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Sample records for acute radiation nephritis

  1. Interstitial nephritis

    MedlinePlus

    Tubulointerstitial nephritis; Nephritis - interstitial; Acute interstitial (allergic) nephritis ... Interstitial nephritis may be temporary ( acute ), or it may be long-lasting ( chronic ) and get worse over ...

  2. Radiation nephritis. Clinical manifestations and pathophysiologic mechanisms

    SciTech Connect

    Krochak, R.J.; Baker, D.G.

    1986-05-01

    Radiation nephritis is both volume and dose related. Clinical experience would indicate that a minimum of one third of the renal volume needs to be excluded from nephrotoxic doses which appears to have a threshold of 2,000 cGy. The site of damage leading to renal failure appears to be the microvasculature ultimately expressed as glomerulosclerosis. How much direct damage to the tubular system contributes to this process is unclear, but undoubtedly the resultant systemic physiologic effects potentiate the expression of damage in the irradiated kidney. The acute syndrome, with all the potential manifestations of renal failure, rarely presents sooner than six months and appears to have no clear prodrome, although it would seem reasonable that a subclinical syndrome consisting of abnormalities detectable by urinalysis may occur. Treatment of radiation-induced nephritis or hypertension is no different from treatment for nephritis from any other cause and should be aggressive with lifelong follow-up. Carcinogenesis is a rare late expression of radiation-induced kidney damage. 25 references.

  3. Bortezomib-induced acute interstitial nephritis.

    PubMed

    Cheungpasitporn, Wisit; Leung, Nelson; Rajkumar, S Vincent; Cornell, Lynn D; Sethi, Sanjeev; Angioi, Andrea; Fervenza, Fernando C

    2015-07-01

    Acute interstitial nephritis (AIN) is one of the important causes of acute kidney injury (AKI) resulting from inflammatory tubulointerstitial injury induced by medications, infections and systemic diseases. Bortezomib has been increasingly used especially in renal related indications such as multiple myeloma and monoclonal gammopathy of renal significance. Severe allergic reactions from bortezomib treatment including AIN have not been described in the literature. We report a 47-year-old white man who developed biopsy-proven allergic AIN after treatment with bortezomib for his C3 glomerulonephritis. The patient's kidney function improved after treatment with glucocorticoid therapy and discontinuation of bortezomib, but worsened with recurrent AKI episode after re-initiation of bortezomib. His renal function improved after glucocorticoid therapy and discontinuation of bortezomib. To our knowledge, this is the first report of a biopsy-proven AIN from bortezomib.

  4. Immunoconglutinin and complement changes in children with acute nephritis

    PubMed Central

    Ngu, J. L.; Soothill, J. F.

    1969-01-01

    Immunoconglutinin and electrophoretically altered forms of complement are detectable only after the fall in complement levels in acute nephritis, and may occur even when the fall is not noted. The delay between the postulated initiating streptococcal infection and the development of immunoconglutinin is longer than would be expected. The immunopathological significance of these findings is discussed. PMID:4189125

  5. Acute tubulointerstitial nephritis and uveitis syndrome in the elderly.

    PubMed Central

    Salu, P; Stempels, N; Vanden Houte, K; Verbeelen, D

    1990-01-01

    A case of acute tubulointerstitial nephritis and uveitis syndrome (TINU syndrome) in an elderly woman is reported. The present case demonstrates that this entity originally observed in children, and more recently in adults, may also occur in the elderly. The aetiology and treatment are briefly discussed. Images PMID:2407289

  6. Drug-induced acute interstitial nephritis: report of 10 cases.

    PubMed Central

    Handa, S P

    1986-01-01

    Between January 1979 and June 1985, 10 patients with acute allergic interstitial nephritis were seen in a clinical nephrology service at a large regional hospital. The onset of renal failure was temporally related to the use of a drug: a nonsteroidal anti-inflammatory agent (NSAID) (in four patients), cimetidine (in three), antibiotics (in two) or allopurinol (in one). The onset of renal failure was acute in three patients and insidious in seven. Two patients also exhibited marked proteinuria. Clinical features such as fever, rash, hematuria, pyuria with or without eosinophiluria, and mild to marked proteinuria had led to suspicion of the disease. The diagnosis was confirmed by renal biopsy findings of inflammatory cells, predominantly lymphocytes, plasma cells and eosinophils. Three patients required hemodialysis; two of them received steroids as well. Steroid therapy was also used in two patients with NSAID-induced proteinuria. Renal function improved in nine patients by 35 days, but one patient continued to have slow but progressive deterioration of renal function. Acute interstitial nephritis can be distinguished from other forms of acute renal failure by heavy renal uptake of gallium 67, maximal 48 hours or more after injection. The improvement in renal function after discontinuation of the implicated drug, the characteristic histopathological findings of allergic interstitial nephritis, and the presence of eosinophils and sometimes IgE in the blood suggest a hypersensitivity reaction. PMID:3779558

  7. Acute tubulo-interstitial nephritis leading to acute renal failure following multiple hornet stings

    PubMed Central

    Sharma, Aman; Wanchu, Ajay; Mahesha, V; Sakhuja, V; Bambery, Pradeep; Singh, Surjit

    2006-01-01

    Background Hornet stings are generally associated with local and occasionally anaphylactic reactions. Rarely systemic complications like acute renal failure can occur following multiple stings. Renal failure is usually due to development of acute tubular necrosis as a result of intravascular haemolysis, rhabdomyolysis or shock. Rarely it can be following development of acute tubulo-interstitial nephritis. Case presentation We describe a young male, who was stung on face, head, shoulders and upper limbs by multiple hornets (Vespa orientalis). He developed acute renal failure as a result of acute tubulo-interstitial nephritis and responded to steroids. Conclusion Rare causes of acute renal failure like tubulo-interstitial nephritis should be considered in a patient with persistent oliguria and azotemia following multiple hornet stings. Renal biopsy should be undertaken early, as institution of steroid therapy may help in recovery of renal function PMID:17118188

  8. Drug-Induced Acute Interstitial Nephritis with Nifedipine

    PubMed Central

    Golbin, Léonard; Dolley-Hitze, Thibault; Lorcy, Nolwenn; Rioux-Leclercq, Nathalie; Vigneau, Cécile

    2016-01-01

    Background. Acute interstitial nephritis (AIN) is a frequent cause of Acute Kidney Injury (AKI). Drug hypersensitivity is the most common etiology and the list of drugs that can induce AIN is not exhaustive yet. Case Report. Here, we describe the case of a 43-year-old man who was treated with nifedipine (Adalate®) for Raynaud's syndrome. After nifedipine introduction, serum creatininemia progressively increased from 91 to 188 μmol/L in a few months and AKI was diagnosed. Laboratory work-up results indicated the presence of tubular proteinuria and nonspecific inflammatory syndrome. Histological analysis found granulomatous interstitial nephropathy without necrosis in 20% of the kidney biopsy without immunofluorescent deposit. Nifedipine was stopped and corticosteroid treatment was started with a rapid but incomplete reduction of serum creatininemia level to 106 μmol/L. Conclusion. This is the first case of AIN caused by nifedipine. PMID:26955492

  9. Phenazopyridine associated acute interstitial nephritis and review of literature.

    PubMed

    Singh, Manisha; Shailesh, Fnu; Tiwari, Upasana; Sharma, Shree G; Malik, Bilal

    2014-06-01

    Phenazopyridine is a urinary analgesic; commonly seen side-effects of this drug include, orange discoloration of urine, methemoglobinemia, yellowish skin discoloration, hepatitis and acute renal failure. Various case reports with phenazopyridine associated acute renal failure secondary to acute tubular necrosis have been reported in the literature. Acute kidney injury in these patients is caused by either direct injury to renal tubular epithelial cells or secondary to pigment induced nephropathy from hemolytic anemia. Hypoxic injury from phenazopyridine-induced methemoglobinemia has been well documented. We report a case of biopsy proven acute interstitial nephritis, associated with therapeutic doses of phenazopyridine without any evidence of methemoglobinemia or other mechanism of renal injury. Clinicians should be aware of the toxicity of this commonly used drug and should look closely for signs of renal insufficiency. Identifying and stopping the offending medication stays as the first step, but recent studies indicate that early steroid administration improves renal recovery, as well as decreasing the risk of progression to chronic kidney disease with fibrosis and consequent permanent renal damage.

  10. Acute interstitial nephritis due to proton pump inhibitors.

    PubMed

    Sampathkumar, K; Ramalingam, R; Prabakar, A; Abraham, A

    2013-07-01

    Proton pump inhibitors (PPI) are commonly prescribed for dyspepsia and acid peptic disease. Acute interstitial nephritis (AIN) is an uncommon though important side-effect of these classes of drugs. We describe four cases: three females and one male. PPIs implicated were pantoprazole in two, omeprazole and esomeprazole in one each. AIN developed after an average period of 4 weeks of drug therapy. The symptoms were vomiting, loin pain, and oliguria. Minimal proteinuria with pyuria were seen and the mean serum creatinine was 4.95 ± 4 mg/dl. Two patients required hemodialysis. Renal biopsy showed interstitial mononuclear, plasma cell and eosinophilic infiltrates in all cases. PPI was stopped and steroids were started in all. Renal recovery was total in two and partial in two. A high index of suspicion is required to diagnose PPI induced AIN. Renal biopsy for confirmation followed up by prompt steroid therapy results in renal functional improvement. PMID:23960351

  11. Acute interstitial nephritis due to proton pump inhibitors

    PubMed Central

    Sampathkumar, K.; Ramalingam, R.; Prabakar, A.; Abraham, A.

    2013-01-01

    Proton pump inhibitors (PPI) are commonly prescribed for dyspepsia and acid peptic disease. Acute interstitial nephritis (AIN) is an uncommon though important side-effect of these classes of drugs. We describe four cases: three females and one male. PPIs implicated were pantoprazole in two, omeprazole and esomeprazole in one each. AIN developed after an average period of 4 weeks of drug therapy. The symptoms were vomiting, loin pain, and oliguria. Minimal proteinuria with pyuria were seen and the mean serum creatinine was 4.95 ± 4 mg/dl. Two patients required hemodialysis. Renal biopsy showed interstitial mononuclear, plasma cell and eosinophilic infiltrates in all cases. PPI was stopped and steroids were started in all. Renal recovery was total in two and partial in two. A high index of suspicion is required to diagnose PPI induced AIN. Renal biopsy for confirmation followed up by prompt steroid therapy results in renal functional improvement. PMID:23960351

  12. Acute interstitial nephritis – a reappraisal and update

    PubMed Central

    Raghavan, Rajeev; Eknoyan, Garabed

    2014-01-01

    Acute interstitial nephritis (AIN) is an under recognized and under diagnosed cause of acute kidney injury (AKI). It is estimated to account for 15 – 20% of cases of AKI; it is the reported diagnosis in 2.8% of all kidney biopsies, and 13.5% of biopsies done specifically for acute renal failure. Considerable evidence implicates antigen initiated cell-mediated injury in the pathogenesis of AIN. Drugs account for 70% of all cases, with over 150 different agents incriminated. The remaining cases are due to infections, autoimmune diseases, and rarely idiopathic. The central component of renal injury in AIN is altered tubular function, which usually precedes decrements in filtration rate. The key to early diagnosis is vigilance for the presence of tubular dysfunction in non-oliguric individuals, especially in patients with modest but gradual increments in creatinine level. The utility of urinary biomarkers to diagnose AIN in its early nascent and potentially reversible stage remains to be determined. Prompt recognition, elimination of the offending source of antigen, and use of a limited course of steroid therapy where indicated, will result in complete resolution in ~ 65% of cases, partial resolution in up to 20%, and irreversible damage in the rest. PMID:25079860

  13. Acute encephalopathy and tubulointerstitial nephritis associated with Yersinia pseudotuberculosis.

    PubMed

    Kaito, Hiroshi; Kamei, Koichi; Ogura, Masao; Kikuchi, Eriko; Hoshino, Hideki; Nakagawa, Satoshi; Matsuoka, Kentaro; Abe, Jun; Ito, Shuichi

    2012-12-01

    We report the case of a 28-month-old boy with encephalopathy and acute tubulointerstitial nephritis possibly associated with Yersinia pseudotuberculosis (Yp) infection. He was transferred to our center because of impairment of renal function and altered consciousness. He had fever for 5 days after recurrent vomiting and diarrhea. Computed tomography scan was normal, but electroencephalogram (EEG) analyses showed generalized slow wave patterns. Continuous hemodialysis was undergone and then his renal function was improved, but altered consciousness persisted. Single photon emission computed tomography (SPECT) revealed abnormally low signals at entire field, which suggested that he was suffered from encephalopathy. Phenobarbital administration and post-encephalopathy rehabilitation were started, and he recovered in fully premorbid state with normal EEG and SPECT findings on the 33rd hospital day. Various bacterial cultures were negative, but both Yp antibody and Yp-derived mitogen (YPM) antibody, the antibody of a specific Yp exotoxin, had an extremely high titer. This is the first report of encephalopathy potentially caused by Yp, indicated by the presence of a high Yp and YPM antibody titer.

  14. Unusual manifestations of acute Q fever: autoimmune hemolytic anemia and tubulointerstitial nephritis.

    PubMed

    Korkmaz, Serdal; Elaldi, Nazif; Kayatas, Mansur; Sencan, Mehmet; Yildiz, Esin

    2012-05-18

    Q fever is a worldwide zoonotic infection that caused by Coxiella burnetii, a strict intracellular bacterium. It may be manifested by some of the autoimmune events and is classified into acute and chronic forms. The most frequent clinical manifestation of acute form is a self-limited febrile illness which is associated with severe headache, muscle ache, arthralgia and cough. Meningoencephalitis, thyroiditis, pericarditis, myocarditis, mesenteric lymphadenopathy, hemolytic anemia, and nephritis are rare manifestations. Here we present a case of acute Q fever together with Coombs' positive autoimmune hemolytic anemia (AIHA) and tubulointerstitial nephritis treated with chlarithromycin, steroids and hemodialysis. Clinicians should be aware of such rare manifestations of the disease.

  15. Synthetic Cannabinoid Induced acute Tubulointerstitial Nephritis and Uveitis Syndrome: A Case Report and Review of Literature

    PubMed Central

    Celik, Vedat; Kockar, Alev; Ecder, Tevfik

    2016-01-01

    Tubulointerstitial Nephritis with Uveitis (TINU) syndrome is a rarely seen syndrome. The interstitial nephritis may be with the concurrent uveitis and can also develop before or after uveitis. The syndrome can resolve after elimination of the culprit destructive factors, such as drugs, toxins and immune reaction. Synthetic cannabinoids have emerged as drugs of abuse with increasing popularity among young adults. Recent literature has documented reports of acute kidney injury in association with the use of synthetic cannabinoids; however, there is no report of TINU syndrome development secondary to using of synthetic cannabinoids. Herein, we report a 42-year-old male with TINU syndrome associated with smoking synthetic cannabinoid. PMID:27437289

  16. Fungal granulomatous interstitial nephritis presenting as acute kidney injury diagnosed by renal histology including PCR assay

    PubMed Central

    Ogura, Makoto; Kagami, Shino; Nakao, Masatsugu; Kono, Midori; Kanetsuna, Yukiko; Hosoya, Tatsuo

    2012-01-01

    We describe two cases of fungal granulomatous interstitial nephritis (GIN) presenting as acute kidney injury (AKI). Increased serum creatinine was detected in Patient 1 after chemotherapy for pharyngeal cancer and in Patient 2 after steroid pulse therapy for bronchial asthma. Renal histology of both patients revealed GIN. Polymerase chain reaction (PCR)-based detection of fungal DNA sequences from kidney tissue demonstrated Trichosporon laibachii and Candida albicans, respectively. When AKI occurs in an immunocompromised host, differential diagnosis of fungal interstitial nephritis should be considered. Furthermore, PCR-based detection of fungal DNA sequences from renal specimens can be useful for rapid diagnosis. PMID:23936627

  17. Fungal granulomatous interstitial nephritis presenting as acute kidney injury diagnosed by renal histology including PCR assay.

    PubMed

    Ogura, Makoto; Kagami, Shino; Nakao, Masatsugu; Kono, Midori; Kanetsuna, Yukiko; Hosoya, Tatsuo

    2012-10-01

    We describe two cases of fungal granulomatous interstitial nephritis (GIN) presenting as acute kidney injury (AKI). Increased serum creatinine was detected in Patient 1 after chemotherapy for pharyngeal cancer and in Patient 2 after steroid pulse therapy for bronchial asthma. Renal histology of both patients revealed GIN. Polymerase chain reaction (PCR)-based detection of fungal DNA sequences from kidney tissue demonstrated Trichosporon laibachii and Candida albicans, respectively. When AKI occurs in an immunocompromised host, differential diagnosis of fungal interstitial nephritis should be considered. Furthermore, PCR-based detection of fungal DNA sequences from renal specimens can be useful for rapid diagnosis.

  18. Synthetic Cannabinoid Induced acute Tubulointerstitial Nephritis and Uveitis Syndrome: A Case Report and Review of Literature.

    PubMed

    Sinangil, Ayse; Celik, Vedat; Kockar, Alev; Ecder, Tevfik

    2016-05-01

    Tubulointerstitial Nephritis with Uveitis (TINU) syndrome is a rarely seen syndrome. The interstitial nephritis may be with the concurrent uveitis and can also develop before or after uveitis. The syndrome can resolve after elimination of the culprit destructive factors, such as drugs, toxins and immune reaction. Synthetic cannabinoids have emerged as drugs of abuse with increasing popularity among young adults. Recent literature has documented reports of acute kidney injury in association with the use of synthetic cannabinoids; however, there is no report of TINU syndrome development secondary to using of synthetic cannabinoids. Herein, we report a 42-year-old male with TINU syndrome associated with smoking synthetic cannabinoid. PMID:27437289

  19. Rare allergic reaction of the kidney: sitagliptin-induced acute tubulointerstitial nephritis.

    PubMed

    Alsaad, Ali A; Dhannoon, Sarah M; Pantin, Sally-Ann L; Porter, Ivan E

    2016-01-01

    A 56-year-old man with a history of diabetes mellitus type-2 and stage-2 chronic kidney disease secondary to diabetic nephropathy presented with an acute deterioration of kidney function. Non-invasive work-up failed to reveal the underlying aetiology for the acute kidney failure. Kidney biopsy revealed acute tubulointerstitial nephritis (ATIN) which was attributed to sitagliptin use. Only few case reports have shown this correlation. Our aim is to alert physicians and other providers of the potential effect of sitagliptin to cause ATIN with this biopsy-proven case. PMID:27436034

  20. Outcome of the acute glomerular injury in proliferative lupus nephritis

    SciTech Connect

    Chagnac, A.; Kiberd, B.A.; Farinas, M.C.; Strober, S.; Sibley, R.K.; Hoppe, R.; Myers, B.D. )

    1989-09-01

    Treatment with total lymphoid irradiation (TLI) and corticosteroids markedly reduced activity of systemic lupus erythematosis in 10 patients with diffuse proliferative lupus nephritis (DPLN) complicated by a nephrotic syndrome. Physiologic and morphometric techniques were used serially before, and 12 and 36 mo post-TLI to characterize the course of glomerular injury. Judged by a progressive reduction in the density of glomerular cells and immune deposits, glomerular inflammation subsided. A sustained reduction in the fractional clearance of albumin, IgG and uncharged dextrans of radius greater than 50 A, pointed to a parallel improvement in glomerular barrier size-selectivity. Corresponding changes in GFR were modest, however. A trend towards higher GFR at 12 mo was associated with a marked increase in the fraction of glomerular tuft area occupied by patent capillary loops as inflammatory changes receded. A late trend toward declining GFR beyond 12 mo was associated with progressive glomerulosclerosis, which affected 57% of all glomeruli globally by 36 mo post-TLI. Judged by a parallel increase in volume by 59%, remaining, patent glomeruli had undergone a process of adaptive enlargement. We propose that an increasing fraction of glomeruli continues to undergo progressive sclerosis after DPLN has become quiescent, and that the prevailing GFR depends on the extent to which hypertrophied remnant glomeruli can compensate for the ensuing loss of filtration surface area.

