity in catastrophic misinterpretation of physical symptoms during a CO(2) challenge.

PubMed

Nillni, Yael I; Rohan, Kelly J; Zvolensky, Michael J

2012-12-01

The current study examined the interactive effects of anxiety sensitivity (AS; fear of anxiety and anxiety-related sensations) and menstrual cycle phase (premenstrual phase vs. follicular phase) on panic-relevant responding (i.e., cognitive and physical panic symptoms, subjective anxiety, and skin conductance level). Women completed a baseline session and underwent a 3-min 10 % CO(2)-enriched air biological challenge paradigm during her premenstrual and follicular menstrual cycle phases. Participants were 55 women with no current or past history of panic disorder recruited from the general community (M (age) = 26.18, SD = 8.9) who completed the biological challenge during both the premenstrual and follicular cycle phases. Results revealed that women higher on AS demonstrated increased cognitive panic symptoms in response to the challenge during the premenstrual phase as compared to the follicular phase, and as compared to women lower on AS assessed in either cycle phase. However, the interaction of AS and menstrual cycle phase did not significantly predict physical panic attack symptoms, subjective ratings of anxiety, or skin conductance level in response to the challenge. Results are discussed in the context of premenstrual exacerbations of cognitive, as opposed to physical, panic attack symptoms for high AS women, and the clinical implications of these findings.

Uterine blood flow responses to ICI 182 780 in ovariectomized oestradiol-17β-treated, intact follicular and pregnant sheep

PubMed Central

Magness, Ronald R; Phernetton, Terrance M; Gibson, Tiffini C; Chen, Dong-bao

2005-01-01

Oestrogen dramatically increases uterine blood flow (UBF) in ovariectomized (Ovx) ewes. Both the follicular phase and pregnancy are normal physiological states with elevated levels of circulating oestrogen. ICI 182 780 is a pure steroidal oestrogen receptor (ER) antagonist that blocks oestrogenic actions in oestrogen-responsive tissue. We hypothesized that an ER-mediated mechanism is responsible for in vivo rises in UBF in physiological states of high oestrogen. The purpose of the study was to examine the effect of an ER antagonist on exogenous and endogenous oestradiol-17β (E2β)-mediated elevations in UBF. Sheep were surgically instrumented with bilateral uterine artery blood flow transducers, and uterine and femoral artery catheters. Ovx animals (n = 8) were infused with vehicle (35% ethanol) or ICI 182 780 (0.1–3.0 μg min−1) into one uterine artery for 10 min before and 50 min after E2β was given (1 μg kg−1i.v. bolus) and UBF was recorded for an additional hour. Intact, cycling sheep were synchronized to the follicular phase using progesterone, prostaglandin F2α(PGF2α) and pregnant mare serum gonadotrophin (PMSG). When peri-ovulatory rises in UBF reached near peak levels, ICI 182 780 (1 or 2 μg (ml uterine blood flow)−1) was infused unilaterally (n = 4 sheep). Ewes in the last stages of pregnancy (late pregnant ewes) were also given ICI 182 780 (0.23–2.0 μg (ml uterine blood flow)−1; 60 min infusion) into one uterine artery (n = 8 sheep). In Ovx sheep, local infusion of ICI 182 780 did not alter systemic cardiovascular parameters, such as mean arterial blood pressure or heart rate; however, it maximally decreased ipsilateral, but not contralateral, UBF vasodilatory responses to exogenous E2β by ∼55–60% (P < 0.01). In two models of elevated endogenous E2β, local ICI 182 780 infusion inhibited the elevated UBF seen in follicular phase and late pregnant ewes in a time-dependent manner by ∼60% and 37%, respectively; ipsilateral �

Increased impulsive choice for saccharin during PCP withdrawal in female monkeys: influence of menstrual cycle phase

PubMed Central

Carroll, Marilyn E.; Kohl, Emily A.; Johnson, Krista M.; LaNasa, Rachel M.

2013-01-01

Background In previous studies with male and female rhesus monkeys withdrawal of access to oral phencyclidine (PCP) self administration reduced responding for food under a high fixed-ratio (FR) schedule more in males than females and with a delay discounting (DD) task with saccharin (SACC) as the reinforcer. Impulsive choice for SACC increased during PCP withdrawal more than females. Objectives The goal of the present study was to examine the effect of PCP (0.25 or 0.5 mg/ml) withdrawal on impulsive choice for SACC in females during the follicular and luteal phases of the menstrual cycle. Materials and methods In Component 1 PCP and water were available from 2 drinking spouts for 1.5 h sessions under concurrent FR 16 schedules. In Component 2 a SACC solution was available for 45 min under a DD schedule. Monkeys had a choice of one immediate SACC delivery (0.6 ml) or 6 delayed SACC deliveries, and the delay was increased by 1 sec after a response on the delayed lever and decreased by 1 sec after a response on the immediate lever. There was then a 10-day water substitution phase, or PCP-withdrawal, that occurred during the mid-folllicular phase (Days 7–11) or the late-luteal (Days 24–28) phase of the menstrual cycle. Access to PCP and concurrent water was then restored, and the PCP withdrawal procedure was repeated over several follicular and luteal menstrual phases. Results PCP deliveries were higher during the luteal vs the follicular phase. Impulsive choice was greater during the luteal (vs follicular) phase during withdrawal of the higher PCP concentration. Conclusions PCP withdrawal was associated with elevated impulsive choice for SACC, especially in the luteal (vs follicular) phase of the menstrual cycle in female monkeys. PMID:23344553

Effects of sex, menstrual cycle phase, and endogenous hormones on cognition in schizophrenia.

PubMed

Rubin, Leah H; Carter, C Sue; Drogos, Lauren L; Pournajafi-Nazarloo, Hossein; Sweeney, John A; Maki, Pauline M

2015-08-01

In women with schizophrenia, cognition has been shown to be enhanced following administration of hormone therapy or oxytocin. We examined how natural hormonal changes across the menstrual cycle influence cognition in women with schizophrenia. We hypothesized that female patients would perform worse on "female-dominant" tasks (verbal memory/fluency) and better on "male-dominant" tasks (visuospatial) during the early follicular phase (low estradiol and progesterone) compared to midluteal phase (high estradiol and progesterone) in relation to estradiol but not progesterone. Fifty-four women (23 with schizophrenia) completed cognitive assessments and provided blood for sex steroid assays and oxytocin at early follicular (days 2-4) and midluteal (days 20-22) phases. Men were included to verify the expected pattern of sex differences on cognitive tests. Expected sex differences were observed on "female-dominant" and "male-dominant" tasks (p<0.001), but the magnitude of those differences did not differ between patients and controls (p=0.44). Cognitive performance did not change across the menstrual cycle on "female-dominant" or "male-dominant" tasks in either group. Estradiol and progesterone levels were unrelated to cognitive performance. Oxytocin levels did not change across the menstrual cycle but were positively related to performance on "female-dominant" tasks in female patients only (p<0.05). Sex differences in cognitive function are preserved in schizophrenia. Oxytocin levels do not change across the cycle, but relate to enhanced performance on female dominant tests in women. Physiological levels of oxytocin may thus have a more powerful benefit in some cognitive domains than estrogens in schizophrenia. Copyright © 2015 Elsevier B.V. All rights reserved.

Follicular delivery of spironolactone via nanostructured lipid carriers for management of alopecia.

PubMed

Shamma, Rehab Nabil; Aburahma, Mona Hassan

2014-01-01

Spironolactone (SL) is a US Food and Drug Administration-approved drug for the treatment of hypertension and various edematous conditions. SL has gained a lot of attention for treating androgenic alopecia due to its potent antiandrogenic properties. Recently, there has been growing interest for follicular targeting of drug molecules for treatment of hair and scalp disorders using nanocolloidal lipid-based delivery systems to minimize unnecessary systemic side effects associated with oral drug administration. Accordingly, the objective of this study is to improve SL efficiency and safety in treating alopecia through the preparation of colloidal nanostructured lipid carriers (NLCs) for follicular drug delivery. SL-loaded NLCs were prepared by an emulsion solvent diffusion and evaporation method using 23 full factorial design. All of the prepared formulations were spherical in shape with nanometric size range (215.6-834.3 nm) and entrapment efficiency >74%. Differential scanning calorimetry thermograms and X-ray diffractograms revealed that SL exists in amorphous form within the NLC matrices. The drug release behavior from the NLCs displayed an initial burst release phase followed by sustained release of SL. Confocal laser scanning microscopy confirmed the potential of delivering the fluorolabeled NLCs within the follicles, suggesting the possibility of using SL-loaded NLCs for localized delivery of SL into the scalp hair follicles.

Proteomic analysis of human follicular fluid associated with successful in vitro fertilization.

PubMed

Shen, Xiaofang; Liu, Xin; Zhu, Peng; Zhang, Yuhua; Wang, Jiahui; Wang, Yanwei; Wang, Wenting; Liu, Juan; Li, Ning; Liu, Fujun

2017-07-27

Human follicular fluid (HFF) provides a key environment for follicle development and oocyte maturation, and contributes to oocyte quality and in vitro fertilization (IVF) outcome. To better understand folliculogenesis in the ovary, a proteomic strategy based on dual reverse phase high performance liquid chromatography (RP-HPLC) coupled to matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometry (LC-MALDI TOF/TOF MS) was used to investigate the protein profile of HFF from women undergoing successful IVF. A total of 219 unique high-confidence (False Discovery Rate (FDR) < 0.01) HFF proteins were identified by searching the reviewed Swiss-Prot human database (20,183 sequences), and MS data were further verified by western blot. PANTHER showed HFF proteins were involved in complement and coagulation cascade, growth factor and hormone, immunity, and transportation, KEGG indicated their pathway, and STRING demonstrated their interaction networks. In comparison, 32% and 50% of proteins have not been reported in previous human follicular fluid and plasma. Our HFF proteome research provided a new complementary high-confidence dataset of folliculogenesis and oocyte maturation environment. Those proteins associated with innate immunity, complement cascade, blood coagulation, and angiogenesis might serve as the biomarkers of female infertility and IVF outcome, and their pathways facilitated a complete exhibition of reproductive process.

Follicular carcinoma of the thyroid with hyperthyroidism. A case report.

PubMed

Sharma, Prashant; Kumar, Neeta; Gupta, Ruchika; Jain, Shyama

2004-01-01

Follicular carcinoma of the thyroid in association with hyperthyroidism is rare. The malignant lesion may remain occult for a long time. Certain clinical and cytologic features may be helpful in raising the alarm. An elderly male with a history of occupational exposure to X rays, long-standing toxic multinodular goiter and clinical hyperthyroidism presented with a rapidly enlarging mass in the neck. Cytologic smears showed a prominent microfollicular pattern, scanty colloid, anisonucleosis and nuclear overlapping. The noteworthy feature was the presence of marginal vacuoles. The cytologic diagnosis of follicular neoplasm with highly suggestive malignancy was made. Subsequently, multiple pulmonary nodules provided radiologic evidence of possible metastatic spread. This case report demonstrates the rare association of follicular carcinoma of the thyroid with hyperthyroidism and analyzes certain high-risk clinical and cytologic features to be considered in the follow-up of long-standing hyperfunctioning multinodular goiter.

Nevoid follicular mucinosis: a new type of hair follicle nevus.

PubMed

Tadini, Gianluca; Boldrini, Maria P; Brena, Michela; Pezzani, Lidia; Marchesi, Lorenzo; Rongioletti, Franco

2013-09-01

Follicular mucinosis represents a term for a histopathologic reaction pattern in follicular epithelium. It is a characteristic of alopecia mucinosa. However, it may also occur in a variety of unrelated conditions. Epidermal nevi are considered to be hamartomatous disorders and they can show a predominant component of non-organoid (keratinocytes) and/or organoid nevi. All the cases of epidermal nevi described with mucin deposits until now are reported as mucinous nevus or mucinous eccrine nevus; in the first type of disorder, diffuse mucin deposition is only seen in the papillary dermis, and in the second type, the mucin is found around the proliferation of eccrine structures. We believe this is the first reported case of epidermal nevus along Blaschko's lines exhibiting typical microscopic findings of mucinosis exclusively distributed inside the follicular epithelia. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A patient presenting with spinal cord compression who had two distinct follicular cell type thyroid carcinomas.

PubMed

Koca, E; Sokmensuer, C; Yildiz, B O; Engin, H; Bozkurt, M F; Aras, T; Barista, I; Gurlek, A

2004-06-01

A 61-yr-old woman presented with complaints of weakness and pain in her legs. A magnetic resonance imaging showed a 3 x 5.6 x 7.8 cm mass lesion destructing the T1 and T2 vertebral bodies and compressing the spinal cord. The mass was excised surgically. It was follicular carcinoma metastasis of the cervicodorsal region. Then, she underwent a total thyroidectomy. Pathological examination showed two different types of carcinomas in two different focuses; follicular carcinoma in the left lobe and follicular variant papillary carcinoma in the isthmic lobe. After the operation she was given 100 mCi 131I. This is the first report of a patient who had both metastatic follicular carcinoma and follicular variant papillary carcinoma together.

Influence of follicular fluid GDF9 and BMP15 on embryo quality.

PubMed

Gode, Funda; Gulekli, Bulent; Dogan, Erbil; Korhan, Peyda; Dogan, Seda; Bige, Ozgur; Cimrin, Dilek; Atabey, Nese

2011-06-01

To evaluate the association between follicular fluid levels of propeptide and mature forms of growth differentiation factor (GDF) 9 and bone morphogenetic protein (BMP) 15 with subsequent oocyte and embryo quality. Prospective clinical study. University hospital. Eighty-one infertile patients who underwent in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI). The expression levels of the propeptide and mature forms of follicular fluid GDF9 and BMP15 were determined by western blot analysis. The levels of follicular fluid hormones (FSH, E2, and P) were measured with automated chemiluminescent enzyme immunoassays. The relationships between the levels of GDF9 and BMP15, hormones, oocyte maturation, and embryo quality. Mature GDF9 levels were significantly correlated with the nuclear maturation of oocytes. The mean mature GDF9 level was 4.87±0.60 in the high-embryo-quality group and 1.45±0.81 in the low-embryo-quality group. There were no statistically significant differences in embryo quality among the patients regarding propeptide GDF9 and BMP15 expression status. There was a negative correlation between follicular fluid levels of P and the mature form of GDF9. Higher mature GDF9 levels in the follicular fluid were significantly correlated with oocyte nuclear maturation and embryo quality. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Association between liver failure and hepatic UDP-glucuronosyltransferase activity in dairy cows with follicular cysts.

PubMed

Tanemura, Kouichi; Ohtaki, Tadatoshi; Kuwahara, Yasushi; Tsumagari, Shigehisa

2017-01-20

Uridine 5'-diphospho-glucuronosyltransferase (UGT) liver activity was measured using estradiol-17β as a substrate in dairy cows with follicular cysts. The activity was significantly lower than that in dairy cows with normal estrous cycles (P<0.01). Liver disorders, such as fatty liver and hepatitis, were observed in half cows with follicular cysts, and liver UGT activity was lower than that in cows with normal estrus cycles. In addition, the liver UGT activity was significantly lower in dairy cows with follicular cysts without liver disorders than in dairy cows with normal estrous cycles. Therefore, the cows were divided into those with low, middle and high liver UGT activities, and liver disorder complication rates were investigated. The complication rate was significantly higher in the low- (78.1%) than in the middle- (22.2%) and high-level (8.3%) groups, suggesting that liver disorders are closely associated with the development of follicular cysts in dairy cows and that steroid hormone metabolism is delayed because of reduced liver UGT activity, resulting in follicular cyst formation. We conclude that reduced estradiol-17β glucuronidation in the liver and liver disorders are associated with follicular cyst occurrence in dairy cows.

Follicular and percutaneous penetration pathways of topically applied minoxidil foam.

PubMed

Blume-Peytavi, Ulrike; Massoudy, Lida; Patzelt, Alexa; Lademann, Jürgen; Dietz, Ekkehart; Rasulev, Utkur; Garcia Bartels, Natalie

2010-11-01

In the past, it was assumed that the intercellular route was the only relevant penetration pathway for topically applied substances. Recent results on follicular penetration emphasize that the hair follicles represent a highly relevant and efficient penetration pathway and reservoir for topically applied substances. This study investigates a selective closure technique of hair follicle orifices in vivo assessing interfollicular and follicular absorption rates of topical minoxidil foam in humans. In delimited skin area, single hair orifices or interfollicular skin were blocked with a microdrop of special varnish-wax-mixture in vivo. Minoxidil foam (5%) was topically applied, and transcutaneous absorption was measured by a new surface ionization mass spectrometry technique in serum. Different settings (open, closed or none of both) enabled to clearly distinguish between interfollicular and follicular penetration of the topically applied minoxidil foam. Five minutes after topical application, minoxidil was detected in blood samples when follicles remained open, whereas with closed follicles 30 min were needed. Highest levels were found first when both pathways were open, followed by open follicles and subsequently by closed follicles. These results demonstrate the high importance of the follicular penetration pathway. Hair follicles are surrounded by a dense network of blood capillaries and dendritic cells and have stem cells in their immediate vicinity, making them ideal targets for drug delivery. Copyright © 2010 Elsevier B.V. All rights reserved.

Effect of different hormonal combinations on follicular wave emergence and superovulatory response in sheep.

PubMed

Souza-Fabjan, Joanna Maria Gonçalves; da Rosa, Rômulo Mendonça; Balaro, Mário Felipe Alvarez; Pinto, Pedro Henrique Nicolau; Dos Santos, Gustavo Bervian; Arashiro, Eduardo Kenji Nunes; da Fonseca, Jeferson Ferreira; Ungerfeld, Rodolfo; Brandão, Felipe Zandonadi

2017-11-01

The aim of the present study was to compare hormonal treatments to induce and synchronize follicular wave emergence to improve the results of superovulatory (SOV) treatments in ewes. In Experiment 1 (n = 66), ewes were treated with a progesterone intravaginal implant plus a PGF 2α analogue (group G P4 ), or with the same treatment plus estradiol benzoate (G P4+EB ), a GnRH agonist (G P4+GnRH ), or both, estradiol benzoate and a GnRH agonist (G P4+EB+GnRH ) in a 2 × 2 factorial arrangement. Follicular wave emergence was determined by ultrasound. Follicular wave did not emerge during the studied period in 10 females (one from G P4 , six from G P4+EB and three from G P4+EB+GnRH ). Follicular emergence was less synchronized (P = 0.007) when estradiol was administered (G P4+EB : 103.6 ± 22.0 h), without any interaction with GnRH treatment (G P4+EB+GnRH : 80.1 ± 21.4 h, G P4+GnRH : 52.5 ± 8.7 h, G P4 : 56.6 ± 10.4 h). Estradiol administration delayed the moment of follicular emergence (P = 0.007) and the follicular wave emergence moment in which follicular dominance was achieved (P = 0.009), without interactions between estradiol and GnRH in the moment of follicular wave emergence or dominance. In Experiment 2 (n = 22), two SOV protocols were compared: the best treatment of Experiment 1 (G P4 ) was used to synchronize follicular wave emergence, initiating the SOV treatment 2.5 days later; in the control treatment, SOV treatment started 80 h after a short-term protocol to synchronize ovulation (G control ). The number of corpora lutea (CL) and the evaluation of the collected embryos were performed six days after estrus. Blood samples were collected daily for plasma progesterone determination. Although the number of CL was similar in G control (7.1 ± 1.0) and G P4 (6.9 ± 5.1), the number of structures and viable embryos recovered were greater in G control (P < 0.05). The occurrence of luteal premature regression was significantly

Gene Expression (mRNA) Markers for Differentiating between Malignant and Benign Follicular Thyroid Tumours

PubMed Central

Wojtas, Bartosz; Pfeifer, Aleksandra; Oczko-Wojciechowska, Malgorzata; Krajewska, Jolanta; Czarniecka, Agnieszka; Kukulska, Aleksandra; Eszlinger, Markus; Musholt, Thomas; Stokowy, Tomasz; Swierniak, Michal; Stobiecka, Ewa; Chmielik, Ewa; Rusinek, Dagmara; Tyszkiewicz, Tomasz; Halczok, Monika; Hauptmann, Steffen; Lange, Dariusz; Jarzab, Michal; Paschke, Ralf; Jarzab, Barbara

2017-01-01

Distinguishing between follicular thyroid cancer (FTC) and follicular thyroid adenoma (FTA) constitutes a long-standing diagnostic problem resulting in equivocal histopathological diagnoses. There is therefore a need for additional molecular markers. To identify molecular differences between FTC and FTA, we analyzed the gene expression microarray data of 52 follicular neoplasms. We also performed a meta-analysis involving 14 studies employing high throughput methods (365 follicular neoplasms analyzed). Based on these two analyses, we selected 18 genes differentially expressed between FTA and FTC. We validated them by quantitative real-time polymerase chain reaction (qRT-PCR) in an independent set of 71 follicular neoplasms from formaldehyde-fixed paraffin embedded (FFPE) tissue material. We confirmed differential expression for 7 genes (CPQ, PLVAP, TFF3, ACVRL1, ZFYVE21, FAM189A2, and CLEC3B). Finally, we created a classifier that distinguished between FTC and FTA with an accuracy of 78%, sensitivity of 76%, and specificity of 80%, based on the expression of 4 genes (CPQ, PLVAP, TFF3, ACVRL1). In our study, we have demonstrated that meta-analysis is a valuable method for selecting possible molecular markers. Based on our results, we conclude that there might exist a plausible limit of gene classifier accuracy of approximately 80%, when follicular tumors are discriminated based on formalin-fixed postoperative material. PMID:28574441

Gene Expression (mRNA) Markers for Differentiating between Malignant and Benign Follicular Thyroid Tumours.

PubMed

Wojtas, Bartosz; Pfeifer, Aleksandra; Oczko-Wojciechowska, Malgorzata; Krajewska, Jolanta; Czarniecka, Agnieszka; Kukulska, Aleksandra; Eszlinger, Markus; Musholt, Thomas; Stokowy, Tomasz; Swierniak, Michal; Stobiecka, Ewa; Chmielik, Ewa; Rusinek, Dagmara; Tyszkiewicz, Tomasz; Halczok, Monika; Hauptmann, Steffen; Lange, Dariusz; Jarzab, Michal; Paschke, Ralf; Jarzab, Barbara

2017-06-02

Distinguishing between follicular thyroid cancer (FTC) and follicular thyroid adenoma (FTA) constitutes a long-standing diagnostic problem resulting in equivocal histopathological diagnoses. There is therefore a need for additional molecular markers. To identify molecular differences between FTC and FTA, we analyzed the gene expression microarray data of 52 follicular neoplasms. We also performed a meta-analysis involving 14 studies employing high throughput methods (365 follicular neoplasms analyzed). Based on these two analyses, we selected 18 genes differentially expressed between FTA and FTC. We validated them by quantitative real-time polymerase chain reaction (qRT-PCR) in an independent set of 71 follicular neoplasms from formaldehyde-fixed paraffin embedded (FFPE) tissue material. We confirmed differential expression for 7 genes ( CPQ , PLVAP , TFF3 , ACVRL1 , ZFYVE21 , FAM189A2 , and CLEC3B ). Finally, we created a classifier that distinguished between FTC and FTA with an accuracy of 78%, sensitivity of 76%, and specificity of 80%, based on the expression of 4 genes ( CPQ , PLVAP , TFF3 , ACVRL1 ). In our study, we have demonstrated that meta-analysis is a valuable method for selecting possible molecular markers. Based on our results, we conclude that there might exist a plausible limit of gene classifier accuracy of approximately 80%, when follicular tumors are discriminated based on formalin-fixed postoperative material.

Age and body size of captive hawksbill turtles at the onset of follicular development.

PubMed

Kawazu, Isao; Kino, Masakatsu; Maeda, Konomi; Teruya, Hideshi

2015-01-01

The aim of this study was to record the age and body size of 23 captive female hawksbill turtles at the onset of follicular development. The age, straight carapace length (SCL), and body mass (BM) of the turtles were recorded between 2006 and 2014 at follicular development (determined via ultrasonography) these parameters were 17.7 ± 1.7 years (range: 13-20 years), 77.7 ± 3.3 cm (73.3-83.5 cm), and 61.1 ± 8.0 kg (48.2-76.1 kg), respectively. When the year of the onset of follicular development was designated year 0, the increase in SCL in years -7-0 and 0-3 averaged 2.2 cm and 1.0 cm, respectively. Correspondingly, the increase in BM in years -7-0 and 0-3 averaged 5.0 kg and 2.2 kg, respectively. This is the first study to report the age and body size of captive female hawksbill turtles at the onset of follicular development, which indicates the beginning of sexual maturation. The reduction in growth after follicular development suggests that at the onset of sexual maturation, female hawksbills may utilize energy for follicular development rather than growth. © 2014 Wiley Periodicals, Inc.

Open-Label, Multicenter, Phase 1/2 Study of Tazemetostat (EZH2 Histone Methyl Transferase [HMT] Inhibitor) as a Single Agent in Subjects With Adv. Solid Tumors or With B-cell Lymphomas and Tazemetostat in Combination With Prednisolone in Subjects With DLBCL

ClinicalTrials.gov

2018-05-31

B-cell Lymphomas (Phase 1); Advanced Solid Tumors (Phase 1); Diffuse Large B-cell Lymphoma (Phase 2); Follicular Lymphoma (Phase 2); Transformed Follicular Lymphoma; Primary Mediastinal Large B-Cell Lymphoma

Effects of menstrual cycle phase and oral contraceptives on alertness, cognitive performance, and circadian rhythms during sleep deprivation

NASA Technical Reports Server (NTRS)

Wright, K. P. Jr; Badia, P.; Czeisler, C. A. (Principal Investigator)

1999-01-01

The influence of menstrual cycle phase and oral contraceptive use on neurobehavioral function and circadian rhythms were studied in healthy young women (n = 25) using a modified constant routine procedure during 24 h of sleep deprivation. Alertness and performance worsened across sleep deprivation and also varied with circadian phase. Entrained circadian rhythms of melatonin and body temperature were evident in women regardless of menstrual phase or oral contraceptive use. No significant difference in melatonin levels, duration, or phase was observed between women in the luteal and follicular phases, whereas oral contraceptives appeared to increase melatonin levels. Temperature levels were higher in the luteal phase and in oral contraceptive users compared to women in the follicular phase. Alertness on the maintenance of wakefulness test and some tests of cognitive performance were poorest for women in the follicular phase especially near the circadian trough of body temperature. These observations suggest that hormonal changes associated with the menstrual cycle and the use of oral contraceptives contribute to changes in nighttime waking neurobehavioral function and temperature level whereas these factors do not appear to affect circadian phase.

Investigation of follicular and non-follicular pathways for polyarginine and oleic acid modified nanoparticles

PubMed Central

Hayden, Patrick; Singh, Mandip

2013-01-01

Purpose The aim of the current study was to investigate the percutaneous permeation pathways of cell penetrating peptide modified lipid nanoparticles and oleic acid modified polymeric nanoparticles. Methods Confocal microscopy was performed on skin cultures (EpiDermFT™) for modified and un-modified nanoparticles. Differential stripping was performed following in vitro skin permeation of Ibuprofen (Ibu) encapsulated nanoparticles to estimate Ibu levels in different skin layers and receiver compartment. The hair follicles (HF) were blocked and in vitro skin permeation of nanoparticles was then compared with unblocked HF. The surface modified nanoparticles were investigated for response on allergic contact dermatitis (ACD). Results Surface modified nanoparticles showed a significant higher (p < 0.05) in fluorescence in EpiDermFT™ cultures compared to controls. The HF play less than 5% role in total nanoparticle permeation into the skin. The Ibu levels were significantly high (p<0.05) for surface modified nanoparticles compared to controls. The Ibu levels in skin and receiver compartment were not significantly different when HF were open or closed. Modified nanoparticles showed significant improvement in treatment of ACD compared to solution. Conclusions Our studies demonstrate that increased skin permeation of surface modified nanoparticles is not only dependent on a follicular pathway but also occur through non-follicular pathway(s). PMID:23187866

Differential Expression of Programmed Cell Death on the Follicular Development in Normal and Miniature Pig Ovary

PubMed Central

Kim, Sang Hwan; Min, Kwan Sik; Kim, Nam Hyung; Yoon, Jong Taek

2012-01-01

Follicles are important in oocyte maturation. Successful estrous cycle requires remodeling of follicular cells, and proper execution of programmed cell death is crucial for normal follicular development. The objectives of the present study were to understand programmed cell death during follicle development, to analyze the differential follicle development patterns, and to assess the patterns of apoptosis and autophagy expression during follicle development in normal and miniature pigs. Through the analysis of differential patterns of programmed cell death during follicular development in porcine, MAP1LC3A, B and other autophagy-associated genes (ATG5, mTOR, Beclin-1) were found to increase in normal pigs, while it decreased in miniature pigs. However, for the apoptosis-associated genes, progression of genes during follicular development increased in miniature pigs, while it decreased in normal pigs. Thus, results show that normal and miniature pigs showed distinct patterns of follicular remodeling manifesting that programmed cell death largely depends on the types of pathway during follicular development (Type II or autophagy for normal pigs and Type I or apoptosis for miniature pigs). PMID:23056260

Identification of Hürthle cell tumor by single-injection, double-phase scintigraphy with technetium-99m-sestamibi.

PubMed

Vattimo, A; Bertelli, P; Cintorino, M; Burroni, L; Volterrani, D; Vella, A

1995-05-01

Early and late (double-phase) scintigraphy with 99mTc-MIBI was used in a comparative study of the scintigraphic aspects of Hürthle cell tumors and other thyroid tumors. Single-injection, dual-phase (15-30 min and 3-4 hr) thyroid scintigraphy with 99mTc-sestamibi (MIBI) was performed on 41 patients who displayed a cold nodule on previous 99mTc scintigraphy. Visual scoring of nodular uptake was done to compare thyroidal and background tracer uptake. In addition, the nodular-to-thyroid (N/T) uptake ratio in the early and late images and the washout rate from the nodule (WON) and thyroidal tissue (WOT) were measured. Cytologic results were obtained for all patients; histopathologic results were obtained for the 20 patients who had surgery. In eight patients (Group A), the nodule displayed intense and persistent uptake of MIBI (N/T = 1.77 +/- 0.46 and 3.20 +/- 1.37; WON = 17.2% +/- 6.3%; WOT = 24.6% +/- 7.5%); histopathology revealed Hürthle cell tumors (two carcinomas and three adenomas) in five surgical patients. In 15 patients (Group B), the nodule displayed intense uptake in the early image with fading activity in the late image (N/T = 1.45 +/- 0.54 and 0.84 +/- 0.30; WON = 30.0% +/- 7.3%; WOT = 24.5% +/- 6.8%); histopathology revealed a colloid nodule (n = 1), papillary carcinoma (n = 4) and follicular carcinoma (n = 5) in 10 surgical patients. In the remaining 18 patients (Group C), the nodule was cold and late images were not acquired. Histopathology revealed colloid nodules (n = 2) and follicular adenoma (n = 3) in five surgical patients. Single-injection, dual-phase MIBI scintigraphy of the thyroid can identify Hürthle cell tumors because these tumors have intense, persistent tracer uptake in contrast to other thyroid tumors.

Decitabine in Treating Patients With Metastatic Papillary Thyroid Cancer or Follicular Thyroid Cancer Unresponsive to Iodine I 131

ClinicalTrials.gov

2014-08-20

Recurrent Thyroid Cancer; Stage IVA Follicular Thyroid Cancer; Stage IVA Papillary Thyroid Cancer; Stage IVB Follicular Thyroid Cancer; Stage IVB Papillary Thyroid Cancer; Stage IVC Follicular Thyroid Cancer; Stage IVC Papillary Thyroid Cancer

Pembrolizumab and Combination Chemotherapy in Treating Patients With Previously Untreated Diffuse Large B-cell Lymphoma or Grade 3b Follicular Lymphoma

ClinicalTrials.gov

2017-10-24

Composite Lymphoma; Grade 3b Follicular Lymphoma; Stage I Diffuse Large B-Cell Lymphoma; Stage I Follicular Lymphoma; Stage II Diffuse Large B-Cell Lymphoma; Stage II Follicular Lymphoma; Stage III Diffuse Large B-Cell Lymphoma; Stage III Follicular Lymphoma; Stage IV Diffuse Large B-Cell Lymphoma; Stage IV Follicular Lymphoma

Follicular patterned lesions of the thyroid gland: a practical algorithmic approach.

PubMed

Chetty, Runjan

2011-09-01

Follicular patterned lesions of the thyroid are problematic and interpretation is often subjective. While thyroid experts are comfortable with their own criteria and thresholds, those encountering these lesions sporadically have a degree of uncertainty with a proportion of cases. The purpose of this review is to highlight the importance of proper diligent sampling of an encapsulated thyroid lesion (in totality in many cases), examination for capsular and vascular invasion, and finally the assessment of nuclear changes that are pathognomonic of papillary thyroid carcinoma (PTC). Based on these established criteria, an algorithmic approach is suggested using known, accepted terminology. The importance of unequivocal, clear-cut nuclear features of PTC as opposed to inconclusive features is stressed. If the nuclear features in an encapsulated, non-invasive follicular patterned lesion fall short of those encountered in classical PTC, but nonetheless are still worrying or concerning, the term 'uncertain malignant potential or behaviour, most likely benign' is suggested. Indubitable, classical PTC nuclei (whether diffuse or restricted to a single high-power field) are diagnostic of a PTC be it classical, non-invasive or invasive follicular variant PTC. Capsular and vascular invasion remain the only reliable predictors of outcome, as non-invasive, encapsulated follicular variant PTC, even with diffuse PTC nuclear change, behaves in an indolent fashion.

Association between liver failure and hepatic UDP-glucuronosyltransferase activity in dairy cows with follicular cysts

PubMed Central

TANEMURA, Kouichi; OHTAKI, Tadatoshi; KUWAHARA, Yasushi; TSUMAGARI, Shigehisa

2016-01-01

Uridine 5’-diphospho-glucuronosyltransferase (UGT) liver activity was measured using estradiol-17β as a substrate in dairy cows with follicular cysts. The activity was significantly lower than that in dairy cows with normal estrous cycles (P<0.01). Liver disorders, such as fatty liver and hepatitis, were observed in half cows with follicular cysts, and liver UGT activity was lower than that in cows with normal estrus cycles. In addition, the liver UGT activity was significantly lower in dairy cows with follicular cysts without liver disorders than in dairy cows with normal estrous cycles. Therefore, the cows were divided into those with low, middle and high liver UGT activities, and liver disorder complication rates were investigated. The complication rate was significantly higher in the low- (78.1%) than in the middle- (22.2%) and high-level (8.3%) groups, suggesting that liver disorders are closely associated with the development of follicular cysts in dairy cows and that steroid hormone metabolism is delayed because of reduced liver UGT activity, resulting in follicular cyst formation. We conclude that reduced estradiol-17β glucuronidation in the liver and liver disorders are associated with follicular cyst occurrence in dairy cows. PMID:27666462

Phase III Early Restoration Meeting | NOAA Gulf Spill Restoration

Science.gov Websites

Louisiana Mississippi Texas Region-wide Open Ocean Data Media & News Publications Press Releases Story programmatic approach to early restoration planning for Phase III and future early restoration plans. Open

Phase III Early Restoration Meeting - Pensacola, FL (rescheduled) | NOAA

Science.gov Websites

Restoration Areas Alabama Florida Louisiana Mississippi Texas Region-wide Open Ocean Data Media & News programmatic approach to early restoration planning for Phase III and future early restoration plans. Open

Thymic pseudotumorous enlargement due to follicular hyperplasia in a human immunodeficiency virus sero-positive patient. Immunohistochemical and molecular biological study of viral infected cells.

PubMed

Prevot, S; Audouin, J; Andre-Bougaran, J; Griffais, R; Le Tourneau, A; Fournier, J G; Diebold, J

1992-03-01

An enlargement of the thymus suggesting a tumor was discovered in a 28-year-old man who had early-stage acquired immune deficiency syndrome. A biopsy was performed. The adipose involuted thymus, with persistence of many Hassall's corpuscles, was judged to be a large lymphoid follicular hyperplasia. This follicular hyperplasia was similar to that previously described for lymph nodes, spleen, and other lymphoid tissues at earlier stages of human immunodeficiency virus infection, before the development of acquired immune deficiency syndrome. Human immunodeficiency virus RNA and p24 human immunodeficiency virus protein were detected in the hyperplastic germinal centers (lymphocytes and follicular dendritic infected cells), and also in many cells that may have been either lymphocytes and/or epithelial cells in the interfollicular areas. The tissue was negative for Epstein-Barr virus DNA sequences, as determined by the polymerase chain reaction. These observations identify the first state of infection of the thymus in a human immune deficiency virus-infected adult, preceding the severe involution with lymphoid depletion observed in all fatal cases of acquired immunodeficiency syndrome in which the thymus has been analyzed.

Follicular variant of seborrheic dermatitis: is it identical to Malassezia folliculitis?

PubMed

Valentine, Mark C

2011-01-01

Follicular accentuation in some patients with seborrheic dermatitis of the back and chest has been recognized for more than a century. The recognition of Malassezia folliculitis in recent decades has led to some confusion regarding categorization of these cases. The author proposes that there is sufficient clinical variation between the typical case of Malassezia folliculitis and patients with follicular seborrheic dermatitis to justify continued separation of these entities until further study provides more clarification.

Follicular regulatory T cells control humoral autoimmunity via NFAT2-regulated CXCR5 expression

PubMed Central

Vaeth, Martin; Müller, Gerd; Stauss, Dennis; Dietz, Lena; Klein-Hessling, Stefan; Serfling, Edgar; Lipp, Martin

2014-01-01

Maturation of high-affinity B lymphocytes is precisely controlled during the germinal center reaction. This is dependent on CD4+CXCR5+ follicular helper T cells (TFH) and inhibited by CD4+CXCR5+Foxp3+ follicular regulatory T cells (TFR). Because NFAT2 was found to be highly expressed and activated in follicular T cells, we addressed its function herein. Unexpectedly, ablation of NFAT2 in T cells caused an augmented GC reaction upon immunization. Consistently, however, TFR cells were clearly reduced in the follicular T cell population due to impaired homing to B cell follicles. This was TFR-intrinsic because only in these cells NFAT2 was essential to up-regulate CXCR5. The physiological relevance for humoral (auto-)immunity was corroborated by exacerbated lupuslike disease in the presence of NFAT2-deficient TFR cells. PMID:24590764

Metacognition in Early Phase Psychosis: Toward Understanding Neural Substrates

PubMed Central

Vohs, Jenifer L.; Hummer, Tom A.; Yung, Matthew G.; Francis, Michael M.; Lysaker, Paul H.; Breier, Alan

2015-01-01

Individuals in the early phases of psychotic illness have disturbed metacognitive capacity, which has been linked to a number of poor outcomes. Little is known, however, about the neural systems associated with metacognition in this population. The purpose of this study was to elucidate the neuroanatomical correlates of metacognition. We anticipated that higher levels of metacognition may be dependent upon gray matter density (GMD) of regions within the prefrontal cortex. Examining whole-brain structure in 25 individuals with early phase psychosis, we found positive correlations between increased medial prefrontal cortex and ventral striatum GMD and higher metacognition. These findings represent an important step in understanding the path through which the biological correlates of psychotic illness may culminate into poor metacognition and, ultimately, disrupted functioning. Such a path will serve to validate and promote metacognition as a viable treatment target in early phase psychosis. PMID:26132568

The follicular variant of papillary thyroid cancer and noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP).

PubMed

Scharpf, Joseph; Kamani, Dipti; Sadow, Peter M; Randolph, Gregory W

2017-01-01

Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) is a new terminology proposed for encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC). Recently, thyroid cancer incidence has increased dramatically, without affecting related mortality rate. This increase is widely attributed to the intensified surveillance leading to a substantial increase in the diagnosis of small classic papillary thyroid cancers and EFVPTCs. Recent studies emphasize the indolent behavior of the EFVPTC. Recently, there has been a reclassification of EFVPTC as NIFTP, a benign entity. The financial and emotional burden of 'cancer' diagnosis and treatment can be significant. This review recapitulates the literature supporting the reclassification of EFVPTC as NIFTP, a benign entity, and reviews standardized diagnostic criteria for EFVPTC. The information highlighted in this review will affect surgical decision making and may promote the offering of hemithyroidectomy over a total thyroidectomy to some patients with 'indeterminate' cytopathological category; postoperative radioiodine ablation will not be required for NIFTP patients.

A comparative analysis of prognostic factor models for follicular lymphoma based on a phase III trial of CHOP-rituximab versus CHOP + 131iodine--tositumomab.

PubMed

Press, Oliver W; Unger, Joseph M; Rimsza, Lisa M; Friedberg, Jonathan W; LeBlanc, Michael; Czuczman, Myron S; Kaminski, Mark; Braziel, Rita M; Spier, Catherine; Gopal, Ajay K; Maloney, David G; Cheson, Bruce D; Dakhil, Shaker R; Miller, Thomas P; Fisher, Richard I

2013-12-01

There is currently no consensus on optimal frontline therapy for patients with follicular lymphoma. We analyzed a phase III randomized intergroup trial comparing six cycles of CHOP-R (cyclophosphamide-Adriamycin-vincristine-prednisone (Oncovin)-rituximab) with six cycles of CHOP followed by iodine-131 tositumomab radioimmunotherapy (RIT) to assess whether any subsets benefited more from one treatment or the other, and to compare three prognostic models. We conducted univariate and multivariate Cox regression analyses of 532 patients enrolled on this trial and compared the prognostic value of the FLIPI (follicular lymphoma international prognostic index), FLIPI2, and LDH + β2M (lactate dehydrogenase + β2-microglobulin) models. Outcomes were excellent, but not statistically different between the two study arms [5-year progression-free survival (PFS) of 60% with CHOP-R and 66% with CHOP-RIT (P = 0.11); 5-year overall survival (OS) of 92% with CHOP-R and 86% with CHOP-RIT (P = 0.08); overall response rate of 84% for both arms]. The only factor found to potentially predict the impact of treatment was serum β2M; among patients with normal β2M, CHOP-RIT patients had better PFS compared with CHOP-R patients, whereas among patients with high serum β2M, PFS by arm was similar (interaction P value = 0.02). All three prognostic models (FLIPI, FLIPI2, and LDH + β2M) predicted both PFS and OS well, though the LDH + β2M model is easiest to apply and identified an especially poor risk subset. In an exploratory analysis using the latter model, there was a statistically significant trend suggesting that low-risk patients had superior observed PFS if treated with CHOP-RIT, whereas high-risk patients had a better PFS with CHOP-R. ©2013 AACR.

Comparison of clinicopathologic characteristics of gastric follicular lymphomas and duodenal follicular lymphomas.

PubMed

Maeshima, Akiko Miyagi; Taniguchi, Hirokazu; Suzuki, Tomotaka; Yuda, Sayako; Toyoda, Kosuke; Yamauchi, Nobuhiko; Makita, Shinichi; Fukuhara, Suguru; Munakata, Wataru; Maruyama, Dai; Kobayashi, Yukio; Saito, Yutaka; Tobinai, Kensei

2017-07-01

We compared the incidence, esophagogastroduodenoscopy (EGD) findings, and histopathologic characteristics of gastric and duodenal follicular lymphomas (FL). Of 626 FL cases, primary gastric FL and secondary gastric involvement of FL were observed in 1% and 5% of the cases, respectively, which were lower incidences than duodenal FL (10% and 9%, respectively). Gastric FL usually appeared as submucosal tumors (primary, 71%; secondary, 79%), whereas duodenal FL, as granular lesions (primary, 92%: secondary, 87%). In the granular duodenal lesions, the neoplastic follicles were located sparsely on the muscularis mucosa and could be found between villi, whereas in the stomach, similar lesions were hidden within the lamina propria, and only larger lesions such as submucosal tumors could be detected on the mucosal surface. The differences in the incidences and EGD findings were considered to be associated with structural differences of the lamina propria. Typical FL features: grades 1-2 histology, follicularity, and CD10 + and/or BCL6 + and BCL2 + were usually observed in all primary and secondary gastric and duodenal FL. Gastroduodenal and bone marrow involvement were found in 12% and 33% of the cases, respectively, and there was no significant correlation between them (P=.095). Twenty-nine cases (5%) were up-staged by gastroduodenal-positive results. In conclusion, the histopathology of gastric FL was similar to that of duodenal and nodal FL; the differences in the incidence and EGD findings between gastric and duodenal FL were considered to be associated with structural difference of the lamina propria, and EGD was useful as a staging procedure. Copyright © 2017 Elsevier Inc. All rights reserved.

Follicular delivery of spironolactone via nanostructured lipid carriers for management of alopecia

PubMed Central

Shamma, Rehab Nabil; Aburahma, Mona Hassan

2014-01-01

Spironolactone (SL) is a US Food and Drug Administration-approved drug for the treatment of hypertension and various edematous conditions. SL has gained a lot of attention for treating androgenic alopecia due to its potent antiandrogenic properties. Recently, there has been growing interest for follicular targeting of drug molecules for treatment of hair and scalp disorders using nanocolloidal lipid-based delivery systems to minimize unnecessary systemic side effects associated with oral drug administration. Accordingly, the objective of this study is to improve SL efficiency and safety in treating alopecia through the preparation of colloidal nanostructured lipid carriers (NLCs) for follicular drug delivery. SL-loaded NLCs were prepared by an emulsion solvent diffusion and evaporation method using 23 full factorial design. All of the prepared formulations were spherical in shape with nanometric size range (215.6–834.3 nm) and entrapment efficiency >74%. Differential scanning calorimetry thermograms and X-ray diffractograms revealed that SL exists in amorphous form within the NLC matrices. The drug release behavior from the NLCs displayed an initial burst release phase followed by sustained release of SL. Confocal laser scanning microscopy confirmed the potential of delivering the fluorolabeled NLCs within the follicles, suggesting the possibility of using SL-loaded NLCs for localized delivery of SL into the scalp hair follicles. PMID:25473283

Transformation of Follicular Lymphoma

PubMed Central

Lossos, Izidore S.; Gascoyne, Randy D.

2011-01-01

Histological transformation of follicular lymphoma (FL) to a more aggressive non-Hodgkin's lymphomas is a pivotal event in the natural history of FL and is associated with poor outcome. While commonly observed in clinical practice and despite multiple studies designed to address its pathogenesis, the biology of this process represents an enigma. In this chapter we present a state of the art review summarizing the definition of histologic transformation, its incidence, pathogenesis, clinical manifestations, treatment and outcome. Furthermore, we specifically emphasize gaps in our knowledge that should be addressed in future studies. PMID:21658615

Predictive value of bovine follicular components as markers of oocyte developmental potential.

PubMed

Matoba, Satoko; Bender, Katrin; Fahey, Alan G; Mamo, Solomon; Brennan, Lorraine; Lonergan, Patrick; Fair, Trudee

2014-01-01

The follicle is a unique micro-environment within which the oocyte can develop and mature to a fertilisable gamete. The aim of this study was to investigate the ability of a panel of follicular parameters, including intrafollicular steroid and metabolomic profiles and theca, granulosa and cumulus cell candidate gene mRNA abundance, to predict the potential of bovine oocytes to develop to the blastocyst stage in vitro. Individual follicles were dissected from abattoir ovaries, carefully ruptured under a stereomicroscope and the oocyte was recovered and individually processed through in vitro maturation, fertilisation and culture. The mean (±s.e.m.) follicular concentrations of testosterone (62.8±4.8 ngmL(-1)), progesterone (616.8±31.9 ngmL(-1)) and oestradiol (14.4±2.4 ngmL(-1)) were not different (P>0.05) between oocytes that formed (competent) or failed to form (incompetent) blastocysts. Principal-component analysis of the quantified aqueous metabolites in follicular fluid showed differences between oocytes that formed blastocysts and oocytes that degenerated; l-alanine, glycine and l-glutamate were positively correlated and urea was negatively correlated with blastocyst formation. Follicular fluid associated with competent oocytes was significantly lower in palmitic acid (P=0.023) and total fatty acids (P=0.031) and significantly higher in linolenic acid (P=0.036) than follicular fluid from incompetent oocytes. Significantly higher (P<0.05) transcript abundance of LHCGR in granulosa cells, ESR1 and VCAN in thecal cells and TNFAIP6 in cumulus cells was associated with competent compared with incompetent oocytes.

A study of the mutational landscape of pediatric-type follicular lymphoma and pediatric nodal marginal zone lymphoma.

PubMed

Ozawa, Michael G; Bhaduri, Aparna; Chisholm, Karen M; Baker, Steven A; Ma, Lisa; Zehnder, James L; Luna-Fineman, Sandra; Link, Michael P; Merker, Jason D; Arber, Daniel A; Ohgami, Robert S

2016-10-01

Pediatric-type follicular lymphoma and pediatric marginal zone lymphoma are two of the rarest B-cell lymphomas. These lymphomas occur predominantly in the pediatric population and show features distinct from their more common counterparts in adults: adult-type follicular lymphoma and adult-type nodal marginal zone lymphoma. Here we report a detailed whole-exome deep sequencing analysis of a cohort of pediatric-type follicular lymphomas and pediatric marginal zone lymphomas. This analysis revealed a recurrent somatic variant encoding p.Lys66Arg in the transcription factor interferon regulatory factor 8 (IRF8) in 3 of 6 cases (50%) of pediatric-type follicular lymphoma. This specific point mutation was not detected in pediatric marginal zone lymphoma or in adult-type follicular lymphoma. Additional somatic point mutations in pediatric-type follicular lymphoma were observed in genes involved in transcription, intracellular signaling, and cell proliferation. In pediatric marginal zone lymphoma, no recurrent mutation was identified; however, somatic point mutations were observed in genes involved in cellular adhesion, cytokine regulatory elements, and cellular proliferation. A somatic variant in AMOTL1, a recurrently mutated gene in splenic marginal zone lymphoma, was also identified in a case of pediatric marginal zone lymphoma. The overall non-synonymous mutational burden was low in both pediatric-type follicular lymphoma and pediatric marginal zone lymphoma (4.6 mutations per exome). Altogether, these findings support a distinctive genetic basis for pediatric-type follicular lymphoma and pediatric marginal zone lymphoma when compared with adult subtypes and to one another. Moreover, identification of a recurrent point mutation in IRF8 provides insight into a potential driver mutation in the pathogenesis of pediatric-type follicular lymphoma with implications for novel diagnostic or therapeutic strategies.

A study of the mutational landscape of pediatric-type follicular lymphoma and pediatric nodal marginal zone lymphoma

PubMed Central

Ozawa, Michael G; Bhaduri, Aparna; Chisholm, Karen M; Baker, Steven A; Ma, Lisa; Zehnder, James L; Luna-Fineman, Sandra; Link, Michael P; Merker, Jason D; Arber, Daniel A; Ohgami, Robert S

2016-01-01

Pediatric-type follicular lymphoma and pediatric marginal zone lymphoma are two of the rarest B-cell lymphomas. These lymphomas occur predominantly in the pediatric population and show features distinct from their more common counterparts in adults: adult-type follicular lymphoma and adult-type nodal marginal zone lymphoma. Here we report a detailed whole-exome deep sequencing analysis of a cohort of pediatric-type follicular lymphomas and pediatric marginal zone lymphomas. This analysis revealed a recurrent somatic variant encoding p.Lys66Arg in the transcription factor interferon regulatory factor 8 (IRF8) in 3 of 6 cases (50%) of pediatric-type follicular lymphoma. This specific point mutation was not detected in pediatric marginal zone lymphoma or in adult-type follicular lymphoma. Additional somatic point mutations in pediatric-type follicular lymphoma were observed in genes involved in transcription, intracellular signaling, and cell proliferation. In pediatric marginal zone lymphoma, no recurrent mutation was identified; however, somatic point mutations were observed in genes involved in cellular adhesion, cytokine regulatory elements, and cellular proliferation. A somatic variant in AMOTL1, a recurrently mutated gene in splenic marginal zone lymphoma, was also identified in a case of pediatric marginal zone lymphoma. The overall non-synonymous mutational burden was low in both pediatric-type follicular lymphoma and pediatric marginal zone lymphoma (4.6 mutations per exome). Altogether, these findings support a distinctive genetic basis for pediatric-type follicular lymphoma and pediatric marginal zone lymphoma when compared with adult subtypes and to one another. Moreover, identification of a recurrent point mutation in IRF8 provides insight into a potential driver mutation in the pathogenesis of pediatric-type follicular lymphoma with implications for novel diagnostic or therapeutic strategies. PMID:27338637

Trefoil factor 3 is required for differentiation of thyroid follicular cells and acts as a context-dependent tumor suppressor.