  1. Severe acute interstitial nephritis after combination immune-checkpoint inhibitor therapy for metastatic melanoma

    PubMed Central

    Murakami, Naoka; Borges, Thiago J.; Yamashita, Michifumi; Riella, Leonardo V.

    2016-01-01

    Immune-checkpoint inhibitors are emerging as revolutionary drugs for certain malignancies. However, blocking the co-inhibitory signals may lead to immune-related adverse events, mainly in the spectrum of autoimmune diseases including colitis, endocrinopathies and nephritis. Here, we report a case of a 75-year-old man with metastatic malignant melanoma treated with a combination of nivolumab (anti-PD1-antibody) and ipilimumab (anti-CTLA-4 antibody) who developed systemic rash along with severe acute tubulointerstitial nephritis after two doses of combination therapy. Kidney biopsy and peripheral blood immune profile revealed highly proliferative and cytotoxic T cell features. Herein, we discuss the pathophysiology and management of immune checkpoint blockade-related adverse events. PMID:27274826

  2. Acute Radiation Syndrome

    MedlinePlus

    ... Dictionary Radiation Emergencies & Your Health Possible Health Effects Contamination and Exposure Acute Radiation Syndrome (ARS) Cutaneous Radiation ... Decision Making in Radiation Emergencies Protective Actions Internal Contamination Clinical Reference (ICCR) Application Psychological First Aid in ...

  3. Acute lobar nephritis in children: Not so easy to recognize and manage

    PubMed Central

    Bibalo, Cristina; Apicella, Andrea; Guastalla, Veronica; Marzuillo, Pierluigi; Zennaro, Floriana; Tringali, Carmela; Taddio, Andrea; Germani, Claudio; Barbi, Egidio

    2016-01-01

    Acute lobar nephritis (ALN) is a localized non-liquefactive inflammatory renal bacterial infection, which typically involves one or more lobes. ALN is considered to be a midpoint in the spectrum of upper urinary tract infection, a spectrum ranging from uncomplicated pyelonephritis to intrarenal abscess. This condition may be difficult to recognize due to the lack of specific symptoms and laboratory findings. Therefore the disease is probably underdiagnosed. Computed tomography scanning represents the diagnostic gold standard for ALN, but magnetic resonance imagine could be considered in order to limit irradiation. The diagnosis is relevant since initial intravenous antibiotic therapy and overall length of treatment should not be shorter than 3 wk. We review the literature and analyze the ALN clinical presentation starting from four cases with the aim to give to the clinicians the elements to suspect and recognize the ALN in children. PMID:26862513

  4. Drug-induced acute tubulointerstitial nephritis: a case with elevated urinary cadmium.

    PubMed

    Subat-Dezulović, Mirna; Slavić, Irena; Rozmanić, Vojko; Persić, Mladen; Medjimurec, Branka; Sćukanec-Spoljar, Mira

    2002-05-01

    Acute tubulointerstitial nephritis (ATIN) has many different causes, but is most frequently caused by drugs. We report a 13-year-old vegetarian girl with drug-induced ATIN, confirmed by renal biopsy, and simultaneous occurrence of elevated urinary cadmium. Four weeks prior to admission she had been treated with antibiotics and acetaminophen for respiratory infection, and remaining febrile, was treated with different "home-made" herbal mixtures. She presented with acute non-oliguric renal failure, tubular dysfunction, and sterile pyuria, but without skin rash or edema. Laboratory data showed a raised erythrocyte sedimentation rate, normal white blood count with eosinophilia, and a serum creatinine of 245 micromol/l. Urinalysis was remarkable for glycosuria, tubular proteinuria, and elevated beta(2)-microglobulin and N-acetyl-beta-D-glucosaminidase excretion. Immunoserological tests characteristic of acute glomerulonephritis and systemic diseases were negative. She was treated with steroids and her renal function improved. Follow-up analyses disclosed normal urinary cadmium and enzyme excretion within 6 months. Heavy metal analysis of herbal preparations that she had taken confirmed the presence of cadmium, but within approved concentrations. In conclusion, elevated urinary cadmium in the case of drug-induced ATIN may be assumed to be an accidental finding. However, consumption of different herbs containing cadmium and cadmium-induced nephro-toxicity could be the reason for such serious renal damage. PMID:12042900

  5. Acute poststreptococcal glomerulo-nephritis in general practice: the contribution of infection to its onset and course.

    PubMed

    Higgins, P M

    1996-04-01

    Twenty-one patients considered to have acute poststreptococcal glumerulo-nephritis were encountered during 35 years of general practice. In ten of them good evidence of active streptococcal infection at the time of discovery of nephritis was recorded. The more complete the data the more convincing was the evidence of active infection. In over half of those whose urine were routinely cultured pathogens were isolated and over a third were treated for infection of the urinary tract. Such infections were associated with adverse effects and prolonged illness. As compared with children, adults in general had a longer history of ill-health, were less likely to present with acute infections and more likely to have urinary tract infections and prolonged illness. Vigorous antistreptococcal treatment was followed by rapid recovery in those patients so treated whose illnesses were not complicated by urinary tract infections. Concurrent streptococcal infection and secondary infection of the urinary tract may contribute more to the onset of acute poststreptococcal glomerulo-nephritis and to its course than is currently believed.

  6. Role of WNT10A-expressing kidney fibroblasts in acute interstitial nephritis.

    PubMed

    Kuma, Akihiro; Yamada, Sohsuke; Wang, Ke-Yong; Kitamura, Noriaki; Yamaguchi, Takahiro; Iwai, Yoshiko; Izumi, Hiroto; Tamura, Masahito; Otsuji, Yutaka; Kohno, Kimitoshi

    2014-01-01

    WNT signaling mediates various physiological and pathological processes. We previously showed that WNT10A is a novel angio/stromagenic factor involved in such processes as tumor growth, wound healing and tissue fibrosis. In this study, we investigated the role of WNT10A in promoting the fibrosis that is central to the pathology of acute interstitial nephritis (AIN). We initially asked whether there is an association between kidney function (estimated glomerular filtration rate; eGFR) and WNT10A expression using kidney biopsies from 20 patients with AIN. Interestingly, patients with WNT10A expression had significantly lower eGFR than WNT10A-negative patients. However, changes in kidney function were not related to the level of expression of other WNT family members. Furthermore, there was positive correlation between WNT10A and α-SMA expression. We next investigated the involvement of WNT10A in kidney fibrosis processes using COS1 cells, a kidney fibroblast cell line. WNT10A overexpression increased the level of expression of fibronectin and peroxiredoxin 5. Furthermore, WNT10A overexpression renders cells resistant to apoptosis induced by hydrogen peroxide and high glucose. Collectively, WNT10A may induce kidney fibrosis and associate with kidney dysfunction in AIN. PMID:25054240

  7. Acute radiation risk models

    NASA Astrophysics Data System (ADS)

    Smirnova, Olga

    Biologically motivated mathematical models, which describe the dynamics of the major hematopoietic lineages (the thrombocytopoietic, lymphocytopoietic, granulocytopoietic, and erythropoietic systems) in acutely/chronically irradiated humans are developed. These models are implemented as systems of nonlinear differential equations, which variables and constant parameters have clear biological meaning. It is shown that the developed models are capable of reproducing clinical data on the dynamics of these systems in humans exposed to acute radiation in the result of incidents and accidents, as well as in humans exposed to low-level chronic radiation. Moreover, the averaged value of the "lethal" dose rates of chronic irradiation evaluated within models of these four major hematopoietic lineages coincides with the real minimal dose rate of lethal chronic irradiation. The demonstrated ability of the models of the human thrombocytopoietic, lymphocytopoietic, granulocytopoietic, and erythropoietic systems to predict the dynamical response of these systems to acute/chronic irradiation in wide ranges of doses and dose rates implies that these mathematical models form an universal tool for the investigation and prediction of the dynamics of the major human hematopoietic lineages for a vast pattern of irradiation scenarios. In particular, these models could be applied for the radiation risk assessment for health of astronauts exposed to space radiation during long-term space missions, such as voyages to Mars or Lunar colonies, as well as for health of people exposed to acute/chronic irradiation due to environmental radiological events.

  8. A FURTHER STUDY OF NITROGEN RETENTION IN THE BLOOD IN EXPERIMENTAL ACUTE NEPHRITIS.

    PubMed

    Karsner, H T; Denis, W

    1914-03-01

    These studies, like all studies of the kidney, are difficult of interpretation because of the impossibility of producing a pure glomerular or pure tubular nephritis. Arsenic nephritis in its early stage is physiologically a vascular nephritis, but anatomically tubular, and shows in this stage almost no retention of nitrogen, although studies of urinary nitrogen indicate an increased catabolism. On the other hand, diphtheria nephritis in the early stages is anatomically a nephritis with marked involvement of the glomerulus anatomically, but it is physiologically a tubular form, and in this early stage there is little or no nitrogen retention although studies of metabolism indicate that protein catabolism is increased by the administration of diphtheria toxin. In both cases, however, there appears to come a time when the excreting power of the kidney is exhausted and nitrogen accumulation occurs in the blood. This is much less marked in the arsenic nephritis, with less tubular change, than in diphtheria toxin nephritis with its marked tubular degeneration. This same late accumulation of blood nitrogen is seen in immune serum nephritis, where the tubular changes are persistent and relatively more severe than the glomerular change. It might well be said that this is no argument for the influence of the tubules in the excretion of waste nitrogen because of the general exhaustion of the organism as a whole and of the kidney in particular, and that no positive conclusions can be drawn is indicated by the opening sentence of this summary. Tartrate nephritis was at first considered as purely tubular; but the appearance of occasional glomerular change, as mentioned by Wells in one of his animals, and the fact that the presence of precipitated albumen in the subcapsular space, pointed out by Pearce and Ringer, probably indicates an increased permeability of the tuft capillaries, all lead to the conclusion that although the tubular change predominates, there is, possibly

  9. A FURTHER STUDY OF NITROGEN RETENTION IN THE BLOOD IN EXPERIMENTAL ACUTE NEPHRITIS

    PubMed Central

    Karsner, Howard T.; Denis, W.

    1914-01-01

    These studies, like all studies of the kidney, are difficult of interpretation because of the impossibility of producing a pure glomerular or pure tubular nephritis. Arsenic nephritis in its early stage is physiologically a vascular nephritis, but anatomically tubular, and shows in this stage almost no retention of nitrogen, although studies of urinary nitrogen indicate an increased catabolism. On the other hand, diphtheria nephritis in the early stages is anatomically a nephritis with marked involvement of the glomerulus anatomically, but it is physiologically a tubular form, and in this early stage there is little or no nitrogen retention although studies of metabolism indicate that protein catabolism is increased by the administration of diphtheria toxin. In both cases, however, there appears to come a time when the excreting power of the kidney is exhausted and nitrogen accumulation occurs in the blood. This is much less marked in the arsenic nephritis, with less tubular change, than in diphtheria toxin nephritis with its marked tubular degeneration. This same late accumulation of blood nitrogen is seen in immune serum nephritis, where the tubular changes are persistent and relatively more severe than the glomerular change. It might well be said that this is no argument for the influence of the tubules in the excretion of waste nitrogen because of the general exhaustion of the organism as a whole and of the kidney in particular, and that no positive conclusions can be drawn is indicated by the opening sentence of this summary. Tartrate nephritis was at first considered as purely tubular; but the appearance of occasional glomerular change, as mentioned by Wells in one of his animals, and the fact that the presence of precipitated albumen in the subcapsular space, pointed out by Pearce and Ringer, probably indicates an increased permeability of the tuft capillaries, all lead to the conclusion that although the tubular change predominates, there is, possibly

  10. Association of Acute Interstitial Nephritis with Carnivora, a Venus Flytrap Extract, in a 30-Year-Old Man with Hodgkin's Lymphoma

    PubMed Central

    Ziolkowski, Susan; Moore, Catherine

    2014-01-01

    Acute interstitial nephritis (AIN) is a common cause of acute kidney injury and has been associated with a variety of medications. This is the case of 30-year-old man with Hodgkin's lymphoma who on routine labs before chemotherapy was found to have acute nonoliguric renal failure. A kidney biopsy was performed and confirmed the diagnosis of acute interstitial nephritis. The patient had taken several medications including a higher dose of Carnivora, a Venus flytrap extract, composed of numerous amino acids. The medication was discontinued and kidney function improved towards the patient's baseline indicating that this may be the possible cause of his AIN. Proximal tubular cell uptake of amino acids increasing transcription of nuclear factor-kappaB is a proposed mechanism of AIN from this compound. PMID:24839571

  11. Association of Acute Interstitial Nephritis with Carnivora, a Venus Flytrap Extract, in a 30-Year-Old Man with Hodgkin's Lymphoma.

    PubMed

    Ziolkowski, Susan; Moore, Catherine

    2014-01-01

    Acute interstitial nephritis (AIN) is a common cause of acute kidney injury and has been associated with a variety of medications. This is the case of 30-year-old man with Hodgkin's lymphoma who on routine labs before chemotherapy was found to have acute nonoliguric renal failure. A kidney biopsy was performed and confirmed the diagnosis of acute interstitial nephritis. The patient had taken several medications including a higher dose of Carnivora, a Venus flytrap extract, composed of numerous amino acids. The medication was discontinued and kidney function improved towards the patient's baseline indicating that this may be the possible cause of his AIN. Proximal tubular cell uptake of amino acids increasing transcription of nuclear factor-kappaB is a proposed mechanism of AIN from this compound.

  12. CCR7 Deficiency Exacerbates Injury in Acute Nephritis Due to Aberrant Localization of Regulatory T Cells

    PubMed Central

    Eller, Kathrin; Weber, Tobias; Pruenster, Monika; Wolf, Anna M.; Mayer, Gert

    2010-01-01

    The homing of dendritic cells and T cells to secondary lymphoid organs requires chemokine receptor 7 (CCR7) expression on these cells. T cells mediate the pathogenesis of experimental accelerated nephrotoxic serum nephritis (NTS), including its suppression by regulatory T cells (Tregs), but the contribution of CCR7 to this disease is unknown. Here, we compared the development of NTS in CCR7-knockout (KO) and wild-type (WT) mice. Compared with WT mice, CCR7KO mice developed more severe disease with significantly more inflammatory cells infiltrating the kidney. These cells included FoxP3+ Tregs, which were virtually absent from WT kidneys. The adoptive transfer of WT Tregs into CCR7KO mice at the time of immunization protected the recipients from disease; these cells homed to secondary lymphoid organs but not to kidneys. Conversely, adoptive transfer of CCR7KO Tregs into WT mice did not inhibit development of NTS. These data suggest that NTS can develop without CCR7 expression, but Treg-mediated disease suppression, which seems to occur in secondary lymphoid organs, requires CCR7. PMID:19917782

  13. A patient with minimal change disease and acute focal tubulointerstitial nephritis due to traditional medicine: a case report and small literature review.

    PubMed

    Lee, Keun-Hyeun; Jeong, Han-Sol; Rhee, Harin

    2014-01-01

    Gongjin-dan (GJD) is a traditional formula that is widely used in Korea and China, and it has been used from 1345 AD in China to improve the circulation between the kidneys and the heart and to prevent all diseases. However, its adverse effects have not yet been reported. We present a patient with minimal change disease and focal tubulointerstitial nephritis associated with GJD. A 72-year-old man visited the clinic for generalized edema 20 days after starting GJD. His serum albumin level was low and nephrotic-range proteinuria was detected. A kidney biopsy showed minimal change disease and acute tubulointerstitial nephritis. After stopping GJD, a spontaneous complete remission was achieved. We discuss the possible pathogenesis of GJD-induced minimal change disease and review the adverse effects of GJD's ingredients and traditional Chinese medicines that can induce proteinuria. We report a new adverse effect of GJD, which might induce increased IL-13 production and an allergic response, leading to minimal change disease and focal tubulointerstitial nephritis.

  14. Lupus nephritis.

    PubMed

    Agrawal, Neerja; Chiang, Lo-Ku; Rifkin, Ian R

    2006-03-01

    Lupus nephritis is one of the more serious manifestations of the systemic autoimmune disease, systemic lupus erythematosus, and is associated with considerable morbidity and even mortality. Treatment remains problematic, particularly in terms of controlling the underlying disease process while at the same time preventing unacceptable side effects of therapy. In recent years, clinical trials have started to define optimum regimens of the immunosuppressive agents presently in use. The etiology and pathogenesis of systemic lupus erythematosus and lupus nephritis still are understood incompletely. Nevertheless, insights gained from basic science research in both animals and human beings now are being translated into newer therapies that have the potential to be safer and more specific than those currently available.

  15. Interstitial nephritis.

    PubMed Central

    Dixon, A J; Winearls, C G; Dunnill, M S

    1981-01-01

    The clinical and pathological findings are reviewed in ten cases where renal biopsy showed abnormalities predominantly within the interstitium. In six the nephritis was considered to be drug-induced; in two the aetiology was slightly obscure but the most likely diagnosis was considered to be sarcoidosis. Of the remaining two cases one was chronic pyelonephritis and the other polyarteritis nodosa. The diagnosis and pathogenesis of the renal lesions are discussed and attention is drawn to the importance of distinguishing primary interstitial changes from those found in association with glomerular disease. Images PMID:7251904

  16. [Treatment and prevention of acute radiation dermatitis].

    PubMed

    Benomar, S; Boutayeb, S; Lalya, I; Errihani, H; Hassam, B; El Gueddari, B K

    2010-06-01

    Acute radiation dermatitis is a common side-effect of radiotherapy which often necessitates interruption of the therapy. Currently, there is no general consensus about its prevention or about the treatment of choice. The goal of this work was to focus on optimal methods to prevent and manage acute skin reactions related to radiation therapy and to determine if there are specific topical or oral agents for the prevention of this acute skin reaction. The prevention and the early treatment are the two focus points of the management of the acute radiation dermatitis.