PubMed

Abols, A; Ducena, K; Andrejeva, D; Sadovska, L; Zandberga, E; Vilmanis, J; Narbuts, Z; Tars, J; Eglitis, J; Pirags, V; Line, A

2015-01-01

Trefoil factor 3 (TFF3) is overexpressed in a variety of solid epithelial cancers, where it has been shown to promote migration, invasion, proliferation, survival and angiogenesis. On the contrary, in the majority of thyroid tumors, it is downregulated, yet its role in the development of thyroid cancer remains unknown. Here we show that TFF3 exhibits strong cytoplasmic staining of normal thyroid follicular cells and colloid and the staining is increased in hyperfunctioning thyroid nodules, while it is decreased in all thyroid cancers of follicular cell origin. By meta-analysis of gene expression datasets, we found that in the thyroid cancer, conversely to the breast cancer, the expression of TFF3 mRNA was downregulated by estrogen signaling and confirmed this by treating thyroid cancer cells with estradiol. Forced expression of TFF3 in anaplastic thyroid cancer cells resulted in decreased cell proliferation, clonal spheroid formation and entry into the S phase. Furthermore, it induced acquisition of epithelial-like cell morphology and expression of the differentiation markers of thyroid follicular cells and transcription factors implicated in the thyroid morphogenesis and function. Taken together, this study provides the first evidence that TFF3 may act as a tumor suppressor or an oncogene depending on the cellular context.

Antinuclear Antibodies (ANA) in Gordon Setters with Symmetrical Lupoid Onychodystrophy and Black Hair Follicular Dysplasia

PubMed Central

Bohnhorst, J Øvrebø; Hanssen, I; Moen, T

2001-01-01

Antinuclear antibodies (ANA) were demonstrated in 3 out of 10 Gordon setters with symmetrical lupoid onychodystrophy and in 5 out of 13 Gordon setters with black hair follicular dysplasia. Two dogs showed both symmetrical lupoid onychodystrophy and black hair follicular dysplasia, and one of these was ANA positive. The results suggest that symmetrical lupoid onychodystrophy and black hair follicular dysplasia in the Gordon setter might be autoimmune diseases that are pathogenetically related, which might indicate a common genetic predisposition. PMID:11887392

Rituximab Retreatment for Low-Tumor Burden Follicular Lymphoma

Cancer.gov

A summary of results from a randomized clinical trial of patients with low–tumor burden follicular lymphoma that compared maintenance therapy with rituximab versus retreatment with rituximab only when there was evidence of disease progression.

Management of untreated advanced stage follicular lymphoma: Role of patient discernment.

PubMed

Umakanthan, Jayadev Manikkam; Lunning, Mathew A

2018-03-01

Follicular lymphoma is the most common indolent non-Hodgkin lymphoma. Advanced stage disease is common at diagnosis. The timing of treatment for follicular lymphoma is best approached by considering the combination of presence or absence of symptoms along with estimation of tumor burden. Upfront treatment strategies should take into initial presentation variables, pace of disease progression and goals of care after discussion with the patient. Treatment approaches remain diverse and patient discernment is paramount. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effects of propylene glycol drenching before and after luteolysis on blood glucose, ovarian steroids and follicular dynamics in heifers.

PubMed

Umeki, A; Tanaka, T; Kamomae, H

2012-02-01

The effect of propylene glycol drenching on ovarian and hormonal dynamics was studied in heifers. Five cycling heifers were used twice (as control and treatment) with crossover design. After the confirmation of ovulation (day 0), the heifers in the treatment group received propylene glycol on days 6, 7 and 8 as an oral drench (250 ml of 90% propylene glycol). On day 10, prostaglandin F2α (PGF2α), 15 mg per head of dinoprost, was administered intramuscularly to induce luteal regression followed by the follicular phase and then propylene glycol was again administered twice daily (500 ml/day) on days 10, 11 and 12. Palpation per rectum and ovarian ultrasonography were performed every other day from days 0 to 10, and daily after PGF2α administration until the subsequent ovulation (second ovulation) for analysis of follicular and luteal dynamics. Blood samples were also collected every other day from days 0 to 10, and then at 6 h intervals after PGF2α administration until the second ovulation. For the samples taken at 6-h intervals after PGF2α administration, the concentrations of glucose showed clear daily fluctuations in both groups. Changes in the plasma concentration of glucose in the treatment group were significantly (P < 0.05) higher than those of the control groups during the period between 0 and 72 h after PGF2α administration. No significant difference was detected in the growth of dominant follicles, maximum diameter of the ovulatory follicles and the changes in oestradiol and progesterone during the follicular phase between treatment and control groups. This study showed the clear daily fluctuations and stimulatory changes in the blood glucose concentrations at 24-h intervals during the short-term treatment of propylene glycol drenching in heifers. However, no significant changes in ovarian and hormonal dynamics were found under such metabolic conditions.

Prognostic relevance of CD163 and CD8 combined with EZH2 and gain of chromosome 18 in follicular lymphoma: a study by the Lunenburg Lymphoma Biomarker Consortium.

PubMed

Stevens, Wendy B C; Mendeville, Matias; Redd, Robert; Clear, Andrew J; Bladergroen, Reno; Calaminici, Maria; Rosenwald, Andreas; Hoster, Eva; Hiddemann, Wolfgang; Gaulard, Philippe; Xerri, Luc; Salles, Gilles; Klapper, Wolfram; Pfreundschuh, Michael; Jack, Andrew; Gascoyne, Randy D; Natkunam, Yasodha; Advani, Ranjana; Kimby, Eva; Sander, Birgitta; Sehn, Laurie H; Hagenbeek, Anton; Raemaekers, John; Gribben, John; Kersten, Marie José; Ylstra, Bauke; Weller, Edie; de Jong, Daphne

2017-08-01

In follicular lymphoma, studies addressing the prognostic value of microenvironment-related immunohistochemical markers and tumor cell-related genetic markers have yielded conflicting results, precluding implementation in practice. Therefore, the Lunenburg Lymphoma Biomarker Consortium performed a validation study evaluating published markers. To maximize sensitivity, an end of spectrum design was applied for 122 uniformly immunochemotherapy-treated follicular lymphoma patients retrieved from international trials and registries. The criteria were: early failure, progression or lymphoma-related death <2 years versus long remission, response duration of >5 years. Immunohistochemical staining for T cells and macrophages was performed on tissue microarrays from initial biopsies and scored with a validated computer-assisted protocol. Shallow whole-genome and deep targeted sequencing was performed on the same samples. The 96/122 cases with complete molecular and immunohistochemical data were included in the analysis. EZH2 wild-type ( P =0.006), gain of chromosome 18 ( P =0.002), low percentages of CD8+ cells ( P =0.011) and CD163+ areas ( P =0.038) were associated with early failure. No significant differences in other markers were observed, thereby refuting previous claims of their prognostic significance. Using an optimized study design, this Lunenburg Lymphoma Biomarker Consortium study substantiates wild-type EZH2 status, gain of chromosome 18, low percentages of CD8+ cells and CD163+ area as predictors of early failure to immunochemotherapy in follicular lymphoma treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP [-like]), while refuting the prognostic impact of various other markers. Copyright© 2017 Ferrata Storti Foundation.

Necrotizing lymphocytic folliculitis: the early lesion of acne necrotica (varioliformis).

PubMed

Kossard, S; Collins, A; McCrossin, I

1987-05-01

Skin biopsy specimens from four patients who had recurrent bouts of lesions conforming to the clinical description of acne necrotica were studied. The pathologic findings were dominated by lymphocytic inflammation around centrally placed follicles evolving to follicular necrosis that extended to the perifollicular epidermis and dermis. Early lesions showed the development of multiple individual necrotic keratinocytes within the follicular sheath and adjacent epidermis with lymphocytic exocytosis. Later lesions showed more intense necrosis and scale crust obscuring the central target but were still dominated by a peripheral lymphocytic infiltrate. The early pathologic findings of acne necrotica (varioliformis) are represented by a necrotizing lymphocytic folliculitis and differ from the pattern seen in association with nonspecific excoriations, acute bacterial folliculitis, classic comedogenic acne, or acnitis.

Occurrence of ovarian follicular dominance during stimulation for IVM impacts usable blastocyst yield.

PubMed

Romero, Sergio; Pella, Ricardo; Escudero, Francisco; Pérez, Ygor; García, Mario; Orihuela, Patricia

2018-03-01

To evaluate the influence of ovarian follicular dominance on the outcome of oocyte in-vitro maturation. This retrospective cohort study included 21 patients with polycystic ovaries or polycystic ovary syndrome (Rotterdam criteria, 2004) subjected to 24 invitro maturation (IVM) cycles between October 2015 and January 2017. Patients undergoing IVM received minimal gonadotropin stimulation starting on day 2 or 3 of the cycle; ovum pick-up typically occurred on days 6 to 8. No hCG-trigger shot was given. Following 30h of IVM, mature oocytes were inseminated by ICSI and the resulting embryos cultured up to the blastocyst stage. Ovarian follicular dominance was observed in nine of the 24 IVM cycles. Oocyte IVM yielded an overall maturation rate of 69.3±23.8%, and no difference was observed when the groups with or without a dominant follicle were assessed independently. The rates of fertilization and usable blastocysts per fertilized oocyte, mature oocyte (Metaphase II) or cumulus-oocyte-complex were nearly three times higher (28.7±22.5%) in the group without ovarian follicular dominance. No differences were found in the clinical pregnancy rates attained by the individuals with or without a dominant follicle after 21 vitrified-warmed blastocyst transfer cycles. Occurrence of ovarian follicular dominance during hormonal stimulation for in-vitro maturation negatively impacted embryological outcomes. Strategies devised to limit the appearance of ovarian follicular dominance must be further explored.

Occurrence of ovarian follicular dominance during stimulation for IVM impacts usable blastocyst yield

PubMed Central

Romero, Sergio; Pella, Ricardo; Escudero, Francisco; Pérez, Ygor; García, Mario; Orihuela, Patricia

2018-01-01

Objective To evaluate the influence of ovarian follicular dominance on the outcome of oocyte in-vitro maturation. Methods This retrospective cohort study included 21 patients with polycystic ovaries or polycystic ovary syndrome (Rotterdam criteria, 2004) subjected to 24 in-vitro maturation (IVM) cycles between October 2015 and January 2017. Patients undergoing IVM received minimal gonadotropin stimulation starting on day 2 or 3 of the cycle; ovum pick-up typically occurred on days 6 to 8. No hCG-trigger shot was given. Following 30h of IVM, mature oocytes were inseminated by ICSI and the resulting embryos cultured up to the blastocyst stage. Results Ovarian follicular dominance was observed in nine of the 24 IVM cycles. Oocyte IVM yielded an overall maturation rate of 69.3±23.8%, and no difference was observed when the groups with or without a dominant follicle were assessed independently. The rates of fertilization and usable blastocysts per fertilized oocyte, mature oocyte (Metaphase II) or cumulus-oocyte-complex were nearly three times higher (28.7±22.5%) in the group without ovarian follicular dominance. No differences were found in the clinical pregnancy rates attained by the individuals with or without a dominant follicle after 21 vitrified-warmed blastocyst transfer cycles. Conclusion Occurrence of ovarian follicular dominance during hormonal stimulation for in-vitro maturation negatively impacted embryological outcomes. Strategies devised to limit the appearance of ovarian follicular dominance must be further explored. PMID:29338139

Establishment of detailed reference values for luteinizing hormone, follicle stimulating hormone, estradiol, and progesterone during different phases of the menstrual cycle on the Abbott ARCHITECT analyzer.

PubMed

Stricker, Reto; Eberhart, Raphael; Chevailler, Marie-Christine; Quinn, Frank A; Bischof, Paul; Stricker, René

2006-01-01

During a normal menstrual cycle, serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol, and progesterone can vary widely between cycles for the same woman, as well as between different woman. Reliable reference values based on the local population are important for correct interpretation of laboratory results. The purpose of our study was to determine detailed reference values for these hormones throughout the menstrual cycle using the Abbott ARCHITECT system. From 20 volunteers (age 20-36 years) with normal cycles and no use of oral contraceptives, samples were taken every day during their cycle. Volunteers received three vaginal ultrasound examinations (days 10 and 13, and 1 or 2 days after ovulation) to measure follicular and corpus luteum development. Hormone levels were measured using the corresponding ARCHITECT assay and were synchronized to the LH peak. Median, and 5th and 95th percentile values were determined for each day of the cycle, as well as for early follicular (days -15 to -6), late follicular (days -5 to -1), LH peak (day 0), early luteal (+1 to +4), mid-luteal (days +5 to +9), and late luteal (days +10 to +14) phases of the cycle. Based on our data, we were able to establish detailed reference values for LH, FSH, estradiol, and progesterone, which should aid in the interpretation of results for these reproductive hormones in a variety of circumstances.

Decreased levels of sRAGE in follicular fluid from patients with PCOS.

PubMed

Wang, BiJun; Li, Jing; Yang, QingLing; Zhang, FuLi; Hao, MengMeng; Guo, YiHong

2017-03-01

This study aimed to explore the association between soluble receptor for advanced glycation end products (sRAGE) levels in follicular fluid and the number of oocytes retrieved and to evaluate the effect of sRAGE on vascular endothelial growth factor (VEGF) in granulosa cells in patients with polycystic ovarian syndrome (PCOS). Two sets of experiments were performed in this study. In part one, sRAGE and VEGF protein levels in follicular fluid samples from 39 patients with PCOS and 35 non-PCOS patients were measured by ELISA. In part two, ovarian granulosa cells were isolated from an additional 10 patients with PCOS and cultured. VEGF and SP1 mRNA and protein levels, as well as pAKT levels, were detected by real-time PCR and Western blotting after cultured cells were treated with different concentrations of sRAGE. Compared with the non-PCOS patients, patients with PCOS had lower sRAGE levels in follicular fluid. Multi-adjusted regression analysis showed that high sRAGE levels in follicular fluid predicted a lower Gn dose, more oocytes retrieved, and a better IVF outcome in the non-PCOS group. Logistic regression analysis showed that higher sRAGE levels predicted favorably IVF outcomes in the non-PCOS group. Multi-adjusted regression analysis also showed that high sRAGE levels in follicular fluid predicted a lower Gn dose in the PCOS group. Treating granulosa cells isolated from patients with PCOS with recombinant sRAGE decreased VEGF and SP1 mRNA and protein expression and pAKT levels in a dose-dependent manner. © 2017 Society for Reproduction and Fertility.

Microorganisms inhabiting follicular contents of facial acne are not only Propionibacterium but also Malassezia spp.

PubMed

Akaza, Narifumi; Akamatsu, Hirohiko; Numata, Shigeki; Yamada, Shunji; Yagami, Akiko; Nakata, Satoru; Matsunaga, Kayoko

2016-08-01

To clarify the relationship between major cutaneous microorganisms (Propionibacterium, Staphylococcus and Malassezia spp.) and acne vulgaris (acne), we examined the microbiota quantitatively in the follicular contents of inflammatory acne and on the facial skin of patients with acne. Fifteen Japanese untreated acne outpatients were studied. The follicular contents from inflammatory acne lesions of the face were collected using a comedo extractor. The skin surface samples were obtained by the swab method from 10 cm(2) of facial skin. The microbiota was analyzed using polymerase chain reaction. The microbiota in follicular contents was similar to that on the skin surface, namely, there were large populations of Propionibacterium spp., Staphylococcus spp. and Malassezia spp. Moreover, the number of Malassezia spp. on the skin surface was correlated with that of inflammatory acne and that in follicular contents. This study clarified that there are large populations of Propionibacterium spp., Staphylococcus spp. and Malassezia spp. in follicular contents. These results suggest the possibility that not only Propionibacterium acnes but also other cutaneous resident microorganisms are related to acne. Particularly, we considered that Malassezia spp. is closely related. © 2015 Japanese Dermatological Association.

Fetal programming: prenatal testosterone treatment leads to follicular persistence/luteal defects; partial restoration of ovarian function by cyclic progesterone treatment.

PubMed

Manikkam, Mohan; Steckler, Teresa L; Welch, Kathleen B; Inskeep, E Keith; Padmanabhan, Vasantha

2006-04-01

Prenatal testosterone (T) excess during midgestation leads to estrous cycle defects and polycystic ovaries in sheep. We hypothesized that follicular persistence causes polycystic ovaries and that cyclic progesterone (P) treatment would overcome follicular persistence and restore cyclicity. Twice-weekly blood samples for P measurements were taken from control (C; n = 16) and prenatally T-treated (T60; n = 14; 100 mg T, im, twice weekly from d 30-90 of gestation) Suffolk sheep starting before the onset of puberty and continuing through the second breeding season. A subset of C and T60 sheep were treated cyclically with a modified controlled internal drug-releasing device for 13-14 d every 17 d during the first anestrus (CP, 7; TP, 6). Transrectal ovarian ultrasonography was performed for 8 d in the first and 21 d in the second breeding season. Prenatal T excess reduced the number, but increased the duration of progestogenic cycles, reduced the proportion of ewes with normal cycles, increased the proportion of ewes with subluteal cycles, decreased the proportion of ewes with ovulatory cycles, induced the occurrence of persistent follicles, and reduced the number of corpora lutea in those that cycled. Cyclic P treatment in anestrus, which produced one third the P concentration seen during luteal phase of cycle, did not reduce the number of persistent follicles, but increased the number of progestogenic cycles while reducing their duration. These findings suggested that follicular persistence might contribute to the polycystic ovarian morphology. Cyclic P treatment was able to only partially restore follicular dynamics, but this may be related to the low replacement concentrations of P achieved.

Ovarian follicular development and the follicular fluid hormones and growth factors in normal women of advanced reproductive age.

PubMed

Klein, N A; Battaglia, D E; Miller, P B; Branigan, E F; Giudice, L C; Soules, M R

1996-05-01

Reproductive aging in women (a physiological decline in the function of the hypothalamic-pituitary-ovarian axis) is an infrequently investigated and poorly understood biological phenomenon. Although menstrual irregularity and anovulation are known to precede the menopause, normal women in their fifth decade experience a profound decrease in fertility while still experiencing regular menstrual cycles. To further our understanding of the physiological changes associated with reproductive aging, this study examined the spontaneous development and function of ovarian follicles in normal women, aged 40-45 yr. The subjects were women (n = 21), aged 40-45 yr, who had regular 25- to 35-day ovulatory menstrual cycles, were not infertile, had no medical problems, and met specific criteria for weight, diet, and exercise. The controls were normal women (n = 20), age 20-25 yr, who met the same criteria. The subjects were monitored with daily hormone measurements [LH, FSH, estradiol (E), progesterone (P), and inhibin] and pelvic sonograms from day 1 of their study cycle until the dominant ovarian follicle reached a mean diameter of 15 mm and/or a serum E level of 550 pmol/L or higher was attained. At that time, 10,000 U hCG were given, and a transvaginal sonographic follicle aspiration was performed 32 h later. The follicular fluid (FF) was collected, stored frozen at -70 C, and later analyzed for E, P, testosterone (T), androstenedione, inhibin, insulin-like growth factor I (IGF-I), and IGF-II. The number of cycle days to aspiration was lower (11.6 vs. 15.6 days; P < 0.001) and the early follicular phase mean FSH and mean E levels were higher (9.3 vs. 6.6 mIU/mL and 305 vs. 160 pmol/L; P < 0.01) in the older (O) group compared to the younger group. There was a strong trend toward higher FF mean E (2280 vs. 1931 nmol/L) and lower FF mean T (978 vs. 2361 pmol/L) levels in group O. The E/T ratio was significantly higher (5253 vs. 2408; P < 0.03) in group O. In group O, the mean FF

Exosomal and Non-Exosomal Transport of Extra-Cellular microRNAs in Follicular Fluid: Implications for Bovine Oocyte Developmental Competence

PubMed Central

Sohel, Md. Mahmodul Hasan; Hoelker, Michael; Noferesti, Sina Seifi; Salilew-Wondim, Dessie; Tholen, Ernst; Looft, Christian; Rings, Franca; Uddin, Muhammad Jasim; Spencer, Thomas E.; Schellander, Karl; Tesfaye, Dawit

2013-01-01

Cell-cell communication within the follicle involves many signaling molecules, and this process may be mediated by secretion and uptake of exosomes that contain several bioactive molecules including extra-cellular miRNAs. Follicular fluid and cells from individual follicles of cattle were grouped based on Brilliant Cresyl Blue (BCB) staining of the corresponding oocytes. Both Exoquick precipitation and differential ultracentrifugation were used to separate the exosome and non-exosomal fraction of follicular fluid. Following miRNA isolation from both fractions, the human miRCURY LNA™ Universal RT miRNA PCR array system was used to profile miRNA expression. This analysis found that miRNAs were present in both exosomal and non-exosomal fraction of bovine follicular fluid. We found 25 miRNAs differentially expressed (16 up and 9 down) in exosomes and 30 miRNAs differentially expressed (21 up and 9 down) in non-exosomal fraction of follicular fluid in comparison of BCB- versus BCB+ oocyte groups. Expression of selected miRNAs was detected in theca, granulosa and cumulus oocyte complex. To further explore the potential roles of these follicular fluid derived extra-cellular miRNAs, the potential target genes were predicted, and functional annotation and pathway analysis revealed most of these pathways are known regulators of follicular development and oocyte growth. In order to validate exosome mediated cell-cell communication within follicular microenvironment, we demonstrated uptake of exosomes and resulting increase of endogenous miRNA level and subsequent alteration of mRNA levels in follicular cells in vitro. This study demonstrates for the first time, the presence of exosome or non-exosome mediated transfer of miRNA in the bovine follicular fluid, and oocyte growth dependent variation in extra-cellular miRNA signatures in the follicular environment. PMID:24223816

Fluctuation-driven electroweak phase transition. [in early universe

NASA Technical Reports Server (NTRS)

Gleiser, Marcelo; Kolb, Edward W.

1992-01-01

We examine the dynamics of the electroweak phase transition in the early Universe. For Higgs masses in the range 46 less than or = M sub H less than or = 150 GeV and top quark masses less than 200 GeV, regions of symmetric and asymmetric vacuum coexist to below the critical temperature, with thermal equilibrium between the two phases maintained by fluctuations of both phases. We propose that the transition to the asymmetric vacuum is completed by percolation of these subcritical fluctuations. Our results are relevant to scenarios of baryogenesis that invoke a weakly first-order phase transition at the electroweak scale.

Nonspecific iodine accumulation in surgical suture material mimicking follicular thyroid cancer bone metastasis in (131)I scintigraphy.

PubMed

Winkens, Thomas; Nietzsche, Sandor; Gottschaldt, Michael; Freesmeyer, Martin

2014-02-01

A 23-year-old man with follicular thyroid carcinoma and cervical lymph node metastases showed a clear I focus on the skull after radioiodine therapy; therefore, an osseous metastasis was suspected. I and MRI fusion suggested the I focus to be adjacent to an epicranial suture from an early childhood trepanation for epidural hematoma. Radio-guided surgery found dark brown material to be the source of the radiation and successfully removed the material. Subsequent electron microscopy revealed a thread within the dark brown material, suggesting suture material as the cause of I accumulation.

Follicular thyroid cancer and Hürthle cell carcinoma: challenges in diagnosis, treatment, and clinical management.

PubMed

Grani, Giorgio; Lamartina, Livia; Durante, Cosimo; Filetti, Sebastiano; Cooper, David S

2018-06-01

Follicular thyroid cancer is the second most common differentiated thyroid cancer histological type and has been overshadowed by its more common counterpart-papillary thyroid cancer-despite its unique biological behaviour and less favourable outcomes. In this Review, we comprehensively review the literature on follicular thyroid cancer to provide an evidence-based guide to the management of these tumours, to highlight the lack of evidence behind guideline recommendations, and to identify changes and challenges over the past decades in diagnosis, prognosis, and treatment. We highlight that correct identification of cancer in indeterminate cytological samples is challenging and ultrasonographic features can be misleading. Despite certain unique aspects of follicular thyroid cancer presentation and prognosis, no specific recommendations exist for follicular thyroid cancer and Hürthle cell carcinoma in evidence-based guidelines. Efforts should be made to stimulate additional research in this field. Copyright © 2018 Elsevier Ltd. All rights reserved.

Follicular variant of papillary thyroid carcinoma: genome-wide appraisal of a controversial entity.

PubMed

Wreesmann, Volkert B; Ghossein, Ronald A; Hezel, Michael; Banerjee, Debenranrath; Shaha, Ashok R; Tuttle, R Michael; Shah, Jatin P; Rao, Pulivarthi H; Singh, Bhuvanesh

2004-08-01

The majority of thyroid tumors are classified as papillary (papillary thyroid carcinomas; PTCs) or follicular neoplasms (follicular thyroid adenomas and carcinomas; FTA/FTC) based on nuclear features and the cellular growth pattern. However, classification of the follicular variant of papillary thyroid carcinoma (FVPTC) remains an issue of debate. These tumors contain a predominantly follicular growth pattern but display nuclear features and overall clinical behavior consistent with PTC. In this study, we used comparative genomic hybridization (CGH) to compare the global chromosomal aberrations in FVPTC to the PTC of classical variant (classical PTC) and FTA/FTC. In addition, we assessed the presence of peroxisome proliferator-activated receptor-gamma (PPARG) alteration, a genetic event specific to FTA/FTC, using Southern blot and immunohistochemistry analyses. In sharp contrast to the findings in classical PTC (4% of cases), CGH analysis demonstrated that both FVPTC (59% of cases) and FTA/FTC (36% of cases) were commonly characterized by aneuploidy (P = 0.0002). Moreover, the pattern of chromosomal aberrations (gains at chromosome arms 2q, 4q, 5q, 6q, 8q, and 13q and deletions at 1p, 9q, 16q, 17q, 19q, and 22q) in the follicular variant of PTC closely resembled that of FTA/FTC. Aberrations in PPARG were uniquely detected in FVPTC and FTA/FTC. Our findings suggest a stronger relationship between the FVPTC and FTA/FTC than previously appreciated and support further consideration of the current classification of thyroid neoplasms. Copyright 2004 Wiley-Liss, Inc.

Expression of hypoxia-inducible factor-1α during ovarian follicular growth and development in Sprague-Dawley rats.

PubMed

Zhang, Z H; Chen, L Y; Wang, F; Wu, Y Q; Su, J Q; Huang, X H; Wang, Z C; Cheng, Y

2015-06-01

Hypoxia-inducible factor-1α (HIF-1α) has been identified as a transcription factor that is involved in diverse physiological and pathological processes in the ovary. In this study, we examined whether HIF-1α is expressed in a cell- and stage-specific manner during follicular growth and development in the mammalian ovaries. Using immunohistochemistry and Western blot analysis, HIF-1α expression was observed in granulosa cells specifically and was significantly increased during the follicular growth and development of postnatal rats. Furthermore, pregnant mare serum gonadotropin also induced HIF-1α expression in granulosa cells and ovaries during the follicular development of immature rats primed with gonadotropin. Moreover, we also examined proliferation cell nuclear antigen, a cell proliferation marker, during follicular growth and development and found that its expression pattern was similar to that of HIF-1α protein. Granulosa cell culture experiments revealed that proliferation cell nuclear antigen expression may be regulated by HIF-1α. These results indicated that HIF-1α plays an important role in the follicular growth and development of these 2 rat models. The HIF-1α-mediated signaling pathway may be an important mechanism regulating follicular growth and development in mammalian ovaries in vivo.

Early Relapse of Follicular Lymphoma After Rituximab Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone Defines Patients at High Risk for Death: An Analysis From the National LymphoCare Study

PubMed Central

Casulo, Carla; Byrtek, Michelle; Dawson, Keith L.; Zhou, Xiaolei; Farber, Charles M.; Flowers, Christopher R.; Hainsworth, John D.; Maurer, Matthew J.; Cerhan, James R.; Link, Brian K.; Zelenetz, Andrew D.; Friedberg, Jonathan W.

2015-01-01

Purpose Twenty percent of patients with follicular lymphoma (FL) experience progression of disease (POD) within 2 years of initial chemoimmunotherapy. We analyzed data from the National LymphoCare Study to identify whether prognostic FL factors are associated with early POD and whether patients with early POD are at high risk for death. Patients and Methods In total, 588 patients with stage 2 to 4 FL received first-line rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Two groups were defined: patients with early POD 2 years or less after diagnosis and those without POD within 2 years, the reference group. An independent validation set, 147 patients with FL who received first-line R-CHOP, was analyzed for reproducibility. Results Of 588 patients, 19% (n = 110) had early POD, 71% (n = 420) were in the reference group, 8% (n = 46) were lost to follow-up, and 2% (n = 12) died without POD less than 2 years after diagnosis. Five-year overall survival was lower in the early-POD group than in the reference group (50% v 90%). This trend was maintained after we adjusted for FL International Prognostic Index (hazard ratio, 6.44; 95% CI, 4.33 to 9.58). Results were similar for the validation set (FL International Prognostic Index–adjusted hazard ratio, 19.8). Conclusion In patients with FL who received first-line R-CHOP, POD within 2 years after diagnosis was associated with poor outcomes and should be further validated as a standard end point of chemoimmunotherapy trials of untreated FL. This high-risk FL population warrants further study in directed prospective clinical trials. PMID:26124482

The effect of pinealectomy, melatonin and leptin hormones on ovarian follicular development in female Syrian hamsters (Mesocricetus auratus).

PubMed

Karakaş, A; Kaya, Aliye; Gündüz, B

2010-12-01

We studied the effects of melatonin and leptin hormones on ovarian follicular development in intact and pinealectomized female Syrian hamsters. We first monitored the oestrous cycle of the hamsters by the vaginal smear samples throughout a ten day period to start the injections simultaneously in all groups and performed saline, melatonin and leptin hormone injection groups for both control and pinealectomized hamsters. Then the injections were applied for four days starting the oestrus phase of the cycle and the ovaries were removed for preparation of histological analysis. We measured the diameters and the numbers of the follicles and we classified the follicles according to the number of the granulosa cell layer. Leptin hormone injection increased melatonin hormone injection decreased the number and the diameter of the follicles. The stimulating effect of the leptin hormone was more pronounced in the pinealectomized group. The results of the present study indicate that the removal of the pineal gland and leptin hormone administration are playing a stimulatory while melatonin hormone administration is playing an inhibitory role on the follicular development in female Syrian hamsters.

Maternal sympathetic stress impairs follicular development and puberty of the offspring.

PubMed

Barra, Rafael; Cruz, Gonzalo; Mayerhofer, Artur; Paredes, Alfonso; Lara, Hernán E

2014-08-01

Chronic cold stress applied to adult rats activates ovarian sympathetic innervation and develops polycystic ovary (PCO) phenotype. The PCO syndrome in humans originates during early development and is expressed before or during puberty, which suggests that the condition derived from in utero exposure to neural- or metabolic-derived insults. We studied the effects of maternal sympathetic stress on the ovarian follicular development and on the onset of puberty of female offspring. Timed pregnant rats were exposed to chronic cold stress (4 °C, 3 h/daily from 1000 to 1300 h) during the entire pregnancy. Neonatal rats exposed to sympathetic stress during gestation had a lower number of primary, primordial, and secondary follicles in the ovary and a lower recruitment of primary and secondary follicles derived from the primordial follicular pool. The expression of the FSH receptor and response of the neonatal ovary to FSH were reduced. A decrease in nerve growth factor (NGF) mRNA was found without change in the low-affinity NGF receptor. The FSH-induced development of secondary follicles was decreased. At puberty, estradiol plasma levels decreased without changes in LH plasma levels. Puberty onset (as shown by the vaginal opening) was delayed. Ovarian norepinephrine (NE) was reduced; there was no change in its metabolite, 3-methoxy-4-hydroxyphenylglycol, in stressed rats and no change in NE turnover. The changes in ovarian NE in prepubertal rats stressed during gestation could represent a lower development of sympathetic nerves as a compensatory response to the chronically increased NE levels during gestation and hence participate in delaying reproductive performance in the rat. © 2014 Society for Reproduction and Fertility.

Microrna-199a-5p Functions as a Tumor Suppressor via Suppressing Connective Tissue Growth Factor (CTGF) in Follicular Thyroid Carcinoma.

PubMed

Sun, Dawei; Han, Shen; Liu, Chao; Zhou, Rui; Sun, Weihai; Zhang, Zhijun; Qu, Jianjun

2016-04-11

BACKGROUND The objective of this study was to explore the role of miR-199a-5p in the development of thyroid cancer, including its anti-proliferation effect and downstream signaling pathway. MATERIAL AND METHODS We conducted qRT-PCR analysis to detect the expressions of several microRNAs in 42 follicular thyroid carcinoma patients and 42 controls. We identified CTGF as target of miR-491, and viability and cell cycle status were determined in FTC-133 cells transfected with CTGF siRNA, miR-199a mimics, or inhibitors. RESULTS We identified an underexpression of miR-199a-5p in follicular thyroid carcinoma tissue samples compared with controls. Then we confirmed CTGF as a target of miR-199a-5p thyroid cells by using informatics analysis and luciferase reporter assay. Additionally, we found that mRNA and protein expression levels of CTGF were both clearly higher in malignant tissues than in benign tissues. miR-199a-5p mimics and CTGF siRNA similarly downregulated the expression of CTGF, and reduced the viability of FTC-133 cells by arresting the cell cycle in G0 phase. Transfection of miR-199a-5p inhibitors increased the expression of CTGF and promoted the viability of the cells by increasing the fraction of cells in G2/M and S phases. CONCLUSIONS Our study proves that the CTGF gene is a target of miR-199a-5p, demonstrating the negatively related association between CTGF and miR-199a. These findings suggest that miR-199a-5p might be a novel therapeutic target in the treatment of follicular thyroid carcinoma.

Alterations in leucocyte subsets and histomorphology in normal-appearing perilesional skin and early and chronic hidradenitis suppurativa lesions.

PubMed

van der Zee, H H; de Ruiter, L; Boer, J; van den Broecke, D G; den Hollander, J C; Laman, J D; Prens, E P

2012-01-01

Current insight into the histopathological course of events during disease progression in hidradenitis suppurativa (HS) is fragmentary. To identify histological alterations and leucocyte subsets in normal-appearing perilesional skin, and early and chronic HS lesions. In this observational study we examined eight perilesional skin samples, and six early and 10 chronic prototypic HS lesions, as well as skin samples from four healthy donors using in situ immunostaining. Perilesional skin showed mild psoriasiform hyperplasia and follicular plugging as well as a low-grade influx of tryptase-positive mast cells, CD3+ T cells, CD138+ plasma cells and factor XIIIa+ dendritic cells. In early HS lesions, neutrophilic abscess formation and influx of mainly macrophages, monocytes and dendritic cells predominated. In chronic disease, the infiltrate expanded with markedly increased frequencies of CD20+ and CD79a+ B cells and CD138+ plasma cells. As in early lesions, free keratin fibres were detected in the dermis and within giant cells. Single detached keratinocytes and strands of follicular epithelium were observed in the dermis, the latter frequently expressing Ki67, indicative of active proliferation. Psoriasiform hyperplasia, follicular plugging and low-grade leucocytic infiltration are already present in normal-appearing perilesional skin. Keratin fibres in the dermis are associated with clinical disease. Early lesions are characterized by neutrophilic abscess formation and influx of mainly histiocytes, and chronic lesions mainly by expansion of B cells and plasma cells in 'pseudo' follicles. Proliferating strands of follicular epithelium may initiate fistula formation. Mast cells are increased in all stages of HS including perilesional skin. © 2011 The Authors. BJD © 2011 British Association of Dermatologists.

Volunteering for early phase gene transfer research in Parkinson disease.

PubMed

Kim, S Y H; Holloway, R G; Frank, S; Beck, C A; Zimmerman, C; Wilson, R; Kieburtz, K

2006-04-11

For early phase trials of novel interventions-such as gene transfer for Parkinson disease (PD)--whose focus is primarily on safety and tolerability, it is important that participants have a realistic understanding of the goals of such research. Recently, some have expressed concern that patients with PD may have unrealistic expectations. The authors examined why patients with PD might volunteer for invasive early phase research by interviewing 92 patients with PD and comparing those who would (n = 46) and those who would not (n = 46) participate in a hypothetical phase I gene-transfer study. The two groups' demographic, clinical, functional, and quality of life measures, as well as their understanding of the research protocol, were similar. The groups did not differ on their perception of potential for personal benefit nor on the level of likelihood of benefit they saw as a precondition for volunteering. However, those willing to participate tended to perceive lower probability of risk, were tolerant of greater probability of risk, and were more optimistic about the phase I study's potential benefits to society. They also appeared more decisive and action-oriented than the unwilling group. It is likely that the decision whether to participate in early phase PD gene transfer studies will depend mostly on patients' attitudes regarding risk, optimism about science, and an action orientation, rather than on their clinical, functional, or demographic characteristics.

Implementing Effective Mission Systems Engineering Practices During Early Project Formulation Phases

NASA Technical Reports Server (NTRS)

Moton, Tryshanda

2016-01-01

Developing and implementing a plan for a NASA space mission can be a complicated process. The needs, goals, and objectives of any proposed mission or technology must be assessed early in the Project Life Cycle. The key to successful development of a space mission or flight project is the inclusion of systems engineering in early project formulation, namely during Pre-phase A, Phase A, and Phase B of the NASA Project Life Cycle. When a space mission or new technology is in pre-development, or "pre-Formulation", feasibility must be determined based on cost, schedule, and risk. Inclusion of system engineering during project formulation is key because in addition to assessing feasibility, design concepts are developed and alternatives to design concepts are evaluated. Lack of systems engineering involvement early in the project formulation can result in increased risks later in the implementation and operations phases of the project. One proven method for effective systems engineering practice during the pre-Formulation Phase is the use of a mission conceptual design or technology development laboratory, such as the Mission Design Lab (MDL) at NASA's Goddard Space Flight Center (GSFC). This paper will review the engineering process practiced routinely in the MDL for successful mission or project development during the pre-Formulation Phase.

Fatty Acid Composition of Human Follicular Fluid Phospholipids and Fertilization Rate in Assisted Reproductive Techniques

PubMed Central

Shaaker, Maghsod; Rahimipour, Ali; Nouri, Mohammad; Khanaki, Korosh; Darabi, Masoud; Farzadi, Laya; Shahnazi, Vahideh; Mehdizadeh, Amir

2012-01-01

Background: Fatty acids are known to be critically important in multiple biological functions. Phospholipid fatty acids of follicular fluid, an important microenvironment for the development of oocytes, may contribute to the women’s fertility and the efficacy of assisted reproduction techniques. The aim of this study was to investigate the effect of fatty acid composition of follicular fluid phospholipids on women undergoing assisted reproductive techniques. Methods: Follicular fluid samples were obtained from 100 patients, referred to Tabriz Alzahra Hospital. Seventy-nine subjects underwent in vitro fertilization (IVF) and the remaining 21 underwent intracytoplasmic sperm injection (ICSI). Total lipid of follicular fluid was extracted and fatty acids were analyzed by gas-liquid chromatography. Results: Saturated fatty acids (SFA, P = 0.002) and the ratio of SFA to polyunsaturated fatty acids (P = 0.001) were correlated negatively with a number of mature oocytes after age adjustment. Linoleic acid (P = 0.006) was positively correlated, while the level of arachidonic acid was negatively correlated with fertility percentage after adjustment for body mass index, sperm count, sperm motility. Conclusion: Since phospholipids are one of the major components of lipid metabolism, the results of this study highlight the importance of this component in follicular fluid lipid metabolism. Consequently, it is proposed as an index in determination of the rate of success in assisted reproductive techniques such as IVF/ICSI. PMID:23023218

Vitellogenin transcytosis in follicular cells of the honeybee Apis mellifera and the wasp Polistes simillimus.

PubMed

Dohanik, Virgínia Teles; Gonçalves, Wagner Gonzaga; Oliveira, Leandro Licursi; Zanuncio, José Cola; Serrão, José Eduardo

2018-05-13

Vitellogenin receptor (VgR) is a low-density lipoprotein receptor responsible for the mediated endocytosis of vitellogenin (Vg) during egg formation in insects. The maturing oocyte is enveloped by a follicular epithelium, which has large intercellular spaces during Vg accumulation (patency). However, Vg has been reported in the cytoplasm of follicular cells, indicating that there may be a transcellular route for its transport. This study verified the presence of VgR in the follicular cells of the ovaries of the honeybee Apis mellifera and the wasp Polistes simillimus in order to evaluate if Vg is transported via transcytosis in these insects. Antibodies specific for vitellogenin receptor (anti-VgR), vitellogenin (anti-Vg), and clathrin (anti-Clt) were used for immunolocalization. The results showed the presence of VgR on the apical and basal plasma membranes of follicular cells of the vitellogenic follicles in both species, indicating that VgR may have been transported from the basal to the apical cell domain, followed by its release into the perivitelline space, evidenced by the presence of apical plasma membrane projections containing VgR. Co-localization proved that Vg bind to VgR and that the transport of this protein is mediated by clathrin. These data suggest that, in these social insects, Vg is transported via clathrin-mediated VgR transcytosis in follicular cells.

Autologous Transplantation in Follicular Lymphoma with Early Therapy Failure: A National LymphoCare Study and Center for International Blood and Marrow Transplant Research Analysis.

PubMed

Casulo, Carla; Friedberg, Jonathan W; Ahn, Kwang W; Flowers, Christopher; DiGilio, Alyssa; Smith, Sonali M; Ahmed, Sairah; Inwards, David; Aljurf, Mahmoud; Chen, Andy I; Choe, Hannah; Cohen, Jonathon; Copelan, Edward; Farooq, Umar; Fenske, Timothy S; Freytes, Cesar; Gaballa, Sameh; Ganguly, Siddhartha; Jethava, Yogesh; Kamble, Rammurti T; Kenkre, Vaishalee P; Lazarus, Hillard; Lazaryan, Aleksandr; Olsson, Richard F; Rezvani, Andrew R; Rizzieri, David; Seo, Sachiko; Shah, Gunjan L; Shah, Nina; Solh, Melham; Sureda, Anna; William, Basem; Cumpston, Aaron; Zelenetz, Andrew D; Link, Brian K; Hamadani, Mehdi

2018-06-01

Patients with follicular lymphoma (FL) experiencing early therapy failure (ETF) within 2 years of frontline chemoimmunotherapy have poor overall survival (OS). We analyzed data from the Center for International Blood and Marrow Transplant Research (CIBMTR) and the National LymphoCare Study (NLCS) to determine whether autologous hematopoietic cell transplant (autoHCT) can improve outcomes in this high-risk FL subgroup. ETF was defined as failure to achieve at least partial response after frontline chemoimmunotherapy or lymphoma progression within 2 years of frontline chemoimmunotherapy. We identified 2 groups: the non-autoHCT cohort (patients from the NLCS with ETF not undergoing autoHCT) and the autoHCT cohort (CIBMTR patients with ETF undergoing autoHCT). All patients received rituximab-based chemotherapy as frontline treatment; 174 non-autoHCT patients and 175 autoHCT patients were identified and analyzed. There was no difference in 5-year OS between the 2 groups (60% versus 67%, respectively; P = .16). A planned subgroup analysis showed that patients with ETF receiving autoHCT soon after treatment failure (≤1 year of ETF; n = 123) had higher 5-year OS than those without autoHCT (73% versus 60%, P = .05). On multivariate analysis, early use of autoHCT was associated with significantly reduced mortality (hazard ratio, .63; 95% confidence interval, .42 to .94; P = .02). Patients with FL experiencing ETF after frontline chemoimmunotherapy lack optimal therapy. We demonstrate improved OS when receiving autoHCT within 1 year of treatment failure. Results from this unique collaboration between the NLCS and CIBMTR support consideration of early consolidation with autoHCT in select FL patients experiencing ETF. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Intra-cellular mechanism of Anti-Müllerian hormone (AMH) in regulation of follicular development.

PubMed

Hayes, Emily; Kushnir, Vitaly; Ma, Xiaoting; Biswas, Anindita; Prizant, Hen; Gleicher, Norbert; Sen, Aritro

2016-09-15

Anti-Müllerian hormone (AMH) is a member of the transforming growth factor-β superfamily and plays a crucial role in testicular and ovarian functions. In clinical practice, AMH is used as a diagnostic and/or prognostic marker in women in association with ovulation induction and in various pathophysiological conditions. Despite widespread clinical use of AMH, our mechanistic understanding of AMH actions in regulating follicular development is limited. Using a mouse model, we in this study report that in vivo AMH treatment while stalls follicular development and inhibits ovulation, also prevents follicular atresia. We further show that these AMH actions are mediated through induction of two miRNAs, miR-181a and miR-181b, which regulate various aspects of FSH signaling and follicular growth, ultimately affecting downstream gene expression and folliculogenesis. We also report that in this mouse model AMH pre-treatment prior to superovulation improves oocyte yield. These studies, therefore, offer new mechanistic insight into AMH actions in folliculogenesis and point toward potential utilization of AMH as a therapeutic agent. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Biochemical and hormonal analysis of follicular fluid and serum of female dromedary camels (Camelus dromedarius) with different sized ovarian follicles.

PubMed

El-Bahr, S M; Ghoneim, I M; Waheed, M M

2015-08-01

The current study aimed to compare some biochemical and hormonal constituents in follicular fluids and serum of female dromedary camels with different sized ovarian follicles. Therefore, follicular fluids from follicles sized 1.1-1.5cm (n=10), 1.6-2.1cm (n=10) and 2.2-2.5cm (n=10) and sera were harvested from 20 female camels. The concentrations of ascorbic acid, glucose, cholesterol and activities of acid phosphatase (ACP) and alkaline phosphatase (ALP) were not changed significantly neither in follicular fluids of all follicle sizes nor in sera of female camels with different sized follicles. The concentrations of estradiol-17β (E2) in the follicular fluid of follicles sized 2.2-2.5cm were significantly lower (P<0.01) than its corresponding value in follicular fluid of other follicle sizes. The concentrations of progesterone (P4), tri-iodothyronine (T3), thyroxin (T4), cortisol and insulin-like growth factor-1 (IGF-1) remained comparable in follicular fluids of all examined different sized follicles. The concentrations of E2, P4, T3, T4, cortisol and IGF-1 were similar in the serum of camels with different sized follicles. Interestingly, mean concentrations of P4 and IGF-1 in follicular fluids were higher than their corresponding values in sera of camels with different sized follicles and the mean concentrations of glucose, cholesterol, ALP and cortisol in sera were higher than their corresponding values in follicular fluids of the examined camels. With the exception of E2, there were no significant differences in biochemical and hormonal constituents between follicular fluids from different sized follicles. Copyright © 2015 Elsevier B.V. All rights reserved.

Clinical and cytological features predictive of malignancy in thyroid follicular neoplasms.

PubMed

Lubitz, Carrie C; Faquin, William C; Yang, Jingyun; Mekel, Michal; Gaz, Randall D; Parangi, Sareh; Randolph, Gregory W; Hodin, Richard A; Stephen, Antonia E

2010-01-01

The preoperative diagnosis of malignancy in nodules suspicious for a follicular neoplasm remains challenging. A number of clinical and cytological parameters have been previously studied; however, none have significantly impacted clinical practice. The aim of this study was to determine predictive characteristics of follicular neoplasms useful for clinical application. Four clinical (age, sex, nodule size, solitary nodule) and 17 cytological variables were retrospectively reviewed for 144 patients with a nodule suspicious for follicular neoplasm, diagnosed preoperatively by fine-needle aspiration (FNA), from a single institution over a 2-year period (January 2006 to December 2007). The FNAs were examined by a single, blinded pathologist and compared with final surgical pathology. Significance of clinical and cytological variables was determined by univariate analysis and backward stepwise logistic regression. Odds ratios (ORs) for malignancy, a receiver operating characteristic curve, and predicted probabilities of combined features were determined. There was an 11% incidence of malignancy (16/144). On univariate analysis, nodule size >OR=4.0 cm nears significance (p = 0.054) and 9 of 17 cytological features examined were significantly associated with malignancy. Three variables stay in the final model after performing backward stepwise selection in logistic regression: nodule size (OR = 0.25, p = 0.05), presence of a transgressing vessel (OR = 23, p < 0.0001), and nuclear grooves (OR = 4.3, p = 0.03). The predicted probability of malignancy was 88.4% with the presence of all three variables on preoperative FNA. When the two papillary carcinomas were excluded from the analysis, the presence of nuclear grooves was no longer significant, and anisokaryosis (OR = 12.74, p = 0.005) and presence of nucleolus (OR = 0.11, p = 0.04) were significantly associated with malignancy. Excluding the two papillary thyroid carcinomas, a nodule size >or=4 cm, with a transgressing

Cell of origin of transformed follicular lymphoma

PubMed Central

Kridel, Robert; Mottok, Anja; Farinha, Pedro; Ben-Neriah, Susana; Ennishi, Daisuke; Zheng, Yvonne; Chavez, Elizabeth A.; Shulha, Hennady P.; Tan, King; Chan, Fong Chun; Boyle, Merrill; Meissner, Barbara; Telenius, Adele; Sehn, Laurie H.; Marra, Marco A.; Shah, Sohrab P.; Steidl, Christian; Connors, Joseph M.; Scott, David W.

2015-01-01

Follicular lymphoma (FL) is an indolent disease but transforms in 2% to 3% of patients per year into aggressive, large cell lymphoma, a critical event in the course of the disease associated with increased lymphoma-related mortality. Early transformation cannot be accurately predicted at the time of FL diagnosis and the biology of transformed FL (TFL) is poorly understood. Here, we assembled a cohort of 126 diagnostic FL specimens including 40 patients experiencing transformation (<5 years) and 86 patients not experiencing transformation for at least 5 years. In addition, we assembled an overlapping cohort of 155 TFL patients, including 114 cases for which paired samples were available, and assessed temporal changes of routinely available biomarkers, outcome after transformation, as well as molecular subtypes of TFL. We report that the expression of IRF4 is an independent predictor of early transformation (Hazard ratio, 13.3; P < .001). We also show that composite histology at the time of transformation predicts favorable prognosis. Moreover, applying the Lymph2Cx digital gene expression assay for diffuse large B-cell lymphoma (DLBCL) cell-of-origin determination to 110 patients with DLBCL-like TFL, we demonstrate that TFL is of the germinal-center B-cell–like subtype in the majority of cases (80%) but that a significant proportion of cases is of the activated B-cell–like (ABC) subtype (16%). These latter cases are commonly negative for BCL2 translocation and arise preferentially from BCL2 translocation-negative and/or IRF4-expressing FLs. Our study demonstrates the existence of molecular heterogeneity in TFL as well as its relationship to the antecedent FL. PMID:26307535

Follicular keratosis of the chin treated with 1.24R-dihydroxyvitamin D3 ointment.