  17. Omeprazole-induced acute interstitial nephritis is not related to CYP2C19 genotype or CYP2C19 phenotype

    PubMed Central

    Helsby, Nuala A; Lo, Wing-Yee; Simpson, Ian J; Voss, David M; Logan, Kaye E; Searle, Martin; Schollum, John B W; de Zoysa, Janak R

    2010-01-01

    AIM Omeprazole-induced acute interstitial nephritis (OIAIN) is a rare adverse event. It is unknown if this is an idiosyncratic immune mediated reaction or if it relates to direct drug toxicity. Individuals who are homozygous for the variant alleles of CYP2C19 are poor metabolizers of omeprazole and have a greater exposure to the drug. The aim of this study was to determine the prevalence of the CYP2C19 poor metabolizer genotype and phenotype in patients with OIAIN. METHODS Twenty patients were genotyped for the CYP2C19 variant alleles (*2, 681G>A and *3, 636G>A) by RFLP-PCR analysis and eighteen phenotyped for CYP2C19 metabolizer status. RESULTS The frequency of the CYP2C19*2 allelic variant was 12.5%, no *3 allelic variants were detected and no patient was a homozygous variant genotype. This was not different from the expected frequency. 33% of subjects were phenotypically CYP2C19 poor metabolizers. CONCLUSIONS There was discordance between CYP2C19 genotype and phenotype. However, up to 45% of healthy elderly subjects have a poor metabolizer phenotype. Thus neither CYP2C19 poor metabolizer genotype nor phenotype is a risk factor for OIAIN. PMID:20573087

  18. Reversible Fluindione-Induced Chronic Interstitial Nephritis

    PubMed Central

    Crepin, Thomas; Bamoulid, Jamal; Courivaud, Cécile; Dahmani, Omar; Felix, Sophie; Ducloux, Didier

    2016-01-01

    Fluindione is well known to induce acute drug-induced interstitial nephritis (IN). Most cases occurred soon after the onset of treatment. We report a unique case of severe subacute fluindione-induced IN diagnosed 2 years after the treatment was begun. Renal function dramatically improved after fluindione withdrawal and steroid therapy. PMID:27127666

  19. [Evaluation and management of acute radiation dermatitis].

    PubMed

    Modesto, A; Faivre, J-C; Granel-Brocard, F; Tao, Y-G; Pointreau, Y

    2012-09-01

    Acute radiation dermatitis remains one of the most commonly observed side effect during radiation therapy leading to complication such as superinfection or treatment disruption. Its management is characterized by a great heterogeneity. Few strategies have demonstrated a benefit in preventing radiation dermatitis, which relies mostly on decreasing dose delivered to the skin and skin care practices. Simple emollients and use of topical steroids can be useful in early stages. The singularity of the skin toxicity seen with cetuximab and radiotherapy warrants a specific grading system and distinctive clinical treatment with use of antibiotics.

  20. Health Impacts from Acute Radiation Exposure

    SciTech Connect

    Strom, Daniel J.

    2003-09-30

    Absorbed doses above1-2 Gy (100-200 rads) received over a period of a day or less lead to one or another of the acute radiation syndromes. These are the hematopoietic syndrome, the gastrointestinal (GI) syndrome, the cerebrovascular (CV) syndrome, the pulmonary syndrome, or the cutaneous syndrome. The dose that will kill about 50% of the exposed people within 60 days with minimal medical care, LD50-60, is around 4.5 Gy (450 rads) of low-LET radiation measured free in air. The GI syndrome may not be fatal with supportive medical care and growth factors below about 10 Gy (1000 rads), but above this is likely to be fatal. Pulmonary and cutaneous syndromes may or may not be fatal, depending on many factors. The CV syndrome is invariably fatal. Lower acute doses, or protracted doses delivered over days or weeks, may lead to many other health outcomes than death. These include loss of pregnancy, cataract, impaired fertility or temporary or permanent sterility, hair loss, skin ulceration, local tissue necrosis, developmental abnormalities including mental and growth retardation in persons irradiated as children or fetuses, radiation dermatitis, and other symptoms listed in Table 2 on page 12. Children of parents irradiated prior to conception may experience heritable ill-health, that is, genetic changes from their parents. These effects are less strongly expressed than previously thought. Populations irradiated to high doses at high dose rates have increased risk of cancer incidence and mortality, taken as about 10-20% incidence and perhaps 5-10% mortality per sievert of effective dose of any radiation or per gray of whole-body absorbed dose low-LET radiation. Cancer risks for non-uniform irradiation will be less.

  1. Medical management of the acute radiation syndrome

    PubMed Central

    López, Mario; Martín, Margarita

    2011-01-01

    The acute radiation syndrome (ARS) occurs after whole-body or significant partial-body irradiation (typically at a dose of >1 Gy). ARS can involve the hematopoietic, cutaneous, gastrointestinal and the neurovascular organ systems either individually or in combination. There is a correlation between the severity of clinical signs and symptoms of ARS and radiation dose. Radiation induced multi-organ failure (MOF) describes the progressive dysfunction of two or more organ systems over time. Radiation combined injury (RCI) is defined as radiation injury combined with blunt or penetrating trauma, burns, blast, or infection. The classic syndromes are: hematopoietic (doses >2–3 Gy), gastrointestinal (doses 5–12 Gy) and cerebrovascular syndrome (doses 10–20 Gy). There is no possibility to survive after doses >10–12 Gy. The Phases of ARS are—prodromal: 0–2 days from exposure, latent: 2–20 days, and manifest illness: 21–60 days from exposure. Granulocyte-colony stimulating factor (G-CSF) at a dose of 5 μg/kg body weight per day subcutaneously has been recommended as treatment of neutropenia, and antibiotics, antiviral and antifungal agents for prevention or treatment of infections. If taken within the first hours of contamination, stable iodine in the form of nonradioactive potassium iodide (KI) saturates iodine binding sites within the thyroid and inhibits incorporation of radioiodines into the gland. Finally, if severe aplasia persists under cytokines for more than 14 days, the possibility of a hematopoietic stem cell (HSC) transplantation should be evaluated. This review will focus on the clinical aspects of the ARS, using the European triage system (METREPOL) to evaluate the severity of radiation injury, and scoring groups of patients for the general and specific management of the syndrome. PMID:24376971

  2. Mesenchymal stem cell therapy for acute radiation syndrome.

    PubMed

    Fukumoto, Risaku

    2016-01-01

    Acute radiation syndrome affects military personnel and civilians following the uncontrolled dispersal of radiation, such as that caused by detonation of nuclear devices and inappropriate medical treatments. Therefore, there is a growing need for medical interventions that facilitate the improved recovery of victims and patients. One promising approach may be cell therapy, which, when appropriately implemented, may facilitate recovery from whole body injuries. This editorial highlights the current knowledge regarding the use of mesenchymal stem cells for the treatment of acute radiation syndrome, the benefits and limitations of which are under investigation. Establishing successful therapies for acute radiation syndrome may require using such a therapeutic approach in addition to conventional approaches. PMID:27182446

  3. Karyomegalic Interstitial Nephritis

    PubMed Central

    Isnard, Pierre; Rabant, Marion; Labaye, Jacques; Antignac, Corinne; Knebelmann, Bertrand; Zaidan, Mohamad

    2016-01-01

    Abstract Karyomegalic interstitial nephritis is a rare cause of hereditary chronic interstitial nephritis, described for the first time over 40 years ago. A 36-year-old woman, of Turkish origin, presented with chronic kidney disease and high blood pressure. She had a history of recurrent upper respiratory tract infections but no familial history of nephropathy. Physical examination was unremarkable. Laboratory tests showed serum creatinine at 2.3 mg/dL with an estimated glomerular filtration rate of 26 mL/min/1.73m2, and gamma-glutamyl transpeptidase and alkaline phosphatase at 3 and 1.5 times the upper normal limit. Urinalysis showed 0.8 g/day of nonselective proteinuria, microscopic hematuria, and aseptic leukocyturia. Immunological tests and tests for human immunodeficiency and hepatitis B and C viruses were negative. Complement level and serum proteins electrophoresis were normal. Analysis of the renal biopsy showed severe interstitial fibrosis and tubular atrophy. Numerous tubular cells had nuclear enlargement with irregular outlines, hyperchromatic aspect, and prominent nucleoli. These findings were highly suggestive of karyomegalic interstitial nephritis, which was further confirmed by exome sequencing of FAN1 gene showing an identified homozygous frameshift mutation due to a one-base-pair deletion in exon 12 (c.2616delA). The present case illustrates a rare but severe cause of hereditary interstitial nephritis, sometimes accompanied by subtle extrarenal manifestations. Identification of mutations in FAN1 gene underscores recent insights linking inadequate DNA repair and susceptibility to chronic kidney disease. PMID:27196444

  4. Acute parotitis and hyperamylasemia following whole-brain radiation therapy

    SciTech Connect

    Cairncross, J.G.; Salmon, J.; Kim, J.H.; Posner, J.B.

    1980-04-01

    Parotitis, an infrequent, previously unreported complication of whole-brain radiation therapy, was observed in 4 patients. The acute symptoms, which include fever, dry mouth, pain, swelling, and tenderness, are accompanied by hyperamylasemia. Among 10 patients receiving whole-brain irradiation, 8 had serum amylase elevations without symptoms. Both acute parotitis and asymptomatic hyperamylasemia result from irradiation of the parotid glands.

  5. Pregnancy and Lupus Nephritis.

    PubMed

    Kattah, Andrea G; Garovic, Vesna D

    2015-09-01

    The management of lupus nephritis in pregnancy presents a diagnostic and therapeutic challenge for providers. Pregnancy creates a series of physiologic changes in the immune system and kidney that may result in an increased risk of disease flare and adverse maternal and fetal outcomes, such as preeclampsia, fetal loss, and preterm delivery. Conception should be delayed until disease is in remission to ensure the best pregnancy outcomes. Maternal disease activity and fetal well-being should be monitored closely by an interdisciplinary team, including obstetricians, rheumatologists, and nephrologists throughout pregnancy. Careful attention must be paid to the dosing and potential teratogenicity of medications.

  6. Pregnancy and Lupus Nephritis.

    PubMed

    Kattah, Andrea G; Garovic, Vesna D

    2015-09-01

    The management of lupus nephritis in pregnancy presents a diagnostic and therapeutic challenge for providers. Pregnancy creates a series of physiologic changes in the immune system and kidney that may result in an increased risk of disease flare and adverse maternal and fetal outcomes, such as preeclampsia, fetal loss, and preterm delivery. Conception should be delayed until disease is in remission to ensure the best pregnancy outcomes. Maternal disease activity and fetal well-being should be monitored closely by an interdisciplinary team, including obstetricians, rheumatologists, and nephrologists throughout pregnancy. Careful attention must be paid to the dosing and potential teratogenicity of medications. PMID:26573551

  7. Radionuclide scintigraphy of bacterial nephritis

    SciTech Connect

    Conway, J.J.; Weiss, S.C.; Shkolnik, A.; Yogev, R.; Firlit, C.; Traisman, E.S.

    1984-01-01

    Pyelonephritis is a leading cause of renal failure and is expected to cost as much as three billion dollars in 1984. The diagnosis of urinary tract infection is usually not difficult. However, localization of the infection within the renal parenchyma as opposed to the collecting system is much more difficult. Flank pain, fever, bacteiuria and evidence of parenchymal involvement by intravenous urography may be absent or unrecognized particularly in the infant. Ultrasound and Nuclear Medicine are advocated as better methods to define parenchymal involvement. Such definition is important in the consideration of treatment since parenchymal involvement of the kidney carries a much more ominous potential outcome than infection restricted to within the collecting system. 38 children with a clinical diagnosis of urinary tract infection were studied. 26 of the patients demonstrated abnormal renal parenchymal findings with Gallium-67 Citrate or Tc-99m Glucoheptonate scintigraphy. Intravenous urography was notably ineffective with only 5 of the 20 interpreted as abnormal due to parenchymal disease or decreased function. 11 were entirely normal while only 5 demonstrated scars or hydronephrosis. Only 10 of 17 patients demonstrated intranvesicoureteral reflux on x-ray or nuclear cystography. Ultrasound depicted 6 of 20 patients as having parenchymal abnormalities. Seven were normal. Nonspecific findings such as dilitation of the renal pelvis or renal enlargement was noted in 11 of the 20 patients. Radionuclide Scintigraphy is the most efficacious modality to detect since acute bacterial nephritis.

  8. Acute Cerebrovascular Radiation Syndrome: Radiation Neurotoxicity , mechanisms of CNS radiation injury, advanced countermeasures for Radiation Protection of Central Nervous System.

    NASA Astrophysics Data System (ADS)

    Popov, Dmitri; Jones, Jeffrey; Maliev, Slava

    Key words: Cerebrovascular Acute Radiation Syndrome (Cv ARS), Radiation Neurotoxins (RNT), Neurotransmitters, Radiation Countermeasures, Antiradiation Vaccine (ArV), Antiradiation Blocking Antibodies, Antiradiation Antidote. Psychoneuroimmunology, Neurotoxicity. ABSTRACT: To review the role of Radiation Neurotoxins in triggering, developing of radiation induced central nervous system injury. Radiation Neurotoxins - rapidly acting blood toxic lethal agent, which activated after irradiation and concentrated, circulated in interstitial fluid, lymph, blood with interactions with cell membranes, receptors and cell compartments. Radiation Neurotoxins - biological molecules with high enzymatic activity and/or specific lipids and activated or modified after irradiation. The Radiation Neurotoxins induce increased permeability of blood vessels, disruption of the blood-brain barrier, blood-cerebrospinal fluid (CSF) barrier and developing severe disorder of blood macro- and micro-circulation. Principles of Radiation Psychoneuro-immunology and Psychoneuro-allergology were applied for determination of pathological processes developed after irradiation or selective administration of Radiation Neurotoxins to radiation naïve mammals. Effects of radiation and exposure to radiation can develop severe irreversible abnormalities of Central Nervous System, brain structures and functions. Antiradiation Vaccine - most effective, advanced methods of protection, prevention, mitigation and treatment and was used for of Acute Radiation Syndromes and elaboration of new technology for immune-prophylaxis and immune-protection against ϒ, Heavy Ion, Neutron irradiation. Results of experiments suggested that blocking, antitoxic, antiradiation antibodies can significantly reduce toxicity of Radiation Toxins. New advanced technology include active immune-prophylaxis with Antiradiation Vaccine and Antiradiation therapy that included specific blocking antibodies to Radiation Neurotoxins

  9. Antiradiation Vaccine: Immunological neutralization of Radiation Toxins at Acute Radiation Syndromes.

    NASA Astrophysics Data System (ADS)

    Popov, Dmitri; Maliev, Slava

    Introduction: Current medical management of the Acute Radiation Syndromes (ARS) does not include immune prophylaxis based on the Antiradiation Vaccine. Existing principles for the treatment of acute radiation syndromes are based on the replacement and supportive therapy. Haemotopoietic cell transplantation is recomended as an important method of treatment of a Haemopoietic form of the ARS. Though in the different hospitals and institutions, 31 pa-tients with a haemopoietic form have previously undergone transplantation with stem cells, in all cases(100%) the transplantants were rejected. Lethality rate was 87%.(N.Daniak et al. 2005). A large amount of biological substances or antigens isolated from bacterias (flagellin and derivates), plants, different types of venom (honeybees, scorpions, snakes) have been studied. This biological active substances can produce a nonspecific stimulation of immune system of mammals and protect against of mild doses of irradiation. But their radioprotection efficacy against high doses of radiation were not sufficient. Relative radioprotection characteristics or adaptive properties of antioxidants were expressed only at mild doses of radiation. However antioxidants demonstrated a very low protective efficacy at high doses of radiation. Some ex-periments demonstrated even a harmful effect of antioxidants administered to animals that had severe forms of the ARS. Only Specific Radiation Toxins roused a specific antigenic stim-ulation of antibody synthesis. An active immunization by non-toxic doses of radiation toxins includes a complex of radiation toxins that we call the Specific Radiation Determinant (SRD). Immunization must be provided not less than 24 days before irradiation and it is effective up to three years and more. Active immunization by radiation toxins significantly reduces the mortality rate (100%) and improves survival rate up to 60% compare with the 0% sur-vival rate among the irradiated animals in control groups

  10. Antiradiation Vaccine: Immunological neutralization of Radiation Toxins at Acute Radiation Syndromes.

    NASA Astrophysics Data System (ADS)

    Popov, Dmitri; Maliev, Slava

    Introduction: Current medical management of the Acute Radiation Syndromes (ARS) does not include immune prophylaxis based on the Antiradiation Vaccine. Existing principles for the treatment of acute radiation syndromes are based on the replacement and supportive therapy. Haemotopoietic cell transplantation is recomended as an important method of treatment of a Haemopoietic form of the ARS. Though in the different hospitals and institutions, 31 pa-tients with a haemopoietic form have previously undergone transplantation with stem cells, in all cases(100%) the transplantants were rejected. Lethality rate was 87%.(N.Daniak et al. 2005). A large amount of biological substances or antigens isolated from bacterias (flagellin and derivates), plants, different types of venom (honeybees, scorpions, snakes) have been studied. This biological active substances can produce a nonspecific stimulation of immune system of mammals and protect against of mild doses of irradiation. But their radioprotection efficacy against high doses of radiation were not sufficient. Relative radioprotection characteristics or adaptive properties of antioxidants were expressed only at mild doses of radiation. However antioxidants demonstrated a very low protective efficacy at high doses of radiation. Some ex-periments demonstrated even a harmful effect of antioxidants administered to animals that had severe forms of the ARS. Only Specific Radiation Toxins roused a specific antigenic stim-ulation of antibody synthesis. An active immunization by non-toxic doses of radiation toxins includes a complex of radiation toxins that we call the Specific Radiation Determinant (SRD). Immunization must be provided not less than 24 days before irradiation and it is effective up to three years and more. Active immunization by radiation toxins significantly reduces the mortality rate (100%) and improves survival rate up to 60% compare with the 0% sur-vival rate among the irradiated animals in control groups

  11. Acute radiation syndrones and their management

    SciTech Connect

    Cronkite, E.P.

    1988-01-01

    Radiation syndromes produced by large doses of ionizing radiation are divided into three general groups depending on dose of radiation and time after exposure. The CNS syndrome requires many thousands of rad, appears in minutes to hours, and kills within hours to days. The GIS appears after doses of a few hundred to 2000 rad. It is characterized by nausea, vomiting, diarrhea, and disturbances of water and electrolyte metabolism. It has a high mortality in the first week after exposure. Survivors will then experience the HS as a result of marrow aplasia. Depending on dose, survival is possible with antibiotic and transfusion therapy. The relationship of granulocyte depression to mortality in dogs and human beings is illustrated. The role of depth dose pattern of mortality of radiation exposure is described and used as an indication of why air exposure doses may be misleading. The therapy of radiation injury is described based on antibiotics, transfusion therapy, and use of molecular regulators. The limited role of matched allogenic bone marrow transplants is discussed. 52 refs., 13 figs.

  12. Medical mitigation strategies for acute radiation exposure during spaceflight.

    PubMed

    Epelman, Slava; Hamilton, Douglas R

    2006-02-01

    The United States Government has recently refocused their space program on manned missions to the Moon by 2018 and later to Mars. While there are many potential risks associated with exploration-class missions, one of the most serious and unpredictable is the effect of acute space radiation exposure, and the space program must make every reasonable effort to mitigate this risk. The two cosmic sources of radiation that could impact a mission outside the Earth's magnetic field are solar particle events (SPE) and galactic cosmic radiation (GCR). Either can cause acute and chronic medical illness. Numerous researchers are currently examining the ability of GCR exposure to induce the development of genetic changes that lead to malignancies and other delayed effects. However, relatively little has been published on the medical management of an acute SPE event and the potential impact on the mission and crew. This review paper will provide the readers with medical management options for an acute radiation event based on recommendations from the Department of Homeland Security (DHS), Centers for Disease Control (CDC), and evidence-based critical analysis of the scientific literature. It is the goal of this paper to stimulate debate regarding the definition of safety parameters for exploration-class missions to determine the level of medical care necessary to provide for the crew that will undertake such missions.

  13. Medical mitigation strategies for acute radiation exposure during spaceflight.

    PubMed

    Epelman, Slava; Hamilton, Douglas R

    2006-02-01

    The United States Government has recently refocused their space program on manned missions to the Moon by 2018 and later to Mars. While there are many potential risks associated with exploration-class missions, one of the most serious and unpredictable is the effect of acute space radiation exposure, and the space program must make every reasonable effort to mitigate this risk. The two cosmic sources of radiation that could impact a mission outside the Earth's magnetic field are solar particle events (SPE) and galactic cosmic radiation (GCR). Either can cause acute and chronic medical illness. Numerous researchers are currently examining the ability of GCR exposure to induce the development of genetic changes that lead to malignancies and other delayed effects. However, relatively little has been published on the medical management of an acute SPE event and the potential impact on the mission and crew. This review paper will provide the readers with medical management options for an acute radiation event based on recommendations from the Department of Homeland Security (DHS), Centers for Disease Control (CDC), and evidence-based critical analysis of the scientific literature. It is the goal of this paper to stimulate debate regarding the definition of safety parameters for exploration-class missions to determine the level of medical care necessary to provide for the crew that will undertake such missions. PMID:16491581

  14. MODELING ACUTE EXPOSURE TO SOLAR RADIATION

    EPA Science Inventory

    One of the major technical challenges in calculating solar flux on the human form has been the complexity of the surface geometry (i.e., the surface normal vis a vis the incident radiation). The American Cancer Society reports that over 80% of skin cancers occur on the face, he...

  15. Granulomatous Interstitial Nephritis Presenting as Hypercalcemia and Nephrolithiasis

    PubMed Central

    Sharmeen, Saika; Kalkan, Esra; Yi, Chunhui; Smith, Steven D.

    2016-01-01

    We report a case of acute kidney injury as the initial manifestation of sarcoidosis. A 55-year-old male was sent from his primary care physician's office with incidental lab findings significant for hypercalcemia and acute kidney injury with past medical history significant for nephrolithiasis. Initial treatment with intravenous hydration did not improve his condition. The renal biopsy subsequently revealed granulomatous interstitial nephritis (GIN). Treatment with the appropriate dose of glucocorticoids improved both the hypercalcemia and renal function. Our case demonstrates that renal limited GIN due to sarcoidosis, although a rare entity, can cause severe acute kidney injury and progressive renal failure unless promptly diagnosed and treated. PMID:26904327

  16. Mitigation Strategies for Acute Radiation Exposure during Space Flight

    NASA Technical Reports Server (NTRS)

    Hamilton, Douglas R.; Epelman, Slava

    2006-01-01

    While there are many potential risks in a Moon or Mars mission, one of the most important and unpredictable is that of crew radiation exposure. The two forms of radiation that impact a mission far from the protective environment of low-earth orbit, are solar particle events (SPE) and galactic cosmic radiation (GCR). The effects of GCR occur as a long-term cumulative dose that results increased longer-term medical risks such as malignancy and neurological degeneration. Unfortunately, relatively little has been published on the medical management of an acute SPE that could potentially endanger the mission and harm the crew. Reanalysis of the largest SPE in August 1972 revealed that the dose rate was significantly higher than previously stated in the literature. The peak dose rate was 9 cGy h(sup -1) which exceeds the low-dose-rate criteria for 25 hrs (National Council on Radiation Protection) and 16 hrs (United Nations Scientific Committee on the Effects of Atomic Radiation). The bone marrow dose accumulated was 0.8 Gy, which exceeded the 25 and 16 hour criteria and would pose a serious medical risk. Current spacesuits would not provide shielding from the damaging effects for an SPE as large as the 1972 event, as increased shielding from 1-5 gm/cm(sup 2) would do little to shield the bone marrow from exposure. Medical management options for an acute radiation event are discussed based on recommendations from the Department of Homeland Security, Centers for Disease Control and evidence-based scientific literature. The discussion will also consider how to define acute exposure radiation safety limits with respect to exploration-class missions, and to determine the level of care necessary for a crew that may be exposed to an SPE similar to August 1972.

  17. Mitigation Strategies for Acute Radiation Exposure during Space Flight

    NASA Technical Reports Server (NTRS)

    Hamilton, Douglas R.; Epelman, Slava

    2006-01-01

    While there are many potential risks in a Moon or Mars mission, one of the most important and unpredictable is that of crew radiation exposure. The two forms of radiation that impact a mission far from the protective environment of low-earth orbit, are solar particle events (SPE) and galactic cosmic radiation (GCR). The effects of GCR occur as a long-term cumulative dose that results increased longer-term medical risks such as malignancy and neurological degeneration. Unfortunately, relatively little has been published on the medical management of an acute SPE that could potentially endanger the mission and harm the crew. Reanalysis of the largest SPE in August 1972 revealed that the dose rate was significantly higher than previously stated in the literature. The peak dose rate was 9 cGy h(sup -1) which exceeds the low dose-rate criteria for 25 hrs (National Council on Radiation Protection) and 16 hrs (United Nations Scientific Committee on the Effects of Atomic Radiation). The bone marrow dose accumulated was 0.8 Gy, which exceeded the 25 and 16 hour criteria and would pose a serious medical risk. Current spacesuits would not provide shielding from the damaging effects for an SPE as large as the 1972 event, as increased shielding from 1-5 grams per square centimeters would do little to shield the bone marrow from exposure. Medical management options for an acute radiation event are discussed based on recommendations from the Department of Homeland Security, Centers for Disease Control and evidence-based scientific literature. The discussion will also consider how to define acute exposure radiation safety limits with respect to exploration-class missions, and to determine the level of care necessary for a crew that may be exposed to an SPE similar to August 1972.

  18. Interstitial nephritis. A brief review.

    PubMed Central

    Heptinstall, R. H.

    1976-01-01

    Interstitial nephritis is a common condition, which in spite of a relatively constant pathologic picture has different etiologic agents and pathogenetic mechanisms. Failure to appreciate this, particularly in the chronic group, has led to considerable confusion and has been largely responsible for the overdiagnosis of chronic pyelonephritis. Although we are still largely ignorant of the causes of interstitial nephritis, it is now possible to define many of them. While experimental studies have not made spectacular contributions to our understanding, an attempt is now being made to develop appropriate models, and we hope these will enable us to still further clarify our understanding of other entities. PMID:776003

  19. Immunotherapy of acute radiation syndromes with antiradiation gamma G globulin.

    NASA Astrophysics Data System (ADS)

    Popov, Dmitri; Maliev, Vecheslav; Casey, Rachael; Jones, Jeffrey; Kedar, Prasad

    Introduction: If an immunotherapy treatment approach to treatment of acute radiation syndromes (ARS) were to be developed; consideration could be given to neutralization of radiation toxins (Specific Radiation Determinants- SRD) by specific antiradiation antibodies. To accomplish this objective, irradiated animals were injected with a preparation of antiradiation immunoglobulin G (IgG) obtained from hyperimmune donors. Radiation-indeced toxins that we call Specific Radiation Determinants (SRD) possess toxic (neurotoxic, haemotoxic and enterotoxic) characteristics as well as specific antigenic properties that combined with the direct physiochemical direct radiation damage, induce the development of many of the pathological processes associated with ARS. We tested several specific hyperimmune IgG preparations against these radiation toxins and observed that their toxic properties were neutralized by specific antiradiation IgGs. Material and Methods: Rabbits were inoculated with SRD radiation toxins to induce hyperimmune serum. The hyperimmune serum was pooled from several animals, purified, and concentrated. Enzyme-linked immunosorbent assays of the hyperimmune serum revealed high titers of IgG with specific binding to radiation toxins. The antiradiation IgG preparation was injected into laboratory animals one hour before and three hours after irradiation, and was evaluated for its ability to protect inoculated animals against the development of acute radiation syndromes. Results: Animals that were inoculated with specific antiradiation antibodies before receiving lethal irradiation at LD 100/30 exhibited 60-75% survival rate at 30 days, whereas all control animals expired by 30 days following exposure. These inoculated animals also exhibited markedly reduced clinical symptoms of ARS, even those that did not survive irradiation. Discussion: The results of our experiments demonstrate that rabbit hyperimmune serum directed against SRD toxins afford significant, albeit

  20. Acute Radiation Disease : Cutaneous Syndrome and Toxic properties of Radiomimetics -Radiation Neurotoxins and Hematotoxins.

    NASA Astrophysics Data System (ADS)

    Popov, Dmitri; Maliev, Slava

    Cutaneous injury is an important complication of a general or local acute irradiation. A type of a skin and tissues lesions depends on a type, intensity, and period of irradiation. Also, the clinical picture, signs, and manifestations of the cutaneous syndrome depend on a type of the radiation toxins circulated in lymph and blood of irradiated mammals. Radiation Toxins were isolated from lymph of the mammals that were irradiated and developed different forms of the Acute Radiation Syndromes (ARS) -Cerebrovascular, Cardiovascular, Gastrointestinal, and Hematopoietic. Radiation Toxins can be divided into the two important types of toxins (Neu-rotoxins and Hematotoxins) or four groups. The effects of Radiation Neurotoxins include severe damages and cell death of brain, heart, gastrointestinal tissues and endothelial cells of blood and lymphatic vessels. The hematotoxicity of Hematotoxic Radiation Toxins includes lym-phopenia, leukopenia, thrombocytopenia, and anemia in the blood circulation and transitory lymphocytosis and leukocytosis in the Central Lymphatic System. In all cases, administration of the Radiomimetics (Radiation Toxins) intramuscularly or intravenously to healthy, radiation naive mammals had induced and developed the typical clinical manifestations of the ARS. In all cases, administration of Radiomimetics by subtoxic doses had demonstrated development of typical clinical signs of the cutaneous syndrome such as hair loss, erythema, swelling, desqua-mation, blistering and skin necrosis. In animal-toxic models, we have activated development of the local skin and tissue injury after injection of Radiation Toxins with cytoxic properties.

  1. Cerebrovascular Acute Radiation Syndrome : Radiation Neurotoxins, Mechanisms of Toxicity, Neuroimmune Interactions.

    NASA Astrophysics Data System (ADS)

    Popov, Dmitri; Maliev, Slava

    Introduction: Cerebrovascular Acute Radiation Syndrome (CvARS) is an extremely severe in-jury of Central Nervous System (CNS) and Peripheral Nervous System (PNS). CvARS can be induced by the high doses of neutron, heavy ions, or gamma radiation. The Syndrome clinical picture depends on a type, timing, and the doses of radiation. Four grades of the CvARS were defined: mild, moderate, severe, and extremely severe. Also, four stages of CvARS were developed: prodromal, latent, manifest, outcome -death. Duration of stages depends on the types, doses, and time of radiation. The CvARS clinical symptoms are: respiratory distress, hypotension, cerebral edema, severe disorder of cerebral blood microcirculation, and acute motor weakness. The radiation toxins, Cerebro-Vascular Radiation Neurotoxins (SvARSn), determine development of the acute radiation syndrome. Mechanism of action of the toxins: Though pathogenesis of radiation injury of CNS remains unknown, our concept describes the Cv ARS as a result of Neurotoxicity and Excitotoxicity, cell death through apoptotic necrosis. Neurotoxicity occurs after the high doses radiation exposure, formation of radiation neuro-toxins, possible bioradicals, or group of specific enzymes. Intracerebral hemorrhage can be a consequence of the damage of endothelial cells caused by radiation and the radiation tox-ins. Disruption of blood-brain barrier (BBB)and blood-cerebrospinal fluid barrier (BCFB)is possibly the most significant effect of microcirculation disorder and metabolic insufficiency. NMDA-receptors excitotoxic injury mediated by cerebral ischemia and cerebral hypoxia. Dam-age of the pyramidal cells in layers 3 and 5 and Purkinje cell layer the cerebral cortex , damage of pyramidal cells in the hippocampus occur as a result of cerebral ischemia and intracerebral bleeding. Methods: Radiation Toxins of CV ARS are defined as glycoproteins with the molec-ular weight of RT toxins ranges from 200-250 kDa and with high enzymatic activity

  2. Linking Doses with Clinical Scores of Hematopoietic Acute Radiation Syndrome.

    PubMed

    Hu, Shaowen

    2016-10-01

    In radiation accidents, determining the radiation dose the victim received is a key step for medical decision making and patient prognosis. To reconstruct and evaluate the absorbed dose, researchers have developed many physical devices and biological techniques during the last decades. However, using the physical parameter "absorbed dose" alone is not sufficient to predict the clinical development of the various organs injured in an individual patient. In operational situations for radiation accidents, medical responders need more urgently to classify the severity of the radiation injury based on the signs and symptoms of the patient. In this work, the author uses a unified hematopoietic model to describe dose-dependent dynamics of granulocytes, lymphocytes, and platelets, and the corresponding clinical grading of hematopoietic acute radiation syndrome. This approach not only visualizes the time course of the patient's probable outcome in the form of graphs but also indirectly gives information of the remaining stem and progenitor cells, which are responsible for the autologous recovery of the hematopoietic system. Because critical information on the patient's clinical evolution can be provided within a short time after exposure and only peripheral cell counts are required for the simulation, these modeling tools will be useful to assess radiation exposure and injury in human-involved radiation accident/incident scenarios. PMID:27575346

  3. BK Nephritis and Venous Thrombosis in Renal Transplant Recipient Detected by 111In Leukocyte Imaging.

    PubMed

    Pucar, Darko; Klein, Kandace; Corley, James; Williams, Hadyn T

    2015-07-01

    Three months after deceased donor kidney transplant, a patient who presented with proteinuric renal dysfunction and fever of undetermined origin was found to have BK viruria by quantitative polymerase chain reaction analysis. An ¹¹¹In leukocyte scan showed increased renal transplant uptake consistent with nephritis and linear uptake in the knee. Venous duplex ultrasound revealed acute occlusive thrombosis in the superficial right lesser saphenous vein in the area of increased radiolabeled leukocyte uptake. This ¹¹¹In leukocyte scan performed for fever of undetermined origin demonstrated findings of BK nephritis in a renal transplant patient and associated acute venous thrombosis related to leukocyte colonization.

  4. Hematopoietic Acute Radiation Syndrome (Bone marrow syndrome, Aplastic Anemia): Molecular Mechanisms of Radiation Toxicity.

    NASA Astrophysics Data System (ADS)

    Popov, Dmitri

    Key Words: Aplastic Anemia (AA), Pluripotential Stem Cells (PSC) Introduction: Aplastic Anemia (AA) is a disorder of the pluripotential stem cells involve a decrease in the number of cells of myeloid, erythroid and megakaryotic lineage [Segel et al. 2000 ]. The etiology of AA include idiopathic cases and secondary aplastic anemia after exposure to drugs, toxins, chemicals, viral infections, lympho-proliferative diseases, radiation, genetic causes, myelodisplastic syndromes and hypoplastic anemias, thymomas, lymphomas. [Brodskyet al. 2005.,Modan et al. 1975., Szklo et al. 1975]. Hematopoietic Acute Radiation Syndrome (or Bone marrow syndrome, or Radiation-Acquired Aplastic Anemia) is the acute toxic syndrome which usually occurs with a dose of irradiation between 0.7 and 10 Gy (70- 1000 rads), depending on the species irradiated. [Waselenko et al., 2004]. The etiology of bone morrow damage from high-level radiation exposure results depends on the radiosensitivity of certain bone marrow cell lines. [Waselenko et al. 2004] Aplastic anemia after radiation exposure is a clinical syndrome that results from a marked disorder of bone marrow blood cell production. [Waselenko et al. 2004] Radiation hematotoxicity is mediated via genotoxic and other specific toxic mechanisms, leading to aplasia, cell apoptosis or necrosis, initiation via genetic mechanisms of clonal disorders, in cases such as the acute radiation-acquired form of AA. AA results from radiation injury to pluripotential and multipotential stem cells in the bone marrow. The clinical signs displayed in reticulocytopenia, anemia, granulocytopenia, monocytopenia, and thrombocytopenia. The number of marrow CD34+ cells (multipotential hematopoietic progenitors) and their derivative colony-forming unit{granulocyte-macrophage (CFU-GM) and burst forming unit {erythroid (BFU{E) are reduced markedly in patients with AA. [Guinan 2011, Brodski et al. 2005, Beutler et al.,2000] Cells expressing CD34 (CD34+ cell) are normally

  5. Cranial radiation in childhood acute lymphocytic leukemia. Neuropsychologic sequelae

    SciTech Connect

    Whitt, J.K.; Wells, R.J.; Lauria, M.M.; Wilhelm, C.L.; McMillan, C.W.

    1984-08-01

    A battery of neuropsychologic tests was administered ''blindly'' to 18 children with acute lymphocytic leukemia (ALL) who had been randomly assigned to treatment regimens with or without cranial radiation. These children were all in complete continuous remission for more than 3 1/2 years and were no longer receiving therapy. The results indicated no substantial differences between groups as a function of radiation therapy. However, decreased neuropsychologic performance was found when the entire sample was compared with population norms. These data do not support the hypothesis that cranial radiation therapy is responsible for the neuropsychologic sequelae seen in these survivors of ALL. Post hoc multiple regression analysis indicated that parental education levels accounted for more of the neuropsychologic variability seen in these children than other factors such as age at diagnosis, type of therapy, or sex of child.

  6. Acute Radiation Effects Resulting from Exposure to Solar Particle Event-Like Radiation

    NASA Astrophysics Data System (ADS)

    Kennedy, Ann; Cengel, Keith

    2012-07-01

    A major solar particle event (SPE) may place astronauts at significant risk for the acute radiation syndrome (ARS), which may be exacerbated when combined with other space flight stressors, such that the mission or crew health may be compromised. The National Space Biomedical Research Institute (NSBRI) Center of Acute Radiation Research (CARR) is focused on the assessment of risks of adverse biological effects related to the ARS in animal models exposed to space flight stressors combined with the types of radiation expected during an SPE. As part of this program, FDA-approved drugs that may prevent and/or mitigate ARS symptoms are being evaluated. The CARR studies are focused on the adverse biological effects resulting from exposure to the types of radiation, at the appropriate energies, doses and dose-rates, present during an SPE (and standard reference radiations, gamma rays or electrons). The ARS is a phased syndrome which often includes vomiting and fatigue. Other acute adverse biologic effects of concern are the loss of hematopoietic cells, which can result in compromised bone marrow and immune cell functions. There is also concern for skin damage from high SPE radiation doses, including burns, and resulting immune system dysfunction. Using 3 separate animal model systems (ferrets, mice and pigs), the major ARS biologic endpoints being evaluated are: 1) vomiting/retching and fatigue, 2) hematologic changes (with focus on white blood cells) and immune system changes resulting from exposure to SPE radiation with and without reduced weightbearing conditions, and 3) skin injury and related immune system functions. In all of these areas of research, statistically significant adverse health effects have been observed in animals exposed to SPE-like radiation. Countermeasures for the management of ARS symptoms are being evaluated. New research findings from the past grant year will be discussed. Acknowledgements: This research is supported by the NSBRI Center of Acute

  7. [Treatment of extensive acute radiation burn and its complications].