PubMed

Yanagihara, Makoto; Takeda, Kiminobu; Tanabe, Hiroshi; Abe, Shinya; Ishizaki, Hiroshi

2007-01-01

In follicular keratosis of the chin, keratotic follicular papules occur on the chin and jaw due to localized prolonged pressure and friction on the naked skin. We present one patient with this disorder. The dermatoscopic examination revealed many well-demarcated yellow spindle bodies in the patchy lesion. Therapy with 1.24R-dihydroxyvitamin D3 ointment was effective during the treatment but had no residual positive effect.

Luteinizing hormone receptors in human ovarian follicles and corpora lutea during the menstrual cycle

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

Yamoto, M.; Nakano, R.; Iwasaki, M.

The binding of /sup 125/I-labeled human luteinizing hormone (hLH) to the 2000-g fraction of human ovarian follicles and corpora lutea during the entire menstrual cycle was examined. Specific high affinity, low capacity receptors for hLH were demonstrated in the 2000-g fraction of both follicles and corpora lutea. Specific binding of /sup 125/I-labeled hLH to follicular tissue increased from the early follicular phase to the ovulatory phase. Specific binding of /sup 125/I-labeled hLH to luteal tissue increased from the early luteal phase to the midluteal phase and decreased towards the late luteal phase. The results of the present study indicate thatmore » the increase and decrease in receptors for hLH during the menstrual cycle might play an important role in the regulation of the ovarian cycle.« less

40 CFR 76.8 - Early election for Group 1, Phase II boilers.

Code of Federal Regulations, 2010 CFR

2010-07-01

... PROGRAMS (CONTINUED) ACID RAIN NITROGEN OXIDES EMISSION REDUCTION PROGRAM § 76.8 Early election for Group 1... plan and: (i) If a Phase I Acid Rain permit governing the source at which the unit is located has been... chapter to include the early election plan; or (ii) If a Phase I Acid Rain permit governing the source at...

40 CFR 76.8 - Early election for Group 1, Phase II boilers.

Code of Federal Regulations, 2014 CFR

2014-07-01

... PROGRAMS (CONTINUED) ACID RAIN NITROGEN OXIDES EMISSION REDUCTION PROGRAM § 76.8 Early election for Group 1... plan and: (i) If a Phase I Acid Rain permit governing the source at which the unit is located has been... chapter to include the early election plan; or (ii) If a Phase I Acid Rain permit governing the source at...

40 CFR 76.8 - Early election for Group 1, Phase II boilers.

Code of Federal Regulations, 2011 CFR

2011-07-01

... PROGRAMS (CONTINUED) ACID RAIN NITROGEN OXIDES EMISSION REDUCTION PROGRAM § 76.8 Early election for Group 1... plan and: (i) If a Phase I Acid Rain permit governing the source at which the unit is located has been... chapter to include the early election plan; or (ii) If a Phase I Acid Rain permit governing the source at...

40 CFR 76.8 - Early election for Group 1, Phase II boilers.

Code of Federal Regulations, 2012 CFR

2012-07-01

... PROGRAMS (CONTINUED) ACID RAIN NITROGEN OXIDES EMISSION REDUCTION PROGRAM § 76.8 Early election for Group 1... plan and: (i) If a Phase I Acid Rain permit governing the source at which the unit is located has been... chapter to include the early election plan; or (ii) If a Phase I Acid Rain permit governing the source at...

40 CFR 76.8 - Early election for Group 1, Phase II boilers.

Code of Federal Regulations, 2013 CFR

2013-07-01

... PROGRAMS (CONTINUED) ACID RAIN NITROGEN OXIDES EMISSION REDUCTION PROGRAM § 76.8 Early election for Group 1... plan and: (i) If a Phase I Acid Rain permit governing the source at which the unit is located has been... chapter to include the early election plan; or (ii) If a Phase I Acid Rain permit governing the source at...

Phase III Early Restoration Meeting - Corpus Christi, TX | NOAA Gulf Spill

Science.gov Websites

Areas Alabama Florida Louisiana Mississippi Texas Region-wide Open Ocean Data Media & News programmatic approach to early restoration planning for Phase III and future early restoration plans. Open

Presence of bile acids in human follicular fluid and their relation with embryo development in modified natural cycle IVF.

PubMed

Nagy, R A; van Montfoort, A P A; Dikkers, A; van Echten-Arends, J; Homminga, I; Land, J A; Hoek, A; Tietge, U J F

2015-05-01

Are bile acids (BA) and their respective subspecies present in human follicular fluid (FF) and do they relate to embryo quality in modified natural cycle IVF (MNC-IVF)? BA concentrations are 2-fold higher in follicular fluid than in serum and ursodeoxycholic acid (UDCA) derivatives were associated with development of top quality embryos on Day 3 after fertilization. Granulosa cells are capable of synthesizing BA, but a potential correlation with oocyte and embryo quality as well as information on the presence and role of BA subspecies in follicular fluid have yet to be investigated. Between January 2001 and June 2004, follicular fluid and serum samples were collected from 303 patients treated in a single academic centre that was involved in a multicentre cohort study on the effectiveness of MNC-IVF. Material from patients who underwent a first cycle of MNC-IVF was used. Serum was not stored from all patients, and the available material comprised 156 follicular fluid and 116 matching serum samples. Total BA and BA subspecies were measured in follicular fluid and in matching serum by enzymatic fluorimetric assay and liquid chromatography-mass spectrometry, respectively. The association of BA in follicular fluid with oocyte and embryo quality parameters, such as fertilization rate and cell number, presence of multinucleated blastomeres and percentage of fragmentation on Day 3, was analysed. Embryos with eight cells on Day 3 after oocyte retrieval were more likely to originate from follicles with a higher level of UDCA derivatives than those with fewer than eight cells (P < 0.05). Furthermore, follicular fluid levels of chenodeoxycholic derivatives were higher and deoxycholic derivatives were lower in the group of embryos with fragmentation compared with those without (each P < 0.05). Levels of total BA were 2-fold higher in follicular fluid compared with serum (P < 0.001), but had no predictive value for oocyte and embryo quality. Only samples originating from first

Pulsatile LH secretion and ovarian follicular wave emergence and growth in anestrous ewes.

PubMed

Seekallu, Srinivas V; Barrett, David M W; Toosi, Behzad M; Clarke, Kelsey; Ewen, Kirk A; Duggavathi, Rajesha; Davies, Kate L; Pattullo, Kim M; Bagu, Edward T; Rawlings, Norman C

2010-10-01

The objective of this study was to determine if pulsatile LH secretion was needed for ovarian follicular wave emergence and growth in the anestrous ewe. In Experiment 1, ewes were either large or small (10 x 0.47 or 5 x 0.47 cm, respectively; n = 5/group) sc implants releasing estradiol-17 beta for 10 d (Day 0 = day of implant insertion), to suppress pulsed LH secretion, but not FSH secretion. Five sham-operated control ewes received no implants. In Experiment 2, 12 ewes received large estradiol-releasing implants for 12 d (Day 0 = day of implant insertion); six were given GnRH (200 ng IV) every 4 h for the last 6 d that the implants were in place (to reinitiate pulsed LH secretion) whereas six Control ewes were given saline. Ovarian ultrasonography and blood sampling were done daily; blood samples were also taken every 12 min for 6 h on Days 5 and 9, and on Days 6 and 12 of the treatment period in Experiments 1 and 2, respectively. Treatment with estradiol blocked pulsatile LH secretion (P < 0.001). In Experiment 1, implant treatment halted follicular wave emergence between Days 2 and 10. In Experiment 2, follicular waves were suppressed during treatment with estradiol, but resumed following GnRH treatment. In both experiments, the range of peaks in serum FSH concentrations that preceded and triggered follicular wave emergence was almost the same as control ewes and those given estradiol implants alone or with GnRH; mean concentrations did not differ (P < 0.05). We concluded that some level of pulsatile LH secretion was required for the emergence of follicular waves that were triggered by peaks in serum FSH concentrations in the anestrous ewe. (c) 2010 Elsevier Inc. All rights reserved.

Constitution and behavior of follicular structures in the human anterior pituitary gland.

PubMed Central

Ciocca, D. R.; Puy, L. A.; Stati, A. O.

1984-01-01

The follicular structures present in the human pituitary gland were studied, at the light-microscopic level, using histochemical and immunocytochemical techniques. The antisera applied in the peroxidase-antiperoxidase procedure were anti-hFSH beta, anti-hLH beta, anti-hPRL, anti-hGH, anti-hTSH beta, anti-hLPH beta, anti-pACTH, and anti-hACTH. In the 10 normal pituitaries examined, follicles were always found in the three areas of the adenohypophysis. The wall of the pars distalis follicles showed the seven immunoreactive cell types studied, while follicle-stimulating hormone (FSH) and luteinizing hormone (LH) cells were the only ones present in the wall of the pars tuberalis follicles. Most of the cell types studied were also present in the wall of the intermediate area follicles, but these follicles had characteristics not found in the other two areas. They were very large, with frequent interconnections forming a three-dimensional network of anastomotic cavities, and the colloid had different histochemical affinity. None of the hormones studied could be detected by immunocytochemistry within the follicular colloid. Three of the ten pituitary adenomas examined showed numerous follicular structures. Some of the follicles in the adenomatous pituitaries were similar to those found in the normal adenohypophysis, but there were also follicles filled with only traces of colloid and numerous blood cells in the cavity, and follicles filled with neoformed connective tissue. In one of these cases, FSH/LH immunoreactive adenoma cells were seen in the wall of the follicles. The results obtained suggest that the finding of pituitary adenomas with follicular structures is not uncommon and that the follicles originate from the tumor cells. In addition, the follicles seem to have several functional stages, explaining the finding of different types of follicular formation. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11

The effects of menstrual phase on orthodontic pain following initial archwire engagement.

PubMed

Long, H; Gao, M; Zhu, Y; Liu, H; Zhou, Y; Liao, L; Lai, W

2017-04-01

To explore the effects of menstrual cycle on orthodontic pain following initial archwire engagement. Female participants with regular menstrual cycles were recruited and assigned into follicular group or luteal group. Demographical and baseline variables were collected: age, education, menstrual duration, anxiety, oral health impact profile-14 (OHIP-14), and index of complexity outcome and need (ICON). Following initial archwire engagement, orthodontic pain was determined through visual analogue scale (VAS) on 1st day, 2nd day, and 3rd day. Demographical and baseline variables were compared between the two groups. Two-way repeated-measures anova was used to examine the effects of menstrual phase, time, and their interactions on orthodontic pain. Multivariate linear regression was employed to examine the independent effect of each variable on orthodontic pain. Finally, 37 and 39 were assigned to the follicular and luteal groups, respectively, with balanced demographical and baseline data. Orthodontic pain was significantly affected by menstrual phase and time (both P < 0.001), but there was no interaction (P > 0.05). Moreover, orthodontic pain was independently predicted by menstrual phase, OHIP, education level, and anxiety (all P < 0.05). We suggest that practitioners arrange female patients to receive initial archwire engagement during their follicular phases to relieve orthodontic pain. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The t(14;18) translocation is absent from endothelial and follicular dendritic cells of follicular lymphoma (FL) and shows heterogeneous presence in preserved FL mantle zones.

PubMed

Kosmidis, Perikles; Mankel, Barbara; Fend, Falko; Adam, Patrick

2018-05-02

The translocation t(14;18)(q32;q21) is the genetic hallmark of follicular lymphoma (FL) and can be observed in 85-90% of cases. Whether the translocation is restricted to cells with germinal center B-cell phenotype or can be observed in other cell types of the microenvironment remains debated. Of interest, cases of associated histiocytic and dendritic cell sarcomas arising in the background of FL have been shown to be clonally related and carry the t(14;18), suggesting a "transdifferentiation" of the malignant FL clone into a neoplasm of a different hematopoietic lineage. We analyzed the presence of the t(14;18)(q32;q21) as a surrogate marker of the malignant clone in cells of the FL microenvironment using combined fluorescence immunophenotyping and interphase cytogenetics targeting the BCL2 gene locus. In addition to non-lymphoid cells in FL, we analysed FL with preserved IgD+ mantle zones and cases of in situ follicular neoplasia (ISFN) to investigate whether cells of non-germinal center B-cell phenotype are part of the malignant clone. Six (40%) of 15 manifest FL cases with preserved IgD+ mantle zones did not harbour the t(14;18)(q32;q21) translocation. In all t(14;18) + FL cases, follicular dendritic cells and endothelial cells lacked the t(14;18) translocation. 2/9 FL revealed t(14;18)- IgD+ mantle zone B-cells. In the seven ISFN cases, the t(14;18) translocation was strictly confined to germinal center cells. The t(14;18) translocation in follicular lymphoma is limited to B-cells. The origin of IgD+ mantle cells is heterogeneous, in the majority of cases belonging to the neoplastic clone, whereas a minority of cases of manifest FL show nonneoplastic mantle zones, similar to ISFN.

Menstrual-cycle dependent fluctuations in ovarian hormones affect emotional memory.

PubMed

Bayer, Janine; Schultz, Heidrun; Gamer, Matthias; Sommer, Tobias

2014-04-01

The hormones progesterone and estradiol modulate neural plasticity in the hippocampus, the amygdala and the prefrontal cortex. These structures are involved in the superior memory for emotionally arousing information (EEM effects). Therefore, fluctuations in hormonal levels across the menstrual cycle are expected to influence activity in these areas as well as behavioral memory performance for emotionally arousing events. To test this hypothesis, naturally cycling women underwent functional magnetic resonance imaging during the encoding of emotional and neutral stimuli in the low-hormone early follicular and the high-hormone luteal phase. Their memory was tested after an interval of 48 h, because emotional arousal primarily enhances the consolidation of new memories. Whereas overall recognition accuracy remained stable across cycle phases, recognition quality varied with menstrual cycle phases. Particularly recollection-based recognition memory for negative items tended to decrease from early follicular to luteal phase. EEM effects for both valences were associated with higher activity in the right anterior hippocampus during early follicular compared to luteal phase. Valence-specific modulations were found in the anterior cingulate, the amygdala and the posterior hippocampus. Current findings connect to anxiolytic actions of estradiol and progesterone as well as to studies on fear conditioning. Moreover, they are in line with differential networks involved in EEM effects for positive and negative items. Copyright © 2014 Elsevier Inc. All rights reserved.

Phase III Early Restoration Meeting - Lake Charles, LA | NOAA Gulf Spill

Science.gov Websites

Areas Alabama Florida Louisiana Mississippi Texas Region-wide Open Ocean Data Media & News early restoration planning for Phase III and future early restoration plans. Open House: 5:30pm Public

Regulation of cell death and cell survival gene expression during ovarian follicular development and atresia.

PubMed

Jiang, Jin-Yi; Cheung, Carmen K M; Wang, Yifang; Tsang, Benjamin K

2003-01-01

Mammalian ovarian follicular development and atresia is closely regulated by the cross talk of cell death and cell survival signals, which include endocrine hormones (gonadotropins) and intra-ovarian regulators (gonadal steroids, cytokines and growth factors). The fate of the follicle is dependent on a delicate balance in the expression and actions of factors promoting follicular cell proliferation, growth and differentiation and of those inducing programmed cell death (apoptosis). As an important endocrine hormone, FSH binds to its granulosa cell receptors and promotes ovarian follicle survival and growth not only by stimulating proliferation and estradiol secretion of these cells, but also inhibiting the apoptosis by up-regulating the expression of intracellular anti-apoptotic proteins, such as XIAP and FLIP. In addition, intra-ovarian regulators, such as TGF-alpha and TNF-alpha, also play an important role in the control of follicular development and atresia. In response to FSH, Estradiol-17 beta synthesized from the granulosa cells stimulates thecal expression of TGF-alpha, which in turn increases granulosa cell XIAP expression and proliferation. The death receptor and ligand, Fas and Fas ligand, are expressed in granulosa cells following gonadotropin withdrawal, culminating in caspase-mediated apoptosis and follicular atresia. In contrast, TNF-alpha has both survival and pro-apoptotic function in the follicle, depending on the receptor subtype activated, but has been shown to promote granulosa cell survival by increasing XIAP and FLIP expression via the IkappaB-NFkappaB pathway. The pro-apoptotic action of TNF-alpha is mediated through the activation of caspases, via its receptor- (i.e. Caspases-8 and -3) and mitochrondria- (i.e. Caspase-9 and -3) death pathways. In the present manuscript, we have reviewed the actions and interactions of gonadotropins and intra-ovarian regulators in the control of granulosa cell fate and ultimately follicular destiny. We have

Long-term alteration of follicular steroid concentrations in relation to subclinical endometritis in postpartum dairy cows.

PubMed

Green, M P; Ledgard, A M; Beaumont, S E; Berg, M C; McNatty, K P; Peterson, A J; Back, P J

2011-11-01

The focus of this study was to investigate the effect of subclinical endometritis (scEndo) on ovarian follicular steroid concentrations in early postpartum pasture-fed dairy cows. Mixed-age lactating dairy cows (n = 169) were examined to ascertain uterine health status on d 21 postpartum (±3 d). From this herd, a cohort of scEndo and uninfected cows (n = 47) were selected using uterine cytology to determine scEndo. To ensure cows with scEndo were selected for the study, a conservative threshold [>18% polymorphonuclear (PMN) cells among uterine nucleated cells] was chosen as a selection threshold. Ovarian follicular dynamics were assessed by ultrasonography on d 21, 42, and 63 postpartum. On the latter 2 d, all follicles >4 mm in diameter were ablated, and 4 d later, the largest (F1) and second largest (F2) follicles were measured and their follicular fluid aspirated. Hematological variables and plasma metabolites were measured also on these days to further characterize scEndo cows. On d 21, the prevalence of scEndo was approximately 9% in this herd; by d 42 infections had self-resolved in the majority (81%) of those cows classified as having scEndo on d 21. The scEndo cows had a delayed return to cyclicity; however, no effect was evident on ovarian follicle size or growth rate. Weeks after scEndo had self-resolved and cyclicity was restored, decreased (P = 0.07) testosterone and increased (P = 0.07) cortisol concentrations were evident in F1 follicles of scEndo compared with uninfected cows. Progesterone concentrations of F1 increased (P < 0.05) in 11- to 16-mm diameter follicles of scEndo cows, whereas estradiol, androstendione, and dehydroepiandrosterone concentrations were decreased (P < 0.05) in F1 8- to 10-mm diameter follicles of scEndo cows. These 3 steroids also differed (P < 0.05) between F1 follicle size categories of scEndo but not uninfected cows. On d 21, mean plasma albumin concentration was decreased (P = 0.02) in scEndo cows. In summary, early

CD4 T Follicular Helper Cells and HIV Infection: Friends or Enemies?

PubMed

Moukambi, Félicien; Rodrigues, Vasco; Fortier, Yasmina; Rabezanahary, Henintsoa; Borde, Chloé; Krust, Bernard; Andreani, Guadalupe; Silvestre, Ricardo; Petrovas, Constantinos; Laforge, Mireille; Estaquier, Jérôme

2017-01-01

Follicular T helper (Tfh) cells, a subset of CD4 T lymphocytes, are essential for memory B cell activation, survival, and differentiation and assist B cells in the production of antigen-specific antibodies. Work performed in recent years pointed out the importance of Tfh cells in the context of HIV and SIV infections. The importance of tissue distribution of Tfh is also an important point since their frequency differs between peripheral blood and lymph nodes compared to the spleen, the primary organ for B cell activation, and differentiation. Our recent observations indicated an early and profound loss of splenic Tfh cells. The role of transcriptional activator and repressor factors that control Tfh differentiation is also discussed in the context of HIV/SIV infection. Because Tfh cells are important for B cell differentiation and antibody production, accelerating the Tfh responses early during HIV/SIV infection could be promising as novel immunotherapeutic approach or alternative vaccine strategies. However, because Tfh cells are infected during the HIV/SIV infection and represent a reservoir, this may interfere with HIV vaccine strategy. Thus, Tfh represent the good and bad guys during HIV infection.

CD4 T Follicular Helper Cells and HIV Infection: Friends or Enemies?

PubMed Central

Moukambi, Félicien; Rodrigues, Vasco; Fortier, Yasmina; Rabezanahary, Henintsoa; Borde, Chloé; Krust, Bernard; Andreani, Guadalupe; Silvestre, Ricardo; Petrovas, Constantinos; Laforge, Mireille; Estaquier, Jérôme

2017-01-01

Follicular T helper (Tfh) cells, a subset of CD4 T lymphocytes, are essential for memory B cell activation, survival, and differentiation and assist B cells in the production of antigen-specific antibodies. Work performed in recent years pointed out the importance of Tfh cells in the context of HIV and SIV infections. The importance of tissue distribution of Tfh is also an important point since their frequency differs between peripheral blood and lymph nodes compared to the spleen, the primary organ for B cell activation, and differentiation. Our recent observations indicated an early and profound loss of splenic Tfh cells. The role of transcriptional activator and repressor factors that control Tfh differentiation is also discussed in the context of HIV/SIV infection. Because Tfh cells are important for B cell differentiation and antibody production, accelerating the Tfh responses early during HIV/SIV infection could be promising as novel immunotherapeutic approach or alternative vaccine strategies. However, because Tfh cells are infected during the HIV/SIV infection and represent a reservoir, this may interfere with HIV vaccine strategy. Thus, Tfh represent the good and bad guys during HIV infection. PMID:28265271

The efficacy of controlled internal drug release (CIDR) in synchronizing the follicular wave in dromedary camels (Camelus dromedarius) during the breeding season.

PubMed

Swelum, Ayman Abdel-Aziz; Alowaimer, Abdullah Nasser

2015-12-01

The present study aimed to evaluate the efficacy of controlled internal drug release (CIDR) to synchronize the follicular wave in dromedary camels (Camelus dromedarius) during the breeding season through ovarian monitoring, evaluating sexual receptivity, and measuring progesterone (P4) and estradiol (E2) levels during and after CIDR treatment. Sixteen camels received a new CIDR containing 1.9 g of P4 for 14 days. Ultrasound ovarian monitoring was performed on the day of insertion and every 3 days until the CIDR was withdrawn. Ultrasound examinations were continued day in day out after the CIDR was withdrawn for 10 days. According to the ultrasound examinations, the percentages of camels in the breeding (follicles: 12-18 mm) and nonbreeding phases were calculated. Blood samples were collected day after day during the experimental period (24 days) from the day that the CIDR was inserted. The serum P4 and E2 concentrations were analyzed using ELISA kits. The sexual receptivity of the camels was tested daily during the course of the experiment. The results revealed that 2 and 4 days after the CIDR was withdrawn, the percentage of camels in the breeding phase (68.75% and 75.00%, respectively) was significantly (P < 0.05) higher than that in the nonbreeding phase (31.25% and 25.00%, respectively). The percentage of camels that were abstinent during CIDR treatment was significantly (P < 0.05) higher than that observed for those who were incompletely receptive or completely receptive. The P4 levels increased significantly (P < 0.05) 2 days after CIDR insertion (1.73 ng/mL) and reached maximum values (2.94 ng/mL) at Day 12. Significant (P < 0.05) decreases in the P4 levels were observed 2 to 4 days after CIDR withdrawal (1.01 and 0.80 ng/mL, respectively). The P4 levels reached minimum values (0.18-0.22 ng/mL) at Day 20 through the end of the experiment. The E2 levels differed insignificantly during and after CIDR treatment in dromedary camels. In

Anti-ICOS Monoclonal Antibody MEDI-570 in Treating Patients With Relapsed or Refractory Peripheral T-cell Lymphoma Follicular Variant or Angioimmunoblastic T-cell Lymphoma

ClinicalTrials.gov

2018-05-25

Follicular T-Cell Lymphoma; Grade 1 Follicular Lymphoma; Grade 2 Follicular Lymphoma; Grade 3a Follicular Lymphoma; Recurrent Angioimmunoblastic T-Cell Lymphoma; Recurrent Follicular Lymphoma; Recurrent Mature T- and NK-Cell Non-Hodgkin Lymphoma; Recurrent Mycosis Fungoides; Recurrent Primary Cutaneous T-Cell Non-Hodgkin Lymphoma; Refractory Angioimmunoblastic T-Cell Lymphoma; Refractory Follicular Lymphoma; Refractory Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Stage IB Mycosis Fungoides AJCC v7; Stage II Mycosis Fungoides AJCC v7; Stage III Cutaneous T-Cell Non-Hodgkin Lymphoma; Stage III Mycosis Fungoides AJCC v7; Stage IV Cutaneous T-Cell Non-Hodgkin Lymphoma; Stage IV Mycosis Fungoides AJCC v7

Statistical controversies in clinical research: early-phase adaptive design for combination immunotherapies.

PubMed

Wages, N A; Slingluff, C L; Petroni, G R

2017-04-01

In recent years, investigators have asserted that the 3 + 3 design lacks flexibility, making its use in modern early-phase trial settings, such as combinations and/or biological agents, inefficient. More innovative approaches are required to address contemporary research questions, such as those posed in trials involving immunotherapies. We describe the implementation of an adaptive design for identifying an optimal treatment regimen, defined by low toxicity and high immune response, in an early-phase trial of a melanoma helper peptide vaccine plus novel adjuvant combinations. Operating characteristics demonstrate the ability of the method to effectively recommend optimal regimens in a high percentage of trials with reasonable sample sizes. The proposed design is a practical, early-phase, adaptive method for use with combined immunotherapy regimens. This design can be applied more broadly to early-phase combination studies, as it was used in an ongoing study of two small molecule inhibitors in relapsed/refractory mantle cell lymphoma. © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Magnifying Endoscopic Features of Follicular Lymphoma Involving the Stomach: A Report of Two Cases

PubMed Central

Takata, Katsuyoshi; Kawano, Seiji; Fujii, Nobuharu; Kawahara, Yoshiro; Yoshino, Tadashi; Okada, Hiroyuki

2016-01-01

A 70-year-old woman presented with follicular lymphoma involving the stomach, duodenum, jejunum, bone, and lymph nodes. Esophagogastroduodenoscopy revealed multiple depressed lesions in the stomach. Examination with magnifying endoscopy showed branched abnormal vessels along with gastric pits, which were irregularly shaped but were preserved. The second case was a 45-year-old man diagnosed with stage II1 follicular lymphoma with duodenal, ileal, and colorectal involvement, as well as lymphadenopathy of the mesenteric lymph nodes. Esophagogastroduodenoscopy performed six years after the diagnosis revealed multiple erosions in the gastric body and angle. Magnifying endoscopic observation with narrow-band imaging showed that the gastric pits were only partially preserved and were destroyed in most of the stomach. Branched abnormal vessels were also seen. Pathological features were consistent with follicular lymphoma in both cases. The structural differences reported between the two cases appear to reflect distinct pathologies. Disappearance of gastric pits in the latter case seems to result from loss of epithelial cells, probably due to chronic inflammation. In both cases, branched abnormal vasculature was observed. These two cases suggest that magnified observations of abnormal branched microvasculature may facilitate endoscopic detection and recognition of the extent of gastric involvement in patients with follicular lymphoma. PMID:27747111

Ultrasonographic Differentiation Between Nodular Hyperplasia and Neoplastic Follicular-Patterned Lesions of the Thyroid Gland.

PubMed

Song, Yong Sub; Kim, Ji-Hoon; Na, Dong Gyu; Min, Hye Sook; Won, Jae-Kyung; Yun, Tae Jin; Choi, Seung Hong; Sohn, Chul-Ho

2016-08-01

We evaluate the gray-scale ultrasonographic characteristics that differentiate between nodular hyperplasia (NH) and neoplastic follicular-patterned lesions (NFPLs) of the thyroid gland. Ultrasonographic features of 750 patients with 832 thyroid nodules (NH, n = 361; or NFPLs, follicular adenoma, n = 123; follicular carcinoma, n = 159; and follicular variant papillary carcinoma, n = 189) were analyzed. Except for echogenicity, over two-thirds of the cases of NH and NFPLs share the ultrasonographic characteristics of solid internal content, a well-defined smooth margin and round-to-ovoid shape. Independent predictors for NH were non-solid internal content (sensitivity 27.1%, specificity 90.2%), isoechogenicity (sensitivity 69.5%, specificity 63.5%) and an ill-defined margin (sensitivity 18.8%, specificity 94.5%). Independent predictors for NFPLs were hypoechogenicity (sensitivity 60.5%, specificity 70.4%), marked hypoechogenicity (sensitivity 2.8%, specificity 99.4%) and taller-than-wide shape (sensitivity 6.6%, specificity 98.1%). Although NH and NFPLs commonly share ultrasonographic characteristics, non-solid internal content and ill-defined margin are specific to NH and marked hypoechogenicity and taller-than-wide shape are specific to NFPLs. Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Correlations between ovarian follicular blood flow and superovulatory responses in ewes.

PubMed

Oliveira, Maria E F; Feliciano, Marcus A R; D'Amato, Carla C; Oliveira, Luís G; Bicudo, Sony D; Fonseca, Jeferson F; Vicente, Wilter R R; Visco, Elise; Bartlewski, Pawel M

2014-01-10

The primary goal of this study was to employ ultrasonography to examine the ovaries of ewes undergoing superovulatory treatment for correlations between antral follicular blood flow and ovarian responses/embryo yields. Five Santa Inês ewes were subjected to a short- (Days 0-6, Group 1) and five to a long-term progesterone-based protocol (Days 0-12, Group 2) to synchronize estrus and ovulations after the superovulatory treatment. Porcine FSH (pFSH, 200mg) was administered in 8 decreasing doses over 4 days, starting on Days 4 and 10 in Groups 1 and 2, respectively. After CIDR removal, all ewes were bred by a ram and embryos were recovered surgically 7 days later. Transrectal ovarian ultrasonography was performed the day before and on all 4 days of the superovulatory treatment. Both an arbitrary-scale [(0) non-detectable; (1) small; (2) moderate; (3) intense blood flow] and quantitative analysis of the blood flow area were used to assess the follicular blood flow in color Doppler images. There were no significant correlations between the arbitrary blood flow scores and superovulatory responses in the ewes of the present study. However, there was a positive correlation between the quantitative estimates of follicular blood flow on the final day of the superovulatory treatment, and the number (DA: r=0.68, P<0.05; DA/TA×100%: r=0.85, P<0.05) and percentage (DA: r=0.65, P<0.05; DA/TA×100%: r=0.91, P<0.001) of unfertilized eggs (DA: Doppler area, TA: total area of the largest ovarian cross section). This experiment presents a commercially practical tool for predicting superovulatory outcomes in ewes and evidence for the existence of follicular blood flow threshold that may impinge negatively on oocyte quality when surpassed during hormonal ovarian superstimulation. Copyright © 2013 Elsevier B.V. All rights reserved.

Changes in the expression of Fox O1 and death ligand genes during follicular atresia in porcine ovary.

PubMed

Lin, F; Fu, Y H; Han, J; Shen, M; Du, C W; Li, R; Ma, X S; Liu, H L

2014-08-28

Follicular atresia, a key phenomenon in follicle development, eliminates most of the follicles in mammalian ovaries. To investigate the molecular mechanism of follicular atresia in porcine ovaries, we investigated the mRNA expression of three important cell death ligand-receptor systems and Fox O1 in follicles with a diameter of 3-5 mm. The phosphorylation and subcellular localization of Fox O1 during granulosa cell apoptosis was also determined. TRAIL and Fas L played an important role in follicular atresia at this stage. Fox O1 expression was upregulated during atresia, and was confined to the nucleus of granulosa cells; however, phosphorylated Fox O1 was localized to the cytoplasm. These results suggest Fox O1 involvement in the regulation of TRAIL and Fas L expression during follicular atresia in pigs.

Subcentimeter noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP).

PubMed

Rosario, Pedro Weslley

2018-05-23

Recently, it was proposed that the noninvasive encapsulated follicular variant of papillary thyroid carcinoma (noninvasive E-FVPTC) start to be called "noninvasive follicular thyroid neoplasm with papillary-like nuclear features" (NIFTP). 1 As the original cohort of 109 patients with NIFTP studied by the consensus conference included only tumors which were equal or more than 1 cm in size, the consensus diagnostic criteria of NIFTP did not explicitly address subcentimeter lesions. 1,2 In fact, in a recent review published in this journal, Hung & Barletta recognize that there are a few published subcentimetre NIFTP in the literature. 3 This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Menstrual cycle effects on perceived exertion and pain during exercise among sedentary women.

PubMed

Hooper, Ann E Caldwell; Bryan, Angela D; Eaton, Melissa

2011-03-01

Increasing cardiovascular fitness through exercise participation among sedentary people is important for decreasing all-cause mortality. From an intervention perspective, identifying modifiable factors that maximize the successful initiation of exercise is of utmost importance. For women, cyclic hormonal variations can influence aspects of health and health behaviors, from smoking cessation efficacy to physiological responses to exercise. The purpose of this study was to examine the influence of menstrual cycle phase and hormonal contraceptive (HC) use on subjective response to an initial bout of moderate intensity exercise among previously sedentary women (n = 117). Women completed a treadmill exercise challenge session at 65% of their previously determined maximum oxygen consumption (Vo(2) max) during the early follicular, late follicular, or luteal phase. Participants reported ratings of perceived exertion and pain using Borg's Rating of Perceived Exertion (RPE) and CR10 scales at 10, 20, and 30 minutes during the exercise session. There was a significant menstrual phase x birth control interaction on change in RPE [F(2, 111) = 3.75, p < 0.05] and change in perceived pain [F(2, 110) = 3.31, p < 0.05]. Women in the early follicular phase who were not using HCs had significantly greater increases in RPE and increases in pain compared with women in the late follicular and luteal phases. Our results indicate that the use of HC and cycle phase influence sedentary women's subjective response to exercise. These results have important implications for the timing of exercise interventions aimed at increasing exercise among sedentary women.

Immunohistochemical, morphological and histometrical analyses of follicular development in Astyanax bimaculatus (Teleostei: Characidae) exposed to an organochlorine insecticide.

PubMed

Marcon, Lucas; Thomé, Ralph Gruppi; Mounteer, Ann Honor; Bazzoli, Nilo; Rizzo, Elizete; Benjamin, Laércio Dos Anjos

2017-09-01

Thiodan ® is an organochlorine insecticide used in agriculture that can reach aquatic ecosystems where it can affect fish reproduction. This research aimed to evaluate follicular development and the expression of integrin β1, collagen type IV and caspase 3 by morphological, histometrical and immunohistochemical analyses of Astyanax bimaculatus exposed to Thiodan ® . Treatments included three sublethal concentrations of Thiodan ® (1.15, 2.30, and 5.60μgL -1 ) for 96h and a control without the insecticide. Mature females with ovaries in advanced follicular development were chosen for study (average weight: 11.52 ± 2.0g; average total length: 9.12 ± 0.64cm). The follicles of A. bimaculatus exhibited normal morphology, while the diameters of secondary follicles showed an increase (P< 0.05) in all concentrations when compared to the control group; a characteristic of follicles undergoing the initial stages of intoxication. Immunohistochemical analysis revealed secondary follicles with greater expression of integrin β1 and collagen type IV in cytoplasm of follicular cells than in the primary follicles in all treatments and in the control. Immunolocalization of caspase 3 was detected in follicular cells during secondary development in all tested concentrations of Thiodan ® and the control. These analyses demonstrate positive immunolocalization throughout the course of follicular development, even in fish exposed to varying concentrations of Thiodan ® for 96h, demonstrating that follicular cells retain their physiological integrity. Copyright © 2017 Elsevier Inc. All rights reserved.

Inverted follicular keratosis: dermoscopic and reflectance confocal microscopic features.

PubMed

Armengot-Carbo, M; Abrego, A; Gonzalez, T; Alarcon, I; Alos, L; Carrera, C; Malvehy, J; Puig, S

2013-01-01

Inverted follicular keratosis (IFK) is a rare benign tumor which usually appears as a firm papule on the face. The diagnosis is generally made by histopathology because the clinical appearance is difficult to differentiate from other lesions. Dermoscopic features of IFK have not been established to date. Herein we describe the dermoscopic findings of 4 cases of IFK. Radial peripheral hairpin vessels surrounded by a whitish halo arranged around a central white-yellowish amorphous area were observed in 3 cases, and glomerular vessels were present in the central area of one of them. The fourth case also presented a central white amorphous area but showed arborizing vessels. Reflectance confocal microscopy (available in 1 case) revealed a broadened honeycomb pattern, epidermal projections and hairpin and glomerular vessels. To our knowledge this is the first case series describing the dermoscopic features of inverted follicular keratosis and the first confocal microscopy description of this entity.

Thyroid Follicular Carcinoma in a Fourteen-year-old Girl with Graves' Disease.

PubMed

Kojima-Ishii, Kanako; Ihara, Kenji; Ohkubo, Kazuhiro; Matsuo, Terumichi; Toda, Naoko; Yamashita, Hiroyuki; Kono, Shinji; Hara, Toshiro

2014-04-01

Here we present the case of a 14-yr-old girl who developed thyroid follicular carcinoma accompanied by Graves' disease. She was diagnosed with Graves' disease at 10 yr of age and soon achieved a euthyroid state after starting treatment. When she was 13 yr of age, her hyperthyroidism and goiter worsened despite medical therapy. Multiple nodules were found in her enlarged thyroid gland by ultrasonography. Her serum Tg level seemed within the normal range. She underwent near-total thyroidectomy for control of thyroid function. Histopathological study demonstrated that multiple oxyphilic follicular neoplasms were surrounded by the thyroid tissue compatible with Graves' disease. Capsular invasion was identified in one of the nodules, and thus the histological diagnosis was minimally invasive follicular carcinoma. She did not have signs suggesting metastasis, and has had no relapse for 18 mo after the operation. Although some previous studies showed a high prevalence of thyroid cancer with an aggressive nature in adult patients with Graves' disease, few reports about thyroid cancer accompanied by Graves' disease are available in children. The present case, however, suggests that careful investigation is needed when we detect thyroid nodules or progressive thyroid enlargement, especially in children with Graves' disease.

Plasma volume and water/sodium balance differences due to sex and menstrual phase after 4 hours of head-down bed rest (HDBR).

NASA Astrophysics Data System (ADS)

Edgell, Heather; Grinberg, Anna; Beavers, Keith; Gagne, Nathalie; Totosy de Zepetnek, Julia; Greaves, Danielle; Hughson, Richard L.

In both sexes, orthostatic responses are impaired by spaceflight or head-down bed-rest (HDBR), with a greater impact in women. Decreased plasma volume (PV) could contribute to reductions in cardiac output and blood pressure upon an orthostatic challenge. We hypothesized that a greater decrease in PV in women might lead to poorer orthostatic responses. We further hypothesized that the responses in women would differ throughout the menstrual cycle. We studied the responses of men (n=6) and women (n= 6) to 4-hr HDBR and 4-hr seated control (SEAT). Furthermore, we studied women in both the follicular (Day 8-11) and luteal (Day 18-24) phases of menstruation in a repeated measures design. After 4-hr HDBR, PV decreased in men (-175.1 ± 56.8 mL; vs. SEAT: P=0.076) and in the follicular phase, but did not change in the luteal phase (Luteal: -55.0 ± 54.6 mL; Follicular: -226.4 ± 88.2 mL (Interaction effect: P=0.01)). After 4-hr HDBR, only men appear to exhibit increased urine volume (Men, difference from SEAT: +298.3 ± 105.5 mL; Luteal, difference from SEAT: +59.4 ± 34.3 mL; Follicular, difference from SEAT: +43.7 ± 190.0 mL; P=0.16). No changes in urinary sodium after 4-hr HDBR were observed in any group (Men, difference from SEAT: -16.5 ± 13.5 µmol; Luteal, difference from SEAT: -8.0 ± 8.8 µmol; Follicular, difference from SEAT: +28.2 ± 29.5 µmol; P=0.264). No changes in urinary osmolarity were observed after 4-hr HDBR in any group (Men, difference from SEAT: -38.8 ± 126.2 mmol/kg; Luteal, difference from SEAT: -85.1 ± 66.9 mmol/kg; Follicular, difference from SEAT: -99.1 ± 98.5 mmol/kg; P=0.906). The changes in plasma volume do not appear to be a result of urinary water and sodium loss. Perhaps actions of atrial natriuretic peptide, urodilatin, the RAAS pathway, and/or capillary filtration are involved. From these observed changes in plasma volume, we surmise that women in the follicular phase of the menstrual cycle may exhibit lower cardiac output and thus

Predictive value of the level of vitamin D in follicular fluid on the outcome of assisted reproductive technology.

PubMed

Aleyasin, Ashraf; Hosseini, Marzieh Agha; Mahdavi, Atossa; Safdarian, Leila; Fallahi, Parvin; Mohajeri, Mohammad Reza; Abbasi, Mohammad; Esfahani, Fatemeh

2011-11-01

To assess the correlation between the levels of vitamin D in follicular fluid and serum, and to determine whether the level of 25-hydroxyvitamin D (25OH-D) in follicular fluid of infertile women undergoing assisted reproductive technology (ART) is associated with the outcome. Eighty-two infertile women undergoing ART at an academic tertiary care centre were recruited for a prospective cohort study. Levels of 25OH-D in follicular fluid and serum were measured. Standardized regimens for pituitary downregulation and controlled ovarian hyperstimulation were employed. Patient and cycle parameters, and clinical pregnancy (defined as evidence of intra-uterine gestation sac plus heart rate on ultrasound) were determined. A significant correlation was found between the levels of vitamin D in follicular fluid and serum (r=0.767, p=0.001). The overall rates of chemical, clinical and ongoing pregnancy were 35.5% (n=29), 29.3% (n=24) and 23.2% (n=19), respectively. No significant difference was found in these pregnancy rates between the tertiles of 25OH-D level in follicular fluid (p=0.959, 0.995 and 0.604, respectively). The median serum level of vitamin D was 8.13 (range 5.37-13.62)ng/ml in the clinically pregnant group and 8.29 (range 5.93-21.23)ng/ml in the non-pregnant group (p=0.235). Interestingly, the median level of vitamin D in follicular fluid was 9.19 (range 5.25-19.51)ng/ml in the clinically pregnant group and 10.34 (range 5.89-29.69)ng/ml in the non-pregnant group (p=0.433). The fertilization rate decreased significantly and the implantation rate increased (not significantly) with increasing tertiles of 25OH-D level in follicular fluid. The level of 25OH-D in follicular fluid is reflective of body stores of vitamin D. Most subjects in this study were deficient in vitamin D, but this study found that vitamin D deficiency does not play a pivotal role in the outcome of ART. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Proteomic analysis of early phase of conidia germination in Aspergillus nidulans.

PubMed

Oh, Young Taek; Ahn, Chun-Seob; Kim, Jeong Geun; Ro, Hyeon-Su; Lee, Chang-Won; Kim, Jae Won

2010-03-01

In order to investigate proteins involved in early phase of conidia germination, proteomic analysis was performed using two-dimensional gel electrophoresis (2D-GE) in conjunction with MALDI-TOF mass spectrometry (MS). The expression levels of 241 proteins varied quantitatively with statistical significance (P<0.05) at the early phase of the germination stage. Out of these 57 were identified by MALDI-TOF MS. Through classification of physiological functions from Conserved Domain Database analysis, among the identified proteins, 21, 13, and 6 proteins were associated with energy metabolism, protein synthesis, and protein folding process, respectively. Interestingly, eight proteins, which are involved in detoxification of reactive oxygen species (ROS) including catalase A, thioredoxin reductase, and mitochondrial peroxiredoxin, were also identified. The expression levels of the genes were further confirmed using Northern blot and reverse transcriptase (RT)-PCR analyses. This study represents the first proteomic analysis of early phase of conidia germination and will contribute to a better understanding of the molecular events involved in conidia germination process. Copyright (c) 2009 Elsevier Inc. All rights reserved.

Hemodynamic and psychological responses to laboratory stressors in women: Assessing the roles of menstrual cycle phase, premenstrual symptomatology, and sleep characteristics

PubMed Central

Lustyk, M. Kathleen B.; Douglas, Haley A.C.; Shilling, Elizabeth A.; Woods, Nancy F.

2016-01-01

This study assessed whether premenstrual symptomatology and/or sleep characteristics explain increased luteal phase psychophysiological reactivity to laboratory stressors. We hypothesized that: (1) premenstrual symptoms and sleep characteristics would explain greater luteal versus follicular phase psychophysiological reactivity, (2) symptoms and sleep characteristics would differentially predict psychophysiological reactivity within each cycle phase, and (3) symptoms and sleep characteristics would interact to affect luteal but not follicular reactivity. Freely cycling women (N=87) completed two laboratory sessions, one follicular (cycle days 5–9) and one luteal (days 7–10 post-ovulation). We employed two stressors: one physical (cold pressor task) and the other cognitive in nature (Paced Auditory Serial Addition Task). During testing, electrocardiography monitored heart rate (HR) while a timed and auto-inflatable sphygmomanometer assessed blood pressure (BP). Participants also completed a one-time self-report measure of sleep characteristics and premenstrual symptomatology as well as a measure of state anxiety pre-post stressor. Results revealed greater luteal HR and systolic BP reactivity compared to follicular reactivity (p<0.001 for both analyses), however neither premenstrual symptoms nor sleep characteristics explained this luteal increase. Within cycle analyses revealed that symptoms and sleep characteristics interacted to affect luteal phase state anxiety reactivity (R2=.32, p=.002) with negative affect being associated with more reactivity when sleep hours were low (β=.333, p=.04). Overall, significant relationships existed during the luteal phase only. Findings are discussed in terms of clinical utility and methodological challenges related to performing laboratory stress testing in women. PMID:23092740

Effect of different doses of monosodium glutamate on the thyroid follicular cells of adult male albino rats: a histological study

PubMed Central

Khalaf, Hanaa A; Arafat, Eetmad A

2015-01-01

Monosodium glutamate (MSG) is a major flavor enhancer used as a food additive. The present study investigates the effects of different doses of MSG on the morphometric and histological changes of the thyroid gland. 28 male albino rats were used. The rats were divided into four groups: group I control, group II, III and IV treated with MSG (0.25 g/kg, 3 g/kg, 6 g/kg daily for one month) respectively. The thyroid glands were dissected out and prepared for light and electron microscopic examination. Light microscopic examination of thyroid gland of group II revealed increase in follicular epithelial height. Groups III & IV showed decrease in the follicular diameter and irregularity in the shape of some follicles with discontinuity of basement membrane. Follicular hyperplasia was detected in some follicles with appearance of multiple pyknotic nuclei in follicular and interfollicular cells and multiple exfoliated cells in the colloid. In addition, areas of loss of follicular pattern were appeared in group IV. Immunohistochemical examination of BCL2 immunoexpression of the thyroid glands of groups III & IV reveals weak positive reaction in the follicular cells cytoplasm. Ultrathin sections examination of groups III & IV revealed follicular cells with irregular hyperchromatic nuclei, marked dilatation of rER and increased lysosomes with areas of short or lost apical microvilli. In addition, vacuolation of mitochondria was detected in group IV. The results displayed that MSG even at low doses is capable of producing alterations in the body weights and thyroid tissue function and histology. PMID:26884820

Maternal plasma concentrations of beta-lipotrophin, beta-endorphin and gamma-lipotrophin throughout pregnancy.

PubMed

Browning, A J; Butt, W R; Lynch, S S; Shakespear, R A

1983-12-01

Plasma beta-LPH, beta-EP and gamma-LPH concentrations were measured by radioimmunoassay in 10 pregnant women from 12 weeks gestation until term and in nine women in the early follicular phase of the cycle. There was a progressive and significant rise in the concentration of all three peptides throughout pregnancy and by 32 weeks the concentrations of beta-LPH and beta-EP were greater than the corresponding concentrations in the follicular phase: gamma-LPH was greater than in the follicular phase by the end of pregnancy in those women who were delivered after 40 weeks. The ratio of beta-LPH to gamma-LPH did not change significantly throughout pregnancy, but there was a progressive fall in the beta-LPH/beta-EP ratio. The possible presence of a 'big LPH' to explain this finding is discussed.

Age, FSH dose and follicular aspiration frequency affect oocyte yield from juvenile donor lambs.

PubMed

Valasi, I; Leontides, L; Papanikolaou, Th; Amiridis, G S

2007-06-01

Experiments were conducted to determine the effects of lamb age, frequency of follicular aspirations, and hormone stimulation by fixed or variable FSH dose, on the number of collected oocytes and their maturational competence. In trial 1, the characteristics of follicular population (number and diameter of follicles) were studied in 40 lambs which were slaughtered at the age of 30 days (S1), 42 days (S2), 60 days (S3) and 5-6 months (S4), each n = 10. In trial 2, 27 lambs were divided into four groups. group MF lambs (n = 6) had follicular aspiration (OPU) in four monthly intervals commencing from the age of 8-9 weeks (sessions MF1, MF2, MF3 and MF4). In groups SF2, SF3 and SF4 (each n = 6), OPU was conducted once during the 12-13, 16-17 and 20-21 week of age, respectively. Ovarian stimulation was conducted with fixed FSH dose (3.52 mg/animal). In trial 3, 10 lambs (group MV) were treated as those of group MF apart from the FSH dose, which was administered according to the body weight in a dose of 0.27 mg/kg. The number and the size of follicles, the number and the quality of collected oocytes and the maturational competence of the oocytes were compared between and within groups. In trial 1, the total number and the number of small follicles were greater in groups S1 and S2 compared with those of S3 and S4 (p < 0.01). Similarly, the follicular population was greater in group MF1 than in group SF3 (p < 0.01). In sessions MF2, MF3, MV2, MV3 and MV4, more oocytes were collected in comparison with those from the respective once-aspirated age mates (groups SF2, SF3 and SF4). In total, more (p = 0.02) oocytes per donor were collected from group MV (15.2 +/- 5.5) than from group MF (9.0 +/- 3.2). An absolute maturational failure was observed in oocytes collected from groups SF2 and SF3. Maturational competence varied between 16.7% and 58.3% (p = 0.017) among sessions of group MF, but it was more uniform among sessions of group MV (range 12.5-42.9%, p > 0.05). Our results

Growth Hormone Supplementation in the Luteal Phase Before Microdose GnRH Agonist Flare Protocol for In Vitro Fertilization.

PubMed

Dunne, Caitlin; Seethram, Ken; Roberts, Jeffrey

2015-09-01

Growth hormone (GH) acts in both early and late follicular development to stimulate the proliferation and differentiation of granulosa cells and to increase the production of estradiol in animal and human ovaries. Investigators have therefore explored GH supplementation to improve outcomes in women undergoing in vitro fertilization, with the greatest interest in women with diminished ovarian reserve. Recent meta-analyses indicate that GH supplementation can be beneficial for poor responders undergoing IVF. In most studies, GH has been given concomitantly with gonadotropins during the follicular phase; this may not be optimal, since follicular recruitment begins during the preceding luteal phase. We therefore wished to examine the effect of GH supplementation in the luteal phase before controlled ovarian stimulation (COH) with a microdose GnRH agonist flare (MDF) protocol in women undergoing in vitro fertilization. We performed a retrospective matched case-control study of patients undergoing treatment at a private IVF facility between June 2012 and July 2013. Patients identified as poor responders to COH were offered adjuvant GH treatment as part of their ovarian stimulation regimen. The patients in the experimental group chose to take GH, 3.33 mg daily by subcutaneous injection for 14 days, before starting COH. All patients had an MDF stimulation protocol using 450 IU of follicle stimulating hormone (FSH) daily. A total of 42 women were included in the study. There were 14 women in the experimental group (GH) and 28 controls (C) matched for age, BMI, and day 3 FSH level. There was no difference between the groups in clinical pregnancy rate (GH = 29%, C = 32%, P = 0.99), number of mature oocytes retrieved (GH = 2.5, C = 5.0, P = 0.13), cycle cancellation rate (GH = 21%, C = 14%, P = 0.88), duration of COH (GH = 10.1, C = 10.1, P = 0.93), or mean peak estradiol level (GH = 4174 pmol/L, C = 5105 pmol/L, P = 0.44). The administration of growth hormone during the

Ovarian follicular dynamics, follicle deviation, and oocyte yield in Gyr breed (Bos indicus) cows undergoing repeated ovum pick-up.