    PubMed

    Li, Ye-yang; Wang, Jin-lun; Li, Gang; Lin, Wei-hua; Liang, Min; Huang, Jun; Sun, Jing-en

    2013-06-01

    This article reports the treatment of a patient suffered from acute radiation burn covering 41% TBSA, with deep partial-thickness and full-thickness injury, produced by exposure to a large-scale industrial electron accelerator. An open wound began to appear and enlarged gradually 10 weeks after the exposure. Serious wound infection with methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa, pneumonia, respiratory failure, systemic inflammatory response syndrome, nephropathy and hypoproteinemia developed successively since 3 weeks after the wound formation. Skin grafts failed to survive, resulting in enlargement of the wound. After being treated with proper measures, including parenteral nutrition, respiratory support with a ventilator, appropriate antibiotics, steroid administration for nephropathy, deep debridement for wounds followed by skin grafting, the patient was cured and discharged after undergoing 15 operations in 500 days. The clinical condition of an extensive acute radiation burn is complicated. We should pay close attention to the changes in functions of organs, and strengthen the therapeutic strategies to support the function of organs to reduce the incidence of systemic complications. The control of the infection and the timely and effective repair of the wound are still the key points of the treatment of an extensive local radiation injury.

  8. Medical Management of Acute Radiation Syndromes : Immunoprophylaxis by Antiradiation Vaccine

    NASA Astrophysics Data System (ADS)

    Popov, Dmitri; Maliev, Vecheslav; Jones, Jeffrey; Casey, Rachael; Kedar, Prasad

    Introduction: Traditionally, the treatment of Acute Radiation Syndrome (ARS) includes supportive therapy, cytokine therapy, blood component transfusions and even stem cell transplantation. Recommendations for ARS treatment are based on clinical symptoms, laboratory results, radiation exposure doses and information received from medical examinations. However, the current medical management of ARS does not include immune prophylaxis based on antiradiation vaccines or immune therapy with hyperimmune antiradiation serum. Immuneprophylaxis of ARS could result from stimulating the immune system via immunization with small doses of radiation toxins (Specific Radiation Determinants-SRD) that possess significant immuno-stimulatory properties. Methods: Principles of immuno-toxicology were used to derive this method of immune prophylaxis. An antiradiation vaccine containing a mixture of Hematotoxic, Neurotoxic and Non-bacterial (GI) radiation toxins, underwent modification into a toxoid forms of the original SRD radiation toxins. The vaccine was administered to animals at different times prior to irradiation. The animals were subjected to lethal doses of radiation that induced different forms of ARS at LD 100/30. Survival rates and clinical symptoms were observed in both control and vaccine-treated animals. Results: Vaccination with non-toxic doses of Radiation toxoids induced immunity from the elaborated Specific Radiation Determinant (SRD) toxins. Neutralization of radiation toxins by specific antiradiation antibodies resulted in significantly improved clinical symptoms in the severe forms of ARS and observed survival rates of 60-80% in animals subjected to lethal doses of radiation expected to induce different forms of ARS at LD 100/30. The most effective vaccination schedule for the antiradiation vaccine consisted of repeated injections 24 and 34 days before irradiation. The vaccine remained effective for the next two years, although the specific immune memory probably

  9. Acute radiation enteritis caused by dose-dependent radiation exposure in dogs: experimental research.

    PubMed

    Xu, Wenda; Chen, Jiang; Xu, Liu; Li, Hongyu; Guo, Xiaozhong

    2014-12-01

    Accidental or intended radiation exposure in mass casualty settings presents a serious and on-going threat. The development of mitigating and treating agents requires appropriate animal models. Unfortunately, the majority of research on radiation enteritis in animals has lacked specific assessments and targeted therapy. Our study showed beagle dogs, treated by intensity-modulated radiation therapy (IMRT) for abdominal irradiation, were administered single X-ray doses of 8-30 Gy. The degree of intestinal tract injury for all of the animals after radiation exposure was evaluated with regard to clinical syndrome, endoscopic findings, histological features, and intestinal function. The range of single doses (8 Gy, 10-14 Gy, and 16-30 Gy) represented the degree of injury (mild, moderate, and severe, respectively). Acute radiation enteritis included clinical syndrome with fever, vomiting, diarrhea, hemafecia, and weight loss; typical endoscopic findings included edema, bleeding, mucosal abrasions, and ulcers; and intestinal biopsy results revealed mucosal necrosis, erosion, and loss, inflammatory cell infiltration, hemorrhage, and congestion. Changes in serum diamine oxides (DAOs) and d-xylose represented intestinal barrier function and absorption function, respectively, and correlated with the extent of damage (P < 0.05 and P < 0.05, respectively). We successfully developed a dog model of acute radiation enteritis, thus obtaining a relatively objective evaluation of intestinal tract injury based on clinical performance and laboratory examination. The method of assessment of the degree of intestinal tract injury after abdominal irradiation could be beneficial in the development of novel and effective therapeutic strategies for acute radiation enteritis.

  10. Hematopoietic Acute Radiation Syndrome (Bone marrow syndrome, Aplastic Anemia): Molecular Mechanisms of Radiation Toxicity.

    NASA Astrophysics Data System (ADS)

    Popov, Dmitri

    Key Words: Aplastic Anemia (AA), Pluripotential Stem Cells (PSC) Introduction: Aplastic Anemia (AA) is a disorder of the pluripotential stem cells involve a decrease in the number of cells of myeloid, erythroid and megakaryotic lineage [Segel et al. 2000 ]. The etiology of AA include idiopathic cases and secondary aplastic anemia after exposure to drugs, toxins, chemicals, viral infections, lympho-proliferative diseases, radiation, genetic causes, myelodisplastic syndromes and hypoplastic anemias, thymomas, lymphomas. [Brodskyet al. 2005.,Modan et al. 1975., Szklo et al. 1975]. Hematopoietic Acute Radiation Syndrome (or Bone marrow syndrome, or Radiation-Acquired Aplastic Anemia) is the acute toxic syndrome which usually occurs with a dose of irradiation between 0.7 and 10 Gy (70- 1000 rads), depending on the species irradiated. [Waselenko et al., 2004]. The etiology of bone morrow damage from high-level radiation exposure results depends on the radiosensitivity of certain bone marrow cell lines. [Waselenko et al. 2004] Aplastic anemia after radiation exposure is a clinical syndrome that results from a marked disorder of bone marrow blood cell production. [Waselenko et al. 2004] Radiation hematotoxicity is mediated via genotoxic and other specific toxic mechanisms, leading to aplasia, cell apoptosis or necrosis, initiation via genetic mechanisms of clonal disorders, in cases such as the acute radiation-acquired form of AA. AA results from radiation injury to pluripotential and multipotential stem cells in the bone marrow. The clinical signs displayed in reticulocytopenia, anemia, granulocytopenia, monocytopenia, and thrombocytopenia. The number of marrow CD34+ cells (multipotential hematopoietic progenitors) and their derivative colony-forming unit{granulocyte-macrophage (CFU-GM) and burst forming unit {erythroid (BFU{E) are reduced markedly in patients with AA. [Guinan 2011, Brodski et al. 2005, Beutler et al.,2000] Cells expressing CD34 (CD34+ cell) are normally

  11. Technetium-99m MDP imaging of acute radiation-induced inflammation

    SciTech Connect

    Ferris, J.V.; Ziessman, H.A.

    1988-06-01

    Tc-99m MDP three-phase bone imaging demonstrated the acute hyperemic inflammatory soft tissue phase of radiation injury to the hand in a patient receiving radiation therapy to bone lesions of multiple myeloma.

  12. Arsenic intoxication associated with tubulointerstitial nephritis.

    PubMed

    Prasad, G V; Rossi, N F

    1995-08-01

    Arsenic poisoning is an often unrecognized cause of renal insufficiency. We report a case of tubulointerstitial nephritis associated with an elevated urinary arsenic concentration. Removal of the putative source of arsenic resulted in symptomatic improvement, resolution of abnormal abdominal radiographs, and stabilization of renal function. This case emphasizes the importance of heavy metal screening in patients with multisystem complaints and tubulointerstitial nephritis.

  13. Antiradiation Antitoxin IgG : Immunological neutralization of Radiation Toxins at Acute Radiation Syndromes.

    NASA Astrophysics Data System (ADS)

    Popov, Dmitri; Maliev, Slava

    Introduction: High doses of radiation induce apoptotic necrosis of radio-sensitive cells. Mild doses of radiation induce apoptosis or controlled programmed death of radio-sensitive cells with-out development of inflammation and formation of Radiation Toxins. Cell apoptotic necrosis initiates Radiation Toxins (RT)formation. Radiation Toxins play an important role as a trig-ger mechanism for inflammation development and cell lysis. If an immunotherapy approach to treatment of the acute radiation syndromes (ARS) were to be developed, a consideration could be given to neutralization of radiation toxins (Specific Radiation Determinants-SRD) by specific antiradiation antibodies. Therapeutic neutralization effects of the blocking anti-radiation antibodies on the circulated RT had been studied. Radiation Toxins were isolated from the central lymph of irradiated animals with Cerebrovascular(Cv ARS),Cardiovascular (Cr ARS),Gastrointestinal(Gi ARS) and Haemopoietic (Hp ARS) forms of ARS. To accomplish this objective, irradiated animals were injected with a preparation of anti-radiation immunoglobulin G (IgG) obtained from hyperimmune donors. Radiation-induced toxins that we call Specific Radiation Determinants (SRD) possess toxic (neurotoxic, haemotoxic) characteristics as well as specific antigenic properties. Depending on direct physiochemical radiation damage, they can induce development of many of the pathological processes associated with ARS. We have tested several specific hyperimmune IgG preparations against these radiation toxins and ob-served that their toxic properties were neutralized by the specific antiradiation IgGs. Material and Methods: A scheme of experiments was following: 1.Isolation of radiation toxins (RT) from the central lymph of irradiated animals with different form of ARS. 2.Transformation of a toxic form of the RT to a toxoid form of the RT. 3.Immunization of radiation naive animals. Four groups of rabbits were inoculated with a toxoid form of SRD

  14. Streptococcal Infection-related Nephritis (SIRN) Manifesting Membranoproliferative Glomerulonephritis Type I.

    PubMed

    Iseri, Ken; Iyoda, Masayuki; Yamamoto, Yasutaka; Kobayashi, Naoto; Oda, Takashi; Yamaguchi, Yutaka; Shibata, Takanori

    2016-01-01

    We herein report the case of an 18-year-old boy who developed nephrotic syndrome and hypertension after upper airway inflammation. Post-streptococcal acute glomerulonephritis was diagnosed on the basis of a high antistreptolysin O titer, hypocomplementemia, proteinuria, and microscopic hematuria. A renal biopsy was performed due to persistent proteinuria, and the pathological diagnosis was membranoproliferative glomerulonephritis (MPGN) type I. Glomeruli showed positive staining for nephritis-associated plasmin receptor (NAPlr), a nephritogenic group A streptococcal antigen, and plasmin activity was found in a similar distribution as NAPlr deposition. This rare case of streptococcal infection-related nephritis (SIRN) manifesting MPGN type I supports the histological diversity of SIRN. PMID:26984084

  15. Tubulointerstitial Nephritis and Uveitis Syndrome in an Elderly Man

    PubMed Central

    Lei, Wen-hui; Xin, Jun; Yu, Xue-ping; Li, Jie; Mao, Ming-feng; Ji, Jian-song; Wu, Chui-fen; Zhu, Chao-yong; Jin, Lie

    2015-01-01

    Abstract Tubulointerstitial nephritis and uveitis (TINU) syndrome is a rare disease of unknown etiology defined by the combination of tubulointerstitial nephritis, uveitis, and biochemical abnormalities. It has been reported that TINU mainly affects adolescents and young women. Here we reported a special case regarding a 60-year-old man with acute renal failure due to TINU syndrome documented by renal biopsy. We present a rare case of an elderly patient, who had been suffering from a fever for 2 weeks, characterized by sudden onset and resolving spontaneously, and accompanied by extreme fatigue, loss of appetite, and shivering. Renal biopsy showed a tubulointerstitial nephritis, with polymorphonuclear infiltration and acute tubulitis. In the outpatient clinic, he was diagnosed with idiopathic bilateral anterior uveitis 1 month ago. Ophthalmological examination revealed anterior asymptomatic bilateral uveitis. Human leukocyte antigen (HLA) typing (HLA-DQA1∗0101/0201 and HLA-DQB1∗0303/0503) was found which supported the suspect of TINU syndrome. The patient was treated with oral prednisone (1 mg/kg) and continued for 8 weeks on tapering doses. Serum creatinine normalized within 3 and 6 months later renal function also recovered completely. This case highlights that TINU syndrome is probably an underdiagnosed disease responsible for some cases of idiopathic anterior uveitis in elderly male patients. It is of critical importance to be aware of this syndrome by nephrologist and ophthalmologists in this special population. Further studies are needed to elucidate clinical characteristic and pathogenesis of TINU syndrome in elderly population. PMID:26632725

  16. Granulomatous interstitial nephritis and Crohn's disease.

    PubMed

    Timmermans, Sjoerd A M E G; Christiaans, Maarten H L; Abdul-Hamid, Myrurgia A; Stifft, Frank; Damoiseaux, Jan G M C; van Paassen, Pieter

    2016-08-01

    Granulomatous interstitial nephritis has been observed in <1% of native renal biopsies. Here, we describe two patients with granulomatous interstitial nephritis in relation to Crohn's disease. Circulating helper and cytotoxic T cells were highly activated, and both cell types predominated in the interstitial infiltrate, indicating a cellular autoimmune response. After immunosuppressive treatment, renal function either improved or stabilized in both patients. In conclusion, granulomatous interstitial nephritis is a genuine extraintestinal manifestation of Crohn's disease, the treatment of which should include immunosuppressive agents. PMID:27478596

  17. Concurrent Kimura disease and lupus nephritis

    PubMed Central

    Wang, Haitao; Fang, Fang; Sun, Ying; Wang, Songlan; Mao, Yonghui

    2016-01-01

    Abstract Background: Kimura disease is a rare chronic inflammatory disorder with peripheral eosinophilia and elevated serum IgE and is also frequently complicated by nephropathy. Methods: We report a rare case of Kimura disease concomitant with lupus nephritis in a 72-year old male patient with recurrent unexplained lymphadenopathy, renal lesions, and immunologic abnormalities. Results: The patient was successfully managed with gamma immunoglobulin, intravenous pulse methylprednisolone therapy, hydroxychloroquine, and prednisone. Conclusion: This is the first report of a case of Kimura disease concomitant with lupus nephritis and highlights the importance of considering lupus nephritis as a possible concurrent disease in patients with Kimura disease that have immunologic abnormalities. PMID:27741124

  18. The role of MRI in the diagnosis of acute radiation reaction in breast cancer patient

    NASA Astrophysics Data System (ADS)

    Startseva, Zh A.; Musabaeva, L. I.; Usova, AV; Frolova, I. G.; Simonov, K. A.; Velikaya, V. V.

    2016-02-01

    A clinical case with acute radiation reaction of the left breast after organ-preserving surgery with 10 Gy IORT (24.8 Gy) conventional radiation therapy has been presented. Comprehensive MRI examination showed signs of radiation- induced damage to skin, soft tissues and vessels of the residual breast.

  19. Allergic Interstitial Nephritis Manifesting as a Striated Nephrogram

    PubMed Central

    Moinuddin, Irfan; Bracamonte, Erika; Thajudeen, Bijin; Sussman, Amy; Madhrira, Machaiah; Costello, James

    2015-01-01

    Allergic interstitial nephritis (AIN) is an underdiagnosed cause of acute kidney injury (AKI). Guidelines suggest that AIN should be suspected in a patient who presents with an elevated serum creatinine and a urinalysis that shows white cells, white cell casts, or eosinophiluria. Drug-induced AIN is suspected if AKI is temporally related to the initiation of a new drug. However, patients with bland sediment and normal urinalysis can also have AIN. Currently, a definitive diagnosis of AIN is made by renal biopsy which is invasive and fraught with risks such as bleeding, infection, and hematoma. Additionally, it is frequently unclear when a kidney biopsy should be undertaken. We describe a biopsy proven case of allergic interstitial nephritis which manifested on contrast enhanced Magnetic Resonance Imaging (MRI) as a striated nephrogram. Newer and more stable macrocyclic gadolinium contrast agents have a well-demonstrated safety profile. Additionally, in the presentation of AKI, gadolinium contrast agents are safe to administer in patients who demonstrate good urine output and a downtrending creatinine. We propose that the differential for a striated nephrogram may include AIN. In cases in which the suspicion for AIN is high, this diagnostic consideration may be further characterized by contrast enhanced MRI. PMID:26664405

  20. Tubulointerstitial Nephritis and Uveitis Syndrome: Are Drugs Offenders or Bystanders?

    PubMed Central

    Kawamata, Mutsumi; Akimoto, Tetsu; Sugase, Taro; Otani-Takei, Naoko; Miki, Takuya; Masuda, Takahiro; Kobayashi, Takahisa; Takeda, Shin-ichi; Muto, Shigeaki; Nagata, Daisuke

    2016-01-01

    A 16-year-old female patient was admitted to our hospital due to progressive renal dysfunction with an increased serum creatinine (sCr) level of 1.7 mg/dL. Her clinical course without any ocular manifestations and results of drug-induced, lymphocyte-stimulating tests, in addition to a renal histological assessment, initially encouraged us to ascribe the patient’s renal abnormalities to drug-induced acute interstitial nephritis (AIN). Four months later, she started to complain about reduced visual acuity when she was found to have anterior bilateral uveitis despite the recovered renal function with almost constant sCr levels around 0.7 mg/dL. Thus, a diagnosis of tubulointerstitial nephritis and uveitis (TINU) syndrome was finally made. Our case illustrates the difficulties in distinguishing late-onset uveitis TINU syndrome from drug-induced AIN at the time of the renal biopsy, thereby suggesting the importance of a longitudinal follow-up to overcome the potential underdiagnosis of the disease. Several diagnostic conundrums that emerged in this case are also discussed. PMID:26997878

  1. Genetics of Lupus Nephritis: Clinical Implications

    PubMed Central

    Munroe, Melissa E.; James, Judith A.