PubMed

Viana, J H M; Palhao, M P; Siqueira, L G B; Fonseca, J F; Camargo, L S A

2010-04-15

The objective of this study was to evaluate ovarian follicular dynamics during intervals between successive ovum pick-up (OPU) and determine its effects on the number and quality of recovered cumulus-oocyte complexes (COCs) in Zebu cows (Bos indicus). Pluriparous nonlactating Gyr cows (Bos indicus; n=10) underwent four consecutive OPU sessions at 96-h intervals. The dynamics of ovarian follicular growth between OPU sessions was monitored by twice-daily ultrasonographic examinations. A single dominant follicle (DF) or two codominant (CDF) follicles (>9mm) were present in 63.3% (19 of 30) of intervals studied, with follicle deviation beginning when the future dominant follicle (F1) achieved a diameter of 6.2+/-0.3mm. The phenomenon of codominance was observed in four (13.3%) of the inter-OPU intervals. The remaining intervals (36.6%, 11 of 30) were characterized by a greater follicular population, lower rate of follicular growth, and a smaller diameter F1 (P<0.0001). There was a tendency (P=0.08) toward an increase in the number of recovered COCs when dominant follicles were not present (NDF). The quality of COCs was not affected by the presence of a single dominant follicle, but codominant follicles resulted in recovery of a lower proportion of viable embryos (40.0%, 62.1%, and 63.6%; P<0.05) and higher proportions of degenerate COCs (56.0%, 30.3%, and 28.6%; P<0.05) for CDF, NDF, and DF respectively. We concluded that, in Zebu cows, (a) repeated follicle aspirations altered ovarian follicular dynamics, perhaps by increasing follicular growth rate; (b) follicular dominance could be established in cows undergoing twice-a-week OPU; and (c) the presence of a dominant follicle during short inter-OPU intervals may not affect COC quality, except when a codominant follicle was present. Copyright 2010 Elsevier Inc. All rights reserved.

Lipid profiles of follicular fluid from cows submitted to ovarian superstimulation.

PubMed

Santos, P H; Fontes, P K; Franchi, F F; Nogueira, M F G; Belaz, K R A; Tata, A; Eberlin, M N; Sudano, M J; Barros, C M; Castilho, A C S

2017-05-01

Ovarian superstimulation with exogenous gonadotropins has been extensively used to produce in vivo-derived embryos for embryo transfer in cattle. This process modifies the antral follicle microenvironment and affects oocyte and embryo quality as well the differentiation of granulosa cells. Lipids play significant roles in the cell, such as energy storage, cell structure, and fine-tuning of the physical properties and functions of biological membranes. The phospholipid (PL) contents as well as the effects of superstimulatory treatments on the PL profile of follicular fluid from cows, however, remain unknown. Therefore, to gain insight into the effects of superstimulation with follicle-stimulating hormone (FSH; P-36 protocol) or FSH combined with equine chorionic gonadotropin (eCG; P-36/eCG protocol) on the profile and abundance of PL from cows submitted or not submitted to superstimulatory protocols, were treated with these two superstimulatory protocols. As a control, non-superstimulated cows were only submitted to estrous synchronization. The follicular fluid was aspirated, the remaining cells removed and the follicular fluid stored at -80 °C until extraction. The lipid screening was performed by matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS) and this technique allowed the identification of sphingomyelins (SM) and phosphatidylcholines (PC) and phosphoethanolamines (PE). The relative abundance of the ions observed in the three experimental groups was analyzed by multivariate and univariate statistical models. The phospholipid SM (16:0) and PC (36:4) and/or PC (34:1) were less (P < 0.05) abundant in the P-36 group compared to the control or P-36/eCG groups. However, the PC (34:2) was more (P < 0.05) abundant in both group of superstimulated cows compared to the control. In summary, ovarian superstimulation seems to modulate the PL content of bovine follicular fluid with a significant increase in PC (34:2), which jointly with others

Impact of Reclassification on Thyroid Nodules with Architectural Atypia: From Non-Invasive Encapsulated Follicular Variant Papillary Thyroid Carcinomas to Non-Invasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features

PubMed Central

Jeon, Min Ji; Song, Dong Eun; Jung, Chan Kwon; Kim, Won Gu; Kwon, Hyemi; Lee, Yu-Mi; Sung, Tae-Yon; Yoon, Jong Ho; Chung, Ki-Wook; Hong, Suck Joon; Baek, Jung Hwan; Lee, Jeong Hyun; Kim, Tae Yong; Shong, Young Kee; Kim, Won Bae

2016-01-01

Background The follicular variant of papillary thyroid cancer (FVPTC), especially the encapsulated non-invasive subtype, is a controversial entity. Recent study suggested using ‘non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP)’ for these indolent carcinomas. We evaluated the impact of reclassification from non-invasive encapsulated FVPTCs (EFVPTCs) to NIFTPs in the diagnosis of thyroid nodules with architectural atypia. Methods We reviewed 1301 thyroid nodules with architectural atypia in core needle biopsy (CNB) specimens obtained from March 2012 to February 2013. Nodules were classified into atypia of undetermined significance with architectural atypia (AUS-A, 984, 76%) or follicular neoplasm/suspicious for a follicular neoplasm (FN/SFN, 317, 24%). Among them, diagnostic surgery was performed in 384 nodules (30%). Results In total, 160 nodules (42%) presented final malignant diagnoses including 39 non-invasive encapsulated FVPTCs (10%). The malignancy rate was estimated to be 7–35% in AUS-A nodules and 28–49% in FN/SFN nodules. After reclassification, the malignancy rate was much decreased and estimated to be 5–24% in AUS-A nodules, and 23–39% in FN/SFN nodules. Thyroid nodules with final malignant diagnoses were significantly more likely to have a FN/SFN CNB diagnosis, malignant US features and concomitant nuclear atypia in CNB specimens. However, these factors could not differentiate NIFTPs from other malignancies. Conclusions After reclassification of non-invasive EFVPTCs to NIFTPs, the malignancy rate of thyroid nodules with architectural atypia in CNB specimens was decreased. However, there were no preoperative factors differentiating other malignancies from NIFTPs. The presence of malignant US features or concomitant nuclear atypia might help clinicians deciding diagnostic surgery but, these features also might indicate NIFTPs. PMID:27936121

Do alterations in follicular fluid proteases contribute to human infertility?

PubMed

Cookingham, Lisa Marii; Van Voorhis, Bradley J; Ascoli, Mario

2015-05-01

Cathepsin L and ADAMTS-1 are known to play critical roles in follicular rupture, ovulation, and fertility in mice. Similar studies in humans are limited; however, both are known to increase during the periovulatory period. No studies have examined either protease in the follicular fluid of women with unexplained infertility or infertility related to advanced maternal age (AMA). We sought to determine if alterations in cathepsin L and/or ADAMTS-1 existed in these infertile populations. Patients undergoing in vitro fertilization (IVF) for unexplained infertility or AMA-related infertility were prospectively recruited for the study; patients with tubal or male factor infertility were recruited as controls. Follicular fluid was collected to determine gene expression (via quantitative polymerase chain reaction), enzyme concentrations (via enzyme-linked immunosorbent assays), and enzymatic activities (via fluorogenic enzyme cleavage assay or Western blot analysis) of cathepsin L and ADAMTS-1. The analysis included a total of 42 patients (14 per group). We found no statistically significant difference in gene expression, enzyme concentration, or enzymatic activity of cathepsin L or ADAMTS-1 in unexplained infertility or AMA-related infertility as compared to controls. We also found no statistically significant difference in expression or concentration with advancing age. Cathepsin L and ADAMTS-1 are not altered in women with unexplained infertility or AMA-related infertility undergoing IVF, and they do not decline with advancing age. It is possible that differences exist in natural cycles, contributing to infertility; however, our findings do not support a role for protease alterations as a common cause of infertility.

Impact of short-term preconceptional exposure to particulate air pollution on treatment outcome in couples undergoing in vitro fertilization and embryo transfer (IVF/ET)

PubMed Central

Maluf, Mariangela; Czeresnia, Carlos Eduardo; Januário, Daniela Aparecida Nicolosi Foltran; Saldiva, Paulo Hilário Nascimento

2010-01-01

Purpose To assess the potential effects of short-term exposure to particulate air pollution during follicular phase on clinical, laboratory, and pregnancy outcomes of women undergoing IVF/ET. Methods Retrospective cohort study of 400 first IVF/ET cycles of women exposed to ambient particulate matter during follicular phase. Particulate matter (PM) was categorized into quartiles (Q1: ≤30.48 µg/m3, Q2: 30.49–42.00 µg/m3, Q3: 42.01–56.72 µg/m3, and Q4: >56.72 µg/m3). Results Clinical, laboratory, or treatment variables were not affected by follicular phase PM exposure periods. Women exposed to Q4 period during the follicular phase of conception cycles had a higher risk of miscarriage (odds ratio, 5.05; 95% confidence interval: 1.04–25.51) when compared to women exposed to Q1–3 periods. Conclusion Our results show an association between brief exposure to high levels of ambient PM during the preconceptional period and early pregnancy loss, although no effect of this exposure on clinical, laboratory, and treatment outcomes was observed. PMID:20405197

Clear cell variant of follicular thyroid carcinoma with normal thyroid-stimulating hormone value: a case report

PubMed Central

2014-01-01

Introduction Clear cell carcinomas of the thyroid gland with normal thyroid-stimulating hormone value are very rare, but clear cell changes are described in most reported cases of thyroidal lesions. Case presentation In this report, we describe the case of a 50-year-old Caucasian woman with a normal thyroid-stimulating hormone level who underwent surgery to treat a multi-nodular goiter. The pathology was a clear cell variant of follicular thyroid carcinoma. The tumor was 1cm in diameter and consisted of pure clear cells. Conclusion Clear cell variants of follicular thyroid carcinoma are rarely seen, especially it is misdiagnosed with metastatic renal cell carcinoma. In this report, we describe the case of a patient with a clear cell variant of follicular thyroid carcinoma with an interesting pathology. PMID:24884725

Thyroid Follicular Carcinoma in a Fourteen-year-old Girl with Graves’ Disease

PubMed Central

Kojima-Ishii, Kanako; Ihara, Kenji; Ohkubo, Kazuhiro; Matsuo, Terumichi; Toda, Naoko; Yamashita, Hiroyuki; Kono, Shinji; Hara, Toshiro

2014-01-01

Abstract Here we present the case of a 14-yr-old girl who developed thyroid follicular carcinoma accompanied by Graves’ disease. She was diagnosed with Graves’ disease at 10 yr of age and soon achieved a euthyroid state after starting treatment. When she was 13 yr of age, her hyperthyroidism and goiter worsened despite medical therapy. Multiple nodules were found in her enlarged thyroid gland by ultrasonography. Her serum Tg level seemed within the normal range. She underwent near-total thyroidectomy for control of thyroid function. Histopathological study demonstrated that multiple oxyphilic follicular neoplasms were surrounded by the thyroid tissue compatible with Graves’ disease. Capsular invasion was identified in one of the nodules, and thus the histological diagnosis was minimally invasive follicular carcinoma. She did not have signs suggesting metastasis, and has had no relapse for 18 mo after the operation. Although some previous studies showed a high prevalence of thyroid cancer with an aggressive nature in adult patients with Graves’ disease, few reports about thyroid cancer accompanied by Graves’ disease are available in children. The present case, however, suggests that careful investigation is needed when we detect thyroid nodules or progressive thyroid enlargement, especially in children with Graves’ disease. PMID:24790388

Iontophoresis-targeted, follicular delivery of minoxidil sulfate for the treatment of alopecia.

PubMed

Gelfuso, Guilherme Martins; Gratieri, Tais; Delgado-Charro, M Begoña; Guy, Richard H; Vianna Lopez, Renata Fonseca

2013-05-01

Although minoxidil (MX) is a drug known to stimulate hair growth, the treatment of androgenic alopecia could be improved by delivery strategies that would favor drug accumulation into the hair follicles. This work investigated in vitro the potential of iontophoresis to achieve this objective using MX sulfate (MXS), a more water-soluble derivative of MX. Passive delivery of MXS was first determined from an ethanol-water solution and from a thermosensitive gel. The latter formulation resulted in greater accumulation of MXS in the stratum corneum (skin's outermost layer) and hair follicles and an overall decrease in absorption through the skin. Anodal iontophoresis of MXS from the same gel formulation was then investigated at pH 3.5 and pH 5.5. Compared with passive delivery, iontophoresis increased the amount of drug reaching the follicular infundibula from 120 to 600 ng per follicle. In addition, drug recovery from follicular casts was threefold higher following iontophoresis at pH 5.5 compared with that at pH 3.5. Preliminary in vivo experiments in rats confirmed that iontophoretic delivery of MXS facilitated drug accumulation in hair follicles. Overall, therefore, iontophoresis successfully and significantly enhanced follicular delivery of MX suggesting a useful opportunity for the improved treatment of alopecia. Copyright © 2013 Wiley Periodicals, Inc.

Characterization of early follicular cDNA library suggests evidence for genetic polymorphisms in the inbred strain C108 of Bombyx mori.

PubMed

Mills, D R; Goldsmith, M R

2000-04-01

Recent work towards the completion of a saturated molecular genetic linkage map for the lepidopteran silkworm, Bombyx mori (n = 28), has provided evidence for existing polymorphisms in the inbred strain C108. Two inbred parental strains, p50 and C108, were crossed to produce the F1 (P/C) hybrid offspring. The populations used in this project were comprised of a combination of 29 F2 (F1 x F1) and 31 reciprocal backcross (P/C x C/C, P/C x P/P) progeny. All restriction fragment length polymorphisms (RFLPs) for the initial analysis were hybridized with anonymous probes derived from a random early follicular cDNA (Rcf) library from Bombyx. A total of 19 Rcf probes were selected as showing scorable codominant polymorphic patterns when screened against F2 and backcross DNAs digested with the restriction enzymes EcoRI, HindIII, or PstI, and Southern blotted to nylon membranes for hybridization. Of the newly reported Rcf probes, 7 (37%) were characterized as producing 'simple' polymorphic patterns, while 12 (63%) were characterized as producing 'complex' polymorphic patterns. Further characterization of the complex patterns subdivided this group into two general classes: polymorphisms that contained an additional allele, and multiple bands that contained an easily scored two banded polymorphism. Because the extra allele class was limited to the (P/C x C/C) backcross progeny, it is suggested that the inbred parental strain C108 harbors polymorphic loci that are inherited in a simple Mendelian fashion. A genetic analysis discussing plausible origins and maintenance of these polymorphisms is presented.

Challenges and perspective of drug repurposing strategies in early phase clinical trials.

PubMed

Kato, Shumei; Moulder, Stacy L; Ueno, Naoto T; Wheler, Jennifer J; Meric-Bernstam, Funda; Kurzrock, Razelle; Janku, Filip

2015-01-01

Despite significant investments in the development of new agents only 5% of cancer drugs entering Phase I clinical trials are ultimately approved for routine clinical cancer care. Drug repurposing strategies using novel combinations of previously tested anticancer agents could reduce the cost and improve treatment outcomes. At MD Anderson Cancer Center, early phase clinical trials with drug repurposing strategies demonstrated promising outcomes in patients with both rare and common treatment refractory advanced cancers. Despite clinical efficacy advancing drug repurposing strategies in the clinical trial trajectory beyond early phase studies has been challenging mainly due to lack of funding and interest from the pharmaceutical industry. In this review, we delineate our experience and challenges with drug repurposing strategies.

The in vitro use of the hair follicle closure technique to study the follicular and percutaneous permeation of topically applied drugs.

PubMed

Stahl, Jessica; Niedorf, Frank; Wohlert, Mareike; Kietzmann, Manfred

2012-03-01

Recent studies on follicular permeation emphasise the importance of hair follicles as diffusion pathways, but only a limited amount of data are available about the follicular permeation of topically applied drugs. This study examines the use of a hair follicle closure technique in vitro, to determine the participation of hair follicles in transdermal drug penetration. Various substances, with different lipophilicities, were tested: caffeine, diclofenac, flufenamic acid, ibuprofen, paracetamol, salicylic acid and testosterone. Diffusion experiments were conducted with porcine skin, the most common replacement material for human skin, in Franz-type diffusion cells over 28 hours. Different experimental settings allowed the differentiation between interfollicular and follicular permeation after topical application of the test compounds. A comparison of the apparent permeability coefficients of the drugs demonstrates that the percutaneous permeations of caffeine and flufenamic acid were significantly higher along the hair follicles. In the cases of paracetamol and testosterone, the follicular pathway appears to be of importance, while no difference was found between interfollicular and follicular permeation for diclofenac, ibuprofen and salicylic acid. Thus, the hair follicle closure technique represents an adequate in vitro method for gaining information about follicular or percutaneous permeation, and can replace in vivo testing in animals or humans. 2012 FRAME.

MALDI Mass Spectrometry Imaging of Lipids and Gene Expression Reveals Differences in Fatty Acid Metabolism between Follicular Compartments in Porcine Ovaries

PubMed Central

Uzbekova, Svetlana; Elis, Sebastien; Teixeira-Gomes, Ana-Paula; Desmarchais, Alice; Maillard, Virginie; Labas, Valerie

2015-01-01

In mammals, oocytes develop inside the ovarian follicles; this process is strongly supported by the surrounding follicular environment consisting of cumulus, granulosa and theca cells, and follicular fluid. In the antral follicle, the final stages of oogenesis require large amounts of energy that is produced by follicular cells from substrates including glucose, amino acids and fatty acids (FAs). Since lipid metabolism plays an important role in acquiring oocyte developmental competence, the aim of this study was to investigate site-specificity of lipid metabolism in ovaries by comparing lipid profiles and expression of FA metabolism-related genes in different ovarian compartments. Using MALDI Mass Spectrometry Imaging, images of porcine ovary sections were reconstructed from lipid ion signals for the first time. Cluster analysis of ion spectra revealed differences in spatial distribution of lipid species among ovarian compartments, notably between the follicles and interstitial tissue. Inside the follicles analysis differentiated follicular fluid, granulosa, theca and the oocyte-cumulus complex. Moreover, by transcript quantification using real time PCR, we showed that expression of five key genes in FA metabolism significantly varied between somatic follicular cells (theca, granulosa and cumulus) and the oocyte. In conclusion, lipid metabolism differs between ovarian and follicular compartments. PMID:25756245

Regulation of prohibitin expression during follicular development and atresia in the mammalian ovary.

PubMed

Thompson, Winston E; Asselin, Eric; Branch, Alicia; Stiles, Jonathan K; Sutovsky, Peter; Lai, Liangxue; Im, Gi-Sun; Prather, Randall S; Isom, S Clay; Rucker, Edmund; Tsang, Benjamin K

2004-07-01

Prohibitin is a ubiquitous and highly conserved protein implicated as an important regulator in cell survival. Prohibitin content is inversely associated with cell proliferation, but it increases during granulosa cell differentiation as well as in earlier events of apoptosis in a temperature-sensitive granulosa cell line. In the present study, we have characterized the spatial expression patterns for prohibitin using established in vivo models for the induction of follicular development and atresia in the mammalian ovary. Comparative Western blot analyses of granulosa cell lysates from control ovaries and from ovaries primed with eCG or treated with eCG plus anti-eCG (gonadotropin withdrawal) were conducted. Prohibitin was immunolocalized in rat ovarian sections probed with antibodies against either proliferating cell nuclear antigen (PCNA) or cholesterol side-chain cleavage cytochrome P450 (P450(scc)) or in terminal deoxynucleotidyl transferase-mediated dUTP nick end labeled sections. Additionally, porcine oocytes, zygotes, and blastocyts were also immunolocalized with prohibitin antibody. Immunolocalization revealed the presence of prohibitin in granulosa cells, theca-interstitial cells, and the oocyte. The results indicate that prohibitin protein expression in the gonadotropin-treated cells was upregulated. Immunoreactivity of prohibitin was inversely related to PCNA expression during follicular maturation and colocalized with P450(scc). Prohibitin appeared to be translocated from the cytoplasm to the nucleus in atretic follicles, germinal vesicle-stage oocytes, zygotes, and blastocysts. These results suggest that prohibitin has several functional regulatory roles in granulosa and theca-interstitial cells and in the ovum during follicular maturation and atresia. It is likely that prohibitin may play an important role in determining the fate of these cells and eventual follicular destiny.

Ex-vivo measurement of scalp follicular infundibulum delivery of zinc pyrithione and climbazole from an anti-dandruff shampoo.

PubMed

Chen, Guoqiang; Ji, Chengdong; Miao, Miao; Yang, Kang; Luo, Yajun; Hoptroff, Michael; Collins, Luisa Z; Janssen, Hans-Gerd

2017-09-05

Efficient delivery of anti-dandruff (AD) actives into the scalp follicular infundibulum as well as onto the scalp surface is critical for the efficacy of AD shampoos. A method involving scalp cyanoacrylate (CA) biopsy sampling, a tailor made cutting device, ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) analysis, scanning electron microscopy (SEM) measurement and Raman imaging has been developed for the measurement of delivery of zinc pyrithione (ZPT) and climbazole (CBZ) from an AD shampoo into the scalp follicular infundibulum. Scalp CA biopsy enables the sampling of ZPT and CBZ delivered into the scalp follicular infundibula as well as onto the scalp surface. Raman imaging of scalp CA biopsy samples allows the visualization of the spatial distribution of ZPT and CBZ deposited on the scalp. A tailor made cutting device enables the separation of the scalp follicular infundibulum sample (20μm below the scalp surface) from the scalp surface samples (including top 20μm of infundibula). UHPLC-MS/MS was used as a sensitive and specific methodology enabling the quantification of ZPT and CBZ without interference. Using this method, both ZPT and CBZ were successfully quantified and spacially visualized within the scalp follicular infundibulum, after scalp was washed with an AD shampoo. Copyright © 2017 Elsevier B.V. All rights reserved.

A Phase 1-2 Multi-Center Study Evaluating Axicabtagene Ciloleucel in Subjects With Refractory Aggressive Non-Hodgkin Lymphoma (ZUMA-1)

ClinicalTrials.gov

2018-06-18

Refractory Diffuse Large B Cell Lymphoma; Refractory Primary Mediastinal B Cell Lymphoma; Refractory Transformed Follicular Lymphoma; Relapsed/Refractory Transplant Ineligible Diffuse Large B Cell Lymphoma; Relapsed/Refractory Transplant Ineligible Primary Mediastinal B Cell Lymphoma; Relapsed/Refractory Transplant Ineligible Transformed Follicular Lymphoma; Relapsed/Refractory Large B Cell Lymphoma Including DLBCL, PMBCL, TFL and HGBCL After Two Systemic Lines of Therapy" in Phase 2 Expanded Cohorts

Cytokine expression during early and late phase of acute Puumala hantavirus infection

PubMed Central

2011-01-01

Background Hantaviruses of the family Bunyaviridae are emerging zoonotic pathogens which cause hemorrhagic fever with renal syndrome (HFRS) in the Old World and hantavirus pulmonary syndrome (HPS) in the New World. An immune-mediated pathogenesis is discussed for both syndromes. The aim of our study was to investigate cytokine expression during the course of acute Puumala hantavirus infection. Results We retrospectively studied 64 patients hospitalised with acute Puumala hantavirus infection in 2010 during a hantavirus epidemic in Germany. Hantavirus infection was confirmed by positive anti-hantavirus IgG/IgM. Cytokine expression of IL-2, IL-5, IL-6, IL-8, IL-10, IFN-γ, TNF-α and TGF-β1 was analysed by ELISA during the early and late phase of acute hantavirus infection (average 6 and 12 days after onset of symptoms, respectively). A detailed description of the demographic and clinical presentation of severe hantavirus infection requiring hospitalization during the 2010 hantavirus epidemic in Germany is given. Acute hantavirus infection was characterized by significantly elevated levels of IL-2, IL-6, IL-8, TGF-β1 and TNF-α in both early and late phase compared to healthy controls. From early to late phase of disease, IL-6, IL-10 and TNF-α significantly decreased whereas TGF-β1 levels increased. Disease severity characterized by elevated creatinine and low platelet counts was correlated with high pro-inflammatory IL-6 and TNF-α but low immunosuppressive TGF-β1 levels and vice versa . Conclusion High expression of cytokines activating T-lymphocytes, monocytes and macrophages in the early phase of disease supports the hypothesis of an immune-mediated pathogenesis. In the late phase of disease, immunosuppressive TGF-β1 level increase significantly. We suggest that delayed induction of a protective immune mechanism to downregulate a massive early pro-inflammatory immune response might contribute to the pathologies characteristic of human hantavirus infection

Pretreatment with myo-inositol in non polycystic ovary syndrome patients undergoing multiple follicular stimulation for IVF: a pilot study.

PubMed

Lisi, Franco; Carfagna, Piero; Oliva, Mario Montanino; Rago, Rocco; Lisi, Rosella; Poverini, Roberta; Manna, Claudio; Vaquero, Elena; Caserta, Donatella; Raparelli, Valeria; Marci, Roberto; Moscarini, Massimo

2012-07-23

Aim of this pilot study is to examine the effects of myo-inositol administration on ovarian response and oocytes and embryos quality in non PolyCystic Ovary Syndrome (PCOS) patients undergoing multiple follicular stimulation and in vitro insemination by conventional in vitro fertilization or by intracytoplasmic sperm injection. One hundred non-PCOS women aged <40 years and with basal FSH <10 mUI/ml were down-regulated with triptorelin acetate from the mid-luteal phase for 2 weeks, before starting the stimulation protocol for oocytes recovery. All patients received rFSH, at a starting dose of 150 IU for 6 days. The dose was subsequently adjusted according to individual response. Group B (n=50) received myo-inositol and folic acid for 3 months before the stimulation period and then during the stimulation itself. Group A (n-50) received only folic acid as additional treatment in the 3 months before and through treatment. Total length of the stimulation was similar between the two groups. Nevertheless, total amount of gonadotropins used to reach follicular maturation was found significantly lower in group B. In addition, the number of oocytes retrieved was significantly reduced in the group pretreated with myo-inositol. Clinical pregnancy and implantation rate were not significantly different in the two groups. Our findings suggest that the addition of myo-inositol to folic acid in non PCOS-patients undergoing multiple follicular stimulation for in-vitro fertilization may reduce the numbers of mature oocytes and the dosage of rFSH whilst maintaining clinical pregnancy rate. Further, a trend in favor of increased incidence of implantation in the group pretreated with myo-inositol was apparent in this study. Further investigations are warranted to clarify this pharmacological approach, and the benefit it may hold for patients.

Pretreatment with myo-inositol in non polycystic ovary syndrome patients undergoing multiple follicular stimulation for IVF: a pilot study

PubMed Central

2012-01-01

Background Aim of this pilot study is to examine the effects of myo-inositol administration on ovarian response and oocytes and embryos quality in non PolyCystic Ovary Syndrome (PCOS) patients undergoing multiple follicular stimulation and in vitro insemination by conventional in vitro fertilization or by intracytoplasmic sperm injection. Methods One hundred non-PCOS women aged <40 years and with basal FSH <10 mUI/ml were down-regulated with triptorelin acetate from the mid-luteal phase for 2 weeks, before starting the stimulation protocol for oocytes recovery. All patients received rFSH, at a starting dose of 150 IU for 6 days. The dose was subsequently adjusted according to individual response. Group B (n = 50) received myo-inositol and folic acid for 3 months before the stimulation period and then during the stimulation itself. Group A (n-50) received only folic acid as additional treatment in the 3 months before and through treatment. Results Total length of the stimulation was similar between the two groups. Nevertheless, total amount of gonadotropins used to reach follicular maturation was found significantly lower in group B. In addition, the number of oocytes retrieved was significantly reduced in the group pretreated with myo-inositol. Clinical pregnancy and implantation rate were not significantly different in the two groups. Conclusions Our findings suggest that the addition of myo-inositol to folic acid in non PCOS-patients undergoing multiple follicular stimulation for in-vitro fertilization may reduce the numbers of mature oocytes and the dosage of rFSH whilst maintaining clinical pregnancy rate. Further, a trend in favor of increased incidence of implantation in the group pretreated with myo-inositol was apparent in this study. Further investigations are warranted to clarify this pharmacological approach, and the benefit it may hold for patients. PMID:22823904

Melatonin levels in follicular fluid as markers for IVF outcomes and predicting ovarian reserve.

PubMed

Tong, Jing; Sheng, Shile; Sun, Yun; Li, Huihui; Li, Wei-Ping; Zhang, Cong; Chen, Zi-Jiang

2017-04-01

Good-quality oocytes are critical for the success of in vitro fertilization (IVF), but, to date, there is no marker of ovarian reserve available that can accurately predict oocyte quality. Melatonin exerts its antioxidant actions as a strong radical scavenger that might affect oocyte quality directly as it is the most potent antioxidant in follicular fluid. To investigate the precise role of endogenous melatonin in IVF outcomes, we recruited 61 women undergoing treatment cycles of IVF or intracytoplasmic sperm injection (ICSI) procedures and classified them into three groups according to their response to ovarian stimulation. Follicular fluid was collected to assess melatonin levels using a direct RIA method. We found good correlations between melatonin levels in follicular fluid with age, anti-Müllerian hormone (AMH) and baseline follicle-stimulating hormone (bFSH), all of which have been used to predict ovarian reserve. Furthermore, as melatonin levels correlated to IVF outcomes, higher numbers of oocytes were collected from patients with higher melatonin levels and consequently the number of oocytes fertilized, zygotes cleaved, top quality embryos on D3, blastocysts obtained and embryos suitable for transplantation was higher. The blastocyst rate increased in concert with the melatonin levels across the gradient between the poor response group and the high response group. These results demonstrated that the melatonin levels in follicular fluid is associated with both the quantity and quality of oocytes and can predict IVF outcomes as well making them highly relevant biochemical markers of ovarian reserve. © 2017 Society for Reproduction and Fertility.

Genome-scale gene expression characteristics define the follicular initiation and developmental rules during folliculogenesis.

PubMed

Shi, Kerong; He, Feng; Yuan, Xuefeng; Zhao, Yaofeng; Deng, Xuemei; Hu, Xiaoxiang; Li, Ning

2013-08-01

The ovarian follicle supplies a unique dynamic system for gametes that ensures the propagation of the species. During folliculogenesis, the vast majority of the germ cells are lost or inactivated because of ovarian follicle atresia, resulting in diminished reproductive potency and potential infertility. Understanding the underlying molecular mechanism of folliculogenesis rules is essential. Primordial (P), preantral (M), and large antral (L) porcine follicles were used to reveal their genome-wide gene expression profiles. Results indicate that primordial follicles (P) process a diverse gene expression pattern compared to growing follicles (M and L). The 5,548 differentially expressed genes display a similar expression mode in M and L, with a correlation coefficient of 0.892. The number of regulated (both up and down) genes in M is more than that in L. Also, their regulation folds in M (2-364-fold) are much more acute than in L (2-75-fold). Differentially expressed gene groups with different regulation patterns in certain follicular stages are identified and presumed to be closely related following follicular developmental rules. Interestingly, functional annotation analysis revealed that these gene groups feature distinct biological processes or molecular functions. Moreover, representative candidate genes from these gene groups have had their RNA or protein expressions within follicles confirmed. Our study emphasized genome-scale gene expression characteristics, which provide novel entry points for understanding the folliculogenesis rules on the molecular level, such as follicular initiation, atresia, and dominance. Transcriptional regulatory circuitries in certain follicular stages are expected to be found among the identified differentially expressed gene groups.

Refractoriness to immunochemotherapy in follicular lymphoma: Predictive factors and outcome.

PubMed

Sorigue, Marc; Mercadal, Santiago; Alonso, Sara; Fernández-Álvarez, Ruben; García, Olga; Moreno, Miriam; Pomares, Helena; Alcoceba, Miguel; González-García, Esther; Motlló, Cristina; González-Barca, Eva; Martin, Alejandro; Sureda, Anna; Caballero, Dolores; Ribera, Josep-María; Sancho, Juan-Manuel

2017-12-01

Follicular lymphoma is characterized by a good response to immunochemotherapy (ICT). However, a small percentage of patients responds poorly to treatment and seems to have a worse outcome. This study attempted to identify the predictive factors and outcome of refractoriness to first-line ICT. All patients diagnosed with stage II to IV follicular lymphoma between 2002 and 2014 and treated with first-line ICT in 4 Spanish institutions were analyzed. Those with no response or progression or relapse within 6 months of first-line response assessment were considered ICT refractory. Three hundred forty-three patients were included (median age 58 years, 48% male), of whom 53 (15%) were ICT refractory. On multivariate analysis, high-risk follicular lymphoma international prognostic index (FLIPI) score, B symptoms, and elevated β2-microglobulin were correlated with refractoriness, and refractoriness, high-risk FLIPI score, and β2-microglobulin were correlated with overall survival (OS). Compared with ICT-sensitive, ICT-refractory patients had a higher incidence of histological transformation (5-year cumulative incidence 25% [14%-39%] vs. 6% [3%-10%], P < .001), a higher rate of refractoriness to second-line therapy (16/33 [48%] vs. 13/57 [23%], P = .01), and a lower OS (5-year OS probability 38% [95% CI 23%-53%] vs. 87% [82%-92%%], P < .001). In conclusion, refractoriness to ICT was seen in 15% of patients and was predicted by high-FLIPI scores, B symptoms, and elevated serum β2-micrglobulin. Immunochemotherapy-refractory patients had a worse prognosis than ICT-sensitive patients, and current treatment options for this subgroup are not satisfactory. Copyright © 2017 John Wiley & Sons, Ltd.

Phase III Early Restoration Meeting - Galveston, TX | NOAA Gulf Spill

Science.gov Websites

Areas Alabama Florida Louisiana Mississippi Texas Region-wide Open Ocean Data Media & News planning for Phase III and future early restoration plans. Open House: 6:00pm Public Meeting: 6:30pm

Impact of incretin on early-phase insulin secretion and glucose excursion.

PubMed

Shen, Jie; Chen, Zhi; Chen, Chaofeng; Zhu, Xiao; Han, Yajuan

2013-10-01

This study investigated the impact of incretin on early-phase insulin secretion and glucose excursion. The normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and type 2 diabetes mellitus (T2DM) groups included 16, 8, and 19 subjects, respectively. Subjects underwent continuous glucose monitoring for 3 days, followed by an oral glucose tolerance test. Plasma glucose, insulin, glucagon, total glucose-dependent insulinotropic polypeptide (GIP), and glucagon-like peptide-l (GLP-1) levels were measured at 30-min increments for 2 h after glucose intake. Differences with P < 0.05 were considered statistically significant. The area under the curve (AUC) of total GIP (120-min GIP-AUC) of the T2DM group was significantly lower than those of the NGT and IGT groups. The 120-min GLP-1-AUC of the NGT group was significantly larger than those of the T2DM and IGT groups. The early-phase insulin secretion index (ΔI30/ΔG30) of the T2DM group was significantly lower than those of the NGT and IGT groups. Mean amplitudes of glycemic excursions (MAGEs) went in the order of NGT < IGT < T2DM (P < 0.01, IGT vs. NGT; P < 0.001, T2DM vs. IGT). The 120-min GIP-AUC was negatively correlated with MAGE (r = -0.464), but uncorrelated with ΔI30/ΔG30. The 120-min GLP-1-AUC was positively correlated with ΔI30/ΔG30 (r = 0.580), but negatively correlated with MAGE (r = -0.606). Incretin may ameliorate glucose excursions, and GLP-1 may exert them by promoting early-phase insulin secretion. No correlation was observed between GIP secretion and early-phase insulin secretion.

Accurate diagnosis of thyroid follicular lesions from nuclear morphology using supervised learning.

PubMed

Ozolek, John A; Tosun, Akif Burak; Wang, Wei; Chen, Cheng; Kolouri, Soheil; Basu, Saurav; Huang, Hu; Rohde, Gustavo K

2014-07-01

Follicular lesions of the thyroid remain significant diagnostic challenges in surgical pathology and cytology. The diagnosis often requires considerable resources and ancillary tests including immunohistochemistry, molecular studies, and expert consultation. Visual analyses of nuclear morphological features, generally speaking, have not been helpful in distinguishing this group of lesions. Here we describe a method for distinguishing between follicular lesions of the thyroid based on nuclear morphology. The method utilizes an optimal transport-based linear embedding for segmented nuclei, together with an adaptation of existing classification methods. We show the method outputs assignments (classification results) which are near perfectly correlated with the clinical diagnosis of several lesion types' lesions utilizing a database of 94 patients in total. Experimental comparisons also show the new method can significantly outperform standard numerical feature-type methods in terms of agreement with the clinical diagnosis gold standard. In addition, the new method could potentially be used to derive insights into biologically meaningful nuclear morphology differences in these lesions. Our methods could be incorporated into a tool for pathologists to aid in distinguishing between follicular lesions of the thyroid. In addition, these results could potentially provide nuclear morphological correlates of biological behavior and reduce health care costs by decreasing histotechnician and pathologist time and obviating the need for ancillary testing. Copyright © 2014 Elsevier B.V. All rights reserved.

Early-Phase 11C-PiB PET in Amyloid Angiopathy-Related Symptomatic Cerebral Hemorrhage: Potential Diagnostic Value?

PubMed Central

Aigbirhio, Franklin I.; Fryer, Tim D.; Menon, David K.; Warburton, Elizabeth A.; Baron, Jean-Claude

2015-01-01

Although late-phase (>35min post-administration) 11C-PiB-PET has good sensitivity in cerebral amyloid angiopathy (CAA), its specificity is poor due to frequently high uptake in healthy aged subjects. By detecting perfusion-like abnormalities, early-phase 11C-PiB-PET might add diagnostic value. Early-frame (1–6min) 11C-PiB-PET was obtained in 11 non-demented patients with probable CAA-related symptomatic lobar intracerebral haemorrhage (70±7yrs), 9 age-matched healthy controls (HCs) and 10 HCs <55yrs. There was a significant decrease in early-phase atrophy-corrected whole-cortex SUV relative to cerebellar vermis (SUVR) in the CAA vs age-matched HC group. None of the age-matched controls fell below the lower 95% confidence limit derived from the young HCs, while 6/11 CAA patients did (sensitivity = 55%, specificity = 100%). Combining both early- and late-phase 11C-PiB data did not change the sensitivity and specificity of late-phase PiB, but combined early- and late-phase positivity entails a very high suspicion of underlying Aβ-related clinical disorder, i.e., CAA or Alzheimer disease (AD). In order to clarify this ambiguity, we then show that the occipital/posterior cingulate ratio is markedly lower in CAA than in AD (N = 7). These pilot data suggest that early-phase 11C-PiB-PET may not only add to late-phase PiB-PET with respect to the unclear situation of late-phase positivity, but also help differentiate CAA from AD. PMID:26439113

Synchronisation of the follicular wave with GnRH and PGF2α analogue for a timed breeding programme in dromedary camels (Camelus dromedarius).

PubMed

Manjunatha, B M; Al-Bulushi, Samir; Pratap, N

2015-09-01

This study was conducted to develop a hormone protocol that precisely synchronises follicular development for a timed breeding (TB) programme in dromedary camels. To examine the effect of GnRH treatment at four known stages of follicular development, animals were treated with GnRH when the largest follicle of the wave was 4-7, 8-11, 12-17 and 18-27 mm in diameter. Transrectal ultrasonography was carried out daily up to 20 days after treatment. A hormone protocol (FWsynch) for the synchronisation of follicular wave and TB consisting of GnRH-1 (GnRH) on Day 0, PG-1 (PGF2α) on Day 7, GnRH-2 on Day 10 and PG-2 on Day 17 was initiated at four known stages of follicular development. Ovarian structures were monitored by ultrasonography. The FWsynch protocol was initiated at random stages of follicle development and animals were bred by natural mating at a fixed time at the research facility and in field. The pregnancy was diagnosed by ultrasonography. GnRH treatment in animals with a dominant follicle (DF) of ≥ 11 mm in diameter resulted in synchronous new follicular wave emergence, whereas in animals with a DF ≤ 10 mm, the treatment did not alter the development of the existing follicular wave. The FWsynch protocol was effective in synchronising the follicular wave for TB irrespective of the stage of follicular development at the beginning of the protocol. TB using FWsynch protocol resulted in a pregnancy rate of 60.2% in a research facility and 53.6% and 45.6% in normal and infertile camels respectively under field conditions. Copyright © 2015 Elsevier B.V. All rights reserved.

p16 expression in follicular dendritic cell sarcoma: a potential mimicker of human papillomavirus-related oropharyngeal squamous cell carcinoma.

PubMed

Zhang, Lingxin; Yang, Chen; Lewis, James S; El-Mofty, Samir K; Chernock, Rebecca D

2017-08-01

Follicular dendritic cell sarcoma is a rare mesenchymal neoplasm that most commonly occurs in cervical lymph nodes. It has histologic and clinical overlap with the much more common p16-positive human papillomavirus (HPV)-related squamous cell carcinoma of the oropharynx, which characteristically has nonkeratinizing morphology and often presents as an isolated neck mass. Not surprisingly, follicular dendritic cell sarcomas are commonly misdiagnosed as squamous cell carcinoma. Immunohistochemistry is helpful in separating the 2 entities. Follicular dendritic cell sarcoma expresses dendritic markers such as CD21 and CD23 and is almost always cytokeratin negative. However, in many cases of HPV-related oropharyngeal carcinoma, only p16 immunohistochemistry as a prognostic and surrogate marker for HPV is performed. p16 expression in follicular dendritic cell sarcoma has not been characterized. Here, we investigate the expression of p16 in follicular dendritic cell sarcoma and correlate it with retinoblastoma protein expression. A pilot study of dendritic marker expression in HPV-related oropharyngeal squamous cell carcinoma was also performed. We found that 4 of 8 sarcomas expressed p16 with strong and diffuse staining in 2 cases. In 2 of the 4 cases, p16 expression corresponded to loss of retinoblastoma protein expression. Dendritic marker expression (CD21 and CD23) was not found in HPV-related oropharyngeal squamous cell carcinomas. As such, positive p16 immunohistochemistry cannot be used as supportive evidence for the diagnosis of squamous cell carcinoma as strong and diffuse p16 expression may also occur in follicular dendritic cell sarcoma. Cytokeratins and dendritic markers are critical in separating the two tumor types. Copyright © 2017 Elsevier Inc. All rights reserved.

Menstrual Cycle Effects on Perceived Exertion and Pain During Exercise Among Sedentary Women

PubMed Central

Bryan, Angela D.; Eaton, Melissa

2011-01-01

Abstract Background Increasing cardiovascular fitness through exercise participation among sedentary people is important for decreasing all-cause mortality. From an intervention perspective, identifying modifiable factors that maximize the successful initiation of exercise is of utmost importance. For women, cyclic hormonal variations can influence aspects of health and health behaviors, from smoking cessation efficacy to physiological responses to exercise. The purpose of this study was to examine the influence of menstrual cycle phase and hormonal contraceptive (HC) use on subjective response to an initial bout of moderate intensity exercise among previously sedentary women (n = 117). Methods Women completed a treadmill exercise challenge session at 65% of their previously determined maximum oxygen consumption (Vo2 max) during the early follicular, late follicular, or luteal phase. Participants reported ratings of perceived exertion and pain using Borg's Rating of Perceived Exertion (RPE) and CR10 scales at 10, 20, and 30 minutes during the exercise session. Results There was a significant menstrual phase × birth control interaction on change in RPE [F(2, 111) = 3.75, p < 0.05] and change in perceived pain [F(2, 110) = 3.31, p < 0.05]. Women in the early follicular phase who were not using HCs had significantly greater increases in RPE and increases in pain compared with women in the late follicular and luteal phases. Conclusions Our results indicate that the use of HC and cycle phase influence sedentary women's subjective response to exercise. These results have important implications for the timing of exercise interventions aimed at increasing exercise among sedentary women. PMID:21219246

The Role of DmCatD, a Cathepsin D-Like Peptidase, and Acid Phosphatase in the Process of Follicular Atresia in Dipetalogaster maxima (Hemiptera: Reduviidae), a Vector of Chagas' Disease

PubMed Central

Leyria, Jimena; Fruttero, Leonardo L.; Nazar, Magalí; Canavoso, Lilián E.

2015-01-01

In this work, we have investigated the involvement of DmCatD, a cathepsin D-like peptidase, and acid phosphatase in the process of follicular atresia of Dipetalogaster maxima, a hematophagous insect vector of Chagas’ disease. For the studies, fat bodies, ovaries and hemolymph were sampled from anautogenous females at representative days of the reproductive cycle: pre-vitellogenesis, vitellogenesis as well as early and late atresia. Real time PCR (qPCR) and western blot assays showed that DmCatD was expressed in fat bodies and ovaries at all reproductive stages, being the expression of its active form significantly higher at the atretic stages. In hemolymph samples, only the immunoreactive band compatible with pro-DmCatD was observed by western blot. Acid phosphatase activity in ovarian tissues significantly increased during follicular atresia in comparison to pre-vitellogenesis and vitellogenesis. A further enzyme characterization with inhibitors showed that the high levels of acid phosphatase activity in atretic ovaries corresponded mainly to a tyrosine phosphatase. Immunofluorescence assays demonstrated that DmCatD and tyrosine phosphatase were associated with yolk bodies in vitellogenic follicles, while in atretic stages they displayed a different cellular distribution. DmCatD and tyrosine phosphatase partially co-localized with vitellin. Moreover, their interaction was supported by FRET analysis. In vitro assays using homogenates of atretic ovaries as the enzyme source and enzyme inhibitors demonstrated that DmCatD, together with a tyrosine phosphatase, were necessary to promote the degradation of vitellin. Taken together, the results strongly suggested that both acid hydrolases play a central role in early vitellin proteolysis during the process of follicular atresia. PMID:26091289

Development of a Two-Dimensional Model for Predicting Transdermal Permeation with the Follicular Pathway: Demonstration with a Caffeine Study.

PubMed

Kattou, Panayiotis; Lian, Guoping; Glavin, Stephen; Sorrell, Ian; Chen, Tao

2017-10-01

The development of a new two-dimensional (2D) model to predict follicular permeation, with integration into a recently reported multi-scale model of transdermal permeation is presented. The follicular pathway is modelled by diffusion in sebum. The mass transfer and partition properties of solutes in lipid, corneocytes, viable dermis, dermis and systemic circulation are calculated as reported previously [Pharm Res 33 (2016) 1602]. The mass transfer and partition properties in sebum are collected from existing literature. None of the model input parameters was fit to the clinical data with which the model prediction is compared. The integrated model has been applied to predict the published clinical data of transdermal permeation of caffeine. The relative importance of the follicular pathway is analysed. Good agreement of the model prediction with the clinical data has been obtained. The simulation confirms that for caffeine the follicular route is important; the maximum bioavailable concentration of caffeine in systemic circulation with open hair follicles is predicted to be 20% higher than that when hair follicles are blocked. The follicular pathway contributes to not only short time fast penetration, but also the overall systemic bioavailability. With such in silico model, useful information can be obtained for caffeine disposition and localised delivery in lipid, corneocytes, viable dermis, dermis and the hair follicle. Such detailed information is difficult to obtain experimentally.

Early Risk Reduction Phase 1 FLIR/Laser Designator Window. Revision

DTIC Science & Technology

1991-12-31

Sandwich-Type FLIR Windows," Air Force AFWAL-TR-83- 4122, Nov 1983. 4-1 Hughes Danbury Optical Systems Final Report, "ATA Window Technology Program," PRBll...Risk Reduction -- Phase I, Optical Properties Measurement Techniques of Three Wide Band Window Materials," 22 August 1991. xii I i 86PR0869 30... Optical Systems, Lexington, MA, 02173, 1 Feb 1991. 5-7 McDonnell Aircraft Company Technical Memorandum TM 256.91.0056.01, "Early Risk Reduction -- Phase

The Effect of Gender and Menstrual Phase on Serum Creatine Kinase Activity and Muscle Soreness Following Downhill Running

PubMed Central

Oosthuyse, Tanja; Bosch, Andrew N.

2017-01-01

Serum creatine kinase (CK) activity reflects muscle membrane disruption. Oestrogen has antioxidant and membrane stabilising properties, yet no study has compared the CK and muscle soreness (DOMS) response to unaccustomed exercise between genders when all menstrual phases are represented in women. Fifteen eumenorrhoeic women (early follicular, EF (n = 5); late follicular, LF (n = 5); mid-luteal, ML (n = 5) phase) and six men performed 20 min of downhill running (−10% gradient) at 9 km/h. Serum CK activity and visual analogue scale rating of perceived muscle soreness were measured before, immediately, 24-h, 48-h and 72-h after exercise. The 24-h peak CK response (relative to pre-exercise) was similar between women and men (mean change (95% confidence interval): 58.5 (25.2 to 91.7) IU/L; 68.8 (31.3 to 106.3) IU/L, respectively). However, serum CK activity was restored to pre-exercise levels quicker in women (regardless of menstrual phase) than men; after 48-h post exercise in women (16.3 (−4.4 to 37.0) IU/L; 56.3 (37.0 to 75.6) IU/L, respectively) but only after 72-h in men (14.9 (−14.8 to 44.6) IU/L). Parallel to the CK response, muscle soreness recovered by 72-h in men. Conversely, the women still reported muscle soreness at 72-h despite CK levels being restored by 48-h; delayed recovery of muscle soreness appeared mainly in EF and LF. The CK and DOMS response to downhill running is gender-specific. The CK response recovers quicker in women than men. The CK and DOMS response occur in concert in men but not in women. The DOMS response in women is prolonged and may be influenced by menstrual phase. PMID:28241459

Heavy metal and trace element concentrations in blood and follicular fluid affect ART outcome.

PubMed

Tolunay, Harun Egemen; Şükür, Yavuz Emre; Ozkavukcu, Sinan; Seval, Mehmet Murat; Ateş, Can; Türksoy, Vugar Ali; Ecemiş, Tolga; Atabekoğlu, Cem Somer; Özmen, Batuhan; Berker, Bülent; Sönmezer, Murat

2016-03-01

To assess the effects of heavy metal and trace element concentrations in blood and follicular fluid on assisted reproductive technology cycle outcome. A prospective study was conducted between January 2012 and July 2012 in a university hospital infertility clinic. One hundred and one patients with unexplained infertility who underwent intracytoplasmic sperm injection using GnRH-antagonist protocol were recruited. Concentrations of four toxic metals (Cd, Pb, Hg, As) and three trace elements (Cu, Zn, Fe) were measured both in blood and follicular fluid specimens. Patients were evaluated in two groups; the study group consisted of patients with ongoing pregnancy (n=20) and the reference group consisted of patients experienced assisted reproductive technology failure, miscarriage or biochemical pregnancy (n=81). Demographics and cycle parameters were comparable between the groups except for median number of day 3 Grade A embryos. Statistically significant negative correlations were found between blood Pb levels and number of MII oocytes, implantation, clinical pregnancy and ongoing pregnancy rates. Results of the log binomial regression revealed 2.2% lower risk for ongoing pregnancy for each 1μg/dL higher blood Pb concentration while holding the other variables in the model constant (RR 0.978; 95% CI 0.956-0.998; P=.041). Also, the results revealed 71.9% lower risk for ongoing pregnancy for each 1μg/dL higher follicular fluid Cu concentration while holding the other variables in the model constant (RR 0.288; 95% CI 0.085-0.92; P=.039). Blood concentrations of Pb and follicular fluid concentrations of Cu seem to have significant impacts on assisted reproductive technology cycle outcome. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Does dietary fat intake influence oocyte competence and embryo quality by inducing oxidative stress in follicular fluid?

PubMed

Kazemi, Ashraf; Ramezanzadeh, Fatemeh; Nasr-Esfahani, Mohammad Hosein; Saboor Yaraghi, Ali Akbar; Ahmadi, Mehdi

2013-12-01

Fat-rich diet may alter oocyte development and maturation and embryonic development by inducing oxidative stress (OS) in follicular environment. To investigate the relationship between fat intake and oxidative stress with oocyte competence and embryo quality. In observational study follicular fluid was collected from 236 women undergoing assisted reproduction program. Malon-di-aldehyde (MDA) levels and total antioxidant capacity (TAC) levels of follicular fluid were assessed as oxidative stress biomarkers. In assisted reproduction treatment cycle fat consumption and its component were assessed. A percentage of metaphase ΙΙ stage oocytes, fertilization rate were considered as markers of oocyte competence and non-fragmented embryo rate, mean of blastomer and good cleavage (embryos with more than 5 cells on 3 days post insemination) rate were considered as markers of embryo quality. The MDA level in follicular fluid was positively related to polyunsaturated fatty acids intake level (p=0.02) and negatively associated with good cleavage rate (p=0.045). Also good cleavage rate (p=0.005) and mean of blastomer (p=0.006) was negatively associated with polyunsaturated fatty acids intake levels. The percentage of metaphase ΙΙ stage oocyte was positively related to the TAC levels in follicular fluid (p=0.046). The relationship between the OS biomarkers in FF and the fertilization rate was not significant. These findings revealed that fat rich diet may induce the OS in oocyte environment and negatively influence embryonic development. This effect can partially be accounted by polyunsaturated fatty acids uptake while oocyte maturation is related to TAC and oocytes with low total antioxidant capacity have lower chance for fertilization and further development.

Mixed primary squamous cell carcinoma, follicular carcinoma, and micropapillary carcinoma of the thyroid gland: A case report.

PubMed

Dong, Su; Song, Xue-Song; Chen, Guang; Liu, Jia

2016-08-01

Primary squamous cell carcinoma of the thyroid gland is rare, and mixed squamous cell and follicular carcinoma is even rarer still, with only a few cases reported in the literature. The simultaneous presentation of three primary cancers of the thyroid has not been reported previously. Here we report a case of primary squamous cell carcinoma of the thyroid, follicular thyroid carcinoma, and micropapillary thyroid carcinoma. A 62-year-old female patient presented with complaints of pain and a 2-month history of progressively increased swelling in the anterior region of the neck. Fine-needle-aspiration cytology of both lobes indicated the possibility of the presence of a follicular neoplasm. Total thyroidectomy with left-sided modified radical neck dissection was performed. Postoperative pathological examination confirmed the diagnosis of thyroid follicular carcinoma with squamous cell carcinoma and micropapillary carcinoma of the thyroid. Thyroid-stimulating hormone suppressive therapy with l-thyroxine was administered. Radioiodine and radiotherapy also were recommended, but the patient did not complete treatment as scheduled. The patient remained alive more than 9 months after operation. The present case report provides an example of the coexistence of multiple distinct malignancies in the thyroid. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

The effects of menstrual cycle phase on physical performance in female soccer players

PubMed Central

Julian, Ross; Hecksteden, Anne; Fullagar, Hugh H. K.; Meyer, Tim

2017-01-01

Background Female soccer has grown extensively in recent years, however differences in gender-specific physiology have rarely been considered. The female reproductive hormones which rise and fall throughout the menstrual cycle, are known to affect numerous cardiovascular, respiratory, thermoregulatory and metabolic parameters, which in turn, may have implications on exercise physiology and soccer performance. Therefore, the main aim of the present study was to investigate potential effects of menstrual cycle phase on performance in soccer specific tests. Methods Nine sub elite female soccer players, all of whom have menstrual cycles of physiological length; performed a series of physical performance tests (Yo-Yo Intermittent endurance test (Yo-Yo IET), counter movement jump (CMJ) and 3x30 m sprints). These were conducted at distinct time points during two main phases of the menstrual cycle (early follicular phase (FP) and mid luteal phase (LP)) where hormones contrasted at their greatest magnitude. Results Yo-Yo IET performance was considerably lower during the mid LP (2833±896 m) as compared to the early FP (3288±800 m). A trend towards significance was observed (p = 0.07) and the magnitude based inferences suggested probabilities of 0/61/39 for superiority/equality/inferiority of performance during the mid LP, leading to the inference of a possibly harmful effect. For CMJ (early FP, 20.0±3.9 cm; mid LP 29.6±3.0 cm, p = 0.33) and sprint (early FP, 4.7±0.1 s; mid LP, 4.7±0.1 s, p = 0.96) performances the results were unclear (8/24/68, 48/0/52, respectively). Conclusion The results of this study are in support of a reduction in maximal endurance performance during the mid LP of the menstrual cycle. However, the same effect was not observed for jumping and sprint performance. Therefore, consideration of cycle phase when monitoring a player’s endurance capacity may be worthwhile. PMID:28288203

Interleukin-6 and Delayed Onset Muscle Soreness Do Not Vary during the Menstrual Cycle

ERIC Educational Resources Information Center

Chaffin, Morgan E.; Berg, Kris E.; Meendering, Jessica R.; Llewellyn, Tamra L.; French, Jeffrey A.; Davis, Jeremy E.

2011-01-01

The purpose of this study was to determine if a difference in interleukin-6 (IL-6) and delayed onset muscles soreness (DOMS) exists in two different phases of the menstrual cycle. Nine runners performed one 75-min high-intensity interval running session during the early follicular (EF) phase and once during the midluteal (ML) phase of the…

Pediatric Type Follicular Lymphoma: A Rare Entity with Excellent Prognosis

DTIC Science & Technology

2018-01-19

lymphomas, has a median age range of 7.5-11.7, and has a male- female ratio of 4:1. This entity occurs most frequently in the tonsils and head and... neck lymph nodes. The pathogenesis of follicular lymphoma in adults is based upon immunoglobulin gene rearrangements with BCL2, BCL6, and MYC

Age, tumor size, and in-office ultrasonography are predictive parameters of malignancy in follicular neoplasms of the thyroid.

PubMed

Paramo, Juan C; Mesko, Thomas

2008-01-01

To identify clinical predictors of malignancy in patients with intraoperative frozen-section diagnosis of follicular neoplasm of the thyroid. We performed a retrospective cross-sectional study of 71 patients with intraoperative frozen-section diagnosis of follicular neoplasm who underwent thyroidectomy between January 1992 and December 2000. Age, sex, tumor size, and in-office ultrasonography characteristics of the lesions were assessed. These clinical factors were compared between cases that had benign definitive pathologic findings and those that were found to be carcinomas on permanent sections. Nine (13%) of the 71 follicular neoplasms were found to be carcinomas after definitive pathologic evaluation. The incidence of malignancy was 13% (2/16) in men and 13% (7/55) in women (P>.5). Patients younger than 45 years had a 27% (8/30) incidence of malignancy compared with 2% (1/41) in patients 45 years or older (P<.01). Of tumors smaller than 4 cm, 7% (4/55) were ultimately diagnosed as carcinomas compared with 31% (5/16) of those 4 cm or larger (P = .05). When the in-office ultrasonography findings were interpreted as benign, only 7% (3/46) of cases were malignant compared with 40% (4/10) when the ultrasonography findings were suspicious (P = .02). Age and tumor size are predictive parameters of malignancy in follicular neoplasm of the thyroid. Suspicious ultrasonography findings also have an important predictive role. Total thyroidectomy is reasonable in patients with follicular neoplasm on frozen section if they are young (<45 years old), with large (>4 cm) tumors or if there are suspicious findings on in-office ultrasonography.

Early Detection of Amyloid Plaque in Alzheimer’s Disease via X-ray Phase CT

DTIC Science & Technology

2016-08-01

AWARD NUMBER: W81XWH-12-1-0138 TITLE: Early Detection of Amyloid Plaque in Alzheimer’s Disease via X-ray Phase CT PRINCIPAL INVESTIGATOR...NUMBER W81XWH-12-1-0138 Early Detection of Amyloid Plaque in Alzheimer’s Disease via X-ray Phase CT 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6...method for early detection of amyloid plaque in Alzheimer’s disease , with three Specific Aims: #1 Develop and optimize an x-ray PCCT to explore the

Iontophoresis of minoxidil sulphate loaded microparticles, a strategy for follicular drug targeting?

PubMed

Gelfuso, Guilherme M; Barros, M Angélica de Oliveira; Delgado-Charro, M Begoña; Guy, Richard H; Lopez, Renata F V

2015-10-01

The feasibility of targeting drugs to hair follicles by a combination of microencapsulation and iontophoresis has been evaluated. Minoxidil sulphate (MXS), which is used in the treatment of alopecia, was selected as a relevant drug with respect to follicular penetration. The skin permeation and disposition of MXS encapsulated in chitosan microparticles (MXS-MP) was evaluated in vitro after passive and iontophoretic delivery. Uptake of MXS was quantified at different exposure times in the stratum corneum (SC) and hair follicles. Microencapsulation resulted in increased (6-fold) drug accumulation in the hair follicles relative to delivery from a simple MXS solution. Application of iontophoresis enhanced follicular delivery for both the solution and the microparticle formulations. It appears, therefore, that microencapsulation and iontophoresis can act synergistically to enhance topical drug targeting to hair follicles. Copyright © 2015 Elsevier B.V. All rights reserved.

Low Iodine in the Follicular Lumen Caused by Cytoplasm Mis-localization of Sodium Iodide Symporter may Induce Nodular Goiter.

PubMed

Huang, Huibin; Shi, Yaxiong; Liang, Bo; Cai, Huiyao; Cai, Qingyan

2017-10-01

Iodine is a key ingredient in the synthesis of thyroid hormones and also a major factor in the regulation of thyroid function. A local reduction of iodine content in follicular lumen leads to overexpression of local thyroid-stimulating hormone receptor (TSHr), which in turn excessively stimulates the regional thyroid tissue, and result in the formation of nodular goiter. In this study, we investigated the relationship between iodine content and sodium iodide symporter (NIS) expression by using the clinical specimens from patients with nodular goiter and explored the pathogenesis triggered by iodine deficiency in nodular goiter. In total, 28 patients were clinically histopathologically confirmed to have nodular goiter and the corresponding adjacent normal thyroid specimens were harvested simultaneously. Western blot and immunohistochemistry were performed to assay NIS expression and localization in thyrocytes of both nodular goiter and adjacent normal thyroid tissues. NIS expression mediated by iodine in follicular lumen was confirmed by follicular model in vitro. Meanwhile, radioscan with iodine-131were conducted on both nodular goiter and adjacent normal thyroid. Our data showed that NIS expression in nodular goiter was significantly higher than that in adjacent normal tissues, which was associated with low iodine in the follicular lumen. Abnormal localization of NIS and lower amount of radioactive iodine-131 were also found in nodular goiter. Our data implied that low iodine in the follicular lumen caused by cytoplasm mis-localization of NIS may induce nodular goiter.

Effects of cycle stage on regionalised galanin, galanin receptors 1-3, GNRH and GNRH receptor mRNA expression in the ovine hypothalamus.

PubMed

Whitelaw, Christine Margaret; Robinson, Jane Elizabeth; Hastie, Peter Mark; Padmanabhan, Vasantha; Evans, Neil Price

2012-03-01

The neurotransmitter galanin has been implicated in the steroidogenic regulation of reproduction based on work mainly conducted in rodents. This study investigated the temporal changes in the expression of galanin and its three receptor isoforms and GNRH and GNRHR mRNA in specific hypothalamic nuclei known to be involved in the regulation of reproductive cyclicity, namely the medial pre-optic area (mPOA), the rostral mPOA/organum vasculosum of the lamina terminalis, the paraventricular nucleus and the arcuate nucleus using an ovine model. Following synchronisation of their oestrous cycles, tissues were collected from ewes at five time points: the early follicular, mid follicular (MF) and late follicular phases and the early luteal and mid luteal phases. The results indicated significant differences in regional expression of most of the genes studied, with galanin mRNA expression being highest during the MF phase at the start of the GNRH/LH surge and the expression of the three galanin receptor (GalR) isoforms and GNRH and its receptor highest during the luteal phase. These findings are consistent with a role for galanin in the positive feedback effects of oestradiol (E(2)) on GNRH secretion and a role for progesterone induced changes in the pattern of expression of GalRs in the regulation of the timing of E(2)'s positive feedback through increased sensitivity of galanin-sensitive systems to secreted galanin.

Histomorphometric comparative study of blood vessels and their pattern in follicular cyst, odontogenic keratocyst, and ameloblastoma.

PubMed

Seifi, Safora; Feizi, Farideh; Khafri, Thoraya; Aram, Mehrdad

2013-03-01

The present study aimed at assessment and histomorphometric analysis of intratumoral and peritumoral (cystic) blood vessels in odontogenic lesions and their pattern on their clinical behavior by immunohistochemistry and morphometry. In a descriptive and analytical cross-sectional study, 45 paraffin blocks of ameloblastoma, odontogenic keratocyst, and follicular cyst were selected and stained immunohistochemically for CD34. In each slide, images of 3 microscopic fields with the highest microvessel density in intratumoral and peritumoral (cystic) areas were captured at 40× magnification with attached camera system. Inner vascular diameter (IVD) and outer vascular diameter (OVD), cross-sectional area (CSA), and the wall thickness (WT) of the vessels were measured with Motic Plus 2 software. The vascular pattern in odontogenic lesions was analyzed. Outer vascular diameter, IVD, and CSA of the vessels in peritumoral (cystic) areas were greater in ameloblastoma than keratocyst (P = 0.001) and follicular cyst (P < 0.001). However, WT of the blood vessels did not show any significant statistical difference among the 3 odontogenic lesions (P = 0.05). The differences in OVD, IVD (P = 0.8), CSA (P = 0.6), and WT (P = 0.4) of the blood vessels in intratumoral (cystic) areas were not statistically significant. The blood vessel pattern was circumferential in ameloblastoma, and it was directional in keratocyst and follicular cyst. Morphometric specifications of blood vessels (IVD, OVD, CSA) and their pattern in peritumoral (cystic) areas may influence the aggressive clinical behavior of ameloblastoma in comparison with keratocyst and follicular cyst.

Effect of follicular flushing on reproductive outcomes in patients with poor ovarian response undergoing assisted reproductive technology.

PubMed

Souza, Anna L M; Sampaio, Marcos; Noronha, Graciele B; Coster, Ludiana G R; de Oliveira, Roberta S G; Geber, Selmo

2017-10-01

The purpose of this study is to investigate the impact of follicular flushing on the number of oocytes retrieved, oocyte maturity, fertilization rate, embryo development, and pregnancy rate of poor ovarian responders (POR). Retrospective study of 524 cycles of 384 patients with POR submitted to assisted reproductive technology (ART) and who had follicular flushing during oocyte retrieval was used in the study. We included patients with <5 oocytes at oocyte retrieval (POR group) and matching the Bologna criteria. POR patients had a mean age of 38.2 ± 4.2 years. A total of 1355 follicles (mean = 3.5 ± 1.6) were aspirated and 1040 oocytes recovered, with 709 (68.2%) obtained by direct aspiration and 331 (31.8%) by follicular flushing. We found a difference between the total number of oocytes and the number of aspirated oocytes. Overall pregnancy rate was 22%. Association was observed between pregnancy rate and the number of oocytes retrieved, the number of MII oocytes, and the number of embryos transferred. The patients matching the Bologna criteria had a mean age of 38.9 ± 3.9 years. A total of 309 follicles were aspirated (mean = 3.1 ± 1.5) and 242 oocytes recovered, with 156 (64.5%) obtained by direct aspiration and 86 (35.5%) by follicular flushing. There was a significant difference between the total number of oocytes and the number of aspirated oocytes. Overall pregnancy rate was 12.1%. There was no association between the pregnancy rate and the number of oocytes retrieved, the number of MII, and the number of embryos. Follicular flushing might be a suitable alternative to increase the number of oocytes and pregnancy rates in patients with POR.

Early serum progesterone and prolactin analysis at day 9 of oocyte retrieval as a predictor of success in fresh ICSI cycles.

PubMed

Pérez, Paulina A Santander; Ceschin, Álvaro P; Moraes, Daniela M P de; Oliveira, Lucileine K S N de; Ceschin, Nathan I; Ichikawa, Nathan

2018-06-01

To analyze progesterone and prolactin plasma levels nine days after oocyte retrieval and evaluate their correlation with pregnancy rates in in vitro fertilization cycles. To achieve pregnancy, several factors are analyzed before and during the in vitro fertilization cycle. Progesterone supplementation for adequate luteal phase support is indicated despite the presence of multiple corpus luteum in IVF stimulation cycles because of blockage caused by hypothalamic agonists and antagonists. The dosage of progesterone and prolactin on day 09 after follicular retrieval could function as a predictive marker of success in fertility treatments. A retrospective study was performed using data from 238 patients submitted to intracytoplasmic sperm injection (ICSI) at a private infertility clinic from January 2013 to December 2015. Hormonal measurements were performed on day 09 after follicular uptake. The data was compared to assess the correlation between prolactin and progesterone dosages and pregnancy rates. The ICSI pregnancy rate was 40.8% (n=238). No statistically significant difference was observed when correlating the success of the procedure with the prolactin dosage (p=0.71). However, progesterone showed a significant difference (p=0.021). The cutoff point, indicated by the ROC curve fit according to which gestation would be identified, is 25.95ng/ml of progesterone. The sensitivity of this point is 61.9% and the specificity is 57.4%. Progesterone dosage may be one of the indicators of gestation on day 09 after follicular uptake. Such data can help physicians to monitoring and provides suitable early gestational care. More studies are needed to corroborate the data found.

NONINVASIVE FOLLICULAR TUMOR WITH PAPILLARY-LIKE NUCLEAR FEATURES: NOT A TEMPEST IN A TEAPOT.

PubMed

Agrawal, Nidhi; Abbott, Collette E; Liu, Cheng; Kang, Stella; Tipton, Laura; Patel, Kepal; Persky, Mark; King, Lizabeth; Deng, Fang-Ming; Bannan, Michael; Ogilvie, Jennifer B; Heller, Keith; Hodak, Steven P

2017-04-02

Encapsulated non-invasive follicular variant papillary thyroid cancer (ENIFVPTC) has recently been retermed noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). This designation specifically omits the word "cancer" to encourage conservative treatment since patients with NIFTP tumors have been shown to derive no benefit from completion thyroidectomy or adjuvant radio-active iodine (RAI) therapy. This was a retrospective study of consecutive cases of tumors from 2007 to 2015 that met pathologic criteria for NIFTP. The conservative management (CM) group included patients managed with lobectomy alone or appropriately indicated total thyroidectomy. Those included in the aggressive management (AM) group received either completion thyroidectomy or RAI or both. From 100 consecutive cases of ENIFVPTC reviewed, 40 NIFTP were included for the final analysis. Of these, 10 (27%) patients treated with initial lobectomy received completion thyroidectomy and 6 of 40 (16%) also received postsurgical adjuvant RAI. The mean per-patient cost of care in the AM group was $17,629 ± 2,865, nearly twice the $8,637 ± 309 costs in the CM group, and was largely driven by the cost of completion thyroidectomy and RAI. The term NIFTP has been recently promulgated to identify a type of thyroid neoplasm, formerly identified as a low-grade cancer, for which initial surgery represents adequate treatment. We believe that since the new NIFTP nomenclature intentionally omits the word "cancer," the clinical indolence of these tumors will be better appreciated, and cost savings will result from more conservative and appropriate clinical management. AM = aggressive management CM = conservative management ENIFVPTC = encapsulated noninvasive form of FVPTC FVPTC = follicular variant of papillary thyroid carcinoma NIFTP = noninvasive follicular thyroid neoplasm with papillary-like nuclear features PTC = papillary thyroid carcinoma PTMC = papillary thyroid microcarcinoma RAI

Wide-field phase imaging for the endoscopic detection of dysplasia and early-stage esophageal cancer

NASA Astrophysics Data System (ADS)

Fitzpatrick, C. R. M.; Gordon, G. S. D.; Sawyer, T. W.; Wilkinson, T. D.; Bohndiek, S. E.

2018-02-01

Esophageal cancer has a 5-year survival rate below 20%, but can be curatively resected if it is detected early. At present, poor contrast for early lesions in white light imaging leads to a high miss rate in standard-of- care endoscopic surveillance. Early lesions in the esophagus, referred to as dysplasia, are characterized by an abundance of abnormal cells with enlarged nuclei. This tissue has a different refractive index profile to healthy tissue, which results in different light scattering properties and provides a source of endogenous contrast that can be exploited for advanced endoscopic imaging. For example, point measurements of such contrast can be made with scattering spectroscopy, while optical coherence tomography generates volumetric data. However, both require specialist interpretation for diagnostic decision making. We propose combining wide-field phase imaging with existing white light endoscopy in order to provide enhanced contrast for dysplasia and early-stage cancer in an image format that is familiar to endoscopists. Wide-field phase imaging in endoscopy can be achieved using coherent illumination combined with phase retrieval algorithms. Here, we present the design and simulation of a benchtop phase imaging system that is compatible with capsule endoscopy. We have undertaken preliminary optical modelling of the phase imaging setup, including aberration correction simulations and an investigation into distinguishing between different tissue phantom scattering coefficients. As our approach is based on phase retrieval rather than interferometry, it is feasible to realize a device with low-cost components for future clinical implementation.

Accumulation of unsaturated lipids in monocytes during early phase pyrogen tolerance.

PubMed

Szewczenko-Pawlikowski, M; Kozak, W

2000-04-12

This paper presents data that inspired a new explanation for the mechanism of early phase endotoxin tolerance. Rabbits injected intravenously with LPS from Salmonella abortus developed a two-phase fever (6 h) and monophasic hyperlipidemia of very low density lipoproteins (two consecutive days). If during these days rabbits were injected with the same dose of LPS at 24-h intervals, the second phase of fever disappeared, i.e. early phase pyrogenic tolerance was obtained. This was correlated with a decrease of lipoprotein hyperlipidemia (measured 1.5 h after LPS injection) and an accumulation of lipids rich in double bonds in monocytes (measured 3.5 h after LPS injection). Results showed that the degree of unsaturation of acyl chains (AC) in monocytes (AC/DB, DB=double bonds) is negatively correlated (r=-0.72) with fever response (fever index). The authors maintain that a gradual increase in monocyte membrane fluidity is an adaptation to repeated exposure of monocytes to lipid A and is responsible for the progressive desensitization of monocytes to endotoxin. It is suggested that disorders of this mechanism lead to an accumulation of abnormal quantities of saturated lipids and cholesterol within macrophages, which, as foam cells, are the starting point for atherosclerosis pathology.

Phase III Early Restoration Meeting - Port Arthur, TX | NOAA Gulf Spill

Science.gov Websites

Areas Alabama Florida Louisiana Mississippi Texas Region-wide Open Ocean Data Media & News planning for Phase III and future early restoration plans. Open House: 6:00pm Public Meeting: 6:30pm

Phase III Early Restoration Meeting - Panama City, FL | NOAA Gulf Spill

Science.gov Websites

Areas Alabama Florida Louisiana Mississippi Texas Region-wide Open Ocean Data Media & News planning for Phase III and future early restoration plans. Open House: 6:00pm Public Meeting: 6:30pm

Dermal papilla cell number specifies hair size, shape and cycling and its reduction causes follicular decline

PubMed Central

Chi, Woo; Wu, Eleanor; Morgan, Bruce A.

2013-01-01

Although the hair shaft is derived from the progeny of keratinocyte stem cells in the follicular epithelium, the growth and differentiation of follicular keratinocytes is guided by a specialized mesenchymal population, the dermal papilla (DP), that is embedded in the hair bulb. Here we show that the number of DP cells in the follicle correlates with the size and shape of the hair produced in the mouse pelage. The same stem cell pool gives rise to hairs of different sizes or types in successive hair cycles, and this shift is accompanied by a corresponding change in DP cell number. Using a mouse model that allows selective ablation of DP cells in vivo, we show that DP cell number dictates the size and shape of the hair. Furthermore, we confirm the hypothesis that the DP plays a crucial role in activating stem cells to initiate the formation of a new hair shaft. When DP cell number falls below a critical threshold, hair follicles with a normal keratinocyte compartment fail to generate new hairs. However, neighbouring follicles with a few more DP cells can re-enter the growth phase, and those that do exploit an intrinsic mechanism to restore both DP cell number and normal hair growth. These results demonstrate that the mesenchymal niche directs stem and progenitor cell behaviour to initiate regeneration and specify hair morphology. Degeneration of the DP population in mice leads to the types of hair thinning and loss observed during human aging, and the results reported here suggest novel approaches to reversing hair loss. PMID:23487317

Follicular wave emergence in Santa Inês ewes subjected to long-term, progesterone-based estrous synchronization protocols at different times of the year.

PubMed

Oliveira, M E F; Ayres, H; Oliveira, L G; Oba, E; Kridli, R T; Bartlewski, P M; Fonseca, J F; Bicudo, S D; Vicente, W R R

2016-11-01

This study was conducted to document the pattern of antral follicular wave emergence throughout the 14-day, progesterone (P 4 )-based estrous synchronization protocol in ewes that were maintained in subtropical conditions, during the period of increasing day lengths (ID), decreasing day lengths (DD), and the transitional period (TP). In addition, the influence of ovarian status (i.e., size of ovarian antral follicles and the presence of corpora lutea) at the outset of P 4 treatment on ensuing ovarian follicular wave development was examined. Sexually mature Santa Inês ewes (n=70) were subjected to one of the two estrous synchronization protocols in the three seasons. On Day 0, the ewes received an i.m. injection of prostaglandin F 2α and an intravaginal P 4 -releasing device that remained in place for 14days (G-1CIDR) or was replaced on Day 7 (G-2CIDR). Daily ultrasonography of ovaries was conducted from Days 0 to 15. Mean (±SEM) numbers of follicular waves per ewe were 3.7±0.1 and 3.6±0.1 for G-1CIDR and G-2CIDR (P>0.05). The number of emerging follicular waves was greater (P<0.05) during the ID period than during the TP and DD periods (4.0±0.1, 3.4±0.1 and 3.6±0.1, respectively). The presence of medium-sized antral follicles (4.0 to 5.75mm) in the absence of corpora lutea at the time of CIDR insertion tended to advance follicular wave emergence. Although the long-term P 4 treatment was not originally designed to synchronize follicular waves, there was a distinctive pattern of follicular wave dynamics during the period of application of CIDRs that was affected mainly by the number of emerging follicular waves and ovarian status at CIDR insertion. Copyright © 2016 Elsevier B.V. All rights reserved.

Beryllium and boron constraints on an early Galactic bright phase

NASA Technical Reports Server (NTRS)

Fields, Brian D.; Schramm, David N.; Truran, James W.

1993-01-01

The recent observations of Be and B in metal-deficient halo dwarfs are used to constrain a 'bright phase' of enhanced cosmic-ray flux in the early Galaxy. Assuming that this Be and B arises from cosmic-ray spallation in the early Galaxy, limits are placed on the intensity of the early (Population II) cosmic-ray flux relative to the present (Population I) flux. A simple estimate of bounds on the flux ratio is 1 - 40. This upper bound would restrict galaxies like our own from producing neutrino fluxes that would be detectable in any currently proposed detectors. It is found that the relative enhancement of the early flux varies inversely with the relative time of enhancement. It is noted that associated gamma-ray production via pp - pi sup 0 pp may be a significant contribution to the gamma-ray background above 100 MeV.

Early Childhood Technology Integrated Instructional System (EC-TIIS) Phase 1: A Final Report

ERIC Educational Resources Information Center

Hutinger, Patricia; Robinson, Linda; Schneider, Carol

2004-01-01

The Early Childhood Technology Integrated Instructional System (EC-TIIS), a Steppingstones of Technology Innovation Phase 1--Development project, was developed by the Center for Best Practices in Early Childhood (the Center) at Western Illinois University as an online instructional system. EC-TIIS' ultimate goal was to improve technology services…

Exploring Genitoanal Injury and HIV Risk Among Women: Menstrual Phase, Hormonal Birth Control, and Injury Frequency and Prevalence.

PubMed

Brawner, Bridgette M; Sommers, Marilyn S; Moore, Kendra; Aka-James, Rose; Zink, Therese; Brown, Kathleen M; Fargo, Jamison D

2016-02-01

Genital, anal, and oral injuries sustained from sexual intercourse may explain HIV transmission among women. We determined the variability in genitoanal injury frequency and prevalence in women after consensual sexual intercourse, exploring the role of menstrual phase and hormonal birth control. We used a longitudinal observational design with a convenience sample of 393 women aged 21 years and older. Participants had a baseline interview with gynecological examination, followed by consensual sexual intercourse with a male partner and a second gynecological examination. We analyzed injury prevalence with logistic regression and injury frequency with negative binomial regression among women who were (1) menstrual, not using hormonal birth control, (2) menstrual, using hormonal birth control, or (3) menopausal. We also compared injury among menstrual women in the follicular, ovulatory, and luteal phases. Women using hormonal birth control had 38% more external genitalia injuries [adjusted rate ratio (ARR) = 1.38, P = 0.030] and more than twice the anal injuries (ARR = 2.67, P = 0.005) as the nonhormonal birth control menstruating group. Menopausal women had more than 3 times the anal injuries (ARR = 3.36, P = 0.020) than those in the nonhormonal menstrual group. Among menstrual women, those in the follicular phase had a greater prevalence and frequency of external genitalia injuries than those in other phases. Increased rates of postcoital genitoanal injuries are noted among women using hormonal birth control and/or in the follicular phase of menstruation. Biological factors that influence women's risk for HIV warrant further investigation.

Exploring genitoanal injury and HIV risk among women: Menstrual phase, hormonal birth control, and injury frequency and prevalence

PubMed Central

Brawner, Bridgette M.; Sommers, Marilyn S.; Moore, Kendra; Aka-James, Rose; Zink, Therese; Brown, Kathleen M.; Fargo, Jamison D.

2015-01-01

Background Genital, anal and oral injuries sustained from sexual intercourse may explain HIV transmission among women. We determined the variability in genitoanal injury frequency and prevalence in women following consensual sexual intercourse, exploring the role of menstrual phase and hormonal birth control. Methods We used a longitudinal, observational design with a convenience sample of 393 women aged 21 and older. Participants had a baseline interview with gynecologic examination, followed by consensual sexual intercourse with a male partner and a second gynecologic examination. We analyzed injury prevalence with logistic regression and injury frequency with negative binomial regression among women who were: a) menstrual, not using hormonal birth control, b) menstrual, using hormonal birth control, or c) menopausal. We also compared injury among menstrual women in the follicular, ovulatory and luteal phases. Findings Women using hormonal birth control had 38% more external genitalia injuries (adjusted rate ratio [ARR] = 1.38, p = 0.030) and more than twice the anal injuries (ARR = 2.67, p = 0.005) as the non-hormonal birth control menstruating group. Menopausal women had more than three times the anal injuries (ARR = 3.36, p = 0.020) than those in the non-hormonal menstrual group. Among menstrual women, those in the follicular phase had a greater prevalence and frequency of external genitalia injuries than those in other phases. Interpretation Increased rates of post-coital genitoanal injuries are noted among women using hormonal birth control and/or in the follicular phase of menstruation. Biological factors that influence women's risk for HIV warrant further investigation. PMID:26334741

Dispositional Optimism and Therapeutic Expectations in Early Phase Oncology Trials

PubMed Central

Jansen, Lynn A.; Mahadevan, Daruka; Appelbaum, Paul S.; Klein, William MP; Weinstein, Neil D.; Mori, Motomi; Daffé, Racky; Sulmasy, Daniel P.

2016-01-01

Purpose Prior research has identified unrealistic optimism as a bias that might impair informed consent among patient-subjects in early phase oncology trials. Optimism, however, is not a unitary construct – it can also be defined as a general disposition, or what is called dispositional optimism. We assessed whether dispositional optimism would be related to high expectations for personal therapeutic benefit reported by patient-subjects in these trials but not to the therapeutic misconception. We also assessed how dispositional optimism related to unrealistic optimism. Methods Patient-subjects completed questionnaires designed to measure expectations for therapeutic benefit, dispositional optimism, unrealistic optimism, and the therapeutic misconception. Results Dispositional optimism was significantly associated with higher expectations for personal therapeutic benefit (Spearman r=0.333, p<0.0001), but was not associated with the therapeutic misconception. (Spearman r=−0.075, p=0.329). Dispositional optimism was weakly associated with unrealistic optimism (Spearman r=0.215, p=0.005). In multivariate analysis, both dispositional optimism (p=0.02) and unrealistic optimism (p<0.0001) were independently associated with high expectations for personal therapeutic benefit. Unrealistic optimism (p=.0001), but not dispositional optimism, was independently associated with the therapeutic misconception. Conclusion High expectations for therapeutic benefit among patient-subjects in early phase oncology trials should not be assumed to result from misunderstanding of specific information about the trials. Our data reveal that these expectations are associated with either a dispositionally positive outlook on life or biased expectations about specific aspects of trial participation. Not all manifestations of optimism are the same, and different types of optimism likely have different consequences for informed consent in early phase oncology research. PMID:26882017

Developmental programming: postnatal estradiol amplifies ovarian follicular defects induced by fetal exposure to excess testosterone and dihydrotestosterone in sheep.

PubMed

Veiga-Lopez, A; Wurst, A K; Steckler, T L; Ye, W; Padmanabhan, V

2014-04-01

Excess of prenatal testosterone (T) induces reproductive defects including follicular persistence. Comparative studies with T and dihydrotestosterone (DHT) have suggested that follicular persistence is programmed via estrogenic actions of T. This study addresses the androgenic and estrogenic contributions in programming follicular persistence. Because humans are exposed to estrogenic environmental steroids from various sources throughout their life span and postnatal insults may also induce organizational and/or activational changes, we tested whether continuous postnatal exposure to estradiol (E) will amplify effects of prenatal steroids on ovarian function. Pregnant sheep were treated with T, DHT, E, or ED (E and DHT) from days 30 to 90 of gestation. Postnatally, a subset of the vehicle (C), T, and DHT females received an E implant. Transrectal ultrasonography was performed in the first breeding season during a synchronized cycle to monitor ovarian follicular dynamics. As expected, number of ≥8 mm follicles was higher in the T versus C group. Postnatal E reduced the number of 4 to 8 mm follicles in the DHT group. Percentage of females bearing luteinized follicles and the number of luteinized follicles differed among prenatal groups. Postnatal E increased the incidence of subluteal cycles in the prenatal T-treated females. Findings from this study confirm previous findings of divergences in programming effects of prenatal androgens and estrogens. They also indicate that some aspects of follicular dynamics are subject to postnatal modulation as well as support the existence of an extended organizational period or the need for a second insult to uncover the previously programmed event.

Follicular Fluid redox involvement for ovarian follicle growth.

PubMed

Freitas, Cláudia; Neto, Ana Catarina; Matos, Liliana; Silva, Elisabete; Ribeiro, Ângela; Silva-Carvalho, João Luís; Almeida, Henrique

2017-07-12

As the human ovarian follicle enlarges in the course of a regular cycle or following controlled ovarian stimulation, the changes in its structure reveal the oocyte environment composed of cumulus oophorus cells and the follicular fluid (FF).In contrast to the dynamic nature of cells, the fluid compartment appears as a reservoir rich in biomolecules. In some aspects, it is similar to the plasma, but it also exhibits differences that likely relate to its specific localization around the oocyte. The chemical composition indicates that the follicular fluid is able to detect and buffer excessive amounts of reactive oxygen species, employing a variety of antioxidants, some of them components of the intracellular milieu.An important part is played by albumin through specific cysteine residues. But the fluid contains other molecules whose cysteine residues may be involved in sensing and buffering the local oxidative conditions. How these molecules are recruited and regulated to intervene such process is unknown but it is a critical issue in reproduction.In fact, important proteins in the FF, that regulate follicle growth and oocyte quality, exhibit cysteine residues at specific points, whose untoward oxidation would result in functional loss. Therefore, preservation of controlled oxidative conditions in the FF is a requirement for the fine-tuned oocyte maturation process. In contrast, its disturbance enhances the susceptibility to the establishment of reproductive disorders that would require the intervention of reproductive medicine technology.

78 FR 39736 - Draft Guidance for Industry: Considerations for the Design of Early-Phase Clinical Trials of...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-02

..., choosing a study population, using a control group and blinding, dose selection, treatment plans...] Draft Guidance for Industry: Considerations for the Design of Early-Phase Clinical Trials of Cellular... document entitled ``Guidance for Industry: Considerations for the Design of Early-Phase Clinical Trials of...

[The use of immunohistochemistry in the differential diagnosis of thyroid gland tumors with follicular growth pattern].

PubMed

Laco, J; Ryska, A

2006-07-01

The aim of the study was to evaluate the expression of galectin-3 (gal3), cytokeratin 19 (CK19), neural cell adhesion molecule (NCAM), and E-cadherin (Ecad) in thyroid gland tumors with follicular growth pattern with particular focus on their use in differential diagnosis. A series of 139 cases - 87 follicular adenomas (FAs), 26 follicular carcinomas (FCs), and 26 cases of the follicular variant of papillary carcinoma (FVPC) was studied. Expression of gal3 was found in 29/87 (33%) of FAs, in 13/26 (50%) of FCs, and in 24/26 (92%) of FVPCs. Expression of CK19 was found in 11/87 (13%) of FAs, in 4/26 (15%) of FCs, and in 17/26 (65%) of FVPCs. Expression of NCAM was found in 60/87 (69%) of FAs, in 20/26 (77%) of FCs, and in 7/26 (27%) FVPCs. Expression of Ecad was found in 81/87 (93%) of FAs, in 22/26 (85%) of FCs, and in 17/26 (65%) of FVPCs. The sensitivity and specificity of gal3 for malignancy were 0.70 and 0.85, of CK19 0.48 and 0.98, of NCAM 0.28 and 0.47, and of Ecad 0.48 and 0.20, respectively. A significant difference (p < 0.05) in expression of all studied markers between FVPC versus FA and FC was found, in contrast to FA and FC. Therefore, the use of gal3 and CK19 in differential diagnosis of FVPC versus FA and FC can be recommended.

Determination of the Elasticity of Breast Tissue during the Menstrual Cycle Using Real-Time Shear Wave Elastography.

PubMed

Li, Xiang; Wang, Jian-Nan; Fan, Zhi-Ying; Kang, Shu; Liu, Yan-Jun; Zhang, Yi-Xia; Wang, Xue-Mei

2015-12-01

We examined breast tissue elasticity during the menstrual cycle using real-time shear wave elastography (RT-SWE), a recent technique developed for soft tissue imaging. Written informed consent for RT-SWE was obtained from all eligible patients, who were healthy women aged between 19 and 52 y. Young's moduli of the breast tissue in the early follicular, late phase and luteal phase were compared. There were no significant differences in the mean, maximum and minimum elasticity values (Emean, Emax and Emin) and standard deviation (ESD). RT-SWE of glandular tissue revealed that ESD was increased in the early follicular phase compared with the luteal phase. Means ± SD of Emin, Emax and Emean in glandular tissue were 5.174 ± 2.138, 8.308 ± 3.166 and 6.593 ± 2.510, respectively, and in adipose tissue, 3.589 ± 2.083, 6.733 ± 3.522 and 4.857 ± 2.564, respectively. There were no significant differences in stiffness between glandular and adipose tissues throughout the menstrual cycle, but glandular tissue stiffness was lower in the luteal phase than in the early follicular phase. On the basis of these observations in normal healthy women, we believe we have obtained sufficient information to establish the baseline changes in human breast elasticity during the menstrual cycle. In the future, we intend to compare the elasticity values of healthy breast tissue with those of breast tissue affected by various pathologies. Our results reveal the significant potential of RT-SWE in the rapid and non-invasive clinical diagnosis of breast diseases, such as breast cancers. Copyright © 2015 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Activin B is produced early in antral follicular development and suppresses thecal androgen production

PubMed Central

Young, J M; Henderson, S; Souza, C; Ludlow, H; Groome, N; McNeilly, A S

2012-01-01

Little is known about the role of activin B during folliculogenesis. This study investigated the expression levels of activin/inhibin subunits (βA, βB, and α), steroid enzyme, and gonadotrophin receptors in theca (TC) and granulosa cells (GC) by QPCR and activin A and B and inhibin A protein levels in follicular fluid (FF) of developing sheep follicles during estrus and anestrus. The effect of activin B on androgen production from primary TC cultures in vitro was also assessed. During folliculogenesis, in anestrus and estrus, FF activin B concentrations and thecal and GC activin βB mRNA levels decreased as follicle diameter increased from 1–3 to >6 mm regardless of estrogenic status. Estrogenic preovulatory follicles had reduced concentrations of FF activins B and A, and TC and GCs expressed higher levels of activin βA mRNA at 3–4 mm, and TCs more inhibin α mRNA at >4 mm stages of development compared with nonestrogenic follicles. Activin B decreased androstenedione production from primary TCs in vitro, an effect blocked by inhibin A. Thus, sheep follicles 1–3 mm in diameter contained high FF levels of activin B, which decreased as the follicle size increased, and, like activin A, suppressed thecal androgen production in vitro, an effect blocked by inhibin. Furthermore, the theca of large estrogenic follicles expressed high levels of inhibin α and activin βA mRNA suggesting local thecal derived inhibin A production. This would inhibit the negative effects of thecal activins B and A ensuring maximum androgen production for enhanced estradiol production by the preovulatory follicle(s). PMID:22450673

The effects of EGF and IGF-1 on FSH-mediated in vitro maturation of domestic cat oocytes derived from follicular and luteal stages.

PubMed

Yıldırım, Koray; Vural, M Rıfat; Küplülü, Sükrü; Ozcan, Ziya; Polat, I Mert

2014-04-01

The objective of this study was to evaluate the influence of epidermal growth factor (EGF) and insulin like growth factor-I (IGF-1) on the in vitro maturation of cat oocytes recovered from follicular and luteal stage ovaries. Oocytes from follicular (n=580) and luteal (n=209) stages were harvested and divided into four groups, which were cultured in FSH-mediated maturation medium supplemented with: (1) EGF alone (25ng/mL); (2) IGF-1 alone (100ng/mL); (3) EGF+IGF-1 (25ng/mL EGF+100ng/mL IGF-I); or (4) no growth factor (control). The proportion of follicular stage oocytes reaching the metaphase II stage was significantly higher than that of oocytes obtained at the luteal stage in both control and study groups (p<0.001). The percentages of oocytes reaching the metaphase II stage during the follicular period were 62.6% in control; 70.9% in EGF; 72.8% in IGF-1, and 78.1% in EGF+IGF-1 groups, whereas the respective values for gametes collected from luteal stage ovaries were 12.5%, 17.5%, 12.5%, and 16.9%. Additionally, the differences between the study and control groups were significant in the case of follicular stage oocytes. Finally, supplementing the maturation medium with EGF and/or IGF-1 significantly enhanced the meiotic maturation of oocytes recovered from follicular stage ovaries. The present study also demonstrated that the combination of EGF and IGF-I provides an additional or synergic effect on meiotic maturation of oocytes recovered from the follicular stage. Copyright © 2014 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

[The treatment of cicatricial alopecia after burn with the technique of synchronously perforating and transplanting hair follicular-units].

PubMed

Wang, Ji-ping; Fan, Jin-cai; Chai, Jia-ke

2009-12-01

To study the effect of the technique of synchronously perforating and transplanting hair follicular-units in the treatment of cicatricial alopecia after burn. One hundred and sixty-six patients with 217 bald scar areas after burn were treated with above-mentioned technique from January 2002 to April 2008. Scalp strips, with conforming the necessity for grafting, were harvested from the occipital or temporal region. A series of follicular-units, each composing 1 - 3 hairs, were dissected from the strips under microscope or magnifying glass. Size-matching micro-slots were made in the scarred recipient area with 16 - 20 G needles to accept the grafts. The prepared follicular-unit was synchronously implanted into the bottom of the micro-slot as the needle being withdrawn. Patients who were not satisfactory with the density of hairs after I stage surgery underwent II stage surgery a half year later. Ten recipient areas with clear boundary in 10 patients were optionally chosen to observe the density of follicular-units and hair amount with naked eyes after I stage surgery. Survived transplanted hairs in above-mentioned 10 areas were counted to calculate hair survival rate at follow-up. Patients' postoperative satisfaction ratings were surveyed with questionnaire. In one half of the patients, treatment was finished after I stage surgery, the other one half received 2 stages of surgery. The follicular-unit density reached 15 - 25 grafts/cm(2) with 40 - 70 hairs/cm(2) after I stage surgery. All patients were followed up for over 8 months. Grafted hairs grew well in a natural way. 96.5% mean hair survival rate was observed in the 10 recipient areas. From patients who received only I stage surgery, 61 patients (73.5%) were very satisfactory and 22 patients (26.5%) satisfactory with the results. From the other half of patients, 76 patients (91.6%) were very satisfactory and 7 patients (8.4%) satisfactory with the results. The technique of perforating and transplanting

Image analysis for TSH mRNA in situ hybridization in pituitary glands from rats with thyroid follicular cell hypertrophy after treatment with three different test compounds.

PubMed

Funk, Juergen; Ebeling, Martin; Singer, Thomas; Landes, Christian

2017-10-01

The goal of this in situ hybridization and image analysis technique is to study the effects of new pharmacological/chemical entities on the thyroid and pituitary gland in rats, reveal the pathogenesis of thyroid follicular cell hypertrophy and to retrospectively exclude the risk of thyroid tumor development in humans. In the present study, we describe the increase of thyroid-stimulating hormone- (TSH-) beta subunit mRNA in the pars distalis of the pituitary gland and the quantitative measurement of TSH mRNA positive cells from rats of three 4-week toxicity studies treated with three different test compounds inducing thyroid follicular cell and hepatocellular hypertrophy in rats. Compared to immunohistochemistry (IHC), in situ hybridization (ISH) for TSH was found to be more sensitive. With this technique we are able to exclude a direct effect of the test compound on the thyroid gland by showing the activation of thyrotrope cells from the pituitary gland and therefore this technique retrospectively enables us to exclude a possible risk for humans at an early stage of drug development. Also in case blood serum samples for evaluation of TSH are not available anymore or hepatocellular hypertrophy is not present (close metabolic relationship between thyroid gland and liver in rodents), the described method allows retrospective investigations on thyroid follicular cell hypertrophy or hyperplasia. This can be of high relevance in human safety assessment for certain drugs in order to exclude a primary effect on the thyroid gland especially when it comes to thyroid neoplasia in rodents as previously described. Copyright © 2017 Elsevier Ltd. All rights reserved.

Bovine ovarian follicular growth and development correlate with lysophosphatidic acid expression.

PubMed

Sinderewicz, Emilia; Grycmacher, Katarzyna; Boruszewska, Dorota; Kowalczyk-Zięba, Ilona; Staszkiewicz, Joanna; Ślężak, Tomasz; Woclawek-Potocka, Izabela

2018-01-15

The basis of successful reproduction is proper ovarian follicular growth and development. In addition to prostaglandins and vascular endothelial growth factor, a number of novel factors are suggested as important regulators of follicular growth and development: PGES, TFG, CD36, RABGAP1, DBI and BTC. This study focuses on examining the expression of these factors in granulosa and thecal cells that originate from different ovarian follicle types and their link with the expression of lysophosphatidic acid (LPA), known local regulator of reproductive functions in the cow. Ovarian follicles were divided into healthy, transitional, and atretic categories. The mRNA expression levels for PGES, TFG, CD36, RABGAP1, DBI and BTC in granulosa and thecal cells in different follicle types were measured by real-time PCR. The correlations among expression of enzymes synthesizing LPA (autotaxin, phospholipase A2), receptors for LPA and examined factors were measured. Immunolocalization of PGES, TFG, CD36, RABGAP1, DBI and BTC was examined by immunohistochemistry. We investigated follicle-type dependent mRNA expression of factors potentially involved in ovarian follicular growth and development, both in granulosa and thecal cells of bovine ovarian follicles. Strong correlations among receptors for LPA, enzymes synthesizing LPA, and the examined factors in healthy and transitional follicles were observed, with its strongest interconnection with TFG, DBI and RABGAP1 in granulosa cells, and TFG in thecal cells; whereas no correlations in atretic follicles were detected. A greater number of correlations were found in thecal cells than in granulosa cells as well as in healthy follicles than in transitional follicles. These data indicate the role of LPA in the growth, development and physiology of the bovine ovarian follicle. Copyright © 2017 Elsevier Inc. All rights reserved.

Tuberculous Lymphadenitis Mimicking Nodal Metastasis in Follicular Variant Papillary Thyroid Carcinoma.

PubMed

Yu, Marc Gregory; Atun, Jenny Maureen

2016-01-01

Tuberculous (TB) lymphadenitis can mimic cervical node metastasis from papillary thyroid carcinoma (PTC) since the distribution and appearance of affected lymph nodes are similar. We present the case of an asymptomatic 50-year-old Filipino who sought consult for a gradually enlarging anterior neck mass and a single palpable cervical lymph node. Preoperative workup suggested a thyroid malignancy with nodal metastasis. He underwent total thyroidectomy with node dissection where histopathology confirmed follicular variant- (FV-) PTC. Lymph node examination, however, revealed TB lymphadenitis, and the patient was given standard antimycobacterial therapy. This is the first documented case in Southeast Asia, a high TB burden region. This is also the first report involving FV-PTC, which has features between those of conventional PTC and follicular thyroid carcinoma. The case suggests that, in endemic areas, TB should be a differential in the etiology of cervical lymphadenopathy in PTC patients. In developed countries, this differential diagnosis is also valuable because of the increasing incidence of HIV and TB coinfection. Proper preoperative evaluation is important and needs to be highlighted in the formulation of local guidelines.

Tuberculous Lymphadenitis Mimicking Nodal Metastasis in Follicular Variant Papillary Thyroid Carcinoma

PubMed Central

Atun, Jenny Maureen

2016-01-01

Tuberculous (TB) lymphadenitis can mimic cervical node metastasis from papillary thyroid carcinoma (PTC) since the distribution and appearance of affected lymph nodes are similar. We present the case of an asymptomatic 50-year-old Filipino who sought consult for a gradually enlarging anterior neck mass and a single palpable cervical lymph node. Preoperative workup suggested a thyroid malignancy with nodal metastasis. He underwent total thyroidectomy with node dissection where histopathology confirmed follicular variant- (FV-) PTC. Lymph node examination, however, revealed TB lymphadenitis, and the patient was given standard antimycobacterial therapy. This is the first documented case in Southeast Asia, a high TB burden region. This is also the first report involving FV-PTC, which has features between those of conventional PTC and follicular thyroid carcinoma. The case suggests that, in endemic areas, TB should be a differential in the etiology of cervical lymphadenopathy in PTC patients. In developed countries, this differential diagnosis is also valuable because of the increasing incidence of HIV and TB coinfection. Proper preoperative evaluation is important and needs to be highlighted in the formulation of local guidelines. PMID:27746818

Surrogate Endpoints and Risk Adaptive Strategies in Previously Untreated Follicular Lymphoma.

PubMed

Narkhede, Mayur S; Cheson, Bruce D

2018-05-05

Follicular lymphoma is the second most common subtype of non-Hodgkin lymphoma with an estimated 3.18 cases per 100,000 people. Despite the prolongation of survival with chemoimmunotherapy, variability in response to initial treatment and outcome still exists. Whereas prolonging overall survival is important, it is generally an unreasonable primary endpoint in the front-line setting. The long follow-up needed and the influence of subsequent therapies creates a potential bias. Thus, clinical trials require approximately 5 to 8 years from activation to completion and analysis of outcomes. This duration results in enormous cost and a delay in developing newer therapies. Thus, there is a need to identify markers or surrogate endpoints that can be used in clinical trials to expedite the development of new treatments. This review will discuss various clinical, radiologic, and laboratory measures used to assess outcomes and overall survival in patients with untreated follicular lymphoma, and gauge their utility in clinical trials as surrogate endpoints. Copyright © 2018 Elsevier Inc. All rights reserved.