    2015-01-01

    Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease marked by the presence of pathogenic autoantibodies, immune dysregulation, and chronic inflammation that may lead to increased morbidity and early mortality from end-organ damage. Over half of all SLE patients will develop lupus nephritis. Genetic association studies have identified more than fifty polymorphisms that contribute to lupus nephritis pathogenesis, including genetic variants associated with altered programmed cell death (PCD) and defective immune clearance of PCD debris. These variants may support the generation of autoantibody-containing immune complexes that contribute to lupus nephritis. Genetic variants associated with lupus nephritis also affect the initial phase of innate immunity and the amplifying, adaptive phase of the immune response. Finally, genetic variants associated with the kidney-specific effector response may influence end-organ damage and the progression to end-stage renal disease and death. This review discusses genetic insights of key pathogenic processes and pathways that may lead to lupus nephritis, as well as the clinical implications of these findings as they apply to recent advances in biologic therapies. PMID:26573543

  2. The Role of Autophagy in Lupus Nephritis.

    PubMed

    Wang, Linlin; Law, Helen Ka Wai

    2015-01-01

    Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disease characterized by the generation of immune responses to self-antigens. Lupus nephritis is one of the most common and severe complications in SLE patients. Though the pathogenesis of lupus nephritis has been studied extensively, unresolved questions are still left and new therapeutic methods are needed for disease control. Autophagy is a conserved catabolic process through which cytoplasmic constituents can be degraded in lysosome and reused. Autophagy plays vital roles in maintaining cell homeostasis and is involved in the pathogenesis of many diseases. In particular, autophagy can affect almost all parts of the immune system and is involved in autoimmune diseases. Based on genetic analysis, cell biology, and mechanism studies of the classic and innovative therapeutic drugs, there are growing lines of evidence suggesting the relationship between autophagy and lupus nephritis. In the present review, we summarize the recent publications investigating the relationship between autophagy and lupus nephritis and provide a new perspective towards the pathogenesis of lupus nephritis. PMID:26506346

  3. Anti-radiation vaccine: Immunologically-based Prophylaxis of Acute Toxic Radiation Syndromes Associated with Long-term Space Flight

    NASA Technical Reports Server (NTRS)

    Popov, Dmitri; Maliev, Vecheslav; Jones, Jeffrey; Casey, Rachael C.

    2007-01-01

    Protecting crew from ionizing radiation is a key life sciences problem for long-duration space missions. The three major sources/types of radiation are found in space: galactic cosmic rays, trapped Van Allen belt radiation, and solar particle events. All present varying degrees of hazard to crews; however, exposure to high doses of any of these types of radiation ultimately induce both acute and long-term biological effects. High doses of space radiation can lead to the development of toxicity associated with the acute radiation syndrome (ARS) which could have significant mission impact, and even render the crew incapable of performing flight duties. The creation of efficient radiation protection technologies is considered an important target in space radiobiology, immunology, biochemistry and pharmacology. Two major mechanisms of cellular, organelle, and molecular destruction as a result of radiation exposure have been identified: 1) damage induced directly by incident radiation on the macromolecules they encounter and 2) radiolysis of water and generation of secondary free radicals and reactive oxygen species (ROS), which induce chemical bond breakage, molecular substitutions, and damage to biological molecules and membranes. Free-radical scavengers and antioxidants, which neutralize the damaging activities of ROS, are effective in reducing the impact of small to moderate doses of radiation. In the case of high doses of radiation, antioxidants alone may be inadequate as a radioprotective therapy. However, it remains a valuable component of a more holistic strategy of prophylaxis and therapy. High doses of radiation directly damage biological molecules and modify chemical bond, resulting in the main pathological processes that drive the development of acute radiation syndromes (ARS). Which of two types of radiation-induced cellular lethality that ultimately develops, apoptosis or necrosis, depends on the spectrum of incident radiation, dose, dose rate, and

  4. Herpes virus infection associated with interstitial nephritis in a beaked whale (Mesoplodon densirostris)

    PubMed Central

    2012-01-01

    Background The capacity for herpesvirus to cause disease in cetaceans is unclear and may be varied depending on the different conditions of individuals and between different species. Kidney pathology and intralesional virus-associated infection have been rarely reported in cetaceans. Result On April 2004, an old adult male Blainville’s beaked whale (Mesoplodon densirostris) 420 cm long with a poor body condition was stranded on Tenerife Island. During necropsy, no gross lesions were observed in the kidneys. However, membranous glomerulonephritis, multifocal interstitial lymphoplasmacytic nephritis and acute multifocal necrotizing tubulointerstitial nephritis with intranuclear inclusion bodies was diagnosed by histological analysis. Tissue samples were submitted for bacteriological analysis and molecular viral screening. Conclusion A novel alpha herpesvirus associated with interstitial nephritis was identified in an old adult male Blainville's beaked whale (M. densirostris) with a poor body condition stranded in the Canary Islands. This report suggests that identification of herpesvirus infection could be used as a differential diagnosis for interstitial nephritis in cetaceans. PMID:23237059

  5. Influence of radiation quality on mouse chromosome 2 deletions in radiation-induced acute myeloid leukaemia.

    PubMed

    Brown, Natalie; Finnon, Rosemary; Manning, Grainne; Bouffler, Simon; Badie, Christophe

    2015-11-01

    Leukaemia is the prevailing neoplastic disorder of the hematopoietic system. Epidemiological analyses of the survivors of the Japanese atomic bombings show that exposure to ionising radiation (IR) can cause leukaemia. Although a clear association between radiation exposure and leukaemia development is acknowledged, the underlying mechanisms remain incompletely understood. A hemizygous deletion on mouse chromosome 2 (del2) is a common feature in several mouse strains susceptible to radiation-induced acute myeloid leukaemia (rAML). The deletion is an early event detectable 24h after exposure in bone marrow cells. Ultimately, 15-25% of exposed animals develop AML with 80-90% of cases carrying del2. Molecular mapping of leukaemic cell genomes identified a minimal deleted region (MDR) on chromosome 2 (chr2) in which a tumour suppressor gene, Sfpi1 is located, encoding the transcription factor PU.1, essential in haematopoiesis. The remaining copy of Sfpi1 has a point mutation in the coding sequence for the DNA-binding domain of the protein in 70% of rAML, which alters a single CpG sequence in the codon for arginine residue R235. In order to identify chr2 deletions and Sfpi.1/PU.1 loss, we performed array comparative genomic hybridization (aCGH) on a unique panel of 79rAMLs. Using a custom made CGH array specifically designed for mouse chr2, we analysed at unprecedentedly high resolution (1.4M array- 148bp resolution) the size of the MDR in low LET and high-LET induced rAMLs (32 X-ray- and 47 neutron-induced). Sequencing of Sfpi1/PU.1DNA binding domain identified the presence of R235 point mutations, showing no influence of radiation quality on R235 type or frequency. We identified for the first time rAML cases with complex del2 in a subset of neutron-induced AMLs. This study allowed us to re-define the MDR to a much smaller 5.5Mb region (still including Sfpi1/PU.1), identical regardless of radiation quality.

  6. Serial Diffusion Tensor Imaging of the Optic Radiations after Acute Optic Neuritis

    PubMed Central

    van der Walt, Anneke; Butzkueven, Helmut; Klistorner, Alexander; Egan, Gary F.; Kilpatrick, Trevor J.

    2016-01-01

    Previous studies have reported diffusion tensor imaging (DTI) changes within the optic radiations of patients after optic neuritis (ON). We aimed to study optic radiation DTI changes over 12 months following acute ON and to study correlations between DTI parameters and damage to the optic nerve and primary visual cortex (V1). We measured DTI parameters [fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD)] from the optic radiations of 38 acute ON patients at presentation and 6 and 12 months after acute ON. In addition, we measured retinal nerve fibre layer thickness, visual evoked potential amplitude, optic radiation lesion load, and V1 thickness. At baseline, FA was reduced and RD and MD were increased compared to control. Over 12 months, FA reduced in patients at an average rate of −2.6% per annum (control = −0.51%; p = 0.006). Change in FA, RD, and MD correlated with V1 thinning over 12 months (FA: R = 0.450, p = 0.006; RD: R = −0.428, p = 0.009; MD: R = −0.365, p = 0.029). In patients with no optic radiation lesions, AD significantly correlated with RNFL thinning at 12 months (R = 0.489, p = 0.039). In conclusion, DTI can detect optic radiation changes over 12 months following acute ON that correlate with optic nerve and V1 damage. PMID:27555964

  7. Serial Diffusion Tensor Imaging of the Optic Radiations after Acute Optic Neuritis.

    PubMed

    Kolbe, Scott C; van der Walt, Anneke; Butzkueven, Helmut; Klistorner, Alexander; Egan, Gary F; Kilpatrick, Trevor J

    2016-01-01

    Previous studies have reported diffusion tensor imaging (DTI) changes within the optic radiations of patients after optic neuritis (ON). We aimed to study optic radiation DTI changes over 12 months following acute ON and to study correlations between DTI parameters and damage to the optic nerve and primary visual cortex (V1). We measured DTI parameters [fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD)] from the optic radiations of 38 acute ON patients at presentation and 6 and 12 months after acute ON. In addition, we measured retinal nerve fibre layer thickness, visual evoked potential amplitude, optic radiation lesion load, and V1 thickness. At baseline, FA was reduced and RD and MD were increased compared to control. Over 12 months, FA reduced in patients at an average rate of -2.6% per annum (control = -0.51%; p = 0.006). Change in FA, RD, and MD correlated with V1 thinning over 12 months (FA: R = 0.450, p = 0.006; RD: R = -0.428, p = 0.009; MD: R = -0.365, p = 0.029). In patients with no optic radiation lesions, AD significantly correlated with RNFL thinning at 12 months (R = 0.489, p = 0.039). In conclusion, DTI can detect optic radiation changes over 12 months following acute ON that correlate with optic nerve and V1 damage.

  8. Serial Diffusion Tensor Imaging of the Optic Radiations after Acute Optic Neuritis.

    PubMed

    Kolbe, Scott C; van der Walt, Anneke; Butzkueven, Helmut; Klistorner, Alexander; Egan, Gary F; Kilpatrick, Trevor J

    2016-01-01

    Previous studies have reported diffusion tensor imaging (DTI) changes within the optic radiations of patients after optic neuritis (ON). We aimed to study optic radiation DTI changes over 12 months following acute ON and to study correlations between DTI parameters and damage to the optic nerve and primary visual cortex (V1). We measured DTI parameters [fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD)] from the optic radiations of 38 acute ON patients at presentation and 6 and 12 months after acute ON. In addition, we measured retinal nerve fibre layer thickness, visual evoked potential amplitude, optic radiation lesion load, and V1 thickness. At baseline, FA was reduced and RD and MD were increased compared to control. Over 12 months, FA reduced in patients at an average rate of -2.6% per annum (control = -0.51%; p = 0.006). Change in FA, RD, and MD correlated with V1 thinning over 12 months (FA: R = 0.450, p = 0.006; RD: R = -0.428, p = 0.009; MD: R = -0.365, p = 0.029). In patients with no optic radiation lesions, AD significantly correlated with RNFL thinning at 12 months (R = 0.489, p = 0.039). In conclusion, DTI can detect optic radiation changes over 12 months following acute ON that correlate with optic nerve and V1 damage. PMID:27555964

  9. Acute Radiation Syndrome Severity Score System in Mouse Total-Body Irradiation Model.

    PubMed

    Ossetrova, Natalia I; Ney, Patrick H; Condliffe, Donald P; Krasnopolsky, Katya; Hieber, Kevin P

    2016-08-01

    Radiation accidents or terrorist attacks can result in serious consequences for the civilian population and for military personnel responding to such emergencies. The early medical management situation requires quantitative indications for early initiation of cytokine therapy in individuals exposed to life-threatening radiation doses and effective triage tools for first responders in mass-casualty radiological incidents. Previously established animal (Mus musculus, Macaca mulatta) total-body irradiation (γ-exposure) models have evaluated a panel of radiation-responsive proteins that, together with peripheral blood cell counts, create a multiparametic dose-predictive algorithm with a threshold for detection of ~1 Gy from 1 to 7 d after exposure as well as demonstrate the acute radiation syndrome severity score systems created similar to the Medical Treatment Protocols for Radiation Accident Victims developed by Fliedner and colleagues. The authors present a further demonstration of the acute radiation sickness severity score system in a mouse (CD2F1, males) TBI model (1-14 Gy, Co γ-rays at 0.6 Gy min) based on multiple biodosimetric endpoints. This includes the acute radiation sickness severity Observational Grading System, survival rate, weight changes, temperature, peripheral blood cell counts and radiation-responsive protein expression profile: Flt-3 ligand, interleukin 6, granulocyte-colony stimulating factor, thrombopoietin, erythropoietin, and serum amyloid A. Results show that use of the multiple-parameter severity score system facilitates identification of animals requiring enhanced monitoring after irradiation and that proteomics are a complementary approach to conventional biodosimetry for early assessment of radiation exposure, enhancing accuracy and discrimination index for acute radiation sickness response categories and early prediction of outcome. PMID:27356057

  10. Acute Radiation Syndrome Severity Score System in Mouse Total-Body Irradiation Model.

    PubMed

    Ossetrova, Natalia I; Ney, Patrick H; Condliffe, Donald P; Krasnopolsky, Katya; Hieber, Kevin P

    2016-08-01

    Radiation accidents or terrorist attacks can result in serious consequences for the civilian population and for military personnel responding to such emergencies. The early medical management situation requires quantitative indications for early initiation of cytokine therapy in individuals exposed to life-threatening radiation doses and effective triage tools for first responders in mass-casualty radiological incidents. Previously established animal (Mus musculus, Macaca mulatta) total-body irradiation (γ-exposure) models have evaluated a panel of radiation-responsive proteins that, together with peripheral blood cell counts, create a multiparametic dose-predictive algorithm with a threshold for detection of ~1 Gy from 1 to 7 d after exposure as well as demonstrate the acute radiation syndrome severity score systems created similar to the Medical Treatment Protocols for Radiation Accident Victims developed by Fliedner and colleagues. The authors present a further demonstration of the acute radiation sickness severity score system in a mouse (CD2F1, males) TBI model (1-14 Gy, Co γ-rays at 0.6 Gy min) based on multiple biodosimetric endpoints. This includes the acute radiation sickness severity Observational Grading System, survival rate, weight changes, temperature, peripheral blood cell counts and radiation-responsive protein expression profile: Flt-3 ligand, interleukin 6, granulocyte-colony stimulating factor, thrombopoietin, erythropoietin, and serum amyloid A. Results show that use of the multiple-parameter severity score system facilitates identification of animals requiring enhanced monitoring after irradiation and that proteomics are a complementary approach to conventional biodosimetry for early assessment of radiation exposure, enhancing accuracy and discrimination index for acute radiation sickness response categories and early prediction of outcome.

  11. Molecular studies of lupus nephritis kidneys.

    PubMed

    Davidson, Anne; Bethunaickan, Ramalingam; Berthier, Celine; Sahu, Ranjit; Zhang, Weijia; Kretzler, Matthias

    2015-12-01

    Lupus nephritis is a devastating complication of systemic lupus erythematosus (SLE) for which current therapies are insufficiently effective. Histologic evaluation of renal biopsies is a poor predictor of therapeutic response or outcome. Integrated immunologic, genomic and proteomic approaches may yield new insights into disease pathogenesis and thereby improve therapeutic strategies for lupus nephritis. Given the lack of sequential biopsies from humans, it also remains essential to study informative animal models of disease. Cross-species analyses can identify cells or pathways that are relevant to human disease and can be further studied in mouse models. Using a systems biology approach in which we compare molecular data from kidneys of three different mouse models of lupus nephritis with data from human lupus biopsies, we have found that inflammatory events escalate rapidly around the time of proteinuria onset. This is followed by hypoxia and metabolic stress, and by tubular and endothelial dysfunction. The failure of complete reversal of these abnormalities may increase the sensitivity of the kidney to further insult. We further found that renal macrophages and dendritic cells are key players in lupus nephritis both in mouse models and humans and that macrophages display a hybrid molecular profile that reflects incomplete resolution of inflammation and excessive tissue remodeling. Finally, our studies have suggested several new biomarkers for disease stage that can now be tested longitudinally in human SLE patients.

  12. Rays Sting: The Acute Cellular Effects of Ionizing Radiation Exposure.

    PubMed

    Franco, A; Ciccarelli, M; Sorriento, D; Napolitano, L; Fiordelisi, A; Trimarco, B; Durante, M; Iaccarino, G

    2016-05-01

    High-precision radiation therapy is a clinical approach that uses the targeted delivery of ionizing radiation, and the subsequent formation of reactive oxygen species (ROS) in high proliferative, radiation sensitive cancers. In particular, in thoracic cancer ratdiation treatments, can not avoid a certain amount of cardiac toxicity. Given the low proliferative rate of cardiac myocytes, research has looked at the effect of radiation on endothelial cells and consequent coronary heart disease as the mechanism of ratdiation induced cardiotoxicity. In fact, little is known concerning the direct effect of radiation on mitochondria dynamis in cardiomyocyte. The main effect of ionizing radiation is the production of ROS and recent works have uncovered that they directly participates to pivotal cell function like mitochondrial quality control. In particular ROS seems to act as check point within the cell to promote either mitochondrial biogenesis and survival or mitochondrial damage and apoptosis. Thus, it appears evident that the functional state of the cell, as well as the expression patterns of molecules involved in mitochondrial metabolism may differently modulate mitochondrial fate in response to radiation induced ROS responses. Different molecules have been described to localize to mitochondria and regulate ROS production in response to stress, in particular GRK2. In this review we will discuss the evidences on the cardiac toxicity induced by X ray radiation on cardiomyocytes with emphasis on the role played by mitochondria dynamism.