Relationship between bcl-2, bax, beclin-1, and cathepsin-D proteins during postovulatory follicular regression in fish ovary.

PubMed

Morais, Roberto D V S; Thomé, Ralph G; Santos, Hélio B; Bazzoli, Nilo; Rizzo, Elizete

2016-04-01

In fish ovaries, postovulatory follicles (POFs) are key biomarkers of breeding and provide an interesting model for studying the relationship between autophagy and apoptosis. In this study, we investigated the immunohistochemical expression of autophagic and apoptotic proteins to improve the knowledge on the mechanisms regulating ovarian remodeling after spawning. Females from three neotropical fish species kept in captivity were submitted to hormonal induction. After ova stripping, ovarian sections were sampled daily until 5 days postspawning (dps). Similar events of POF regression were detected by histology, terminal transferase-mediated dUTP nick-end labeling (TUNEL), and electron microscopy in the three species: follicular cells hypertrophy, progressive disintegration of the basement membrane, gradual closing of the follicular lumen, theca thickening, and formation of large autophagic vacuoles preceding apoptosis of the follicular cells. Autophagic and apoptotic proteins were assessed by immunohistochemistry. Morphometric analysis of the immunolabeling revealed a more intense reaction for bcl-2 and beclin-1 (BECN1) in POFs at 0 to 1 dps and for bax at 2 to 3 dps (P < 0.001), the later period being the peak of apoptosis of the follicular cells. The immunostaining for cathepsin-D was more elevated until 2 to 3 dps and decreased significantly at 4 to 5 dps, when the POFs were in late stage of regression. Double labeling for BECN1 and caspase-3 indicated a shift in the relationship between autophagy and apoptosis at 2 to 3 dps, a critical period in determining the fate of follicular cells in POFs. Together, these results indicate that the bcl-2 family, BECN1, and cathepsin-D can be involved in the regulation of ovarian remodeling in teleost fish. Copyright © 2016 Elsevier Inc. All rights reserved.

Metabolomic changes in follicular fluid induced by soy isoflavones administered to rats from weaning until sexual maturity

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

Wang, Wenxiang; Zhang, Wenchang, E-mail: wenchang2002@sina.com; Liu, Jin

Female Wistar rats at 21 days of age were treated with one of three concentrations of soy isoflavones (SIF) (50, 100 or 200 mg/kg body weight, orally, once per day) from weaning until sexual maturity (3 months) in order to evaluate the influence of SIF on ovarian follicle development. After treatment, the serum sex hormone levels and enumeration of ovarian follicles of the ovary were measured. The metabolic profile of follicular fluid was determined using HPLC-MS. Principal component analysis (PCA) and partial least-squares-discriminant analysis (PLS-DA) was used to identify differences in metabolites and reveal useful toxic biomarkers. The results indicatedmore » that modest doses of SIF affect ovarian follicle development, as demonstrated by decreased serum estradiol levels and increases in both ovarian follicle atresia and corpora lutea number in the ovary. SIF treatment-related metabolic alterations in follicular fluid were also found in the PCA and PLS-DA models. The 24 most significantly altered metabolites were identified, including primary sex hormones, amino acids, fatty acids and metabolites involved in energy metabolism. These findings may indicate that soy isoflavones affect ovarian follicle development by inducing metabolomic variations in the follicular fluid. - Highlights: ► Modest doses of soy isoflavones (SIF) do affect ovarian follicle development. ► SIF treatment-related metabolic alterations in follicular fluid were found. ► The 24 most significantly altered metabolites were identified.« less

Numerical investigation of the early flight phase in ski-jumping.

PubMed

Gardan, N; Schneider, A; Polidori, G; Trenchard, H; Seigneur, J M; Beaumont, F; Fourchet, F; Taiar, R

2017-07-05

The purpose of this study is to develop a numerical methodology based on real data from wind tunnel experiments to investigate the effect of the ski jumper's posture and speed on aerodynamic forces in a wide range of angles of attack. To improve our knowledge of the aerodynamic behavior of the ski jumper and his equipment during the early flight phase of the ski jump, we applied CFD methodology to evaluate the influence of angle of attack (α=14°, 21.5°, 29°, 36.5° and 44°) and speed (u=23, 26 and 29m/s) on aerodynamic forces in the situation of stable attitude of the ski jumper's body and skis. The standard k-ω turbulence model was used to investigate both the influence of the ski jumper's posture and speed on aerodynamic performance during the early flight phase. Numerical results show that the ski jumper's speed has very little impact on the lift and drag coefficients. Conversely, the lift and drag forces acting on the ski jumper's body during the early flight phase of the jump are strongly influenced by the variations of the angle of attack. The present results suggest that the greater the ski jumper's angle of inclination, with respect to the relative flow, the greater the pressure difference between the lower and upper parts of the skier. Further studies will focus on the dependency of the parameters with both the angle of attack α and the body-ski angle β as control variables. It will be possible to test and optimize different ski jumping styles in different ski jumping hills and investigate different environmental conditions such as temperature, altitude or crosswinds. Copyright © 2017 Elsevier Ltd. All rights reserved.

Dispositional optimism and therapeutic expectations in early-phase oncology trials.

PubMed

Jansen, Lynn A; Mahadevan, Daruka; Appelbaum, Paul S; Klein, William M P; Weinstein, Neil D; Mori, Motomi; Daffé, Racky; Sulmasy, Daniel P

2016-04-15

Prior research has identified unrealistic optimism as a bias that might impair informed consent among patient-subjects in early-phase oncology trials. However, optimism is not a unitary construct; it also can be defined as a general disposition, or what is called dispositional optimism. The authors assessed whether dispositional optimism would be related to high expectations for personal therapeutic benefit reported by patient-subjects in these trials but not to the therapeutic misconception. The authors also assessed how dispositional optimism related to unrealistic optimism. Patient-subjects completed questionnaires designed to measure expectations for therapeutic benefit, dispositional optimism, unrealistic optimism, and the therapeutic misconception. Dispositional optimism was found to be significantly associated with higher expectations for personal therapeutic benefit (Spearman rank correlation coefficient [r], 0.333; P<.0001), but was not associated with the therapeutic misconception (Spearman r, -0.075; P = .329). Dispositional optimism was found to be weakly associated with unrealistic optimism (Spearman r, 0.215; P = .005). On multivariate analysis, both dispositional optimism (P = .02) and unrealistic optimism (P<.0001) were found to be independently associated with high expectations for personal therapeutic benefit. Unrealistic optimism (P = .0001), but not dispositional optimism, was found to be independently associated with the therapeutic misconception. High expectations for therapeutic benefit among patient-subjects in early-phase oncology trials should not be assumed to result from misunderstanding of specific information regarding the trials. The data from the current study indicate that these expectations are associated with either a dispositionally positive outlook on life or biased expectations concerning specific aspects of trial participation. Not all manifestations of optimism are the same, and different types of optimism likely have

Shear-Wave Elastography for the Preoperative Risk Stratification of Follicular-patterned Lesions of the Thyroid: Diagnostic Accuracy and Optimal Measurement Plane.

PubMed

Samir, Anthony E; Dhyani, Manish; Anvari, Arash; Prescott, Jason; Halpern, Elkan F; Faquin, William C; Stephen, Antonia

2015-11-01

To evaluate the diagnostic accuracy of shear-wave elastography (SWE) for the diagnosis of malignancy in follicular lesions and to identify the optimal SWE measurement plane. The institutional review board approved this HIPAA-compliant, single-institution, prospective pilot study. Subjects scheduled for surgery after a previous fine-needle aspiration report of "atypia of undetermined significance" or "follicular lesion of undetermined significance," "suspicion for follicular neoplasm," or "suspicion for Hurthle cell neoplasm," were enrolled after obtaining informed consent. Subjects underwent conventional ultrasonography (US), Doppler evaluation, and SWE preoperatively, and their predictive value for thyroid malignancy was evaluated relative to the reference standard of surgical pathologic findings. Thirty-five patients (12 men, 23 women) with a mean age of 55 years (range, 23-85 years) and a fine-needle aspiration diagnosis of atypia of undetermined significance or follicular lesion of undetermined significance (n = 16), suspicion for follicular neoplasm (n = 14), and suspicion for Hurthle cell neoplasm (n = 5) were enrolled in the study. Male sex was a statistically significant (P = .02) predictor of malignancy, but age was not. No sonographic morphologic parameter, including nodule size, microcalcification, macrocalcification, halo sign, taller than wide dimension, or hypoechogenicity, was associated with malignancy. Similarly, no Doppler feature, including intranodular vascularity, pulsatility index, resistive index, or peak-systolic velocity, was associated with malignancy. Higher median SWE tissue Young modulus estimates from the transverse insonation plane were associated with malignancy, yielding an area under the receiver operating characteristic curve of 0.81 (95% confidence interval: 0.62, 1.00) for differentiation of malignant from benign nodules. At a cutoff value of 22.3 kPa, sensitivity, specificity, positive predictive value, and negative predictive

Comparison of pregnancy rates in PCOS patients undergoing clomiphene citrate and IUI treatment with different leading follicular sizes.

PubMed

Seckin, Berna; Pekcan, Meryem Kuru; Bostancı, Esra Isci; Inal, Hasan Ali; Cicek, Mahmut Nedim

2016-04-01

The objective of the study was to compare the pregnancy rates in PCOS patients undergoing clomiphene citrate (CC) and intrauterine insemination (IUI) treatment with different leading follicular sizes. A total of 358 infertile women with PCOS who underwent 563 clomiphene citrate and IUI treatment cycles were included in this prospective study. Treatment cycles were divided into three groups according to leading follicular size on the day of hCG administration: Group I: follicular size 17-18 mm (n = 177), Group II: 19-22 mm (n = 321), and Group III : >22 mm (n = 65). Pregnancy rates were evaluated. Treatment outcomes of the groups were further analyzed related to endometrial thickness measurement on the day of hCG. For this purpose, cycles were placed into three subgroups as follows: endometrial thickness <7, 8-9, and >9 mm. There was no statistically significant difference in clinical pregnancy rate per cycle between the groups (8.5, 10, and 9.2 % for Group I, II, and III, respectively, p = 0.86). In further analyses related to endometrial thickness, no significant difference was also found in pregnancy rate among the groups. This results suggest that pregnancy rate is not related to leading follicle size on the day of hCG administration in PCOS patients treated with CC and IUI. In addition, pregnancy rate in women with different follicular sizes is not influenced by the endometrial thickness.

Discovery of human immunodeficiency virus infection by immunohistochemistry on lymph node biopsies from patients with unexplained follicular hyperplasia.

PubMed

de Paiva, Geisilene Russano; Laurent, Camille; Godel, Aurélie; da Silva, Nivaldo Adolfo; March, Michel; Delsol, Georges; Brousset, Pierre

2007-10-01

Over the last 10 years, 240 cases of hyperplasic lymphadenitis have been systematically tested in our institution for the presence of the human immunodeficiency virus (HIV). This series comprised patients between 15 and 90 years (median of age: 38.51) without a past history of HIV infection. The technical approach consisted in an immunohistochemical procedure with a monoclonal antibody against the p24-gag protein of HIV. Among the 240 cases, 105 had a true follicular hyperplasia. Overall, this survey found that 4 cases (3 males and 1 female) were positive for p24-gag without previous knowledge of HIV infection (4/240=1.66%). HIV infection was further confirmed by serologic and molecular investigations in all cases. These results were seen exclusively in those cases with prominent follicular hyperplasia (4/105=3.80%). Staining with the anti-p24 antibody was intense and restricted to the follicular dendritic cell networks. In one case, beside hyperplasic germinal centers, one could see a regressed onion bulblike structure. One important conclusion can be drawn from this study. A systematic research of HIV proteins should be performed in all lymph node biopsies with marked follicular hyperplasia, in a context of polyadenopathy, fever, and general status alteration. Besides giving an accurate diagnosis, this approach may be helpful in cases of recent infection in which anti-p24 antibodies are not yet detectable in the serum.

Clinicopathological and genomic analysis of double-hit follicular lymphoma: comparison with high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements.

PubMed

Miyaoka, Masashi; Kikuti, Yara Y; Carreras, Joaquim; Ikoma, Haruka; Hiraiwa, Shinichiro; Ichiki, Akifumi; Kojima, Minoru; Ando, Kiyoshi; Yokose, Tomoyuki; Sakai, Rika; Hoshikawa, Masahiro; Tomita, Naoto; Miura, Ikuo; Takata, Katsuyoshi; Yoshino, Tadashi; Takizawa, Jun; Bea, Silvia; Campo, Elias; Nakamura, Naoya

2018-02-01

Most high-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements are aggressive B-cell lymphomas. Occasional double-hit follicular lymphomas have been described but the clinicopathological features of these tumors are not well known. To clarify the characteristics of double-hit follicular lymphomas, we analyzed 10 cases of double-hit follicular lymphomas and 15 cases of high-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements for clinicopathological and genome-wide copy-number alterations and copy-neutral loss-of-heterozygosity profiles. For double-hit follicular lymphomas, the median age was 67.5 years (range: 48-82 years). The female/male ratio was 2.3. Eight patients presented with advanced clinical stage. The median follow-up time was 20 months (range: 1-132 months). At the end of the follow-up, 8 patients were alive, 2 patients were dead including 1 patient with diffuse large B-cell lymphoma transformation. Rearrangements of MYC/BCL2, MYC/BCL6, and MYC/BCL2/BCL6 were seen in 8, 1, and 1 cases, respectively. The partner of MYC was IGH in 6 cases. There were no cases of histological grade 1, 4 cases of grade 2, 5 cases of grade 3a, and 1 case of grade 3b. Two cases of grade 3a exhibited immunoblast-like morphology. Immunohistochemistry demonstrated 9 cases with ≥50% MYC-positive cells. There was significant difference in MYC intensity (P=0.00004) and MIB-1 positivity (P=0.001) between double-hit follicular lymphomas and high-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements. The genome profile of double-hit follicular lymphomas was comparable with conventional follicular lymphomas (GSE67385, n=198) with characteristic gains of 2p25.3-p11.1, 7p22.3-q36.3, 12q11-q24.33, and loss of 18q21.32-q23 (P<0.05). In comparison with high-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements, double-hit follicular lymphomas had fewer copy-number alterations and minimal common region of gain at 2p16.1 (70%), locus

Assessment of Correlation Between Early and Late Efficacy Endpoints to Identify Potential Surrogacy Relationships in Non-Hodgkin Lymphoma: a Literature-Based Meta-analysis of 108 Phase II and Phase III Studies.

PubMed

Zhu, Rui; Lu, Dan; Chu, Yu-Waye; Chai, Akiko; Green, Michelle; Zhang, Nancy; Jin, Jin Yan

2017-05-01

Correlations between early and late efficacy endpoints were assessed to identify potential surrogate endpoints for overall survival (OS) or progression-free survival (PFS) with clinical trial-level data in three non-Hodgkin lymphoma (NHL) subtypes: diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and mantle cell lymphoma (MCL). One hundred and eight phase II-III trials (129 trial arms) in DLBCL, FL, and MCL were identified and included in the database. Correlations between efficacy endpoints were analyzed using weighted linear regression and Pearson's coefficient of determination (R 2 ). In newly diagnosed DLBCL, 6-month PFS was strongly correlated with 2-year OS (R 2  = 0.81, 95% confidence interval [CI] 0.51-0.96). Six-month PFS was strongly correlated with 3-year PFS (R 2  = 0.89, 95% CI 0.62-0.96) in FL and was moderately correlated with 2-year OS (R 2  = 0.69, 95% CI 0.40-0.91) in MCL trials. Linear regression determined that a 10% increase in 6-month PFS would yield a 13% ± 1.2% increase in 2-year OS in DLBCL, a 23% ± 1.1% increase in 3-year PFS in FL, or a 6.7% ± 1.0% increase in 2-year OS in MCL. Both 6-month PFS and complete response (CR) rate were moderately correlated with median PFS in FL trials with R 2  = 0.66 (95% CI 0.52-0.98) and R 2  = 0.69 (95% CI 0.22-0.89), respectively. Six-month PFS is a potential surrogate endpoint for 2-year OS in newly diagnosed DLBCL and MCL and for 3-year PFS in FL. Both 6-month PFS and CR rate are potential surrogate endpoints for median PFS in FL patients. Confirmation and validation of these correlations may facilitate early interpretation of NHL trials.

Dermoscopy of inverted follicular keratosis: study of 12 cases.

PubMed

Llambrich, A; Zaballos, P; Taberner, R; Terrasa, F; Bañuls, J; Pizarro, A; Malvehy, J; Puig, S

2016-07-01

Inverted follicular keratosis (IFK) is an uncommon benign tumour of the follicular infundibulum, which is often misdiagnosed clinically as other keratinizing tumours, and commonly diagnosed correctly by histopathology. There are few reports about the dermoscopic findings of this lesion. To evaluate the dermoscopic features of IFK. The dermoscopic structures and patterns in digital dermoscopic images of 12 histopathologically confirmed cases of IFK collected from 5 hospitals in Spain were evaluated. A keratoacanthoma (KA)-like pattern composed of central keratin surrounded by hairpin vessels in a radial arrangement was the most common pattern in IFK (58.3%). The second most common pattern was composed of a yellowish-white amorphous central area surrounded by vascular structures in a radial arrangement (33.3%). The remaining case showed a pattern composed of a yellowish-white amorphous central area with milky red globules. Vascular structures were present in all cases, with a monomorphic pattern in seven cases and a polymorphic pattern in five, mainly with radial arrangement. Arborizing vessels, linear irregular vessels, corkscrew vessels and milky red globules were present in some cases. We describe the two main patterns of IFK. Lesions with a KA-like pattern are clinically and dermoscopically undistinguishable from KA and squamous cell carcinoma. Cases with a polymorphic vascular pattern could be confused with malignant tumours, including basal cell carcinoma and amelanotic melanoma. © 2016 British Association of Dermatologists.

Pros and cons of rituximab maintenance in follicular lymphoma.

PubMed

Zhang, Lu; Ghielmini, Michele; Cheson, Bruce D; Ujjani, Chaitra

2017-07-01

Follicular lymphoma (FL) is the most prevalent indolent non-Hodgkin lymphoma. Most patients present with advanced disease and are incurable with current therapy. The approval of rituximab has revolutionized the treatment of follicular lymphoma when administered in the induction setting for high-tumor burden disease, but the use of rituximab as a maintenance therapy (MR) continues to be a point of controversy. In this article, we review the main data and arguments in favor and against MR in FL. In summary, most studies have demonstrated a significant benefit in progression-free or event-free survival in this notoriously recurrent disease; however, long-term outcomes could not consistently demonstrate to be improved with this intervention. In a meta-analysis of randomized trials overall survival (OS) showed a tendency to improvement when given to patients in relapse, but no single study reached a significant OS advantage. The risk of high-grade transformation does not seem to be reduced in prospective trials. On the other hand, MR clearly increases toxicity without an improvement in quality of life. Finally, MR is expensive, and it is not proven that the delayed relapse time can compensate for these costs. In conclusion, despite the proven increase in progression-free survival, MR can't be recommended as a standard for the treatment of FL. Copyright © 2017 Elsevier Ltd. All rights reserved.

Serum hormone concentrations and ovarian follicular wave emergence in Jilin sika deer (Cervus nippon hortulorum) after synchronization of estrous cycles.

PubMed

Chen, X M; Wei, H J; Yang, Y F; Xue, H L; Zhao, W G; Zhao, M

2015-02-01

The study was conducted to investigate the serum hormone concentrations and follicular dynamics present after synchronous treatment (CIDR) in female Jilin sika deer (n = 15) of estrous cycles. Blood samples were collected to analyze the FSH, LH, estradiol and progesterone during the estrous cycles. Manual transrectal ultrasonography examination was conducted at least thrice weekly to monitor the follicular wave. Ultrasonography showed that follicle development occurred in waves, and most estrous cycles in Jilin sika deer consist of one, two, or three waves. The largest follicles of the interwaves of two- and three-wave cycles were different (P < 0.05). The mean interovulatory interval was 15.0 ± 4.6 d. There was a surge in circulating FSH in two- and three-wave cycles. The emergence of the largest follicle was related to the peak of serum concentration of estradiol. Serum progesterone concentrations were not different between one- and three-wave cycles (P < 0.05). We concluded that FSH and estradiol concentration may have an important role in controlling follicular development, that the estrous cycle in Jilin sika deer is characterized by one, two, or three waves of follicular development after synchronization. Copyright © 2015. Published by Elsevier B.V.

Cytopathology of non-invasive follicular thyroid neoplasm with papillary-like nuclear features: A comparative study with similar patterned papillary thyroid carcinoma variants.

PubMed

Mahajan, S; Agarwal, S; Kocheri, N; Jain, D; Mathur, S R; Iyer, V K

2018-06-01

Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) is a recently described, indolent thyroid tumor, with well-defined histopathological diagnostic criteria. Cytology features are not well documented. We reviewed cytology of histologically proven cases of NIFTP and some of its common differentials to look for salient diagnostic features. Cases reported on histopathology as follicular variant of papillary thyroid carcinoma (FVPTC), or NIFTP between July 2015 and April 2017 having available cytology smears were retrieved and reclassified as NIFTP, FVPTC, and classical papillary thyroid carcinoma with predominant follicular pattern (PTC-FP). Cytological features were assessed, classified as per The Bethesda System for Reporting Cytopathology and compared. There were 23 NIFTP cases, 18 FVPTC and 8 PTC-FP. A microfollicle-predominant pattern was seen in all. Nuclear score was 2 in most NIFTP cases (61%). Pseudoinclusions were absent. NIFTP showed features of atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) (III) in 61%, follicular neoplasm/suspicious for a follicular neoplasm (FN/SFN) (IV) in 35% and suspicious for malignancy (SFM) (V) in 4%. Most of the FVPTCs were also called FN/SFN (IV) (56%) or AUS/FLUS (III) (22%). Nuclear features did not statistically differ from NIFTP. PTC-FP showed high-grade cytology in 75%, and higher nuclear score (3 in 75%) in contrast to NIFTP (P = .003). NIFTP and FVPTC show a similar distribution among the Bethesda categories hence precluding conclusive distinction on cytology. PTC-FP, in contrast, was found to have a statistically significant higher nuclear score and more commonly showed malignant cytology. © 2018 John Wiley & Sons Ltd.

Development of Environmental Load Estimation Model for Road Drainage Systems in the Early Design Phase

NASA Astrophysics Data System (ADS)

Park, Jin-Young; Lee, Dong-Eun; Kim, Byung-Soo

2017-10-01

Due to the increasing concern about climate change, efforts to reduce environmental load are continuously being made in construction industry, and LCA (life cycle assessment) is being presented as an effective method to assess environmental load. Since LCA requires information on construction quantity used for environmental load estimation, however, it is not being utilized in the environmental review in the early design phase where it is difficult to obtain such information. In this study, computation system for construction quantity based on standard cross section of road drainage facilities was developed to compute construction quantity required for LCA using only information available in the early design phase to develop and verify the effectiveness of a model that can perform environmental load estimation. The result showed that it is an effective model that can be used in the early design phase as it revealed a 13.39% mean absolute error rate.

Double-hit follicular lymphoma with MYC and BCL2 translocations: a study of 7 cases with a review of literature.

PubMed

Miao, Yuan; Hu, Shimin; Lu, Xinyan; Li, Shaoying; Wang, Wei; Medeiros, L Jeffrey; Lin, Pei

2016-12-01

Follicular lymphoma with MYC and BCL2 translocations, so-called double-hit follicular lymphoma (DH-FL), is rare. Here, we report the clinicopathological features of 7 cases of DH-FL. All neoplasms had a follicular pattern (1 partially diffuse). Five cases were predominantly low grade, 4 of which had focal (≤20%) grade 3A areas, and 2 cases were of grade 3. All cases were positive for pan-B-cell antigens, CD10, and BCL6; 6 cases were positive for BCL2. Ki-67 was less than or equal to 50% in 6 cases and 90% in 1 grade 3 case. Three patients presented with stage IV disease and 3 had a Follicular Lymphoma International Prognostic Index score of greater than 2. Six patients received immunochemotherapy, and 1 is still under induction therapy with rituximab, ibrutinib, and lenalidomide. Four achieved complete remission and two had a partial response with persistent or refractory disease. The median follow-up time was 25 months (range, 8.5-53.7 months). Two patients treated with standard regimen for follicular lymphoma had relapsed or refractory disease, and 1 died from complications of allogeneic stem cell transplant administered for relapse. In contrast, all 4 patients treated with more intensive regimen for double-hit lymphoma achieved complete remission. In summary, despite predominantly low-grade histology, cases of DH-FL in this study were aggressive and responded better to more intensive than standard treatment regimens, suggesting DH-FL is part of the spectrum of double-hit high-grade lymphoma. Copyright © 2016 Elsevier Inc. All rights reserved.

Imaging of early acceleration phase of the 2013-2014 Boso slow slip event

NASA Astrophysics Data System (ADS)

Fukuda, J.; Kato, A.; Obara, K.; Miura, S.; Kato, T.

2014-12-01

Based on GPS and seismic data, we examine the spatiotemporal evolution of a slow slip event (SSE) and associated seismic activity that occurred off the Boso peninsula, central Japan, from December 2013 to January 2014. We use GPS data from 71 stations of the GEONET and 6 stations operated by Earthquake Research Institute of the University of Tokyo and Tohoku University around the Boso peninsula. We apply a modified version of the Network Inversion Filter to the GPS time series at the 77 stations to estimate the spatiotemporal evolution of daily cumulative slip and slip rate on the subducting Philippine Sea plate. In addition, we create an improved earthquake catalog by applying a matched filter technique to continuous seismograms and examine the spatiotemporal relations between slow slip and seismicity. We find that the SSE started in early December 2013. The spatiotemporal evolution of slow slip and seismicity is divided into two distinct phases, an earlier slow phase from early to 30 December 2013 (Phase I) and a subsequent faster phase from 30 December 2013 to 9 January 2014 (Phase II). During Phase I, slip accelerated slowly up to a maximum rate of 1.6 m/yr with potentially accelerating　along-strike propagation at speeds on the order of 1 km/day or less and no accompanying seismicity. On the other hand, during Phase II, slip accelerated rapidly up to a maximum rate of 4.5 m/yr and then rapidly decelerated. The slip front propagated along strike at a constant speed of ~10 km/day. During the Phase II, slow slip was accompanied by seismic swarm activity that was highly correlated in space and time with slip rate, suggesting that the swarm activity was triggered by stress loading due to slow slip. Early slow acceleration of slip has not been identified in the past Boso SSEs in 1996, 2002, 2007, and 2011. It is not clear at this point whether the past Boso SSEs started with slow acceleration similarly to the 2013-2014 SSE. The transition from the slow to the

Perspectives and Open Problems in the Early Phases of Left-Right Patterning

PubMed Central

Vandenberg, Laura N.; Levin, Michael

2009-01-01

Summary Embryonic left-right (LR) patterning is a fascinating aspect of embryogenesis. The field currently faces important questions about the origin of LR asymmetry, the mechanisms by which consistent asymmetry is imposed on the scale of the whole embryo, and the degree of conservation of early phases of LR patterning among model systems. Recent progress on planar cell polarity and cellular asymmetry in a variety of tissues and species provides a new perspective on the early phases of LR patterning. Despite the huge diversity in body-plans over which consistent LR asymmetry is imposed, and the apparent divergence in molecular pathways that underlie laterality, the data reveal conservation of physiological modules among phyla and a basic scheme of cellular chirality amplified by a planar cell polarity-like pathway over large cell fields. PMID:19084609

The arrector pili muscle, the bridge between the follicular stem cell niche and the interfollicular epidermis.

PubMed

Torkamani, Niloufar; Rufaut, Nicholas; Jones, Leslie; Sinclair, Rodney

2017-01-01

Proximally, the arrector pili muscle (APM) attaches to the follicular stem cell niche in the bulge, but its distal properties are comparatively unclear. In this work, a novel method employing an F-actin probe, phalloidin, was employed to visualize the APM anatomy. Phalloidin staining of the APM was validated by comparison with conventional antibodies/stains and by generating three-dimensional reconstructions. The proximal attachment of the APM to the bulge in 8 patients with androgenic alopecia was studied using Masson's trichrome stain. Phalloidin visualized extensive branching of the APM. The distal end of the human APM exhibits a unique "C"-shaped structure connecting to the dermal-epidermal junction. The proximal APM attachment was observed to be lost or extremely miniaturized in androgenic alopecia. The unique shape, location, and attachment sites of the APM suggest a significant role for this muscle in maintaining follicular integrity. Proximally, the APM encircles the follicular unit and only attaches to the primary hair follicle in the bulge; this attachment is lost in irreversible hair loss. The APM exhibits an arborized morphology as it ascends toward the epidermis, and anchors to the basement membrane.

Gene expression of matrix metalloproteinases and LH receptors in mare follicular development.

PubMed

Bastos, H B A; Kretzmann, N A; Santos, G O; Esmeraldino, A T; Rechsteiner, S Fiala; Mattos, R C; Neves, A P

2014-11-01

The period from the emergence of a dominant follicle until its formation requires tissue remodeling. Enzymes promoting collagen lysis, such as matrix metalloproteinases (MMPs), are fundamental for the process of extracellular matrix remodeling, which allows changes in ovarian tissue architecture during follicular growth. It has been suggested that the production of these enzymes may be affected by the rise in circulating concentrations of LH, which acts on the ovarian surface epithelium (OSE). The aim of this study was to determine the expression of MMP-1, MMP-2, and LH receptor (LHR) in the ovulation fossa and in the central portion of the equine ovary during follicular deviation and dominance. Ovaries of 12 cyclic mares were selected and subsequently divided into two groups: development (DEV) group and dominant (DOM) group. The DEV group consisted of ovaries from six animals whose follicles were less than 28 mm in diameter (follicular deviation), and the DOM group consisted of ovaries from six animals whose follicles measured 28 mm or more in diameter (dominant follicles). The latter group was divided into two subgroups: the group of ovaries with a dominant follicle (DOM-D) and the group of contralateral ovaries (DOM-C). Our results showed that mRNA for MMP-1, MMP-2, and LHR was present in the equine ovary during follicle development, in the ovulation fossa, and in the central portion of the ovary. MMP-1 and LHR gene expression was greater (P < 0.05) for the DOM-D group compared with the DOM-C group. In the DOM-D group, MMP-1, MMP-2, and LHR gene expression was greater (P < 0.05) in the ovarian stroma compared with the ovulation fossa. Using immunohistochemistry, OSE from the DOM group showed increased expression compared with the DEV group (P < 0.05). In conclusion, we demonstrated that MMP-1 and MMP-2 might be fundamental for events related to tissue remodeling, which occurs during follicular development until the formation of the dominant follicle. We also

Utility of color Doppler indices of dominant follicular blood flow for prediction of clinical factors in in vitro fertilization-embryo transfer cycles.

PubMed

Ozaki, T; Hata, K; Xie, H; Takahashi, K; Miyazaki, K

2002-12-01

To investigate the relationship between color Doppler indices of dominant follicular blood flow and clinical factors in in vitro fertilization-embryo transfer cycles. This was a prospective study involving 26 patients completing a total of 33 in vitro fertilization cycles. Dominant follicular blood flow indices, peak systolic velocities, the resistance index and the pulsatility index were evaluated using transvaginal color Doppler. The indices were compared to the clinical outcomes of in vitro fertilization-embryo transfer. There was a significant correlation between dominant follicular peak systolic velocities and the number of oocytes retrieved, as well as the number of mature oocytes obtained. There was no significant correlation between dominant follicular resistance index or pulsatility index and the number of follicles > 10 mm in diameter, the number of oocytes retrieved or the number of mature oocytes. There were no significant differences between dominant follicular peak systolic velocities, resistance index or pulsatility index, and fertilization rate or the ratio of good quality embryos. However, significant differences were found between the number of oocytes retrieved, as well as the number of mature oocytes for those patients in which the peak systolic velocity was below 25 cm/s. Doppler assessment of dominant follicle blood flow alone is useful for predicting the number of retrievable oocytes. However, morphological quality of the embryo produced or the pregnancy rate cannot be predicted by this method.

Bethlem myopathy: An autosomal dominant myopathy with flexion contractures, keloids, and follicular hyperkeratosis.

PubMed

Saroja, Aralikatte Onkarappa; Naik, Karkal Ravishankar; Nalini, Atcharayam; Gayathri, Narayanappa

2013-10-01

Bethlem myopathy and Ullrich congenital muscular dystrophy form a spectrum of collagenopathies caused by genetic mutations encoding for any of the three subunits of collagen VI. Bethlem phenotype is relatively benign and is characterized by proximal dominant myopathy, keloids, contractures, distal hyperextensibility, and follicular hyperkeratosis. Three patients from a single family were diagnosed to have Bethlem myopathy based on European Neuromuscular Centre Bethlem Consortium criteria. Affected father and his both sons had slowly progressive proximal dominant weakness and recurrent falls from the first decade. Both children aged 18 and 20 years were ambulant at presentation. All had flexion contractures, keloids, and follicular hyperkeratosis without muscle hypertrophy. Creatinine kinase was mildly elevated and electromyography revealed myopathic features. Muscle imaging revealed severe involvement of glutei and vasti with "central shadow" in rectus femoris. Muscle biopsy in the father showed dystrophic changes with normal immmunostaining for collagen VI, sarcoglycans, and dysferlin.

Ultra-Early Phase pathologies of Alzheimer's disease and other neurodegenerative diseases.

PubMed

Okazawa, Hitoshi

2017-01-01

The concept of neurodegenerative diseases and the therapeutics targeting these intractable diseases are changing rapidly. Protein aggregation as the top of pathological cascade is now challenged, and many alternative ideas are proposed. Early molecular pathologies before microscopic detection of diseases protein aggregates, which I propose to call "Ultra-Early Phase pathologies or phase 0 pathologies", are the focus of research that might explain the failures of clinical trials with anti-Aβ antibodies against Alzheimer's disease. In this review article, I summarize the critical issues that should be successfully and consistently answered by a new concept of neurodegeneration. For reevaluating old concepts and reconstructing a new concept of neurodegeneration that will replace the old ones, non-biased comprehensive approaches including proteome combined with systems biology analyses will be a powerful tool. I introduce our recent efforts in this orientation that have reached to the stage of non-clinical proof of concept applicable to clinical trials.

Role of GPER1, EGFR and CXCR1 in differentiating between malignant follicular thyroid carcinoma and benign follicular thyroid adenoma.

PubMed

Zhao, Le; Zhu, Xiao-Yun; Jiang, Rong; Xu, Man; Wang, Ni; Chen, George G; Liu, Zhi-Min

2015-01-01

It is extremely difficult to discriminate between follicular thyroid carcinoma (FTC) and follicular thyroid adenoma (FTA) before surgery, because the morphologies of carcinoma cells and adenoma cells obtained by fine needle aspiration biopsy (FNAB) are similar. Molecular markers may be helpful on this issue. The purpose of this study was to assess the role of GPER1, EGFR and CXCR1 in differential diagnosis between FTC and FTA. GPER1, EGFR and CXCR1 mRNA expression levels were examined in 15 FTCs and 10 FTAs using real-time RT-PCR. FTC showed to have significantly increased mRNA levels of the three molecules compared to FTA (P < 0.001 for all the three molecules). GPER1, EGFR and CXCR1 protein expression in 106 FTCs and 128 FTAs were analyzed using immunohistochemistry. The rates of GPER1, EGFR and CXCR1 high expression were 73.6%, 72.6% and 70.8% in FTC and 30.5%, 28.1% and 27.3% in FTA, respectively. Statistical analysis showed that GPER1, EGFR and CXCR1 protein expression were correlated with one another in FTC and concomitant high expression of the three molecules had stronger correlation with the occurrence of FTC than did each alone. The positive predictive values (PPV) for concomitant high expression of the three molecules for discriminating between FTC and FTA were 91.0% for GPER1/EGFR, 93.8% for GPER1/CXCR1, 92.3% for EGFR/CXCR1 and 98.2% for GPER1/EGFR/CXCR1, respectively. These results indicated that the evaluation of GPER1, EGFR and CXCR1 concomitant high expression may be helpful in differential diagnosis between FTC and FTA.

Histological Transformation and Progression in Follicular Lymphoma: A Clonal Evolution Study.

PubMed

Kridel, Robert; Chan, Fong Chun; Mottok, Anja; Boyle, Merrill; Farinha, Pedro; Tan, King; Meissner, Barbara; Bashashati, Ali; McPherson, Andrew; Roth, Andrew; Shumansky, Karey; Yap, Damian; Ben-Neriah, Susana; Rosner, Jamie; Smith, Maia A; Nielsen, Cydney; Giné, Eva; Telenius, Adele; Ennishi, Daisuke; Mungall, Andrew; Moore, Richard; Morin, Ryan D; Johnson, Nathalie A; Sehn, Laurie H; Tousseyn, Thomas; Dogan, Ahmet; Connors, Joseph M; Scott, David W; Steidl, Christian; Marra, Marco A; Gascoyne, Randy D; Shah, Sohrab P

2016-12-01

Follicular lymphoma (FL) is an indolent, yet incurable B cell malignancy. A subset of patients experience an increased mortality rate driven by two distinct clinical end points: histological transformation and early progression after immunochemotherapy. The nature of tumor clonal dynamics leading to these clinical end points is poorly understood, and previously determined genetic alterations do not explain the majority of transformed cases or accurately predict early progressive disease. We contend that detailed knowledge of the expansion patterns of specific cell populations plus their associated mutations would provide insight into therapeutic strategies and disease biology over the time course of FL clinical histories. Using a combination of whole genome sequencing, targeted deep sequencing, and digital droplet PCR on matched diagnostic and relapse specimens, we deciphered the constituent clonal populations in 15 transformation cases and 6 progression cases, and measured the change in clonal population abundance over time. We observed widely divergent patterns of clonal dynamics in transformed cases relative to progressed cases. Transformation specimens were generally composed of clones that were rare or absent in diagnostic specimens, consistent with dramatic clonal expansions that came to dominate the transformation specimens. This pattern was independent of time to transformation and treatment modality. By contrast, early progression specimens were composed of clones that were already present in the diagnostic specimens and exhibited only moderate clonal dynamics, even in the presence of immunochemotherapy. Analysis of somatic mutations impacting 94 genes was undertaken in an extension cohort consisting of 395 samples from 277 patients in order to decipher disrupted biology in the two clinical end points. We found 12 genes that were more commonly mutated in transformed samples than in the preceding FL tumors, including TP53, B2M, CCND3, GNA13, S1PR2, and P2RY

Histological Transformation and Progression in Follicular Lymphoma: A Clonal Evolution Study

PubMed Central

Mottok, Anja; Boyle, Merrill; Tan, King; Meissner, Barbara; Bashashati, Ali; Roth, Andrew; Shumansky, Karey; Nielsen, Cydney; Giné, Eva; Moore, Richard; Morin, Ryan D.; Sehn, Laurie H.; Tousseyn, Thomas; Dogan, Ahmet; Scott, David W.; Steidl, Christian; Gascoyne, Randy D.; Shah, Sohrab P.

2016-01-01

Background Follicular lymphoma (FL) is an indolent, yet incurable B cell malignancy. A subset of patients experience an increased mortality rate driven by two distinct clinical end points: histological transformation and early progression after immunochemotherapy. The nature of tumor clonal dynamics leading to these clinical end points is poorly understood, and previously determined genetic alterations do not explain the majority of transformed cases or accurately predict early progressive disease. We contend that detailed knowledge of the expansion patterns of specific cell populations plus their associated mutations would provide insight into therapeutic strategies and disease biology over the time course of FL clinical histories. Methods and Findings Using a combination of whole genome sequencing, targeted deep sequencing, and digital droplet PCR on matched diagnostic and relapse specimens, we deciphered the constituent clonal populations in 15 transformation cases and 6 progression cases, and measured the change in clonal population abundance over time. We observed widely divergent patterns of clonal dynamics in transformed cases relative to progressed cases. Transformation specimens were generally composed of clones that were rare or absent in diagnostic specimens, consistent with dramatic clonal expansions that came to dominate the transformation specimens. This pattern was independent of time to transformation and treatment modality. By contrast, early progression specimens were composed of clones that were already present in the diagnostic specimens and exhibited only moderate clonal dynamics, even in the presence of immunochemotherapy. Analysis of somatic mutations impacting 94 genes was undertaken in an extension cohort consisting of 395 samples from 277 patients in order to decipher disrupted biology in the two clinical end points. We found 12 genes that were more commonly mutated in transformed samples than in the preceding FL tumors, including TP53, B2

T Follicular Helper Cell Plasticity Shapes Pathogenic T Helper 2 Cell-Mediated Immunity to Inhaled House Dust Mite.

PubMed

Ballesteros-Tato, André; Randall, Troy D; Lund, Frances E; Spolski, Rosanne; Leonard, Warren J; León, Beatriz

2016-02-16

Exposure to environmental antigens, such as house dust mite (HDM), often leads to T helper 2 (Th2) cell-driven allergic responses. However, the mechanisms underlying the development of these responses are incompletely understood. We found that the initial exposure to HDM did not lead to Th2 cell development but instead promoted the formation of interleukin-4 (IL-4)-committed T follicular helper (Tfh) cells. Following challenge exposure to HDM, Tfh cells differentiated into IL-4 and IL-13 double-producing Th2 cells that accumulated in the lung and recruited eosinophils. B cells were required to expand IL-4-committed Tfh cells during the sensitization phase, but did not directly contribute to disease. Impairment of Tfh cell responses during the sensitization phase or Tfh cell depletion prevented Th2 cell-mediated responses following challenge. Thus, our data demonstrate that Tfh cells are precursors of HDM-specific Th2 cells and reveal an unexpected role of B cells and Tfh cells in the pathogenesis of allergic asthma. Copyright © 2016 Elsevier Inc. All rights reserved.

[Cranial metastasis of thyroid follicular carcinoma. Report of a case].

PubMed

Calderón-Garcidueñas, A L; González-Schaffinni, M A; Farías-García, R; Rey-Laborde, R

2001-01-01

Thyroid follicular carcinoma is able to produce metastatic lesions before the vanishing of the primary lesion. We present a case of a woman with a lytic, solitary, asymptomatic parietal bone lesion of 2 years of evolution. Autopsy revealed a thyroid gland with two small cystic areas and renal metastasis. Thyroid carcinoma should be included in the differential diagnosis in cases of lytic bone lesions with long evolution in patients 60 years of age or older.

Effect of nutrition and superovulation on oocyte morphology, follicular fluid composition and systemic hormone concentrations in ewes.

PubMed

O'Callaghan, D; Yaakub, H; Hyttel, P; Spicer, L J; Boland, M P

2000-03-01

The objective was to determine the effect of dietary intake on follicle and oocyte morphology in unstimulated and superovulated ewes. Fifty-four ewes were fed grass meal at 0.5, 1.0 or 2.0 times maintenance energy requirements (M) for 32 days. Oestrous cycles were synchronized using progestagen pessaries and either unstimulated or superovulated with 200 mg pig FSH. The ewes were killed and ovaries were collected either 36 or 12 h before the anticipated LH surge. Serum progesterone concentrations in ewes on day 10 after withdrawal of the pessary were lower in ewes fed 2.0M than in ewes fed 0.5M or 1.0M (P < 0.05). LH pulse frequency tended to be higher in ewes fed 2M than 1M (1.0 +/- 0.3 versus 0.3 +/- 0.2 pulses per 8 h) on day 6 after removal of the pessary but the effect was not significant. In unstimulated ewes, more follicles (>/= 3 mm) were observed when the animals were killed in ewes fed 2.0M (3.5 +/- 0.3) than in ewes fed 0.5M (2.4 +/- 0.3) or 1.0M (2.4 +/- 0.5; P < 0. 05). Fewer follicles were observed in superovulated ewes on 0.5M (7. 5 +/- 1.2) than in ewes on 1.0M (12.0 +/- 0.5) or 2.0M (12.3 +/- 1. 4; P < 0.05). Follicular fluid progesterone concentrations were higher in ewes fed 0.5M compared with those fed 1M or 2M (P < 0.05). Insulin-like growth factor (IGF)-I concentrations were higher in follicular fluid from ewes on 1M compared with either those on 0.5M or 2M (P < 0.05), whereas IGF-II concentrations were lower in follicular fluid from ewes on 2M compared with those on 1M or 0.5M (P < 0.05). Superovulation increased follicular fluid progesterone, oestradiol, IGF-I and IGF-II concentrations (P < 0.01). Concentrations of the 34, 22 and 20 kDa IGF binding proteins were lower in follicles from superovulated ewes compared with unstimulated ewes (P < 0.05). Oocytes from superovulated ewes showed abnormalities such as premature activation of cumulus expansion and vacuolation of the nucleolus and increased frequency of detachment of interchromatin

Association between expression of cumulus expansion markers and real-time proliferation of porcine follicular granulosa cells in a primary cell culture model.

PubMed

Ciesiółka, S; Budna, J; Bryja, A; Kranc, W; Chachuła, A; Dyszkiewicz-Konwińska, M; Piotrowska, H; Bukowska, D; Antosik, P; Bruska, M; Brüssow, K P; Nowicki, M; Zabel, M; Kempisty, B

2016-01-01

Folliculogenesis is a compound process that involves both ovarian follicle growth and oocyte development, which is tightly attached to the follicular wall. During this process, cells that form the follicle structure undergo substantial morphological and molecular modifications that finally lead to differentiation and specialization of ovarian follicular cells. The differentiation of ovarian cells encompasses formation of follicle, which is composed of theca (TCs), mural granulosa (GCs), and cumulus cells (CCs). It was previously hypothesized that GCs and CCs represent undifferentiated and highly specialized follicular cells, respectively, which may have similar primordial cell origins. In this study, we investigated the expression pattern of cumulus expansion markers such as COX2, HAS2, PTX3, and TSG6 in porcine GCs during short-term, in vitro culture. We hypothesized that these genes may display an important function in GCs in relation to cellular real-time proliferation. The expression pattern of COX2, HAS2, PTX3, and TSG6 was evaluated after using RT-qPCR in relation to confocal microscopy observations of protein expression and distribution during real-time proliferation of porcine follicular GCs. The COX2 and HAS2 mRNAs were highly expressed after 120 h of in vitro culture (IVC), whereas PTX3 and TSG6 mRNAs were increased during the first 24-48 h of IVC (P less than 0.001, P less than 0.01). Conversely, all of the encoded proteins were highly expressed after 144-168 h of IVC as compared to other culture periods (P less than 0.001, P less than 0.01). When analyzing the realtime proliferation of GCs in vitro, we observed a logarithmic increase of cell proliferation between 0 h and 120 h of IVC. However, after 120-168 h of IVC, the cells reached the lag phase of proliferation. Since it is well accepted that porcine GCs undergo luteinization shortly after 24-48 h of IVC, the expression pattern of investigated genes indicated that Cox2 and Has2 are independent from

Randomized, open trial comparing a modified double-lumen needle follicular flushing system with a single-lumen aspiration needle in IVF patients with poor ovarian response.

PubMed

von Horn, Kyra; Depenbusch, Marion; Schultze-Mosgau, Askan; Griesinger, Georg

2017-04-01

Is a modified double-lumen aspiration needle system with follicular flushing able to increase the mean oocyte yield by at least one in poor response IVF patients as compared to single-lumen needle aspiration without flushing? Follicular flushing with the modified flushing system did not increase the number of oocytes, but increased the procedure duration. Most studies on follicular flushing were performed with conventional double-lumen needles in patients who were normal responders. Overall, these studies indicated no benefit of follicular flushing. Prospective, single-centre, randomized, controlled, open, superiority trial comparing the 17 G Steiner-Tan Needle® flushing system with a standard 17 G single-lumen aspiration needle (Gynetics®); time frame February 2015-March 2016. Eighty IVF patients, 18-45 years, BMI >18 kg/m2 to <35 kg/m2, presenting with ≤ five follicles >10 mm in both ovaries at the end of the follicular phase were randomized to either aspirating and flushing each follicle 3× with the Steiner-Tan-Needle® automated flushing system (n = 40) or a conventional single-lumen needle aspiration (n = 40). Primary outcome was the number of cumulus-oocyte-complexes (COCs). Procedure duration, burden (Depression Anxiety and Stress Scale; DASS-21) and post-procedure pain were also assessed. Flushing was not superior with a mean (SD) number of COCs of 2.4 (2.0) and 3.1 (2.3) in the Steiner-Tan Needle® and in the Gynectics® group, respectively (mean difference -0.7, 95% CI: 0.3 to -1.6; P = 0.27). Likewise no differences were observed in metaphase II  oocytes, two pronuclear oocytes, number of patients having an embryo transfer and DASS 21 scores. The procedure duration was significantly 2-fold increased. Testing for differences in the number of patients achieving an embryo transfer or differences in pregnancy rate would require a much larger sample size. The use of follicular flushing is unlikely to benefit the prognosis of patients with poor ovarian

Potential role for GnRH in the synchronization of follicular emergence before the superovulatory Day 0 protocol.

PubMed

Balaro, M F A; Fonseca, J F; Barbosa, T G B; Souza-Fabjan, J M G; Figueira, L M; Teixeira, T A; Carvalheira, L R; Brandão, F Z

2016-01-01

The ability of gonadotropin-releasing hormone (GnRH) to synchronize ovulation and new follicular wave emergence before a "superovulatory Day 0" protocol was assessed in Santa Inês ewes. For estrus synchronization, a 60-mg medroxyprogesterone acetate sponge was inserted for 6 d. One day before sponge removal, 37.5-μg d-cloprostenol and 300 IU equine chorionic gonadotropin were injected intramuscularly (i.m.). After sponge removal, ewes were assigned to the following 3 groups: (1) GC-1 mL saline at 12 h (n = 10); (2) G24h-0.025-mg lecirelin (GnRH agonist) i.m. at 24 h (n = 10); or (3) G36h-0.025-mg lecirelin i.m. at 36 h (n = 9). Ovarian ultrasonography was conducted to assess follicular dynamics. Blood was collected to determine plasma concentrations of progesterone and estradiol. Females from G36h and GC had a greater (P < 0.05) estrous response than those from the G24h group (78.0 and 90.0 vs 0.0%, respectively). Ewes from G24h and G36h had earlier (P < 0.05) ovulation (48.0 ± 10.2 and 56.7 ± 5.7 h) compared with those from Gc (64.1 ± 9.7 h). The mean number of ovulations per ewe was greater (P < 0.05) in Gc (1.9 ± 0.6) and G36h (2.0 ± 1.0) than G24h (1.2 ± 0.4). Plasma concentrations of progesterone and estradiol differed over time. Follicular growth during the postovulatory day was affected (P < 0.05) by day of the estrus cycle as well as by the interaction (P < 0.05) of treatment and day of the estrus cycle. There was a larger (P < 0.05) population of medium follicles during the first 24 h after the ovulation in G24h compared with Gc, and there was an absence of large follicles in G36h between 36 and 72 h after ovulation. In conclusion, the use of GnRH agonist at 36 h more efficiently synchronized ovulation and promoted the absence of dominant follicles during early diestrus and may be used at the start of superovulatory treatment at 80 h in Santa Inês ewes. Copyright © 2016 Elsevier Inc. All rights reserved.

The Role of Follicular Fluid Thiol/Disulphide Homeostasis in Polycystic Ovary Syndrome.

PubMed

Tola, Esra Nur; Köroğlu, Nadiye; Ergin, Merve; Oral, Hilmi Baha; Turgut, Abdülkadir; Erel, Özcan

2018-04-04

Oxidative stress is suggested as a potential triggering factor in the etiopathogenesis of Polycystic ovary syndrome related infertility. Thiol/disulphide homeostasis, a recently oxidative stress marker, is one of the antioxidant mechanism in human which have critical roles in folliculogenesis and ovulation. The aim of our study is to investigate follicular fluid thiol/disulphide homeostasis in the etiopathogenesis of Polycystic ovary syndrome and to determine its' association with in vitro fertilization outcome. The study procedures were approved by local ethic committee. Cross sectional design Methods: Follicular fluid of twenty-two Polycystic ovary syndrome women and twenty ovulatory controls undergoing in vitro fertilization treatment were recruited. Thiol/disulphide homeostasis was analyzed via a novel spectrophotometric method. Follicular native thiol levels were found to be lower in Polycystic ovary syndrome group than non- Polycystic ovary syndrome group (p=0.041) as well as native thiol/total thiol ratio (p<0.0001). Disulphide level, disulphide/native thiol and disulphide/total thiol ratios were increased in Polycystic ovary syndrome group (p<0.0001). A positive correlation between fertilization rate and native thiol (p=0.01, r=0.53) and total thiol (p=0.01, r=0.052) among Polycystic ovary syndrome patients was found. A positive predictive effect of native thiol on fertilization rate among Polycystic ovary syndrome group was also found (p=0.03, β=0.45, 95% CI=0.031-0.643). Deterioration in thiol/disulphide homeostasis, especially elevated disulphide levels could be one of the etiopathogenetic mechanism in Polycystic ovary syndrome. Increased native thiol levels is related to fertilization rate among Polycystic ovary syndrome patients and also positive predictor marker of fertilization rate among Polycystic ovary syndrome patients. Improvement of thiol/disulphide homeostasis could be of importance in the treatment of Polycystic ovary syndrome to increase in

Increased platelet factor 4 and aberrant permeability of follicular fluid in PCOS.

PubMed

Huang, Chu-Chun; Chou, Chia-Hung; Chen, Shee-Uan; Ho, Hong-Nerng; Yang, Yu-Shih; Chen, Mei-Jou

2018-05-17

Abnormal folliculogenesis is one of the cardinal presentations of polycystic ovarian syndrome (PCOS) and permeability of follicular wall has been proposed to be involved in the normal follicular growth. However, whether or not there is a change in intrafollicular permeability underlies PCOS is unknown. This was a tertiary center-based case-control study. From 2014 to 2015, thirteen patients with PCOS who underwent in vitro fertilization-embryo transfer (IVF-ET) were enrolled. Eleven normo-ovulatory patients who underwent IVF-ET due to male factor and/or tubal factor infertility were enrolled as the control group. The influence of ovarian follicular fluid (FF) on endothelial cell permeability was evaluated using a human umbilical vein endothelial cell monolayer permeability assay. The intrafollicular expression profiles of angiogenesis-related proteins were analyzed using a Human Angiogenesis Protein Array Kit. The FF from PCOS patients caused significantly poorer endothelial cell permeability comparing with the effect of FF from the control group (46% ± 12% vs. 58% ± 9%, P = 0.023). Among the 55 angiogenesis-related proteins tested, there was a significantly higher level of intrafollicular platelet factor 4 (PF4) and PF4/IL-8 complex in the PCOS group (p = 0.004). The anti-permeability effect of PF4 was related to the decrease in the intercellular gaps and antagonistic binding with IL-8. Our study provides the first evidence of the pathophysiologic contribution of the well-known angiostatic protein, PF4, on human reproductive biology. The increase of the intrafollicular PF4 and its anti-permeability effect might affect the formation of FF and folliculogenesis in PCOS. Copyright © 2018. Published by Elsevier B.V.

Research Resource: Preovulatory LH Surge Effects on Follicular Theca and Granulosa Transcriptomes

PubMed Central

Gunewardena, Sumedha; Hong, Xiaoman; Spitschak, Marion; Baufeld, Anja

2013-01-01

The molecular mechanisms that regulate the pivotal transformation processes observed in the follicular wall following the preovulatory LH surge, are still not established, particularly for cells of the thecal layer. To elucidate thecal cell (TC) and granulosa cell (GC) type-specific biologic functions and signaling pathways, large dominant bovine follicles were collected before and 21 hours after an exogenous GnRH-induced LH surge. Antral GCs (aGCs; aspirated by follicular puncture) and membrane-associated GCs (mGCs; scraped from the follicular wall) were compared with TC expression profiles determined by mRNA microarrays. Of the approximately 11 000 total genes expressed in the periovulatory follicle, only 2% of thecal vs 25% of the granulosa genes changed in response to the LH surge. The majority of the 203 LH-regulated thecal genes were also LH regulated in GCs, leaving a total of 57 genes as LH-regulated TC-specific genes. Of the 57 thecal-specific LH-regulated genes, 74% were down-regulated including CYP17A1 and NR5A1, whereas most other genes are being identified for the first time within theca. Many of the newly identified up-regulated thecal genes (eg, PTX3, RND3, PPP4R4) were also up-regulated in granulosa. Minimal expression differences were observed between aGCs and mGCs; however, transcripts encoding extracellular proteins (NID2) and matrix modulators (ADAMTS1, SASH1) dominated these differences. We also identified large numbers of unknown LH-regulated GC genes and discuss their putative roles in ovarian function. This Research Resource provides an easy-to-access global evaluation of LH regulation in TCs and GCs that implicates numerous molecular pathways heretofore unknown within the follicle. PMID:23716604

Research resource: preovulatory LH surge effects on follicular theca and granulosa transcriptomes.

PubMed

Christenson, Lane K; Gunewardena, Sumedha; Hong, Xiaoman; Spitschak, Marion; Baufeld, Anja; Vanselow, Jens

2013-07-01

The molecular mechanisms that regulate the pivotal transformation processes observed in the follicular wall following the preovulatory LH surge, are still not established, particularly for cells of the thecal layer. To elucidate thecal cell (TC) and granulosa cell (GC) type-specific biologic functions and signaling pathways, large dominant bovine follicles were collected before and 21 hours after an exogenous GnRH-induced LH surge. Antral GCs (aGCs; aspirated by follicular puncture) and membrane-associated GCs (mGCs; scraped from the follicular wall) were compared with TC expression profiles determined by mRNA microarrays. Of the approximately 11 000 total genes expressed in the periovulatory follicle, only 2% of thecal vs 25% of the granulosa genes changed in response to the LH surge. The majority of the 203 LH-regulated thecal genes were also LH regulated in GCs, leaving a total of 57 genes as LH-regulated TC-specific genes. Of the 57 thecal-specific LH-regulated genes, 74% were down-regulated including CYP17A1 and NR5A1, whereas most other genes are being identified for the first time within theca. Many of the newly identified up-regulated thecal genes (eg, PTX3, RND3, PPP4R4) were also up-regulated in granulosa. Minimal expression differences were observed between aGCs and mGCs; however, transcripts encoding extracellular proteins (NID2) and matrix modulators (ADAMTS1, SASH1) dominated these differences. We also identified large numbers of unknown LH-regulated GC genes and discuss their putative roles in ovarian function. This Research Resource provides an easy-to-access global evaluation of LH regulation in TCs and GCs that implicates numerous molecular pathways heretofore unknown within the follicle.

Follicular progesterone concentrations and messenger RNA expression of MATER and OCT-4 in immature bovine oocytes as predictors of developmental competence.

PubMed

Urrego, R; Herrera-Puerta, E; Chavarria, N A; Camargo, O; Wrenzycki, C; Rodriguez-Osorio, N

2015-04-15

The ability of bovine embryos to develop to the blastocyst stage and to implant and generate healthy offspring depends greatly on the competence of the oocyte. Oocyte competence is attributed to its close communication with the follicular environment and to its capacity to synthesize and store substantial amounts of messenger RNA. Higher developmental competence of bovine oocytes has been associated with both the expression of a cohort of developmental genes and the concentration of sex steroids in the follicular fluid. The aim of this study was to identify differences in the expression of FST in cumulus cells and OCT-4 and MATER in oocytes and the influence of the follicular progesterone and follicular estrogen concentration on the competence of bovine oocytes retrieved 30 minutes or 4 hours after slaughter. Cumulus-oocyte complexes (COCs) were left in postmortem ovaries for 30 minutes (group I) or 4 hours (group II) at 30 °C. Aspirated oocytes were then subjected to IVM, IVF, and IVC or were evaluated for MATER and OCT-4 messenger RNA abundance by quantitative real-time polymerase chain reaction. Total RNA was isolated from pools of 100 oocytes for each experimental replicate. Progesterone and estradiol concentration in follicular fluid was evaluated by immunoassay using an IMMULITE 2000 analyzer. Three repeats of in vitro embryo production were performed with a total of 455 (group I) and 470 (group II) COCs. There were no significant differences between the cleavage rates (72 hours postinsemination [hpi]) between both groups (63.5% vs. 69.1%). However, blastocyst (168 hpi) and hatching (216 hpi) rates were higher (P < 0.05) in group II compared with those of group I (21.3% vs. 30.7% and 27.6% vs. 51.5%, respectively). Group II oocytes exhibited the highest MATER and OCT-4 abundance (P < 0.05). Follicular estradiol concentration was not different between both the groups, whereas the progesterone concentration was lower (P ≤ 0.05) in group II follicles. These

Ibrutinib as Treatment for Patients With Relapsed/Refractory Follicular Lymphoma: Results From the Open-Label, Multicenter, Phase II DAWN Study.

PubMed

Gopal, Ajay K; Schuster, Stephen J; Fowler, Nathan H; Trotman, Judith; Hess, Georg; Hou, Jing-Zhou; Yacoub, Abdulraheem; Lill, Michael; Martin, Peter; Vitolo, Umberto; Spencer, Andrew; Radford, John; Jurczak, Wojciech; Morton, James; Caballero, Dolores; Deshpande, Sanjay; Gartenberg, Gary J; Wang, Shean-Sheng; Damle, Rajendra N; Schaffer, Michael; Balasubramanian, Sriram; Vermeulen, Jessica; Cheson, Bruce D; Salles, Gilles

2018-05-31

Purpose The Bruton's tyrosine kinase inhibitor ibrutinib has demonstrated clinical activity in B-cell malignancies. The DAWN study assessed the efficacy and safety of single-agent ibrutinib in chemoimmunotherapy relapsed/refractory follicular lymphoma (FL) patients. Methods DAWN was an open-label, single-arm, phase II study of ibrutinib in patients with FL with two or more prior lines of therapy. Patients received ibrutinib 560 mg daily until progressive disease/unacceptable toxicity. The primary objective was independent review committee-assessed overall response rate (ORR; complete response plus partial response). Exploratory analyses of T-cell subsets in peripheral blood (baseline/cycle 3) and cytokines/chemokines (baseline/cycle 2) were performed for available samples. Results Between March 2013 and May 2016, 110 patients with a median of three prior lines of therapy were enrolled. At median follow-up of 27.7 months, ORR was 20.9% (95% CI, 13.7% to 29.7%, which did not meet the 18% lower-bound threshold for the primary end point). Twelve patients achieved a complete response (11%; 95% CI, 5.8% to 18.3%). Median duration of response was 19.4 months (range, 1 to ≥ 33 months), with a median progression-free survival of 4.6 months and a 30-month overall survival of 61% (95% CI, 0.51% to 0.70%). Lymphoma symptoms resolved in 67%. Seven of 32 patients who experienced initial radiologic progression responded upon continuing therapy (pseudoprogression). The most common adverse events were diarrhea, fatigue, cough, and muscle spasms; 48.2% of patients reported serious adverse events. In patients who experienced a response, regulatory T cells were downregulated at C3D1 ( P = .02), and Th1-promoting (antitumor) cytokines interferon-γ and interleukin-12 increased ( P ≤ .035). Conclusion With an ORR of 20.9%, ibrutinib failed to meet its primary efficacy end point in chemoimmunotherapy in patients with relapsed/refractory FL, although responses were durable and

HIV and T follicular helper cells: a dangerous relationship

PubMed Central

Vinuesa, Carola G.

2012-01-01

HIV infection leads to progressive destruction of infected CD4 T cells, hypergammaglobulinemia, and loss of memory B cells. Germinal centers, which are key to memory B cell formation and protective antibody responses, are major HIV reservoirs in which the virus replicates within T follicular helper (TFH) cells. In this issue of the JCI, the Koup and Streeck groups report that chronic SIV/HIV infection promotes TFH cell accumulation, which may drive B cell dysregulation. Their discoveries suggest that HIV harnesses TFH cells to evade the antibody response. PMID:22922252

Hormone phase influences sympathetic responses to high levels of lower body negative pressure in young healthy women.

PubMed

Usselman, Charlotte W; Nielson, Chantelle A; Luchyshyn, Torri A; Gimon, Tamara I; Coverdale, Nicole S; Van Uum, Stan H M; Shoemaker, J Kevin

2016-11-01

We tested the hypothesis that sympathetic responses to baroreceptor unloading may be affected by circulating sex hormones. During lower body negative pressure at -30, -60, and -80 mmHg, muscle sympathetic nerve activity (MSNA), heart rate, and blood pressure were recorded in women who were taking (n = 8) or not taking (n = 9) hormonal contraceptives. All women were tested twice, once during the low-hormone phase (i.e., the early follicular phase of the menstrual cycle and the placebo phase of hormonal contraceptive use), and again during the high-hormone phase (i.e., the midluteal phase of the menstrual cycle and active phase of contraceptive use). During baroreceptor unloading, the reductions in stroke volume and resultant increases in MSNA and total peripheral resistance were greater in high-hormone than low-hormone phases in both groups. When normalized to the fall in stroke volume, increases in MSNA were no longer different between hormone phases. While stroke volume and sympathetic responses were similar between women taking and not taking hormonal contraceptives, mean arterial pressure was maintained during baroreceptor unloading in women not taking hormonal contraceptives but not in women using hormonal contraceptives. These data suggest that differences in sympathetic activation between hormone phases, as elicited by lower body negative pressure, are the result of hormonally mediated changes in the hemodynamic consequences of negative pressure, rather than centrally driven alterations to sympathetic regulation. Copyright © 2016 the American Physiological Society.

The not-so-bitter pill: Effects of combined oral contraceptives on peripheral physiological indicators of emotional reactivity.

PubMed

Armbruster, Diana; Kirschbaum, Clemens; Strobel, Alexander

2017-08-01

Combined oral contraceptives (COC) are used by millions of women worldwide. Although findings are not entirely consistent, COC have been found to impact on brain function and, thus, to modulate affective processes. Here, we investigated electro-physiological responses to emotional stimuli in free cycling women in both the early follicular and late luteal phase as well as in COC users. Skin conductance response (SCR), startle reflex, corrugator and zygomaticus activity were assessed. COC users showed reduced overall startle magnitude and SCR amplitude, but heightened overall zygomaticus activity, although effect sizes were small. Thus, COC users displayed reduced physiological reactions indicating negative affect and enhanced physiological responses signifying positive affect. In free cycling women, endogenous 17β-estradiol levels were associated with fear potentiated startle in both cycle phases as well as with SCR and zygomaticus activity during the follicular phase. Testosterone was associated with corrugator and zygomaticus activity during the luteal phase, while progesterone levels correlated with corrugator activity in the follicular phase. To the contrary, in COC users, endogenous hormones were not associated with electro-physiological measures. The results further underscore the importance of considering COC use in psychophysiological studies on emotional processing. Copyright © 2017 Elsevier Inc. All rights reserved.

Functional neuroanatomical correlates of episodic memory impairment in early phase psychosis

PubMed Central

Hummer, Tom A.; Vohs, Jenifer L.; Yung, Matthew G.; Liffick, Emily; Mehdiyoun, Nicole F.; Radnovich, Alexander J.; McDonald, Brenna C.; Saykin, Andrew J.; Breier, Alan

2015-01-01

Studies have demonstrated that episodic memory (EM) is often preferentially disrupted in schizophrenia. The neural substrates that mediate EM impairment in this illness are not fully understood. Several functional magnetic resonance imaging (fMRI) studies have employed EM probe tasks to elucidate the neural underpinnings of impairment, though results have been inconsistent. The majority of EM imaging studies have been conducted in chronic forms of schizophrenia with relatively few studies in early phase patients. Early phase schizophrenia studies are important because they may provide information regarding when EM deficits occur and address potential confounds more frequently observed in chronic populations. In this study, we assessed brain activation during the performance of visual scene encoding and recognition fMRI tasks in patients with earlyphase psychosis (n=35) and age, sex, and race matched healthy control subjects (n = 20). Patients demonstrated significantly lower activation than controls in the right hippocampus and left fusiform gyrus during scene encoding and lower activation in the posterior cingulate, precuneus, and left middle temporal cortex during recognition of target scenes. Symptom levels were not related to the imaging findings, though better cognitive performance in patients was associated with greater right hippocampal activation during encoding. These results provide evidence of altered function in neuroanatomical circuitry subserving EM early in the course of psychotic illness, which may have implications for pathophysiological models of this illness. PMID:25749917

Pathways of Prion Spread during Early Chronic Wasting Disease in Deer.

PubMed

Hoover, Clare E; Davenport, Kristen A; Henderson, Davin M; Denkers, Nathaniel D; Mathiason, Candace K; Soto, Claudio; Zabel, Mark D; Hoover, Edward A

2017-05-15

Among prion infections, two scenarios of prion spread are generally observed: (i) early lymphoid tissue replication or (ii) direct neuroinvasion without substantial antecedent lymphoid amplification. In nature, cervids are infected with chronic wasting disease (CWD) prions by oral and nasal mucosal exposure, and studies of early CWD pathogenesis have implicated pharyngeal lymphoid tissue as the earliest sites of prion accumulation. However, knowledge of chronological events in prion spread during early infection remains incomplete. To investigate this knowledge gap in early CWD pathogenesis, we exposed white-tailed deer to CWD prions by mucosal routes and performed serial necropsies to assess PrP CWD tissue distribution by real-time quaking-induced conversion (RT-QuIC) and tyramide signal amplification immunohistochemistry (TSA-IHC). Although PrP CWD was not detected by either method in the initial days (1 and 3) postexposure, we observed PrP CWD seeding activity and follicular immunoreactivity in oropharyngeal lymphoid tissues at 1 and 2 months postexposure (MPE). At 3 MPE, PrP CWD replication had expanded to all systemic lymphoid tissues. By 4 MPE, the PrP CWD burden in all lymphoid tissues had increased and approached levels observed in terminal disease, yet there was no evidence of nervous system invasion. These results indicate the first site of CWD prion entry is in the oropharynx, and the initial phase of prion amplification occurs in the oropharyngeal lymphoid tissues followed by rapid dissemination to systemic lymphoid tissues. This lymphoid replication phase appears to precede neuroinvasion. IMPORTANCE Chronic wasting disease (CWD) is a universally fatal transmissible spongiform encephalopathy affecting cervids, and natural infection occurs through oral and nasal mucosal exposure to infectious prions. Terminal disease is characterized by PrP CWD accumulation in the brain and lymphoid tissues of affected animals. However, the initial sites of prion

Pathways of Prion Spread during Early Chronic Wasting Disease in Deer

PubMed Central

Hoover, Clare E.; Davenport, Kristen A.; Henderson, Davin M.; Denkers, Nathaniel D.; Mathiason, Candace K.; Soto, Claudio; Zabel, Mark D.

2017-01-01

ABSTRACT Among prion infections, two scenarios of prion spread are generally observed: (i) early lymphoid tissue replication or (ii) direct neuroinvasion without substantial antecedent lymphoid amplification. In nature, cervids are infected with chronic wasting disease (CWD) prions by oral and nasal mucosal exposure, and studies of early CWD pathogenesis have implicated pharyngeal lymphoid tissue as the earliest sites of prion accumulation. However, knowledge of chronological events in prion spread during early infection remains incomplete. To investigate this knowledge gap in early CWD pathogenesis, we exposed white-tailed deer to CWD prions by mucosal routes and performed serial necropsies to assess PrPCWD tissue distribution by real-time quaking-induced conversion (RT-QuIC) and tyramide signal amplification immunohistochemistry (TSA-IHC). Although PrPCWD was not detected by either method in the initial days (1 and 3) postexposure, we observed PrPCWD seeding activity and follicular immunoreactivity in oropharyngeal lymphoid tissues at 1 and 2 months postexposure (MPE). At 3 MPE, PrPCWD replication had expanded to all systemic lymphoid tissues. By 4 MPE, the PrPCWD burden in all lymphoid tissues had increased and approached levels observed in terminal disease, yet there was no evidence of nervous system invasion. These results indicate the first site of CWD prion entry is in the oropharynx, and the initial phase of prion amplification occurs in the oropharyngeal lymphoid tissues followed by rapid dissemination to systemic lymphoid tissues. This lymphoid replication phase appears to precede neuroinvasion. IMPORTANCE Chronic wasting disease (CWD) is a universally fatal transmissible spongiform encephalopathy affecting cervids, and natural infection occurs through oral and nasal mucosal exposure to infectious prions. Terminal disease is characterized by PrPCWD accumulation in the brain and lymphoid tissues of affected animals. However, the initial sites of prion

Role of GPER1, EGFR and CXCR1 in differentiating between malignant follicular thyroid carcinoma and benign follicular thyroid adenoma

PubMed Central

Zhao, Le; Zhu, Xiao-Yun; Jiang, Rong; Xu, Man; Wang, Ni; Chen, George G; Liu, Zhi-Min

2015-01-01

It is extremely difficult to discriminate between follicular thyroid carcinoma (FTC) and follicular thyroid adenoma (FTA) before surgery, because the morphologies of carcinoma cells and adenoma cells obtained by fine needle aspiration biopsy (FNAB) are similar. Molecular markers may be helpful on this issue. The purpose of this study was to assess the role of GPER1, EGFR and CXCR1 in differential diagnosis between FTC and FTA. GPER1, EGFR and CXCR1 mRNA expression levels were examined in 15 FTCs and 10 FTAs using real-time RT-PCR. FTC showed to have significantly increased mRNA levels of the three molecules compared to FTA (P < 0.001 for all the three molecules). GPER1, EGFR and CXCR1 protein expression in 106 FTCs and 128 FTAs were analyzed using immunohistochemistry. The rates of GPER1, EGFR and CXCR1 high expression were 73.6%, 72.6% and 70.8% in FTC and 30.5%, 28.1% and 27.3% in FTA, respectively. Statistical analysis showed that GPER1, EGFR and CXCR1 protein expression were correlated with one another in FTC and concomitant high expression of the three molecules had stronger correlation with the occurrence of FTC than did each alone. The positive predictive values (PPV) for concomitant high expression of the three molecules for discriminating between FTC and FTA were 91.0% for GPER1/EGFR, 93.8% for GPER1/CXCR1, 92.3% for EGFR/CXCR1 and 98.2% for GPER1/EGFR/CXCR1, respectively. These results indicated that the evaluation of GPER1, EGFR and CXCR1 concomitant high expression may be helpful in differential diagnosis between FTC and FTA. PMID:26617848

Cytological features of "noninvasive follicular thyroid neoplasm with papillary-like nuclear features" and their correlation with tumor histology.

PubMed

Maletta, Francesca; Massa, Federica; Torregrossa, Liborio; Duregon, Eleonora; Casadei, Gian Piero; Basolo, Fulvio; Tallini, Giovanni; Volante, Marco; Nikiforov, Yuri E; Papotti, Mauro

2016-08-01

Among thyroid papillary carcinomas (PTCs), the follicular variant is the most common and includes encapsulated forms (EFVPTCs). Noninvasive EFVPTCs have very low risk of recurrence or other adverse events and have been recently proposed to be designated as noninvasive follicular thyroid neoplasm with papillary-like nuclear features or NIFTP, thus eliminating the term carcinoma. This proposal is expected to significantly impact the risk of malignancy associated with the currently used diagnostic categories of thyroid cytology. In this study, we analyzed the fine needle aspiration biopsy (FNAB) cytology features of 96 histologically proven NIFTPs and determined how the main nuclear features of NIFTP correlate between cytological and histological samples. Blind review of FNAB cytology from NIFTP nodules yielded the diagnosis of "follicular neoplasm" (Bethesda category IV) in 56% of cases, "suspicious for malignancy" (category V) in 27%, "atypia of undetermined significance/follicular lesion of undetermined significance" (category III) in 15%, and "malignant" (category VI) in 2%. We found good correlation (κ=0.62) of nuclear features between histological and cytological specimens. NIFTP nuclear features (size, irregularities of contours, and chromatin clearing) were significantly different from those of benign nodules but not from those of invasive EFVPTC. Our data indicate that most of the NIFTP nodules yield an indeterminate cytological diagnosis in FNAB cytology and nuclear features found in cytology samples are reproducibly identified in corresponding histology samples. Because of the overlapping nuclear features with invasive EFVPTC, NIFTP cannot be reliably diagnosed preoperatively but should be listed in differential diagnosis of all indeterminate categories of thyroid cytology. Copyright © 2016 Elsevier Inc. All rights reserved.

Germinal center reentries of BCL2-overexpressing B cells drive follicular lymphoma progression

PubMed Central

Sungalee, Stéphanie; Mamessier, Emilie; Morgado, Ester; Grégoire, Emilie; Brohawn, Philip Z.; Morehouse, Christopher A.; Jouve, Nathalie; Monvoisin, Céline; Menard, Cédric; Debroas, Guilhaume; Faroudi, Mustapha; Mechin, Violaine; Navarro, Jean-Marc; Drevet, Charlotte; Eberle, Franziska C.; Chasson, Lionel; Baudimont, Fannie; Mancini, Stéphane J.; Tellier, Julie; Picquenot, Jean-Michel; Kelly, Rachel; Vineis, Paolo; Ruminy, Philippe; Chetaille, Bruno; Jaffe, Elaine S.; Schiff, Claudine; Hardwigsen, Jean; Tice, David A.; Higgs, Brandon W.; Tarte, Karin; Nadel, Bertrand; Roulland, Sandrine

2014-01-01

It has recently been demonstrated that memory B cells can reenter and reengage germinal center (GC) reactions, opening the possibility that multi-hit lymphomagenesis gradually occurs throughout life during successive immunological challenges. Here, we investigated this scenario in follicular lymphoma (FL), an indolent GC-derived malignancy. We developed a mouse model that recapitulates the FL hallmark t(14;18) translocation, which results in constitutive activation of antiapoptotic protein B cell lymphoma 2 (BCL2) in a subset of B cells, and applied a combination of molecular and immunofluorescence approaches to track normal and t(14;18)+ memory B cells in human and BCL2-overexpressing B cells in murine lymphoid tissues. BCL2-overexpressing B cells required multiple GC transits before acquiring FL-associated developmental arrest and presenting as GC B cells with constitutive activation–induced cytidine deaminase (AID) mutator activity. Moreover, multiple reentries into the GC were necessary for the progression to advanced precursor stages of FL. Together, our results demonstrate that protracted subversion of immune dynamics contributes to early dissemination and progression of t(14;18)+ precursors and shapes the systemic presentation of FL patients. PMID:25384217

The follicular hormonal profile in low-responder patients undergoing unstimulated cycles: Is it hypoandrogenic?

PubMed

de los Santos, M J; García-Laez, V; Beltrán, D; Labarta, E; Zuzuarregui, Jose Luis; Alamá, P; Gámiz, P; Crespo, J; Bosch, E; Pellicer, A

2013-01-01

What is the final hormonal milieu of pre-ovulatory follicles of low-responder (LR) patients undergoing unstimulated cycles? Neither androgen secretion nor LH was impaired in pre-ovulatory follicles of LR women. Therapies currently used to improve ovarian response in LR women have an impact on the final hormonal follicular milieu, and these changes are believed to be partially responsible for determining the success rate in these women. Surprisingly, as far as we know, there is no report of the final hormonal profile of LR women undergoing unstimulated cycles or evidence that follicular androgen secretion in LR women is impaired. A prospective case-control study including 94 women, 36 normal controls and 58 LR patients (19 Young ≤ 35 years LR and 39 Aged >35 years LR) from 2009 to 2011. Fifty-eight LR women were divided into two groups: Young LR (age ≤ 35; n = 19) and Aged LR (ALR; age >35; n = 39). The control group (group C) comprised 36 egg donors undergoing an unstimulated cycle in our IVF unit. Serum and follicular fluid hormonal concentrations for estradiol (E₂), progesterone, testosterone and androstendione were measured. The spindle parameters of metaphase II oocytes generated from these groups were also analysed. Pre-ovulatory follicles from LR patients had similar androgenic and LH concentrations to those observed in the control group. However, higher intrafollicular concentrations of FSH and progesterone were observed in ALR. Moreover, no differences were found for the spindle evaluation of oocytes between groups by the Oosight technology. The controls were younger and had a lower BMI than the LR women. The sample size available restricted statistical power. This study suggests that the problem with LR women is not the final pre-ovulatory follicular androgen concentration since this is similar to normal responders, but in the ability to respond to controlled ovarian stimulation protocols. Therefore, efforts should be focused on long

The Science and Art of Eyebrow Transplantation by Follicular Unit Extraction

PubMed Central

Gupta, Jyoti; Kumar, Amrendra; Chouhan, Kavish; Ariganesh, C; Nandal, Vinay

2017-01-01

Eyebrows constitute a very important and prominent feature of the face. With growing information, eyebrow transplant has become a popular procedure. However, though it is a small area it requires a lot of precision and knowledge regarding anatomy, designing of brows, extraction and implantation technique. This article gives a comprehensive view regarding eyebrow transplant with special emphasis on follicular unit extraction technique, which has become the most popular technique. PMID:28852290

An Atypical Metastasis of Follicular-Type Adenocarcinoma of the Thyroid Gland to Thumb

PubMed Central

Huri, Gazi

2011-01-01

Bone metastasis in the hand is rare. The etiology of metastatic hand cancers is different from other bones. Bronchogenic carcinoma is the most common primary tumor metastasis to hand. In this paper a rare case of thumb metastasis from “follicular-type carcinoma” of the thyroid is presented. PMID:23198224

Comparison of chemical-activated luciferase gene expression bioassay and gas chromatography for PCB determination in human serum and follicular fluid.

PubMed Central

Pauwels, A; Cenijn, P H; Schepens, P J; Brouwer, A

2000-01-01

We assessed exposure to dioxin-like compounds using chemical and bioassay analysis in different matrices in a female population. A total of 106 serum and 9 follicular fluid samples were collected from infertile women attending Centers for Reproductive Medicine in Belgium from 1996 to 1998. Major polychlorinated biphenyl (PCB) congeners were quantified by chemical analysis using gas chromatography with electron-capture detection, and the chemical-activated luciferase gene expression (CALUX) bioassay was used to determine the total dioxin-like toxic equivalence (TEQ) of mixtures of polyhalogenated aromatic hydrocarbons present in body fluids, such as serum and follicular fluid. To the best of our knowledge, this is the first investigation to determine TEQ values by the CALUX bioassay in follicular fluid. The TEQ levels in both matrices are well correlated (r = 0.83, p = 0.02). As the chemical and bioassay analysis executed in this study do not cover the same span of polyhalogenated aromatic hydrocarbons, we did not expect totally correlated results. Moreover, the sample workup and quantification of the analytes differed completely. Nonetheless, the TEQ values in human extracts correlated well with the sum of four major PCB congeners chemically determined in both serum and follicular fluid. These results indicate that the CALUX bioassay may serve as a simple, relatively inexpensive prescreening tool for exposure assessment in epidemiologic surveys. Images Figure 1 Figure 2 PMID:10856030

Intertriginous mycosis fungoides: a distinct presentation of cutaneous T-cell lymphoma that may be caused by malignant follicular helper T cells.

PubMed

Gammon, Bryan; Guitart, Joan

2012-09-01

Follicular helper T cells are a subset of helper T cells that facilitate B-cell recruitment and maturation. Rare cases of cutaneous T-cell lymphoma manifesting as de novo tumor lesions in intertriginous skin contain an infiltrate rich in B cells. These cases may represent malignant counterparts of skin-homing follicular helper T cells. Two men and 1 woman (age range, 35-58 years) were seen with predominantly intertriginous tumor-stage cutaneous T-cell lymphoma lesions characterized by the absence of epidermotropism and the presence of a mixed infiltrate rich in B cells. Two of the patients died of the disease less than 3 years from the initial diagnosis. The surviving patient has aggressive disease and underwent hematopoietic stem cell transplantation. Two of the patients had a prominent CXCL13+, Bcl6/CD3+, and programmed death protein 1-positive follicular helper T-cell population. The intertriginous tumor variant of cutaneous T-cell lymphoma is heterogeneous but may be associated in some cases with a follicular helper T-cell immunophenotype. These patients may follow an aggressive clinical course. Tumor progression in sanctuary sites on patients receiving phototherapy may manifest as a similar clinical phenotype. Further characterization of the disease process is needed to confirm this observation.

78 FR 5816 - Guidance for Industry on Clinical Pharmacogenomics: Premarket Evaluation in Early-Phase Clinical...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-28

.... The guidance provides recommendations on when and how genomic principles should be considered and... recommendations on when and how genomic principles should be considered and applied in early-phase clinical... the larger, later adequate, and well-controlled trials (phase 3) that are needed to support marketing...

Geoeffectiveness during the early phase of Solar Cycle 24

NASA Astrophysics Data System (ADS)

Pande, Bimal

Geoeffectiveness during the early phase of Solar Cycle 24 \\underline{} Abstract\\underline{} It is very important and interesting to understand the solar eruptions because it produces the geoeffectiveness in our Earth environment. In the rise phase of the solar cycle, geoeffective events are less frequent, thus this provide us better opportunity to study these events including the detection of their source regions. Keeping this in mind, we have analysed the data of rise phase of current solar cycle 24 ( 2009-2012). During above time period, we have selected 59 geoeffective events having Disturbance Storm Time (Dst) index < -50 nT. Based on the Dst index, we divided the events into two categories i.e. moderate (< -50 nT > -100 nT ) and intense ( <-100 nT). To locate the solar source regions of geoeffective and SEPs associated events, we have used available images, movies and Solar Geophysical data (SGD) list: for example movies from SOHO/EIT, images and movies from the Solar Dynamic Observatory (SDO). In this study, we will discuss and compare the different properties of associated CMEs, flares and their relation with geoeffectiveness.

Effects of gonadotropin-releasing hormone agonist/recombinant follicle-stimulating hormone versus gonadotropin-releasing hormone antagonist/recombinant follicle-stimulating hormone on follicular fluid levels of adhesion molecules during in vitro fertilization.

PubMed

Fornaro, Felice; Cobellis, Luigi; Mele, Daniela; Tassou, Argyrò; Badolati, Barbara; Sorrentino, Simona; De Lucia, Domenico; Colacurci, Nicola

2007-01-01

To compare the effects of GnRH-agonist/recombinant rFSH versus GnRH-antagonist/recombinant FSH stimulation on follicular fluid levels of soluble intercellular adhesion molecule (sICAM)-1 and vascular cell adhesion molecule-1 (sVCAM-1) during in vitro fertilization (IVF). Prospective, randomized study. University hospital. Seventy-three women underwent IVF. GnRH-agonist/rFSH or GnRH-antagonist/rFSH administration and collection of follicular fluid from 3 small (11-14 mm in diameter) and 3 large (18-21 mm in diameter) follicles on the day of oocyte retrieval. Follicular fluid levels of sICAM-1 and sVCAM-1 and intrafollicular estradiol and progesterone were also measured. Women who underwent GnRH-agonist/rFSH showed higher concentrations of sICAM-1 in both small and large follicles were compared with patients who received GnRH-antagonist/rFSH treatment; follicular fluid levels of sVCAM-1 were similar between the 2 stimulation protocols. Content of sICAM-1 in small and large follicles positively correlated with the number of follicles of > or =15 mm and the number of oocytes that were retrieved in both study groups. Concentrations of follicular fluid sVCAM-1 and progesterone were higher in large than in small follicles and were correlated positively to each other in both follicular classes. In IVF, GnRH-agonist/rFSH is associated with higher follicular fluid levels of sICAM-1 compared with GnRH-antagonist/rFSH regimen. Intrafollicular sICAM-1 content may predict ovarian response, and sVCAM-1 appears as an indicator of the degree of follicular luteinization.

Intact follicular maturation and defective luteal function in mice deficient for cyclin- dependent kinase-4.

PubMed

Moons, David S; Jirawatnotai, Siwanon; Tsutsui, Tateki; Franks, Roberta; Parlow, A F; Hales, Dale B; Gibori, Geula; Fazleabas, Asgerally T; Kiyokawa, Hiroaki

2002-02-01

Cell cycle progression of granulosa cells is critical for ovarian function, especially follicular maturation. During follicular maturation, FSH induces cyclin D2, which promotes G1 progression by activating cyclin-dependent kinase-4 (Cdk4). Because cyclin D2-deficient mice exhibit a block in follicular growth, cyclin D2/Cdk4 has been hypothesized to be required for FSH-dependent proliferation of granulosa cells. Here we investigate ovarian function in Cdk4-knockout mice we recently generated. Cdk4(-/-) females were sterile, but the morphology of their ovaries appeared normal before sexual maturation. The number of preovulatory follicles and the ovulation efficiency were modestly reduced in gonadotropin-treated Cdk4(-/-) mice. However, unlike cyclin D2-deficient mice, Cdk4(-/-) mice showed no obvious defect in FSH-induced proliferation of granulosa cells. Cdk4(-/-) ovaries displayed normal preovulatory expression of aromatase, PR, and cyclooxygenase-2. Postovulatory progesterone secretion was markedly impaired in Cdk4(-/-) mice, although granulosa cells initiated luteinization with induction of p450 side-chain cleavage cytochrome and p27(Kip1). Progesterone treatment rescued implantation and restored fertility in Cdk4(-/-) mice. Serum PRL levels after mating were significantly reduced in Cdk4(-/-) mice, suggesting the involvement of perturbed PRL regulation in luteal failure. Thus, Cdk4 is critical for luteal function, and some redundant protein(s) can compensate for the absence of Cdk4 in proliferation of granulosa cells.

Isolated orbital mass as the primary presentation of a triple-hit lymphoma transformed from a systemic follicular lymphoma.

PubMed

Zhou, Xiao Yi; Lu, Xinyan; Raparia, Kirtee; Chen, Yi-Hua

2018-06-01

Triple-hit lymphoma is a highly aggressive B-cell lymphoma. We report a case of triple-hit lymphoma transformed from systemic follicular lymphoma (FL) after 9-year remission and presented primarily as an isolated orbital mass without systemic symptoms or lymphadenopathy. A 58-year-old female presented with intermittent vertical binocular diplopia, left upper eyelid swelling and pain and was found to have a 2.9 cm orbital mass. Histological section revealed a CD10-positive large B-cell lymphoma, consistent with transformation of FL. Fluorescent in situ hybridization (FISH) analysis demonstrated rearrangements involving C-MYC, BCL-2 and BCL-6 genes, indicating a high grade, triple-hit lymphoma. Triple-hit lymphoma transformed from a low-grade lymphoma may initially present as an isolated orbital mass without systemic evidence of transformation. Early recognition of double or triple-hit lymphomas is important since these patients require aggressive chemotherapy.

Follicular dermal papilla structures by organization of epithelial and mesenchymal cells in interfacial polyelectrolyte complex fibers.

PubMed

Lim, Tze Chiun; Leong, Meng Fatt; Lu, Hongfang; Du, Chan; Gao, Shujun; Wan, Andrew C A; Ying, Jackie Y

2013-09-01

The hair follicle is a regenerating organ that produces a new hair shaft during each growth cycle. Development and cycling of the hair follicle is governed by interactions between the epithelial and mesenchymal components. Therefore, development of an engineered 3D hair follicle would be useful for studying these interactions to identify strategies for treatment of hair loss. We have developed a technique suitable for assembly of different cell types in close proximity in fibrous hydrogel scaffolds with resolutions of ∼50 μm. By assembly of dermal papilla (DP) and keratinocytes, structures similar to the native hair bulb arrangement are formed. Gene expression of these constructs showed up-regulation of molecules involved in epithelial-mesenchymal interactions of the hair follicle. Implantation of the follicular structures in SCID mice led to the formation of hair follicle-like structures, thus demonstrating their hair inductive ability. The transparency of the fiber matrix and the small dimensions of the follicular structures allowed the direct quantitation of DP cell proliferation by confocal microscopy, clearly illustrating the promoting or inhibitory effects of hair growth regulating agents. Collectively, our results suggested a promising application of these 3D engineered follicular structures for in vitro screening and testing of drugs for hair growth therapy. Copyright © 2013 Elsevier Ltd. All rights reserved.

Effect of stratum corneum heterogeneity, anisotropy, asymmetry and follicular pathway on transdermal penetration.

PubMed

Barbero, Ana M; Frasch, H Frederick

2017-08-28

The impact of the complex structure of the stratum corneum on transdermal penetration is not yet fully described by existing models. A quantitative and thorough study of skin permeation is essential for chemical exposure assessment and transdermal delivery of drugs. The objective of this study is to analyze the effects of heterogeneity, anisotropy, asymmetry, follicular diffusion, and location of the main barrier of diffusion on percutaneous permeation. In the current study, the solution of the transient diffusion through a two-dimensional-anisotropic brick-and-mortar geometry of the stratum corneum is obtained using the commercial finite element program COMSOL Multiphysics. First, analytical solutions of an equivalent multilayer geometry are used to determine whether the lipids or corneocytes constitute the main permeation barrier. Also these analytical solutions are applied for validations of the finite element solutions. Three illustrative compounds are analyzed in these sections: diethyl phthalate, caffeine and nicotine. Then, asymmetry with depth and follicular diffusion are studied using caffeine as an illustrative compound. The following findings are drawn from this study: the main permeation barrier is located in the lipid layers; the flux and lag time of diffusion through a brick-and-mortar geometry are almost identical to the values corresponding to a multilayer geometry; the flux and lag time are affected when the lipid transbilayer diffusivity or the partition coefficients vary with depth, but are not affected by depth-dependent corneocyte diffusivity; and the follicular contribution has significance for low transbilayer lipid diffusivity, especially when flux between the follicle and the surrounding stratum corneum is involved. This study demonstrates that the diffusion is primarily transcellular and the main barrier is located in the lipid layers. Published by Elsevier B.V.

[EEG alpha indices in dependence on the menstrual cycle phase and salivary progesterone].

PubMed

Bazanova, O M; Kondratenko, A V; Kuz'minova, O I; Muravleva, K B; Petrova, S E

2014-01-01

The effects of the neurohumoral status on the EEG alpha - activity indices were studied in a within-subject design with 78 women aged 18-27 years during 1-2 menstrual cycle. Psychometric and EEG indices of alpha waves basal body temperature, saliva progesterone and cortisol level were monitored every 2-3 days. Menstrual and follicular recording sessions occurred before the ovulatory temperature rise, luteal recording session--after increasing progesterone level more than 20% respect to previous day and premenstrual sessions after decreasing progesterone level more that 20% respect to previous day. The design consisted of rest and task periods EEG, EMG and ECG recordings. Half the subjects began during their menstrual phase and half began during their luteal phase. All 5 phases were compared for differences between psychometric features EEG alpha activity, EMG and ECG baseline resting levels, as well as for reactivity to cognitive task. The results showed menstrual phase differences in all psychometric and alpha EEG indices. The cognitive fluency, alpha peak frequency, alpha band width, power in alpha-2 frequency range are maximal at luteal, alpha visual activation and reactivity to cognitive task performance--at follicular phase. The hypothesis that the EEG alpha activity depends on the hormonal status supported by the positive association salivary progesterone level with the alpha peak frequency, power in the alpha-2 band and negative--with the power of the alpha-1 band. According these results, we conclude that psycho-physiological recording sessions with women might be provided with a glance to phase of menstrual cycle.

Thyroxine to triiodothyronine hyperconversion thyrotoxicosis in patients with large metastases of follicular thyroid carcinoma.

PubMed

Takano, Toru; Miyauchi, Akira; Ito, Yasuhiro; Amino, Nobuyuki

2006-06-01

We experienced two cases of follicular thyroid carcinoma with distant metastases, which showed high levels of free triiodothyronine (T(3)) while free thyroxine (T(4)) levels remained in the low or normal range. In this report, we described the detail of these cases and examined the cause of T(3) thyrotoxicosis. In one of the cases, quantitative measurement of types I and II iodothyronine deiodinase mRNAs was performed using a surgically dissected tissue from the primary tumor and a distant metastasis. In the both tissues, types I and II iodothyronine deiodinase mRNAs were expressed in the same level as in the normal thyroid tissues. These results suggest that T(3) thyrotoxicosis in our patients was caused by hyperconversion of administered levothyroxine to T(3). In the follow-up of patients with distant metastases of follicular carcinoma, not only free T(4), but also free T(3) should be tested to avoid the excessive administration of levothyroxine.

Programmed death-ligand 1 expression by digital image analysis advances thyroid cancer diagnosis among encapsulated follicular lesions.

PubMed

Hsieh, Anne M-Y; Polyakova, Olena; Fu, Guodong; Chazen, Ronald S; MacMillan, Christina; Witterick, Ian J; Ralhan, Ranju; Walfish, Paul G

2018-04-13

Recognition of noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP) that distinguishes them from invasive malignant encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC) can prevent overtreatment of NIFTP patients. We and others have previously reported that programmed death-ligand 1 (PD-L1) is a useful biomarker in thyroid tumors; however, all reports to date have relied on manual scoring that is time consuming as well as subject to individual bias. Consequently, we developed a digital image analysis (DIA) protocol for cytoplasmic and membranous stain quantitation (ThyApp) and evaluated three tumor sampling methods [Systemic Uniform Random Sampling, hotspot nucleus, and hotspot nucleus/3,3'-Diaminobenzidine (DAB)]. A patient cohort of 153 cases consisting of 48 NIFTP, 44 EFVPTC, 26 benign nodules and 35 encapsulated follicular lesions/neoplasms with lymphocytic thyroiditis (LT) was studied. ThyApp quantitation of PD-L1 expression revealed a significant difference between invasive EFVPTC and NIFTP; but none between NIFTP and benign nodules. ThyApp integrated with hotspot nucleus tumor sampling method demonstrated to be most clinically relevant, consumed least processing time, and eliminated interobserver variance. In conclusion, the fully automatic DIA algorithm developed using a histomorphological approach objectively quantitated PD-L1 expression in encapsulated thyroid neoplasms and outperformed manual scoring in reproducibility and higher efficiency.

Basaloid Follicular Hamartoma

PubMed Central

Cooper, Hassie; Hogan, Daniel J.; Miller, Richard; Heaphy, Michael; Spencer, James

2018-01-01

Introduction: Basaloid follicular hamartoma (BFH) is a rare, benign neoplasm of the hair follicle, characterized by multiple brown papules involving the face, scalp, and trunk. It is described by multiple clinical forms, and can present as localized or generalized. Diagnosis is made histologically via biopsy, which is important in order to distinguish BFH from basal cell carcinoma (BCC) or other malignant epithelial neoplasms. Correct diagnosis allows for the avoidance of unnecessary surgeries to remove benign lesions. While benign, lesions can be cosmetically unacceptable. Case Report: A 68-year-old man with a two-year history of brown, homogenous papules on his face presented to discuss treatment options. A physical examination revealed hundreds of dark brown, 1- to 3mm verrucous papules distributed throughout the face. Two punch biopsies revealed histologic features consistent with BFH. Discussion: BFHs classically present with multiple 1- to 2mm tan-to-brown-colored papules distributed on the face, scalp, neck, axilla, trunk, and pubic area. Differential diagnoses can include nevus sebaceous, lichen striatus, linear epidermal nevus, and basal cell nevus. BFH arises from a mutation in the patch gene, the same gene thought to cause nevoid BCC syndrome. Histologic examination of BFH lesions is essential to diagnosis. No standard of care exists for BFH; treatment options remain limited. This patient was treated with three rounds of pulsed dye laser (PDL) therapy and showed marked improvement in the treated areas. The authors propose PDL to be a safe, effective, and novel cosmetic treatment for BFH and potentially other adnexal tumors. PMID:29607000

Molecular imaging with (99m)Tc-MIBI and molecular testing for mutations in differentiating benign from malignant follicular neoplasm: a prospective comparison.

PubMed

Giovanella, L; Campenni, A; Treglia, G; Verburg, F A; Trimboli, P; Ceriani, L; Bongiovanni, M

2016-06-01

To compare mutation analysis of cytology specimens and (99m)Tc-MIBI thyroid scintigraphy for differentiating benign from malignant thyroid nodules in patients with a cytological reading of follicular neoplasm. Patients ≥18 years of age with a solitary hypofunctioning thyroid nodule (≥10 mm), normal thyrotropin and calcitonin levels, and a cytological diagnosis of follicular neoplasm were prospectively enrolled. Mutation analysis and (99m)Tc-MIBI scintigraphy were performed and patients were subsequently operated on to confirm or exclude a malignant lesion. Mutations for KRAS, HRAS and NRAS and for BRAF and translocations of PAX8/PPARγ, RET/PTC1 and RET/PTC3 were investigated. Static thyroid scintigraphic images were acquired 10 and 60 min after intravenous injection of 200 MBq of (99m)Tc-MIBI and visually assessed. Additionally, the MIBI washout index was calculated using a semiquantitative method. In our series, 26 % of nodules with a follicular pattern on cytology were malignant with a prevalence of follicular carcinomas. (99m)Tc-MIBI scintigraphy was found to be significantly more accurate (positive likelihood ratio 4.56 for visual assessment and 12.35 for semiquantitative assessment) than mutation analysis (positive likelihood ratio 1.74). A negative (99m)Tc-MIBI scan reliably excluded malignancy. In patients with a thyroid nodule cytologically diagnosed as a follicular proliferation, semiquantitative analysis of (99m)Tc-MIBI scintigraphy should be the preferred method for differentiating benign from malignant nodules. It is superior to molecular testing for the presence of differentiated thyroid cancer-associated mutations in fine-needle aspiration cytology sample material.

Solitary liver metastasis from follicular variant papillary thyroid carcinoma: A case report and literature review

PubMed Central

Djenic, Brano; Duick, Daniel; Newell, James O.; Demeure, Michael J.

2014-01-01

Introduction Papillary (PTC) and follicular (FTC) thyroid carcinomas, together known as differentiated thyroid carcinomas (DTC), are among the most curable of cancers. Sites of metastases from FTC are usually osseous and those from PTC are in regional nodal basins and the lungs. Visceral metastases are rare and when they do occur, they tend do so in multiple sites. We present the case of a patient with a follicular variant of PTC and a solitary metastasis to the liver then review the relevant literature. Presentation of case An otherwise healthy 68-year-old woman was diagnosed with follicular variant papillary thyroid cancer in 2003 and subsequently underwent thyroidectomy. The patient’s endocrinologist conducted surveillance of her thyroid cancer. In 2012, due to rise in thyroglobulin, a whole body radioiodine scan was obtained which revealed an iodine-avid left liver lobe mass. Three cycles of radioiodine ablation therapy were unsuccessful and eventually the patient was referred for surgical resection. Metastatic evaluation including a PET scan was negative with the exception of an isolated enhancing 4 cm mass in segment 4B of the liver. Anatomic segmental resection of liver was performed without complications. Intraoperative ultrasonography was used to guide resection of the liver mass. Pathology reports confirmed metastatic follicular variant of PTC. Surgical margins were free of tumor. Patient was discharged home and is doing well one year after surgery. The latest thyroglobulin level was undetectable. Discussion Post-operative surveillance by PCP, endocrinologist or surgeon for patients with thyroid carcinoma should be performed routinely. If identified, a solitary liver metastasis from primary thyroid carcinoma should be considered for surgical resection. Due to sparse data available in literature, collecting more data to establish algorithms for treatment of such rare metastatic cancers may be able to aid physicians to achieve better outcomes. Conclusion

Decreased endometrial vascularity and receptivity in unexplained recurrent miscarriage patients during midluteal and early pregnancy phases.