  13. Rays Sting: The Acute Cellular Effects of Ionizing Radiation Exposure

    PubMed Central

    Franco, A; Ciccarelli, M; Sorriento, D; Napolitano, L; Fiordelisi, A; Trimarco, B; Durante, M; Iaccarino, G

    2016-01-01

    High-precision radiation therapy is a clinical approach that uses the targeted delivery of ionizing radiation, and the subsequent formation of reactive oxygen species (ROS) in high proliferative, radiation sensitive cancers. In particular, in thoracic cancer ratdiation treatments, can not avoid a certain amount of cardiac toxicity. Given the low proliferative rate of cardiac myocytes, research has looked at the effect of radiation on endothelial cells and consequent coronary heart disease as the mechanism of ratdiation induced cardiotoxicity. In fact, little is known concerning the direct effect of radiation on mitochondria dynamis in cardiomyocyte. The main effect of ionizing radiation is the production of ROS and recent works have uncovered that they directly participates to pivotal cell function like mitochondrial quality control. In particular ROS seems to act as check point within the cell to promote either mitochondrial biogenesis and survival or mitochondrial damage and apoptosis. Thus, it appears evident that the functional state of the cell, as well as the expression patterns of molecules involved in mitochondrial metabolism may differently modulate mitochondrial fate in response to radiation induced ROS responses. Different molecules have been described to localize to mitochondria and regulate ROS production in response to stress, in particular GRK2. In this review we will discuss the evidences on the cardiac toxicity induced by X ray radiation on cardiomyocytes with emphasis on the role played by mitochondria dynamism. PMID:27326395

  14. Rays Sting: The Acute Cellular Effects of Ionizing Radiation Exposure.

    PubMed

    Franco, A; Ciccarelli, M; Sorriento, D; Napolitano, L; Fiordelisi, A; Trimarco, B; Durante, M; Iaccarino, G

    2016-05-01

    High-precision radiation therapy is a clinical approach that uses the targeted delivery of ionizing radiation, and the subsequent formation of reactive oxygen species (ROS) in high proliferative, radiation sensitive cancers. In particular, in thoracic cancer ratdiation treatments, can not avoid a certain amount of cardiac toxicity. Given the low proliferative rate of cardiac myocytes, research has looked at the effect of radiation on endothelial cells and consequent coronary heart disease as the mechanism of ratdiation induced cardiotoxicity. In fact, little is known concerning the direct effect of radiation on mitochondria dynamis in cardiomyocyte. The main effect of ionizing radiation is the production of ROS and recent works have uncovered that they directly participates to pivotal cell function like mitochondrial quality control. In particular ROS seems to act as check point within the cell to promote either mitochondrial biogenesis and survival or mitochondrial damage and apoptosis. Thus, it appears evident that the functional state of the cell, as well as the expression patterns of molecules involved in mitochondrial metabolism may differently modulate mitochondrial fate in response to radiation induced ROS responses. Different molecules have been described to localize to mitochondria and regulate ROS production in response to stress, in particular GRK2. In this review we will discuss the evidences on the cardiac toxicity induced by X ray radiation on cardiomyocytes with emphasis on the role played by mitochondria dynamism. PMID:27326395

  15. Glucagon-Like Peptide-2 Improves Both Acute and Late Experimental Radiation Enteritis in the Rat

    SciTech Connect

    Torres, Sandra

    2007-12-01

    Purpose: Acute and/or chronic radiation enteritis can develop after radiotherapy for pelvic cancers. Experimental and clinical observations have provided evidence of a role played by acute mucosal disruption in the appearance of late effects. The therapeutic potential of acute administration of glucagon-like peptide-2 (GLP-2) against acute and chronic intestinal injury was investigated in this study. Methods and Materials: Intestinal segments were surgically exteriorized and exposed to 16.7 or 19 Gy X-rays. The rats were treated once daily with vehicle or a protease-resistant GLP-2 derivative for 14 days before irradiation, with or without 7 days of GLP-2 after treatment. Macroscopic and microscopic observations were made 2 and 15 weeks after radiation exposure. Results: In the control animals, GLP-2 induced an increase in intestinal mucosal mass, along with an increase in villus height and crypt depth. GLP-2 administration before and after irradiation completely prevented the acute radiation-induced mucosal ulcerations observed after exposure to 16.7 Gy. GLP-2 treatment strikingly reduced the late radiation damage observed after 19 Gy irradiation. Microscopic observations revealed an improved organization of the intestinal wall and an efficient wound healing process, especially in the smooth muscle layers. Conclusion: GLP-2 has a clear therapeutic potential against both acute and chronic radiation enteritis. This therapeutic effect is mediated through an increased mucosal mass before tissue injury and the stimulation of still unknown mechanisms of tissue response to radiation damage. Although these preliminary results still need to be confirmed, GLP-2 might be a way to limit patient discomfort during radiotherapy and reduce the risk of consequential late effects.

  16. Antiphospholipid Antibodies in Lupus Nephritis

    PubMed Central

    Arnaud, Laurent; Gerhardsson, Jakob; Zickert, Agneta; Sundelin, Birgitta; Malmström, Vivianne; Svenungsson, Elisabet; Gunnarsson, Iva

    2016-01-01

    Lupus nephritis (LN) is a major manifestation of systemic lupus erythematosus (SLE). It remains unclear whether antiphospholipid antibodies (aPL) alter the course of LN. We thus investigated the impact of aPL on short-term and long-term renal outcomes in patients with LN. We assessed levels of aPL cross-sectionally in SLE patients diagnosed with (n = 204) or without (n = 294) LN, and prospectively in 64 patients with active biopsy-proven LN (52 proliferative, 12 membranous), before and after induction treatment (short-term outcomes). Long-term renal outcome in the prospective LN cohort was determined by the estimated glomerular filtration rate (eGFR) and the Chronic Kidney Disease (CKD) stage, after a median follow-up of 11.3 years (range: 3.3–18.8). Cross-sectional analysis revealed no association between LN and IgG/IgM anticardiolipin or anti-β2-glycoprotein I antibodies, or lupus anticoagulant. Both aPL positivity and levels were similar in patients with active LN and non-renal SLE. Following induction treatment for LN, serum IgG/IgM aPL levels decreased in responders (p<0.005 for all), but not in non-responders. Both at active LN and post-treatment, patients with IgG, but not IgM, aPL had higher creatinine levels compared with patients without IgG aPL. Neither aPL positivity nor levels were associated with changes in eGFR from either baseline or post-treatment through long-term follow-up. Moreover, aPL positivity and levels both at baseline and post-treatment were similar in patients with a CKD stage ≥3 versus 1–2 at the last follow-up. In conclusion, neither aPL positivity nor levels were found to be associated with the occurrence of LN in SLE patients. However, IgG aPL positivity in LN patients was associated with a short-term impairment of the renal function while no effect on long-term renal outcome was observed. Furthermore, IgG and IgM aPL levels decreased following induction treatment only in responders, indicating that aPL levels are affected by

  17. Acute Radiation Hypotension in the Rabbit: a Model for the Human Radiation Shock Syndrome.

    NASA Astrophysics Data System (ADS)

    Makale, Milan Theodore

    This study has shown that total body irradiation (TBI) of immature (40 to 100 day old) rabbits leads to an acute fall in mean arterial pressure (MAP) 30 to 90 minutes after exposure, which takes no more than about three minutes, and often results in pressures which are less than 50% of the lowest pre-exposure MAP. This is termed acute cardiovascular collapse (ACC). ACC is often accompanied by ECG T-wave elevation, a sharp rise in ear temperature, labored breathing, pupillary constriction, bladder emptying, and loss of abdominal muscle tone. About 73% of 40 to 100 day rabbits exhibit ACC; the others and most older rabbits display gradual pressure reductions (deliberate hypotension) which may be profound, and which may be accompanied by the same changes associated with ACC. ACC and deliberate hypotension occurred in rabbits cannulated in the dorsal aorta, and in non-operated animals. The decline in MAP for all 40 to 100 day cannulated rabbits (deliberate and ACC responders) is 55.4%. The experiments described below only involved 40 to 100 day cannulated TBI rabbits. Heart region irradiation resulted in an average MAP decline of 29.1%, with 1/15 rabbits showing ACC. Heart shielding during TBI reduced the decline in MAP to 19%, with 1/10 rabbits experiencing ACC. These results imply that the heart region, which includes the heart, part of the lungs, neural receptors, roots of the systemic vessels, and the blood, is a sensitive target. Bilateral vagotomy reduced the decline in MAP to 24.9%, and abolished ACC. Atropine (6 mg/kg) reduced the frequency of ACC to 26%, and the decline in MAP to 41.4%. In 11/13 rabbits the voltage generated by left vagal transmission rose after TBI. The vagi appear to participate in radiation hypotension. Heart shielding together with bilateral vagotomy reduced the decline in MAP to only 9.9%, with no ACC responders. The mean right ventricular pressure (MRVP) rose after TBI in 8/10 rabbits. In animals which displayed either ACC or steep

  18. Breast Intensity-Modulated Radiation Therapy Reduces Time Spent With Acute Dermatitis for Women of All Breast Sizes During Radiation

    SciTech Connect

    Freedman, Gary M. Li Tianyu; Nicolaou, Nicos; Chen Yan; Ma, Charlie C.-M.; Anderson, Penny R.

    2009-07-01

    Purpose: To study the time spent with radiation-induced dermatitis during a course of radiation therapy for breast cancer in women treated with conventional or intensity-modulated radiation therapy (IMRT). Methods and Materials: The study population consisted of 804 consecutive women with early-stage breast cancer treated with breast-conserving surgery and radiation from 2001 to 2006. All patients were treated with whole-breast radiation followed by a boost to the tumor bed. Whole-breast radiation consisted of conventional wedged photon tangents (n = 405) earlier in the study period and mostly of photon IMRT (n = 399) in later years. All patients had acute dermatitis graded each week of treatment. Results: The breakdown of the cases of maximum acute dermatitis by grade was as follows: 3%, Grade 0; 34%, Grade 1; 61%, Grade 2; and 2%, Grade 3. The breakdown of cases of maximum toxicity by technique was as follows: 48%, Grade 0/1, and 52%, Grade 2/3, for IMRT; and 25%, Grade 0/1, and 75%, Grade 2/3, for conventional radiation therapy (p < 0.0001). The IMRT patients spent 82% of weeks during treatment with Grade 0/1 dermatitis and 18% with Grade 2/3 dermatitis, compared with 29% and 71% of patients, respectively, treated with conventional radiation (p < 0.0001). Furthermore, the time spent with Grade 2/3 toxicity was decreased in IMRT patients with small (p = 0.0015), medium (p < 0.0001), and large (p < 0.0001) breasts. Conclusions: Breast IMRT is associated with a significant decrease both in the time spent during treatment with Grade 2/3 dermatitis and in the maximum severity of dermatitis compared with that associated with conventional radiation, regardless of breast size.

  19. Visceral leishmaniasis in a kidney transplant recipient: parasitic interstitial nephritis, a cause of renal dysfunction.

    PubMed

    Dettwiler, S; McKee, T; Hadaya, K; Chappuis, F; van Delden, C; Moll, S

    2010-06-01

    Visceral leishmaniasis (VL) due to Leishmania infantum is an endemic parasitic infection in the Mediterranean area. It most commonly affects immunosuppressed individuals, especially HIV patients and less frequently organ transplant recipients. Renal involvement seems to be frequent and is mostly associated with tubulointerstitial nephritis, as described in autopsy reports. In the 61 cases of renal transplant recipients with VL reported in the literature, renal dysfunction was noted at clinical presentation and was more frequently observed as a complication of antiparasitic therapy. However, no pathological analysis of the allograft lesions was reported. We present the case of a Swiss renal transplant recipient who developed VL after vacations in Spain and Tunisia, complicated by acute parasitic nephritis in the renal allograft 3 months after a well-conducted treatment of liposomal amphotericin B.

  20. Subacute radiation dermatitis: a histologic imitator of acute cutaneous graft-versus-host disease

    SciTech Connect

    LeBoit, P.E.

    1989-02-01

    The histopathologic changes of radiation dermatitis have been classified either as early effects (necrotic keratinocytes, fibrin thrombi, and hemorrhage) or as late effects (vacuolar changes at the dermal-epidermal junction, atypical radiation fibroblasts, and fibrosis). Two patients, one exposed to radiation therapeutically and one accidentally, are described. Skin biopsy specimens showed an interface dermatitis characterized by numerous dyskeratotic epidermal cells with lymphocytes in close apposition (satellite cell necrosis); that is, the epidermal changes were similar to those in acute graft-versus-host disease. Because recipients of bone marrow transplants frequently receive total body irradiation as part of their preparatory regimen, the ability of radiation to cause persistent epidermal changes similar to those in acute graft-versus-host disease could complicate the interpretation of posttransplant skin biopsy specimens.

  1. Evaluation of acute radiation optic neuropathy by B-scan ultrasonography

    SciTech Connect

    Lovato, A.A.; Char, D.H.; Quivey, J.M.; Castro, J.R. )

    1990-09-15

    We studied the accuracy of B-scan ultrasonography to diagnose radiation-induced optic neuropathy in 15 patients with uveal melanoma. Optic neuropathy was diagnosed by an observer masked as to clinical and photographic data. We analyzed planimetry area measurements of the retrobulbar nerve before and after irradiation. The retrobulbar area of the optic nerve shadow on B-scan was quantitated with a sonic digitizer. Increased optic nerve shadow area was confirmed in 13 of 15 patients who had radiation optic neuropathy (P less than .004). The correct diagnosis was confirmed when the results of ultrasound were compared to fundus photography and fluorescein angiography. In 13 patients there was acute radiation optic neuropathy. Two patients did not show an enlarged retrobulbar optic nerve, and the clinical appearance suggested early progression to optic atrophy. Ultrasonography documents the enlargement of the optic nerve caused by acute radiation changes.

  2. Countermeasures for Space Radiation Induced Malignancies and Acute Biological Effects

    NASA Astrophysics Data System (ADS)

    Kennedy, Ann

    The hypothesis being evaluated in this research program is that control of radiation induced oxidative stress will reduce the risk of radiation induced adverse biological effects occurring as a result of exposure to the types of radiation encountered during space travel. As part of this grant work, we have evaluated the protective effects of several antioxidants and dietary supplements and observed that a mixture of antioxidants (AOX), containing L-selenomethionine, N-acetyl cysteine (NAC), ascorbic acid, vitamin E succinate, and alpha-lipoic acid, is highly effective at reducing space radiation induced oxidative stress in both in vivo and in vitro systems, space radiation induced cytotoxicity and malignant transformation in vitro [1-7]. In studies designed to determine whether the AOX formulation could affect radiation induced mortality [8], it was observed that the AOX dietary supplement increased the 30-day survival of ICR male mice following exposure to a potentially lethal dose (8 Gy) of X-rays when given prior to or after animal irradiation. Pretreatment of animals with antioxidants resulted in significantly higher total white blood cell and neutrophil counts in peripheral blood at 4 and 24 hours following exposure to doses of 1 Gy and 8 Gy. Antioxidant treatment also resulted in increased bone marrow cell counts following irradiation, and prevented peripheral lymphopenia following 1 Gy irradiation. Supplementation with antioxidants in irradiated animals resulted in several gene expression changes: the antioxidant treatment was associated with increased Bcl-2, and decreased Bax, caspase-9 and TGF-β1 mRNA expression in the bone marrow following irradiation. These results suggest that modulation of apoptosis may be mechanistically involved in hematopoietic system radioprotection by antioxidants. Maintenance of the antioxidant diet was associated with improved recovery of the bone marrow following sub-lethal or potentially lethal irradiation. Taken together

  3. Potential for a pluripotent adult stem cell treatment for acute radiation sickness

    PubMed Central

    Rodgerson, Denis O; Reidenberg, Bruce E; Harris, Alan G; Pecora, Andrew L

    2012-01-01

    Accidental radiation exposure and the threat of deliberate radiation exposure have been in the news and are a public health concern. Experience with acute radiation sickness has been gathered from atomic blast survivors of Hiroshima and Nagasaki and from civilian nuclear accidents as well as experience gained during the development of radiation therapy for cancer. This paper reviews the medical treatment reports relevant to acute radiation sickness among the survivors of atomic weapons at Hiroshima and Nagasaki, among the victims of Chernobyl, and the two cases described so far from the Fukushima Dai-Ichi disaster. The data supporting the use of hematopoietic stem cell transplantation and the new efforts to expand stem cell populations ex vivo for infusion to treat bone marrow failure are reviewed. Hematopoietic stem cells derived from bone marrow or blood have a broad ability to repair and replace radiation induced damaged blood and immune cell production and may promote blood vessel formation and tissue repair. Additionally, a constituent of bone marrow-derived, adult pluripotent stem cells, very small embryonic like stem cells, are highly resistant to ionizing radiation and appear capable of regenerating radiation damaged tissue including skin, gut and lung. PMID:24520532

  4. Potential for a pluripotent adult stem cell treatment for acute radiation sickness.

    PubMed

    Rodgerson, Denis O; Reidenberg, Bruce E; Harris, Alan G; Pecora, Andrew L

    2012-06-20

    Accidental radiation exposure and the threat of deliberate radiation exposure have been in the news and are a public health concern. Experience with acute radiation sickness has been gathered from atomic blast survivors of Hiroshima and Nagasaki and from civilian nuclear accidents as well as experience gained during the development of radiation therapy for cancer. This paper reviews the medical treatment reports relevant to acute radiation sickness among the survivors of atomic weapons at Hiroshima and Nagasaki, among the victims of Chernobyl, and the two cases described so far from the Fukushima Dai-Ichi disaster. The data supporting the use of hematopoietic stem cell transplantation and the new efforts to expand stem cell populations ex vivo for infusion to treat bone marrow failure are reviewed. Hematopoietic stem cells derived from bone marrow or blood have a broad ability to repair and replace radiation induced damaged blood and immune cell production and may promote blood vessel formation and tissue repair. Additionally, a constituent of bone marrow-derived, adult pluripotent stem cells, very small embryonic like stem cells, are highly resistant to ionizing radiation and appear capable of regenerating radiation damaged tissue including skin, gut and lung.

  5. Radiation injury and acute death in Armadillidium vulgare (terrestrial isopod, Crustacea) subjected to ionizing radiation. [/sup 137/Cs

    SciTech Connect

    Nakatsuchi, Y.; Egami, N.

    1981-01-01

    From whole- and partial-body irradiation experiments with adult Armadillidium vulgare, the following conclusions were drawn: the LD/sub 50/-30 days for this animal when subjected to ..gamma.. radiation at 25 +- 2/sup 0/C was about 30 kR. Radiosensitivity of the animal changed during the molt cycle. Ionizing radiation increased mortality at ecdysis and during intermolt stages. Anatomical and histological observations indicated that (1) gastrointestinal injury as the major cause of acute death does not apply to this animal because the intestine is not a cell-proliferative organ: (2) the epidermis may be the critical target organ.

  6. Prophylaxis and management of acute radiation-induced skin reactions: a systematic review of the literature

    PubMed Central

    Salvo, N.; Barnes, E.; van Draanen, J.; Stacey, E.; Mitera, G.; Breen, D.; Giotis, A.; Czarnota, G.; Pang, J.; De Angelis, C.

    2010-01-01

    Radiation therapy is a common treatment for cancer patients. One of the most common side effects of radiation is acute skin reaction (radiation dermatitis) that ranges from a mild rash to severe ulceration. Approximately 85% of patients treated with radiation therapy will experience a moderate-to-severe skin reaction. Acute radiation-induced skin reactions often lead to itching and pain, delays in treatment, and diminished aesthetic appearance—and subsequently to a decrease in quality of life. Surveys have demonstrated that a wide variety of topical, oral, and intravenous agents are used to prevent or to treat radiation-induced skin reactions. We conducted a literature review to identify trials that investigated products for the prophylaxis and management of acute radiation dermatitis. Thirty-nine studies met the pre-defined criteria, with thirty-three being categorized as prophylactic trials and six as management trials. For objective evaluation of skin reactions, the Radiation Therapy Oncology Group criteria and the U.S. National Cancer Institute Common Toxicity Criteria were the most commonly used tools (65% of the studies). Topical corticosteroid agents were found to significantly reduce the severity of skin reactions; however, the trials of corticosteroids evaluated various agents, and no clear indication about a preferred corticosteroid has emerged. Amifostine and oral enzymes were somewhat effective in preventing radiation-induced skin reactions in phase ii and phase iii trials respectively; further large randomized controlled trials should be undertaken to better investigate those products. Biafine cream (Ortho–McNeil Pharmaceuticals, Titusville, NJ, U.S.A.) was found not to be superior to standard regimes in the prevention of radiation-induced skin reactions (n = 6). In conclusion, the evidence is insufficient to support the use of a particular agent for the prevention and management of acute radiation-induced skin reactions. Future trials should focus

  7. Use of iron colloid-enhanced MRI for study of acute radiation-induced hepatic injury

    SciTech Connect

    Suto, Yuji; Ametani, Masaki; Kato, Takashi; Hashimoto, Masayuki; Kamba, Masayuki; Sugihara, Syuji; Ohta, Yoshio

    1996-03-01

    We present a case with acute radiation-induced hepatic injury using chondroitin sulfate iron colloid (CSIC)-enhanced MRI. Uptake of CSIC was decreased in the irradiated portion of the liver. CSIC-enhanced MRI is useful for obtaining information on the function of the reticuloendothelial system and demarcates between irradiated and nonirradiated zones. 18 refs., 3 figs

  8. [Karyomegalic interstitial nephritis: A new French case].