PubMed

Tan, Shu-Yin; Hang, Fu; Purvarshi, Gowreesunkur; Li, Min-Qing; Meng, Da-Hua; Huang, Ling-Ling

2015-10-01

To evaluate the predictive value of three-dimensional (3D)-power Doppler sonography on recurrent miscarriage. The study patients were divided into a recurrent miscarriage group (30 cases) and a normal pregnancy group (21 cases). Measurement of endometrial thickness was performed using two-dimensional transvaginal ultrasound in the midluteal phase. The endometrial volume, vascularization index (VI), flow index (FI), and vascularization-flow index (VFI) in midluteal and placenta volume, as well as the VI, FI, and VFI of early pregnancy were measured using Virtual Organ Computer-aided Analysis of 3D-power Doppler ultrasound. Endometrial thickness, endometrial volume, endometrial vascular data, VI, FI, and VFI of the midluteal phase were lower in the recurrent miscarriage group compared with the normal pregnancy group (p < 0.05). Placental volume, VI, and VFI during early pregnancy were lower in the miscarriage group compared with the normal pregnancy group (p < 0.05). There was no significant change in FI between the recurrent miscarriage and control groups during early pregnancy (p > 0.05). The predictive accuracy of endometrial thickness, endometrial volume, VI, FI, and VFI in the midluteal phase, and placenta volume, VI, FI, and VFI in early pregnancy as measured by the receiver operating characteristic curve to predict miscarriage before 12 gestational weeks in participants was 0.681, 0.876, 0.770, 0.720, 0.879, 0.771, 0.907, 0.592, respectively. The 3D-power Doppler ultrasound is a more comprehensive and sensitive method for evaluating endometrial receptivity. Endometrial volume, VI, FI, and VFI in the midluteal phase, as well as VI in early pregnancy, can be considered as predictive factors for recurrent miscarriage. Copyright © 2015. Published by Elsevier B.V.

Sweet taste threshold for sucrose inversely correlates with depression symptoms in female college students in the luteal phase.

PubMed

Nagai, Masanori; Matsumoto, Sayaka; Endo, Junko; Sakamoto, Reiko; Wada, Maki

2015-03-15

Influences of depression symptoms on the sweet taste threshold were investigated in healthy college students (30 males and 40 females). Depression symptoms were scored by SDS (Self-Rating Depression Scale), and anxiety levels by STAI (State- and Trait-Anxiety Inventory). Recognition thresholds for sucrose were determined. In female students, the menstrual phase on the day of the experiment was self-reported. Depression symptoms, anxiety levels, and the recognition threshold for sucrose were not different among the 3 groups, i.e. males, females in the follicular phase, and females in the luteal phase. Depression symptoms were positively correlated with state and trait anxiety in all groups. The sweet taste threshold was inversely correlated with depression symptoms (r=-0.472, p=0.031) and trait anxiety (r=-0.506, p=0.019) in females in the luteal phase. In males as well as females in the follicular phase, however, no correlation between sweet taste threshold and depression was found. The results show that the recognition threshold for sucrose reduces with increased depression in females with a higher anxiety trait, but only in the luteal phase. It is hypothesized that brain regions, which spatially overlap and are responsible for both aversive emotions and gustatory processing, are susceptible to periodic changes in gonadal hormones due to the menstrual cycle. Copyright © 2015 Elsevier Inc. All rights reserved.

Oxidative stress in follicular units during hair transplantation surgery.

PubMed

Crisóstomo, Márcio Rocha; Guimarães, Sérgio Botelho; de Vasconcelos, Paulo Roberto Leitão; Crisóstomo, Marília Gabriela Rocha; Benevides, André Nunes

2011-02-01

Hair transplantation surgery currently is a well-established procedure in plastic surgery. It consists of harvesting a strip of scalp from the back of the head, then obtaining grafts called follicular units (FUs) from this strip and implanting them in the bald area. The FUs undergo oxidative stress during cold ischemia and after their implantation. Surgery was performed for 18 patients between April and July 2008. Follicular units were preserved in solutions containing different growth-stimulating hormone (GSH) concentrations (5, 10, and 20 mmol). Saline solution was used as a control condition. Spectrophotometry was used to measure the thiobarbituric acid-reactive substance (TBARS) and GSH concentrations before ischemia (control group) in the FUs preserved in the four proposed solutions, then after 30 min of cold ischemia and 30 min after grafting. The data obtained were submitted to analysis of variance, t test, and linear regression analysis. The TBARS (μmol of malondialdehyde [MDA]/g) and GSH (μmol/g) concentrations were not significantly different between the four solutions in either the ischemia or grafting group. The GSH concentration did not differ significantly between the control (59.801 ± 30.639 μmol/g) and ischemia (56.284 ± 28.404 μmol/g) groups. The GSH concentrations were significantly greater (p < 0.05) in the postgrafting group (63.815 ± 28.404 μmol/g) than in the group subjected to ischemia. Increasing the GSH concentrations used in FU preservation solutions does not reduce the oxidative effects of cold ischemia and reperfusion injury during hair transplantation surgery.

Association of the Helicobacter pylori cagA, vacA, and iceA genotypes with chronic follicular gastritis in a Colombian population at high risk for gastric cancer.

PubMed

Carlosama-Rosero, Y H; Bolaños-Bravo, H; Sierra-Tórres, C H; Rosero, E A

2018-05-16

Follicular gastritis is associated with Helicobacter pylori infection, but little is known of its relation to bacterial genotypes. Our aim was to establish the relation between follicular gastritis and different H. pylori strains. An analytic case-control study was conducted that included 36 patients with follicular gastritis (cases) and 83 with nonatrophic gastritis (controls). The sociodemographic information was obtained through a questionnaire. Biopsies were evaluated according to the Sydney System and the Wotherspoon scoring system. Helicobacter pylori genotyping was performed using the polymerase chain reaction technique. The quantitative variables were presented as mean and standard deviation and the qualitative variables as proportions and absolute frequency. The effect of each variable on outcome (follicular gastritis) was evaluated through the odds ratio and its 95% confidence interval. Statistical significance was set at a P<.05. Follicular gastritis was associated with Helicobacter pylori infection (OR: 13.41, CI: 1.7-103, P=.01). The CagA+ genotype was present in 56.5% of the cases and 58% of the controls. The cytotoxic VacAs1m1strain was present in 82% of the isolates in both groups. IceA1 frequency was 34.8% in the cases and 26% in the controls and the difference was not statistically significant. The population studied had elevated frequencies of cytotoxic Helicobacter pylori strains and the iceA1 genotype was more frequent in follicular gastritis. Copyright © 2018 Asociación Mexicana de Gastroenterología. Publicado por Masson Doyma México S.A. All rights reserved.

GLIS3 is indispensable for TSH/TSHR-dependent thyroid hormone biosynthesis and follicular cell proliferation

PubMed Central

Kang, Hong Soon; Kumar, Dhirendra; Liao, Grace; Lichti-Kaiser, Kristin; Gerrish, Kevin; Liao, Xiao-Hui; Refetoff, Samuel; Jothi, Raja; Jetten, Anton M.

2017-01-01

Deficiency in Krüppel-like zinc finger transcription factor GLI-similar 3 (GLIS3) in humans is associated with the development of congenital hypothyroidism. However, the functions of GLIS3 in the thyroid gland and the mechanism by which GLIS3 dysfunction causes hypothyroidism are unknown. In the current study, we demonstrate that GLIS3 acts downstream of thyroid-stimulating hormone (TSH) and TSH receptor (TSHR) and is indispensable for TSH/TSHR-mediated proliferation of thyroid follicular cells and biosynthesis of thyroid hormone. Using ChIP-Seq and promoter analysis, we demonstrate that GLIS3 is critical for the transcriptional activation of several genes required for thyroid hormone biosynthesis, including the iodide transporters Nis and Pds, both of which showed enhanced GLIS3 binding at their promoters. The repression of cell proliferation of GLIS3-deficient thyroid follicular cells was due to the inhibition of TSH-mediated activation of the mTOR complex 1/ribosomal protein S6 (mTORC1/RPS6) pathway as well as the reduced expression of several cell division–related genes regulated directly by GLIS3. Consequently, GLIS3 deficiency in a murine model prevented the development of goiter as well as the induction of inflammatory and fibrotic genes during chronic elevation of circulating TSH. Our study identifies GLIS3 as a key regulator of TSH/TSHR-mediated thyroid hormone biosynthesis and proliferation of thyroid follicular cells and uncovers a mechanism by which GLIS3 deficiency causes neonatal hypothyroidism and prevents goiter development. PMID:29083325

Sex and menstrual cycle phase at encoding influence emotional memory for gist and detail

PubMed Central

Nielsen, Shawn E.; Ahmed, Imran; Cahill, Larry

2013-01-01

Sex influences on emotional memory have received increasing interest over the past decade. However, only a subset of this previous work explored the influence of sex on memory for central information (gist) and peripheral detail in emotional versus neutral contexts. Here we examined the influence of sex and menstrual cycle phase at encoding on memory for either an emotional or neutral story, specifically with respect to the retention of gist and peripheral detail. Healthy naturally cycling women and men viewed a brief, narrated, three-phase story containing neutral or emotionally arousing elements. One week later, participants received a surprise free recall test for story elements. The results indicate that naturally cycling women in the luteal (high hormone) phase of the menstrual cycle at encoding show enhanced memory for peripheral details, but not gist, when in the emotional compared with neutral stories (p<.05). In contrast, naturally cycling women in the follicular (low hormone) phase of the menstrual cycle at encoding did not show enhanced memory for gist or peripheral details in the emotional compared with neutral stories. Men show enhanced memory for gist, but not peripheral details, in the emotional versus neutral stories (p<.05). In addition, these sex influences on memory cannot be attributed to differences in attention or arousal; luteal women, follicular women, and men performed similarly on measures of attention (fixation time percentage) and arousal (pupil diameter changes) during the most arousing phase of the emotional story. These findings suggest that sex and menstrual cycle phase at encoding influence long term memory for different types of emotional information. PMID:23891713

Effects of temperature on early-phase transmission of Yersina pestis by the flea, Xenopsylla cheopis.

PubMed

Schotthoefer, Anna M; Bearden, Scott W; Vetter, Sara M; Holmes, Jennifer; Montenieri, John A; Graham, Christine B; Woods, Michael E; Eisen, Rebecca J; Gage, Kenneth L

2011-03-01

Sharp declines in human and animal cases of plague, caused by the bacterium Yersinia pestis (Yersin), have been observed when outbreaks coincide with hot weather. Failure of biofilm production, or blockage, to occur in the flea, as temperatures reach 30 degrees C has been suggested as an explanation for these declines. Recent work demonstrating efficient flea transmission during the first few days after fleas have taken an infectious blood meal, in the absence of blockage (e.g., early-phase transmission), however, has called this hypothesis into question. To explore the potential effects of temperature on early-phase transmission, we infected colony-reared Xenopsylla cheopis (Rothchild) fleas with a wild-type strain of plague bacteria using an artificial feeding system, and held groups of fleas at 10, 23, 27, and 30 degrees C. Naive Swiss Webster mice were exposed to fleas from each of these temperatures on days 1-4 postinfection, and monitored for signs of infection for 21 d. Temperature did not significantly influence the rates of transmission observed for fleas held at 23, 27, and 30 degrees C. Estimated per flea transmission efficiencies for these higher temperatures ranged from 2.32 to 4.96% (95% confidence interval [CI]: 0.96-8.74). In contrast, no transmission was observed in mice challenged by fleas held at 10 degrees C (per flea transmission efficiency estimates, 0-1.68%). These results suggest that declines in human and animal cases during hot weather are not related to changes in the abilities of X. cheopis fleas to transmit Y. pestis infections during the early-phase period. By contrast, transmission may be delayed or inhibited at low temperatures, indicating that epizootic spread of Y. pestis by X. cheopis via early-phase transmission is unlikely during colder periods of the year.

Early phase drugs and biologicals clinical trials on worldwide leading causes of death: a descriptive analysis.

PubMed

Dal-Ré, Rafael

2011-06-01

To describe the global effort targeting the major causes of mortality in terms of "open" early phase clinical trials with drugs and biologicals. Sixteen of the 20 leading causes of death were chosen; 9 of these were also amongst the top 10 causes of death in low-income countries. Studies were identified from the ClinicalTrials.gov database and included phase 1 and/or 2 "interventional" "open" trials, i.e. those recruiting or about to start recruitment. Trials were considered in terms of sponsorship [industry, universities and other organisations (UNO), and US federal agencies (NIH included)], genders and age groups included, and whether they were conducted with drugs and/or biologicals. The search was performed in March 2010. A total of 2,298 (824 phase 1; 1,474 phase 2) trials were retrieved. Of these, 67% were on trachea, bronchus, and lung cancers (25%); diabetes mellitus (15%); colon and rectum cancers (14%); and HIV/AIDS (12%). In contrast, only 4% were trials on diarrhoeal disease, nephrosis and nephritis, liver cirrhosis, and prematurity and low birth weight. UNO were the first source of funding. Fifty-two percent of phase 1 non-cancer trials were on healthy volunteers. Twenty-nine percent of all trials were co-funded. There were 4.6 times as many drug trials as those with biologicals. Only 7% were conducted with a combination of drugs and biologicals, the majority (78%) on cancers. Discrimination in terms of gender or age group was not observed. Four of the 16 diseases considered represented 2/3 of early phase trials. Cancers were a top priority for all sponsors. Increasing attention should be given to conditions with current and projected global high mortality rates that had few "open" early phase trials.

Ovarian steroids, oxytocin, and tumor necrosis factor modulate equine oviduct function.

PubMed

Pinto-Bravo, P; Galvão, A; Rebordão, M R; Amaral, A; Ramilo, D; Silva, E; Szóstek-Mioduchowska, A; Alexandre-Pires, G; Roberto da Costa, R; Skarzynski, D J; Ferreira-Dias, G

2017-10-01

The oviduct plays important roles in the early reproductive process. The aim of this study was to evaluate gene transcription and protein expression of progesterone receptor (PGR), estrogen receptors 1 (ESR1) and 2 (ESR2); oxytocin receptor (OXTR); prostaglandin F2α synthase (AKR1C3), and prostaglandin E2 synthase (Ptges) in mare oviduct in different estrous cycle stages. Estradiol (E 2 ), progesterone (P 4 ), oxytocin (OXT), and tumor necrosis factor α (TNF) effect on in vitro PGE 2 and prostaglandin F2α (PGF 2α ) secretion by equine oviduct explants or by oviductal epithelial cells (OECs) were also assessed. During the breeding season, oviduct tissue was obtained post mortem from cyclic mares. Protein of ESR1, ESR2, PGR, AKR1C3, and Ptges was present in OECs, whereas OXTR was shown in oviduct stroma. In follicular phase, protein expression of ESR1, ESR2, PGR, and OXTR increased in oviduct explants (P < 0.05), whereas no estrous cycle effect was noted for AKR1C3 or Ptges. In follicular phase, mRNA transcription was upregulated for Pgr but downregulated for Oxtr, Ptges, and Akr1c3 (P < 0.05). Nevertheless, Esr1 and Esr2 mRNA levels did not change with the estrous cycle. In the ampulla, Esr1, Esr2, and Oxtr mRNA transcription increased, but not for Pgr or Ptges. In contrast, Akr1c3 mRNA level was upregulated in the infundibulum (P < 0.05). In follicular phase, E 2 , P 4 , and OXT downregulated PGE 2 production by OEC (P < 0.05), but no difference was observed in mid-luteal phase. Explants production of PGE 2 rose when treated with OXT in follicular phase; with TNF or OXT in early luteal phase; or with TNF, OXT, or P 4 in mid-luteal phase. PGF 2α production by OEC was downregulated by all treatments in follicular phase but upregulated in mid-luteal phase (P < 0.05). Oviduct explants PGF 2α production was stimulated by TNF or OXT in all estrous cycle phases. In conclusion, this work has shown that ESR1, ESR2, OXTR, Ptges, and AKRLC3 gene transcription and

Surgical orthodontic treatment of an impacted canine in the presence of dens invaginatus and follicular cyst.

PubMed

Spallarossa, Marialuce; Canevello, Carola; Silvestrini Biavati, Francesca; Laffi, Nicola

2014-01-01

Introduction. "Dens invaginatus" is a dental anomaly which originates from the invagination of the ameloblastic epithelium into the lingual surface of the dental crown during the odontogenesis. It can cause early pulpal necrosis, abscesses, retention or dislocation of contiguous elements, cysts, and internal resorptions. It normally affects the upper lateral incisors. In the following study the authors will discuss the etiology, the physiopathology, and the surgical-orthodontic management of a rare case of impacted canine associated with dens invaginatus and follicular cyst, with the aim of highlighting the importance of taking any therapeutic decision based on the data available in the literature. Case Report. The present study describes a combined surgical-orthodontic treatment of an impacted canine associated with a lateral incisor (2.2) suffering from type III dens invaginatus with radicular cyst, in a 15-year-old patient. Discussion. When treating a dens invaginatus there are different therapeutic solutions: they depend on the gravity of the anomaly and on the association with the retention of a permanent tooth. The aesthetic and functional restoration becomes extremely important when performing a surgical-orthodontic repositioning.

The E3 ubiquitin ligase Itch is required for the differentiation of follicular helper T cells

PubMed Central

Xiao, Nengming; Eto, Danelle; Elly, Chris; Peng, Guiying; Crotty, Shane; Liu, Yun-Cai

2014-01-01

Follicular helper T cells (TFH cells) are responsible for effective B cell–mediated immunity, and Bcl-6 is a central factor for the differentiation of TFH cells. However, the molecular mechanisms that regulate the induction of TFH cells remain unclear. Here we found that the E3 ubiquitin ligase Itch was essential for the differentiation of TFH cells, germinal center responses and immunoglobulin G (IgG) responses to acute viral infection. Itch acted intrinsically in CD4+ T cells at early stages of TFH cell development. Itch seemed to act upstream of Bcl-6 expression, as Bcl-6 expression was substantially impaired in Itch−/− cells, and the differentiation of Itch−/− T cells into TFH cells was restored by enforced expression of Bcl-6. Itch associated with the transcription factor Foxo1 and promoted its ubiquitination and degradation. The defective TFH differentiation of Itch−/− T cells was rectified by deletion of Foxo1. Thus, our results indicate that Itch acts as an essential positive regulator in the differentiation of TFH cells. PMID:24859451

Risk of thyroid follicular adenoma among children and adolescents in Belarus exposed to iodine-131 after the Chornobyl accident.

PubMed

Zablotska, Lydia B; Nadyrov, Eldar A; Polyanskaya, Olga N; McConnell, Robert J; O'Kane, Patrick; Lubin, Jay; Hatch, Maureen; Little, Mark P; Brenner, Alina V; Veyalkin, Ilya V; Yauseyenka, Vasilina V; Bouville, Andre; Drozdovitch, Vladimir V; Minenko, Viktor F; Demidchik, Yuri E; Mabuchi, Kiyohiko; Rozhko, Alexander V

2015-11-01

Several studies reported an increased risk of thyroid cancer in children and adolescents exposed to radioactive iodines, chiefly iodine-131 ((131)I), after the 1986 Chornobyl (Ukrainian spelling) nuclear power plant accident. The risk of benign thyroid tumors following such radiation exposure is much less well known. We have previously reported a novel finding of significantly increased risk of thyroid follicular adenoma in a screening study of children and adolescents exposed to the Chornobyl fallout in Ukraine. To verify this finding, we analyzed baseline screening data from a cohort of 11,613 individuals aged ≤18 years at the time of the accident in Belarus (mean age at screening = 21 years). All participants had individual (131)I doses estimated from thyroid radioactivity measurements and were screened according to a standardized protocol. We found a significant linear dose response for 38 pathologically confirmed follicular adenoma cases. The excess odds ratio per gray of 2.22 (95% confidence interval: 0.41, 13.1) was similar in males and females but decreased significantly with increasing age at exposure (P < 0.01), with the highest radiation risks estimated for those exposed at <2 years of age. Follicular adenoma radiation risks were not significantly modified by most indicators of past and current iodine deficiency. The present study confirms the (131)I-associated increases in risk of follicular adenoma in the Ukrainian population and adds new evidence on the risk increasing with decreasing age at exposure. © The Author 2015. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Variation of Reaction Time in Different Phases of Menstrual Cycle

PubMed Central

Kumar, Sunil; Mufti, Mehak; Kisan, Ravikiran

2013-01-01

Objective: To evaluate the influence of menstrual cycle on auditory and visual reaction times. Method: This study was conducted on thirty, healthy, regularly menstruating female subjects who were in the age group of 18-25 years. Influence of different phases of menstrual cycle on Auditory Reaction Time (ART) and Visual Reaction Time (VRT) was evaluated by using a portable audiovisual reaction time apparatus. Result: The statistical tests which were used were ANOVA and Students ‘t’ test, which showed that there were significant increases in ART and VRT during luteal phase, as compared to those in follicular phase. Conclusion: Changes in ART and VRT during different phases of menstrual cycle could be due to changes in the levels of female sex hormones, which in turn may lead to salt and water retention. PMID:24086851

Differential Expression of Glycolysis-Related Proteins in Follicular Neoplasms versus Hürthle Cell Neoplasms: A Retrospective Analysis

PubMed Central

Kim, Hye Min

2017-01-01

Purpose Although currently classified as variants of follicular neoplasms (FNs), Hürthle cell neoplasms (HCNs) exhibit distinct biological characteristics. Hence, the metabolism of both neoplasms may also be different. The aims of this study were to investigate and compare the expression of glycolysis-related proteins in HCNs and FNs and to determine the clinical implications of such expression. Methods Tissue microarrays were constructed with 265 samples of FNs (112 follicular carcinomas (FCs) and 153 follicular adenomas (FAs)) as well as 108 samples of HCNs (27 Hürthle cell carcinomas (HCCs) and 81 Hürthle cell adenomas (HCAs)). Immunohistochemical staining for the glycolysis-related molecules Glut-1, hexokinase II, CAIX, and MCT4 was performed. Results The expression levels of Glut-1, hexokinase II, CAIX, and MCT4 were significantly higher in HCNs than in FNs (p < 0.001). Glut-1, hexokinase II, CAIX, and MCT4 expression levels were highest in HCC, followed by HCA, FC, and FA (all p < 0.001). In HCC, hexokinase II positivity was associated with large tumor size (>4 cm) (p = 0.046), CAIX positivity with vascular invasion (p = 0.005), and MCT4 positivity with extrathyroidal extension (p = 0.030). Conclusion The expression levels of the glycolysis-related proteins Glut-1, hexokinase II, CAIX, and MCT4 were higher in HCNs than in FNs and in HCCs than in HCAs. PMID:28790533

Effect of serum paraoxonase-1 (PON1) activity on follicular development and pregnancy rate in cattle.

PubMed

Castro, Natália A; Pfeifer, Luiz F M; Andrade, Jéssica S; Rincón, Joao A A; Pegoraro, Ligia M Cantarelli; Schneider, Augusto

2018-01-01

Paraoxonase-1 (PON1) activity has been associated with improvement in ovarian function in early postpartum dairy cows and improved in vitro embryo development. The aim of the current study was to evaluate the potential association among PON1 activity and follicular growth, diameter of the preovulatory follicle and pregnancy per artificial insemination (AI) service in cattle. In Experiment 1, cows (n=33) were subjected to an estradiol-progesterone based protocol to control time of ovulation. Starting on Day 8 of the protocol, follicular growth and serum PON1 activity were monitored. Cows were separated according to the occurrence of ovulation into two groups: Ovulatory (Ov; n=22) and Anovulatory (Anov; n=11). The serum activity of PON1 was not different between Ov and Anov cows (P=0.94). In addition, using a regression model there was no effect of serum PON1 activity on the diameter of dominant follicle (r 2 =0.00; P=0.99). In Experiment 2, cows (n=193) were submitted to the same hormonal protocol as in Experiment 1. On the day of the timed artificial insemination (TAI), the diameter of dominant follicle was evaluated and blood samples were collected for analysis of PON1 activity. According to the serum PON1 activity, cows were divided into three groups: Low (<70U/mL), Medium (70-90U/mL) or High (>90U/mL) PON1 activity. The overall pregnancy rate was 62.7% (121/193), with no difference among PON1 activity groups. Additionally, using a regression model there was no effect of serum PON1 activity on the diameter of the preovulatory follicle (r 2 =0.03; P=0.65) and pregnancy rate (r 2 =0.005; P=0.94). The results of this study indicate that there is no effect of serum PON1 activity on the diameter of preovulatory follicle or establishment of pregnancy in cows submitted to time of ovulation synchronization protocols. Copyright © 2017 Elsevier B.V. All rights reserved.

Worldwide isotope ratios of the Fukushima release and early-phase external dose reconstruction

PubMed Central

Chaisan, Kittisak; Smith, Jim T.; Bossew, Peter; Kirchner, Gerald; Laptev, Gennady V.

2013-01-01

Measurements of radionuclides (RNs) in air made worldwide following the Fukushima accident are quantitatively compared with air and soil measurements made in Japan. Isotopic ratios RN:137Cs of 131I, 132Te, 134,136Cs, are correlated with distance from release. It is shown, for the first time, that both within Japan and globally, ratios RN:137Cs in air were relatively constant for primarily particle associated radionuclides (134,136Cs; 132Te) but that 131I shows much lower local (<80 km) isotope ratios in soils relative to 137Cs. Derived isotope ratios are used to reconstruct external dose rate during the early phase post-accident. Model “blind” tests show more than 95% of predictions within a factor of two of measurements from 15 sites to the north, northwest and west of the power station. It is demonstrated that generic isotope ratios provide a sound basis for reconstruction of early-phase external dose rates in these most contaminated areas. PMID:24018776

Follicular fluid soluble receptor for advanced glycation end-products (sRAGE): a potential indicator of ovarian reserve.

PubMed

Merhi, Zaher; Irani, Mohamad; Doswell, Angela D; Ambroggio, Jennifer

2014-02-01

The interaction of advanced glycation end-products (AGEs) with their cellular receptor (RAGE) is implicated in the pathogenesis of abnormal ovarian follicular growth. RAGE has a circulating secretory receptor form, soluble RAGE (sRAGE), which neutralizes the action of AGEs and might exert a protective role on the follicular environment. The objective of the study was to investigate whether serum or follicular fluid (FF) sRAGE levels are associated with markers of ovarian reserve. Serum anti-Mullerian hormone (AMH) and sRAGE protein levels were correlated in 31 reproductive-aged women. An additional 33 women who underwent oocyte retrieval for in vitro fertilization were enrolled. AMH and its receptor (AMHR-II) mRNA levels were quantified in cumulus granulosa cells and FF sRAGE and AMH protein levels were measured. Granulosa cell AMH and AMHR-II gene expression, serum and FF AMH and sRAGE protein concentration, and number of oocytes retrieved were measured. In the serum, sRAGE levels were negatively correlated with body mass index (BMI) (r = -0.5, P < .001) but not with age or serum AMH. The higher the FF sRAGE, the lower the number of international units of gonadotropin needed per cycle independent of age, BMI, or day 3 FSH level (r = -0.4, P = .04). After adjusting for age, BMI, day 3 FSH, and the total dose of gonadotropins, FF sRAGE predicted the number of oocytes retrieved (R(2) = 0.27, P = .045). FF sRAGE positively correlated with FF AMH levels (r = 0.5, P = .0085). RT-PCR results showed no correlation between the FF sRAGE and AMH or AMHR-II mRNA levels. These data support a relationship between FF sRAGE and measures of ovarian reserve. The pathological significance of the harmful inflammatory AGEs in follicular health clearly requires further investigation. Targeting AGEs might offer potential therapeutic options for the treatment of diminished ovarian response.

Sciatica as a presenting feature of thyroid follicular adenocarcinoma in a 79-year-old woman

PubMed Central

Ogbodo, Elisha; Kaliaperumal, Chandrasekaran; Keohane, Catherine; Bermingham, Niamh; Kaar, George

2011-01-01

The authors describe an unusual case of metastatic thyroid follicular adenocarcinoma presenting with sciatica in a 79-year-old woman. The primary thyroid tumour was undiagnosed until this clinical presentation. The patient gave a short history of back pain and right-sided sciatica, which was progressive and nocturnal in nature. Neuroimaging revealed an enhancing intradural mass lesion, which was completely excised through a right L1-L3 hemilaminectomy. Histopathological examination of the excised tissue revealed a follicular thyroid carcinoma. Subsequent metastatic investigation revealed a heterogeneously attenuating mixed solid cystic mass in a retrosternal thyroid gland, with multiple solid pulmonary nodules suggestive of metastatic disease. She opted for palliative radiotherapy for the primary thyroid cancer and made remarkable postoperative improvement. The authors conclude that surgical treatment of solitary metastatic lesion may produce good symptomatic relief irrespective of patient’s age and primary pathology, while emphasising the need for detailed clinical evaluation of patients with ‘red flag’ symptoms. PMID:22674960

Interleukin-10 from CD4+ follicular regulatory T cells promotes the germinal center response.

PubMed

Laidlaw, Brian J; Lu, Yisi; Amezquita, Robert A; Weinstein, Jason S; Vander Heiden, Jason A; Gupta, Namita T; Kleinstein, Steven H; Kaech, Susan M; Craft, Joe

2017-10-20

CD4 + follicular regulatory T (T fr ) cells suppress B cell responses through modulation of follicular helper T (T fh ) cells and germinal center (GC) development. We found that T fr cells can also promote the GC response through provision of interleukin-10 (IL-10) after acute infection with lymphocytic choriomeningitis virus (LCMV). Sensing of IL-10 by B cells was necessary for optimal development of the GC response. GC B cells formed in the absence of T reg cell-derived IL-10 displayed an altered dark zone state and decreased expression of the transcription factor Forkhead box protein 1 (FOXO1). IL-10 promoted nuclear translocation of FOXO1 in activated B cells. These data indicate that T fr cells play a multifaceted role in the fine-tuning of the GC response and identify IL-10 as an important mediator by which T fr cells support the GC reaction. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Three steps to writing adaptive study protocols in the early phase clinical development of new medicines

PubMed Central

2014-01-01

This article attempts to define terminology and to describe a process for writing adaptive, early phase study protocols which are transparent, self-intuitive and uniform. It provides a step by step guide, giving templates from projects which received regulatory authorisation and were successfully performed in the UK. During adaptive studies evolving data is used to modify the trial design and conduct within the protocol-defined remit. Adaptations within that remit are documented using non-substantial protocol amendments which do not require regulatory or ethical review. This concept is efficient in gathering relevant data in exploratory early phase studies, ethical and time- and cost-effective. PMID:24980283

Cosmological QCD phase transition in steady non-equilibrium dissipative Hořava–Lifshitz early universe

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

Khodadi, M., E-mail: M.Khodadi@sbu.ac.ir; Sepangi, H.R., E-mail: hr-sepangi@sbu.ac.ir

We study the phase transition from quark–gluon plasma to hadrons in the early universe in the context of non-equilibrium thermodynamics. According to the standard model of cosmology, a phase transition associated with chiral symmetry breaking after the electro-weak transition has occurred when the universe was about 1–10 μs old. We focus attention on such a phase transition in the presence of a viscous relativistic cosmological background fluid in the framework of non-detailed balance Hořava–Lifshitz cosmology within an effective model of QCD. We consider a flat Friedmann–Robertson–Walker universe filled with a non-causal and a causal bulk viscous cosmological fluid respectively and investigatemore » the effects of the running coupling constants of Hořava–Lifshitz gravity, λ, on the evolution of the physical quantities relevant to a description of the early universe, namely, the temperature T, scale factor a, deceleration parameter q and dimensionless ratio of the bulk viscosity coefficient to entropy density (ξ)/s . We assume that the bulk viscosity cosmological background fluid obeys the evolution equation of the steady truncated (Eckart) and full version of the Israel–Stewart fluid, respectively. -- Highlights: •In this paper we have studied quark–hadron phase transition in the early universe in the context of the Hořava–Lifshitz model. •We use a flat FRW universe with the bulk viscosity cosmological background fluid obeying the evolution equation of the steady truncated (Eckart) and full version of the Israel–Stewart fluid, respectively.« less

Changes in neural circuitry associated with depression at pre-clinical, pre-motor and early motor phases of Parkinson's disease.

PubMed

Borgonovo, Janina; Allende-Castro, Camilo; Laliena, Almudena; Guerrero, Néstor; Silva, Hernán; Concha, Miguel L

2017-02-01

Although Parkinson's Disease (PD) is mostly considered a motor disorder, it can present at early stages as a non-motor pathology. Among the non-motor clinical manifestations, depression shows a high prevalence and can be one of the first clinical signs to appear, even a decade before the onset of motor symptoms. Here, we review the evidence of early dysfunction in neural circuitry associated with depression in the context of PD, focusing on pre-clinical, pre-motor and early motor phases of the disease. In the pre-clinical phase, structural and functional changes in the substantia nigra, basal ganglia and limbic structures are already observed. Some of these changes are linked to motor compensation mechanisms while others correspond to pathological processes common to PD and depression and thus could underlie the appearance of depressive symptoms during the pre-motor phase. Studies of the early motor phase (less than five years post diagnosis) reveal an association between the extent of damage in different monoaminergic systems and the appearance of emotional disorders. We propose that the limbic loop of the basal ganglia and the lateral habenula play key roles in the early genesis of depression in PD. Alterations in the neural circuitry linked with emotional control might be sensitive markers of the ongoing neurodegenerative process and thus may serve to facilitate an early diagnosis of this disease. To take advantage of this, we need to improve the clinical criteria and develop biomarkers to identify depression, which could be used to determine individuals at risk to develop PD. Copyright © 2016 Elsevier Ltd. All rights reserved.

Untargeted metabolomics reveal disparate metabolite profile in follicular fluid between obese and normal weight women

USDA-ARS?s Scientific Manuscript database

The microenvironment of follicular fluid is thought to provide a rich source of nutrients and other factors that promotes oocyte growth and viability; however, it is not known if obesity or related sequelae impacts this environment. To address this research gap, we designed a clinical study to asses...

[The role of apoptosis of granulosa cells in follicular atresia].

PubMed

Grotowski, W; Lecybył, R; Warenik-Szymankiewicz, A; Trzeciak, W H

1997-07-01

Apoptosis plays an important role in the process of morphogenesis and embryogenesis. Its increase or inhibition is an etiopathological factor in many different diseases. It has recently been shown that apoptosis of granulosa cells is one of the main mechanisms responsible for follicular atresia. There are many other factors influencing the process of granulosa cells apoptosis, among them the most important are: RnGH, FSH, LH, sex hormones (estrogens and androgens), growth factors and their receptors (EGF/TGF-alpha, FGF, IGF-1) and cytokines (e.g. TNF-alpha). The article presents data concerning the regulatory mechanisms of granulosa cells apoptosis in the ovary.

Decision making and distress among individuals diagnosed with follicular lymphoma.

PubMed

Poe, Jennifer K; Hayslip, John W; Studts, Jamie L

2012-01-01

Follicular lymphoma (FL) is an indolent lymphoma that generally responds well to treatment. However, individuals with FL commonly face multiple complex treatment decision-making (TDM) experiences because it frequently follows a relapsing and remitting course. This study explored TDM and distress among individuals with FL (N = 32). Results indicated that most participants reported little decisional conflict or regret and wanted to be actively involved in TDM. However, more than 25% of participants reported clinically-relevant cancer-specific distress, and 60% indicated moderate or higher anxiety symptoms. Research is needed to clarify the cause and course of the psychological distress revealed in this study.

Treatment of localized-stage follicular lymphoma.

PubMed

Sorigue, Marc; Tuset, Victòria; Sancho, Juan-Manuel

2018-05-12

Follicular lymphoma (FL) is the most common indolent lymphoma and it most frequently presents in an advanced-stage. Therapeutic considerations for advanced-stage are different from those of localized-stage FL, in which radiotherapy (RT) is generally recommended. However, the available evidence suffers from shortcomings that are relatively specific to this clinical entity due to its rarity and long survival with all available treatment modalities, including that most of the existing evidence originated at a time when diagnostic classifications, staging procedures and radiotherapeutic standards were different from those available today and when anti-CD20 monoclonal antibodies were not available. Available treatment modalities include observation, systemic therapy only, RT only and RT in combination with systemic therapy. We review the evidence available with each of them and the data from present day clinical practice studies as well as briefly discuss what diagnostic and therapeutic developments may take place in the next few years. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Endothelial gaps and adherent leukocytes in allergen-induced early- and late-phase plasma leakage in rat airways.

PubMed Central

Baluk, P.; Bolton, P.; Hirata, A.; Thurston, G.; McDonald, D. M.

1998-01-01

Exposure of sensitized individuals to antigen can induce allergic responses in the respiratory tract, manifested by early and late phases of vasodilatation, plasma leakage, leukocyte influx, and bronchoconstriction. Similar responses can occur in the skin, eye, and gastrointestinal tract. The early-phase response involves mast cell mediators and the late-phase response is leukocyte dependent, but the mechanism of leakage is not understood. We sought to identify the leaky blood vessels, to determine whether these vessels contained endothelial gaps, and to analyze the relationship of the gaps to adherent leukocytes, using biotinylated lectins or silver nitrate to stain the cells in situ and Monastral blue as a tracer to quantify plasma leakage. Most of the leakage occurred in postcapillary venules (< 40-microns diameter), whereas most of the leukocyte migration (predominantly neutrophils) occurred in collecting venules. Capillaries and arterioles did not leak. Endothelial gaps were found in the leaky venules, both by silver nitrate staining and by scanning electron microscopy, and 94% of the gaps were distinct from sites of leukocyte adhesion or migration. We conclude that endothelial gaps contribute to both early and late phases of plasma leakage induced by antigen, but most leakage occurs upstream to sites of leukocyte adhesion. Images Figure 3 Figure 5 Figure 6 Figure 7 PMID:9626051

Synchronization of follicular wave emergence in the seasonally anestrous ewe: the effects of estradiol with or without medroxyprogesterone acetate.

PubMed

Barrett, D M W; Bartlewski, P M; Duggavathi, R; Davies, K L; Huchkowsky, S L; Epp, T; Rawlings, N C

2008-04-15

Fertility is often lower in anestrous compared to cyclic ewes, after conventional estrus synchronization. We hypothesized that synchronization of ovarian follicular waves and ovulation could improve fertility at controlled breeding in anestrous ewes. Estradiol-17beta synchronizes follicular waves in cattle. The objectives of the present experiments were to study the effect of an estradiol injection, with or without a 12-d medroxyprogesterone acetate (MAP) sponge treatment, on synchronization of follicular waves and ovulation in anestrous ewes. Twenty ewes received sesame oil (n=8) or estradiol-17beta (350 microg; n=12). Eleven ewes received MAP sponges for 12d and were treated with oil (n=5) or estradiol-17beta (n=6) 6d before sponge removal. Saline (n=6) or eCG (n=6) was subsequently given to separate groups of ewes at sponge removal in the MAP/estradiol-17beta protocol. Estradiol treatment alone produced a peak in serum FSH concentrations (4.73+/-0.53 vs. 2.36+/-0.39 ng/mL for treatment vs. control; mean+/-S.E.M.) after a short-lived (6 h) suppression. Six of twelve ewes given estradiol missed a follicular wave around the time of estradiol injection. Medroxyprogesterone acetate-treated ewes given estradiol had more prolonged suppression of serum FSH concentrations (6-18 h) and a delay in the induced FSH peak (32.3+/-3.3 vs. 17.5+/-0.5 h). Wave emergence was delayed (5.7+/-0.3 vs. 1.4+/-0.7d from the time of estradiol injection), synchronized, and occurred at a predictable time (5-7 vs. 0-4d) compared to ewes given MAP alone. All ewes given eCG ovulated 3-4d after injection; this predictable time of ovulation may be efficacious for AI and embryo transfer.

Obesity is not a descriptive factor for oxidative stress and viscosity in follicular fluid of in vitro fertilization patients.

PubMed

Yuksel, B; Kilic, S; Yilmaz, N; Goktas, T; Keskin, U; Seven, A; Ulubay, M; Batioglu, S

2017-08-01

Obesity's impact on micro-environmental oxidative stress and follicular fluid (FF) viscosity and whether or not it has any effect on in vitro fertilization (IVF) success is a matter of debate. In this study, our aim was to evaluate the levels of oxidative stress markers and the FF viscosity in obese and non-obese patients. Eighty norm-responder patients undergoing IVF were prospectively grouped according to their body mass indexes (BMI). Group 1 (n = 40) and group 2 (n = 40) had BMI values of ≤24.9 and ≥25.0, respectively. Total sulfhydryl (RSH) levels (nmol/m) and the formation of thiobarbituric acid-reactive substances (malondialdehyde, or MDA) (µmol/ml) in FFs were quantified. For the first time in our study, FF viscosity with changing BMI values was also determined. The mean levels of MDA (µmol/ml) and RSH (nmol/ml) were not significantly different between groups (1.37 ± 0.51; 1.51 ± 0.51; p > 0.05 for MDA and 0.42 ± 0.30; 0.41 ± 0.20; p > 0.05 for RSH, respectively). Similarly, the FF viscosity (centipoise) was not different between groups (1.28 ± 0.28; 1.30 ± 0.19; p < 0.05, respectively). Independent of BMI, no correlation was found between FF levels of oxidative markers and the number of oocytes retrieved or the fertilization rates. In our study, we found no difference in the levels of follicular oxidative and anti-oxidative markers or the follicular fluid viscosity with changing BMI values. We also demonstrated that the levels of oxidative stress markers and the viscosity of follicular fluid did not affect clinical outcomes.

The effect of active immunization against inhibin on gonadotropin secretions and follicular dynamics during the estrous cycle in cows.

PubMed

Medan, Mohamed S; Takedom, Toshiro; Aoyagi, Yoshito; Konishi, Masato; Yazawa, Shigeto; Watanabe, Gen; Taya, Kazuyoshi

2006-02-01

The hypothesis of the present study is that active immunization of cows against inhibin would neutralize endogenous inhibin, increase circulating levels of follicle stimulating hormone, and subsequently affect follicular dynamics and the ovulation rate during the estrous cycle. Thirteen cows were immunized against inhibin alpha-subunit and, 6 cows were immunized with a placebo. Both groups were given 4 booster immunizations 7, 14, 21, and 34 weeks after the primary injection. Ovaries were examined daily after the 2nd, 3rd, and 4th booster immunizations by transrectal ultrasonography for 25 days. After the 4th booster immunization, blood samples were collected daily for one complete estrous cycle to measure FSH and LH. The results showed that the immunized cows generated antibodies against inhibin, and that they had higher FSH levels compared with the controls. The number of follicular waves during the estrous cycle was higher in the immunized cows (3 or 4 waves) than in the controls (2 or 3 waves). Moreover, the immunized cows had a greater number of follicles during the estrous cycle compared with the control cows. The maximum number of follicles was 14.8 +/- 1.7 vs 5.4 +/- 0.2 in inhibin-immunized and control cows, respectively, during the first follicular wave and 13.9 +/- 1.9 vs 5.6 +/- 0.7, respectively, during the ovulatory wave. Multiple ovulations were increased in the immunized cows. However, the ovulation rate varied greatly in the immunized animals. In conclusion, immunization against inhibin increased FSH secretions during the estrous cycle in the cows. Moreover, the immunized cows had a greater number of follicular waves during the estrous cycle and a greater number of follicles, and this could be used as a potential source of oocytes for use in IVF/embryo transfer programs.

Does flushing the endometrial cavity with follicular fluid after oocyte retrieval affect pregnancy rates in subfertile women undergoing intracytoplasmic sperm injection? A randomized controlled trial.

PubMed

Hashish, N M; Badway, H S; Abdelmoty, H I; Mowafy, A; Youssef, M A F M

2014-05-01

Follicular fluid of mature oocytes is rich in growth factors and cytokines that may exert paracrine and autocrine effects on implantation. The aim of this study was to investigate if flushing the endometrial cavity with follicular fluid after oocyte retrieval improved pregnancy rates in subfertile women undergoing intracytoplasmic sperm injection (ICSI). One hundred subfertile women undergoing ICSI between April 2012 and September 2012 at the centre for reproductive medicine, Cairo University, Egypt were enrolled in this open label, parallel randomized controlled study. Patients were randomized into two groups at the start of treatment using a computer-generated programme and sealed opaque envelopes: the follicular fluid group (n=50) and the control group (n=50). Inclusion criteria were: age 20-38 years; basal follicle-stimulating hormone <10mIU/ml; body mass index <35kg/m(2); and ostradiol >1000pg/ml and <4000pg/ml on the day of human chorionic gonadotrophin administration. Exclusion criteria were: evidence of endometriosis; uterine myoma; hydrosalpinges; endocrinological disorders; history of implantation failure in previous in-vitro fertilization/ICSI cycles; and severe male factor infertility. Clinical pregnancy and implantation rates were higher in the follicular fluid group compared with the control group [354% (17/48) vs 319% (15/47); p=0718] and (18.6% vs 11.3%; p=0.153), respectively. However, the difference was not statistically significant. Flushing the endometrial cavity with follicular fluid after oocyte retrieval neither improved nor adversely affected clinical pregnancy and implantation rates in subfertile women undergoing ICSI. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Follicular contact dermatitis due to coloured permanent-pressed sheets

PubMed Central

Panaccio, François; Montgomery, D. C.; Adam, J. E.

1973-01-01

A delayed hypersensitivity type of allergic contact dermatitis was observed following exposure to certain brands of 50% cotton, 50% polyester coloured permanent-pressed sheets produced by a particular manufacturer. The dermatitis presented as an extremely pruritic follicular eczema of the body and vesicular edema of the ears and face. Patch testing excluded formalin as the allergen but suggested permanent-pressing chemicals as a possibility. Several washings of the sheets did not prevent the development of the dermatitis. The removal of sheets did not immediately result in improvement: the condition could persist for up to eight weeks after their discontinuance. ImagesFIG. 1FIG. 2FIG. 3FIG. 4FIG. 5 PMID:4268628

Contribution of economic evaluation to decision making in early phases of product development: a methodological and empirical review.

PubMed

Hartz, Susanne; John, Jürgen

2008-01-01

Economic evaluation as an integral part of health technology assessment is today mostly applied to established technologies. Evaluating healthcare innovations in their early states of development has recently attracted attention. Although it offers several benefits, it also holds methodological challenges. The aim of our study was to investigate the possible contributions of economic evaluation to industry's decision making early in product development and to confront the results with the actual use of early data in economic assessments. We conducted a literature research to detect methodological contributions as well as economic evaluations that used data from early phases of product development. Economic analysis can be beneficially used in early phases of product development for various purposes including early market assessment, R&D portfolio management, and first estimations of pricing and reimbursement scenarios. Analytical tools available for these purposes have been identified. Numerous empirical works were detected, but most do not disclose any concrete decision context and could not be directly matched with the suggested applications. Industry can benefit from starting economic evaluation early in product development in several ways. Empirical evidence suggests that there is still potential left unused.

Hemoglobin phase of oxygenation and deoxygenation in early brain development measured using fNIRS

PubMed Central

Watanabe, Hama; Shitara, Yoshihiko; Aoki, Yoshinori; Inoue, Takanobu; Tsuchida, Shinya; Takahashi, Naoto; Taga, Gentaro

2017-01-01

A crucial issue in neonatal medicine is the impact of preterm birth on the developmental trajectory of the brain. Although a growing number of studies have shown alterations in the structure and function of the brain in preterm-born infants, we propose a method to detect subtle differences in neurovascular and metabolic functions in neonates and infants. Functional near-infrared spectroscopy (fNIRS) was used to obtain time-averaged phase differences between spontaneous low-frequency (less than 0.1 Hz) oscillatory changes in oxygenated hemoglobin (oxy-Hb) and those in deoxygenated hemoglobin (deoxy-Hb). This phase difference was referred to as hemoglobin phase of oxygenation and deoxygenation (hPod) in the cerebral tissue of sleeping neonates and infants. We examined hPod in term, late preterm, and early preterm infants with no evidence of clinical issues and found that all groups of infants showed developmental changes in the values of hPod from an in-phase to an antiphase pattern. Comparison of hPod among the groups revealed that developmental changes in hPod in early preterm infants precede those in late preterm and term infants at term equivalent age but then, progress at a slower pace. This study suggests that hPod measured using fNIRS is sensitive to the developmental stage of the integration of circular, neurovascular, and metabolic functions in the brains of neonates and infants. PMID:28196885

Biomarkers of ovarian reserve as predictors of reproductive potential.

PubMed

Steiner, Anne Z

2013-11-01

The size of the oocyte pool, the ovarian reserve, can determine a woman's reproductive stage. Chronologic age, anti-Müllerian hormone (AMH) levels, early follicular phase follicle-stimulating hormone levels, and early follicular phase inhibin B levels are correlated with ovarian reserve. Therefore, these biomarkers of ovarian reserve should serve as predictors of reproductive potential. Clinical and epidemiologic studies suggest that historical and laboratory biomarkers of ovarian reserve are associated with natural and treatment-related fertility. However, controversy remains as to their ability to predict reproductive potential. For infertile women undergoing assisted reproductive technology treatment, these biomarkers tend to be highly specific but not sensitive for cycle failure (nonpregnancy). While these biomarkers are being used as "fertility tests" in the general population, their value as predictors of unassisted fertility is still uncertain. Among laboratory biomarkers, AMH appears to have the most promise; however, further studies are needed to refine cutoff values and to determine test characteristics in the prediction of natural fertility or infertility in the general population. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Melatonin and exposure to constant light/darkness affects ovarian follicular kinetics and estrous cycle in Indian desert gerbil Meriones hurrianae.

PubMed

Sinhasane, S V; Joshi, B N

1997-12-01

Melatonin mediates photoperiodic influence on reproduction and constant light and darkness affect pineal biosynthesis of melatonin. The present study was undertaken to assess the effects of melatonin and drastic photoperiodic changes on reproduction in a tropical desert species with a fossorial lifestyle. Ovarian follicular kinetics and estrous cycle were studied in the Indian desert gerbil Meriones hurrianae, after treatment with melatonin and exposure to constant light (LL) and darkness (DD) regimes. Melatonin treatment increased (P < 0.001) ovarian weights without changing the uterine weights. While exposure to LL decreased (P < 0.001) both ovarian and uterine weights, exposure to DD had no effect on these weights. Follicular kinetics of growing and regressing follicles revealed that ovaries of melatonin-treated and DD-exposed animals had significantly more growing follicles. Melatonin treatment increased all types of growing follicles, especially antral and Graafian follicles. Exposure to DD increased all types of growing follicles, with the medium sized antral and Graafian follicles being significant (P < 0.01). In contrast to stimulation of follicular growth by melatonin and DD, LL caused regression of all stages of follicular growth and also reduced the number of small preantral follicles. Melatonin treatment increased (P < 0.001) the length of estrous cycle (5.08 to 7.29 days). Gerbils treated with melatonin, exposed to LL and DD, had a longer (P < 0.001) metestrus. Animals held in LL, had the least number (P < 0.001) of estrous smears (1 in 30 days). The results suggest that melatonin is involved in growth of ovarian follicles in the Indian desert gerbil. Copyright 1997 Academic Press.

Impact of the accuracy of automatic segmentation of cell nuclei clusters on classification of thyroid follicular lesions.

PubMed

Jung, Chanho; Kim, Changick

2014-08-01