    PubMed

    Verine, Jérôme; Reade, Richard; Janin, Anne; Droz, Dominique

    2010-06-01

    Karyomegalic interstitial nephritis (KIN) is a rare and slowly progressive chronic interstitial nephritis (CIN) (28 cases reported), described for the first time by Mihatsch et al. in 1979. Here, we report on a 50-year-old woman who presented with asymptomatic renal failure and mild proteinuria without hematuria. Renal biopsy showed large tubulo-interstitial fibrosis and massively enlarged tubular epithelial cell nuclei, without viral inclusion. KIN is a rare CIN defined by a karyomegaly of tubular epithelial cell nuclei. Its pathogenesis remains obscure. Nevertheless, an exogenous factor is suspected, ochratoxin A particularly. The familial clustering of patients and the frequency of HLA-A9 and HLA-B35 haplotypes suggest the presence of a possible genetic susceptibility to this disorder.

  9. The Complement System in Lupus Nephritis.

    PubMed

    Birmingham, Daniel J; Hebert, Lee A

    2015-09-01

    The complement system is composed of a family of soluble and membrane-bound proteins that historically has been viewed as a key component of the innate immune system, with a primary role of providing a first-line defense against microorganisms. Although this role indeed is important, complement has many other physiological roles, including the following: (1) influencing appropriate immune responses, (2) disposing of waste in the circulation (immune complexes, cellular debris), and (3) contributing to damage of self-tissue through inflammatory pathways. These three roles are believed to be significant factors in the pathogenesis of systemic lupus erythematosus, particularly its renal manifestation (lupus nephritis), contributing both protective and damaging effects. In this review, we provide an overview of the human complement system and its functions, and discuss its intricate and seemingly contradictory roles in the pathogenesis of lupus nephritis.

  10. Mometasone Furoate Cream Reduces Acute Radiation Dermatitis in Patients Receiving Breast Radiation Therapy: Results of a Randomized Trial

    SciTech Connect

    Hindley, Andrew; Zain, Zakiyah; Wood, Lisa; Whitehead, Anne; Sanneh, Alison; Barber, David; Hornsby, Ruth

    2014-11-15

    Purpose: We wanted to confirm the benefit of mometasone furoate (MF) in preventing acute radiation reactions, as shown in a previous study (Boström et al, Radiother Oncol 2001;59:257-265). Methods and Materials: The study was a double-blind comparison of MF with D (Diprobase), administered daily from the start of radiation therapy for 5 weeks in patients receiving breast radiation therapy, 40 Gy in 2.67-Gy fractions daily over 3 weeks. The primary endpoint was mean modified Radiation Therapy Oncology Group (RTOG) score. Results: Mean RTOG scores were significantly less for MF than for D (P=.046). Maximum RTOG and mean erythema scores were significantly less for MF than for D (P=.018 and P=.012, respectively). The Dermatology Life Quality Index (DLQI) score was significantly less for MF than for D at weeks 4 and 5 when corrected for Hospital Anxiety and Depression (HAD) questionnaire scores. Conclusions: MF cream significantly reduces radiation dermatitis when applied to the breast during and after radiation therapy. For the first time, we have shown a significantly beneficial effect on quality of life using a validated instrument (DLQI), for a topical steroid cream. We believe that application of this cream should be the standard of care where radiation dermatitis is expected.

  11. Supplemental vitamin A prevents the acute radiation-induced defect in wound healing

    SciTech Connect

    Levenson, S.M.; Gruber, C.A.; Rettura, G.; Gruber, D.K.; Demetriou, A.A.; Seifter, E.

    1984-10-01

    Acute radiation injury leads to thymic involution, adrenal enlargement, leukopenia, thrombocytopenia, gastrointestinal ulceration, and impaired wound healing. The authors hypothesized that supplemental vitamin A would mitigate these adverse effects in rats exposed to acute whole-body radiation. To test their hypothesis, dorsal skin incisions and subcutaneous implantation of polyvinyl alcohol sponges were performed in anesthetized Sprague-Dawley rats at varying times following sham radiation or varying doses of whole-body radiation (175-850 rad). In each experiment, the control diet (which contains about 18,000 IU vit. A/kg chow (3 X the NRC RDA for normal rats)) was supplemented with 150,000 IU vit. A/kg diet beginning at, before, or after sham radiation and wounding or radiation and wounding. The supplemental vitamin A prevented the impaired wound healing and lessened the weight loss, leukopenia, thrombocytopenia, thymic involution, adrenal enlargement, decrease in splenic weight, and gastric ulceration of the radiated (750-850 rad) wounded rats. This was true whether the supplemental vitamin A was begun before (2 or 4 days) or after (1-2 hours to 4 days) radiation and wounding; the supplemental vitamin A was more effective when started before or up to 2 days after radiation and wounding. The authors believe that prevention of the impaired wound healing following radiation by supplemental vitamin A is due to its enhancing the early inflammatory reaction to wounding, including increasing the number of monocytes and macrophages at the wound site; possible effect on modulating collagenase activity; effect on epithelial cell (and possible mesenchymal cell) differentiation; stimulation of immune responsiveness; and lessening of the adverse effects of radiation.

  12. Gastrointestinal Acute Radiation Syndrome in Göttingen Minipigs (Sus Scrofa Domestica)

    PubMed Central

    Elliott, Thomas B; Deutz, Nicolaas E; Gulani, Jatinder; Koch, Amory; Olsen, Cara H; Christensen, Christine; Chappell, Mark; Whitnall, Mark H; Moroni, Maria

    2014-01-01

    In the absence of supportive care, exposing Göttingen minipigs to γ-radiation doses of less than 2 Gy achieves lethality due to hematopoietic acute radiation syndrome. Doses of 2 to 5 Gy are associated with an accelerated hematopoietic syndrome, characterized by villus blunting and fusion, the beginning of sepsis, and a mild transient reduction in plasma citrulline concentration. We exposed male Göttingen minipigs (age, 5 mo; weight, 9 to 11 kg) to γ-radiation doses of 5 to 12 Gy (total body; 60Co, 0.6 Gy/min) to test whether these animals exhibit classic gastrointestinal acute radiation syndrome (GI-ARS). After exposure, the minipigs were monitored for 10 d by using clinical signs, CBC counts, and parameters associated with the development of the gastrointestinal syndrome. Göttingen minipigs exposed to γ radiation of 5 to 12 Gy demonstrate a dose-dependent occurrence of all parameters classically associated with acute GI-ARS. These results suggest that Göttingen minipigs may be a suitable model for studying GI-ARS after total body irradiation, but the use of supportive care to extend survival beyond 10 d is recommended. This study is the first step toward determining the feasibility of using Göttingen minipigs in testing the efficacy of candidate drugs for the treatment of GI-ARS after total body irradiation. PMID:25527026

  13. An Overlapping Case of Lupus Nephritis and IgG4-Related Kidney Disease

    PubMed Central

    Zaarour, Mazen; Weerasinghe, Chanudi; Eter, Ahmad; El-Sayegh, Suzanne; El-Charabaty, Elie

    2015-01-01

    We report a case of a 71-year-old Filipino female who was admitted to the hospital for abdominal pain, vomiting and diarrhea of 8 days duration. The patient was found to have marked acute kidney injury (AKI), which required hemodialysis in the next 3 days. Extensive workup revealed hematuria, subnephrotic range proteinuria, elevated anti-nuclear antibody (ANA) and elevated total immunoglobulin G (IgG) levels, with normal IgG4 and anti-dsDNA levels. On kidney biopsy, mild membranous glomerulonephritis was found, along with autoimmune tubulointerstitial nephritis (TIN) with a “full-house” pattern of immune deposits. These findings were suggestive of lupus interstitial nephritis. However, IgG4+ plasma cells were detected in the interstitium by immunostaining, favoring a diagnosis of IgG4-related kidney disease (IgG4-RKD). Our case highlights the difficulty in differentiating lupus nephritis (LN) from IgG4-RKD in some patients, raising the suspicion that these two entities can co-exist. PMID:26015827

  14. Countermeasure development : Specific Immunoprophylaxis and Immunotherapy of Combined Acute Radiation Syndromes.

    NASA Astrophysics Data System (ADS)

    Popov, Dmitri; Maliev, Slava

    Introduction: Combined Acute Radiation Syndromes (CARS) are extremely severe injuries. Combination of Radiation and Thermal factors induce development of the acute pathologi-cal processes in irradiated mammals: systemic inflammatory response syndrome (SIRS), toxic multiple organ injury (TMOI), toxic multiple organ dysfunction syndromes (TMOD), toxic multiple organ failure (TMOF). Also, high doses of Radiation and Thermal injury induce for-mation of following Toxin groups: A. Specific Radiation Toxins; B. Specific Thermal Toxins; C. Nonspecific Histiogenic Pro-inflammatory and Inflammatory Toxins (NHIT). Specific Radi-ation Toxins (SRT) include four major group of Toxins: Cerebrovascular Radiation Toxins (Cv RT), Cardiovascular Radiation Toxins (Cr RT), Gastrointestinal Radiation Toxins (Gi RT), and Hematopoietic Radiation Toxins (Hp RT). CvRT, Cr RT, Gi RT groups of toxins are defined as Neurotoxins and Hp RT group is defined as Hematotoxins. Specific Thermal Toxins (STT) were isolated from the burned skin (Voul S., Colker I. 1972). The group of Nonspecific Histio-genic Inflammatory Toxins (NHIT) includes high amount of tissue toxins which are peptides with medium molecular weight. This group of polypeptides can be a significant factor as a part of developing of the general inflammation reaction. However, NHIT toxins can't induce many reactions and changes which are specific for radiation. Specific Radiation Toxins (SRT) can induce specific processes and reactions such as clonogenic cell death -programmed apoptotic necrosis. Although besides high doses of radiation, other forms of cell death such as Pyroptosis or Oncosis should be considered. We postulate that NHIT toxins are similar for high doses of radiation and thermal injury. Specific Radiation Toxins (SRT) are induced by high doses of radiation. Specific Thermal Toxins (STT) toxins which formation is induced by a Thermal Factor are different from SRT. Administration of STT toxins or NHIT toxins (IV or IM) to

  15. Karyomegalic interstitial nephritis with focal segmental glomerulosclerosis: A rare association.

    PubMed

    Radha, S; Tameem, A; Rao, B S

    2014-03-01

    Karyomegalic interstitial nephritis (KIN) is a rare form of, progressive chronic interstitial nephritis. We present a case of KIN in a child, who was also found to have nephrotic syndrome because of focal segmental glomerulosclerosis on renal biopsy. To our knowledge, this is the first case of KIN associated with glomerulopathy.

  16. Karyomegalic interstitial nephritis with focal segmental glomerulosclerosis: A rare association

    PubMed Central

    Radha, S.; Tameem, A.; Rao, B. S.

    2014-01-01

    Karyomegalic interstitial nephritis (KIN) is a rare form of, progressive chronic interstitial nephritis. We present a case of KIN in a child, who was also found to have nephrotic syndrome because of focal segmental glomerulosclerosis on renal biopsy. To our knowledge, this is the first case of KIN associated with glomerulopathy. PMID:24701046

  17. Radiation-induced glioblastoma multiforme in a remitted acute lymphocytic leukemia patient.

    PubMed

    Joh, Daewon; Park, Bong Jin; Lim, Young Jin

    2011-09-01

    Radiation therapy has been widely applied for cancer treatment. Childhood acute lymphocytic leukemia (ALL), characterized by frequent central nervous system involvement, is a well documented disease for the effect of prophylactic cranio-spinal irradiation. Irradiation, however, acts as an oncogenic factor as a delayed effect and it is rare that glioblastoma multiforme develops during the remission period of ALL. We experienced a pediatric radiation-induced GBM patient which developed during the remission period of ALL, who were primarily treated with chemotherapeutic agents and brain radiation therapy for the prevention of central nervous system (CNS) relapse. Additionally, we reviewed the related literature regarding on the effects of brain irradiation in childhood and on the prognosis of radiation induced GBM.

  18. Immuno-therapy of Acute Radiation Syndromes : Extracorporeal Immuno-Lympho-Plasmo-Sorption.

    NASA Astrophysics Data System (ADS)

    Popov, Dmitri; Maliev, Slava

    Methods Results Summary and conclusions Introduction: Existing Medical Management of the Acute Radiation Syndromes (ARS) does not include methods of specific immunotherapy and active detoxication. Though the Acute Radiation Syndromes were defined as an acute toxic poisonous with development of pathological processes: Systemic Inflammatory Response Syndrome (SIRS), Toxic Multiple Organ Injury (TMOI), Toxic Multiple Organ Dysfunction Syndrome(TMODS), Toxic Multiple Organ Failure (TMOF). Radiation Toxins of SRD Group play an important role as the trigger mechanisms in development of the ARS clinical symptoms. Methods: Immuno-Lympho-Plasmo-Sorption is a type of Immuno-therapy which includes prin-ciples of immunochromato-graphy, plasmopheresis, and hemodialysis. Specific Antiradiation Antitoxic Antibodies are the active pharmacological agents of immunotherapy . Antiradia-tion Antitoxic Antibodies bind selectively to Radiation Neurotoxins, Cytotoxins, Hematotox-ins and neutralize their toxic activity. We have developed the highly sensitive method and system for extracorporeal-immune-lypmh-plasmo-sorption with antigen-specific IgG which is clinically important for treatment of the toxic and immunologic phases of the ARS. The method of extracorporeal-immune-lypmh-plasmo-sorption includes Antiradiation Antitoxic Antibodies (AAA) immobilized on microporous polymeric membranes with a pore size that is capable to provide diffusion of blood-lymph plasma. Plasma of blood or lymph of irradiated mammals contains Radiation Toxins (RT) that have toxic and antigenic properties. Radiation Toxins are Antigen-specific to Antitoxic blocking antibodies (Immunoglobulin G). Plasma diffuses through membranes with immobilized AAA and AA-antibodies bind to the polysaccharide chain of tox-ins molecules and complexes of AAA-RT that are captured on membrane surfaces. RT were removed from plasma. Re-transfusion of plasma of blood and lymph had been provided. We show a statistical significant

  19. Supplemental vitamin A prevents the acute radiation-induced defect in wound healing.

    PubMed Central

    Levenson, S M; Gruber, C A; Rettura, G; Gruber, D K; Demetriou, A A; Seifter, E

    1984-01-01

    Acute radiation injury leads to thymic involution, adrenal enlargement, leukopenia, thrombocytopenia, gastrointestinal ulceration, and impaired wound healing. The authors hypothesized that supplemental vitamin A would mitigate these adverse effects in rats exposed to acute whole-body radiation. This hypothesis was based on previous experiments in their laboratory that showed that supplemental vitamin A is thymotropic for normal rodents and lessens the thymic involution, lymphopenia, and adrenal enlargement that follows stress, trauma, and neoplasia, largely obviates the impaired wound healing induced by the radiomimetic drugs streptozotocin and cyclophosphamide, lessens the systemic response (thymic involution, adrenal enlargement, leukopenia, lymphocytopenia) to local radiation, and shifts the median lethal dose (LD50/30) following whole-body radiation to the right. To test their hypothesis, dorsal skin incisions and subcutaneous implantation of polyvinyl alcohol sponges were performed in anesthetized Sprague-Dawley rats at varying times following sham radiation or varying doses of whole-body radiation (175-850 rad). In each experiment, the control diet [which contains about 18,000 IU vit. A/kg chow (3 X the NRC RDA for normal rats)] was supplemented with 150,000 IU vit. A/kg diet beginning at, before, or after sham radiation and wounding or radiation and wounding. The supplemental vitamin A prevented the impaired wound healing and lessened the weight loss, leukopenia, thrombocytopenia, thymic involution, adrenal enlargement, decrease in splenic weight, and gastric ulceration of the radiated (750-850 rad) wounded rats. This was true whether the supplemental vitamin A was begun before (2 or 4 days) or after (1-2 hours to 4 days) radiation and wounding; the supplemental vitamin A was more effective when started before or up to 2 days after radiation and wounding. The authors believe that prevention of the impaired wound healing following radiation by supplemental

  20. Effects of acute exposure to ultrahigh radiofrequency radiation on three antenna engineers.

    PubMed

    Schilling, C J

    1997-04-01

    Three men were accidentally exposed to high levels of ultrahigh frequency radiofrequency radiation (785 MHz mean frequency) while working on a television mast. They experienced an immediate sensation of intense heating of the parts of the body in the electromagnetic field followed by a variety of symptoms and signs which included pain, headache, numbness, and parasthesiae, malaise, diarrhoea, and skin erythema. The most notable problem was that of acute then chronic headache involving the part of the head which was most exposed.

  1. Acute myelogenous leukemia following radiation therapy and chemotherapy for osteogenic sarcoma

    SciTech Connect

    Jacobs, A.D.; Gale, R.P.

    1984-06-01

    Patients receiving ionizing radiation therapy or cytotoxic chemotherapy are at increased risk of developing acute myelogenous leukemia. Ten cases of therapy-linked myelogenous leukemia have been reported in patients with sarcoma, and the authors report here the first case in a patient who received combined-modality therapy for treatment of an osteogenic sarcoma. As treatment for this disease becomes more intensive and survival improves, the incidence of leukemia following therapy for osteogenic sarcoma may increase.

  2. Novel Autoantigens Associated with Lupus Nephritis

    PubMed Central

    Onishi, Sachiko; Adnan, Endy; Ishizaki, Jun; Miyazaki, Tatsuhiko; Tanaka, Yuki; Matsumoto, Takuya; Suemori, Koichiro; Shudou, Masachika; Okura, Takafumi; Takeda, Hiroyuki; Sawasaki, Tatsuya; Yasukawa, Masaki; Hasegawa, Hitoshi

    2015-01-01

    Systemic lupus erythematosus (SLE) is characterized by production of a variety of autoantibodies. Although anti-double-stranded DNA (anti-dsDNA) antibodies contribute to the pathogenesis of lupus nephritis (LN), they are not sufficient for diagnosis and evaluation of disease activity. To obtain other autoantibodies associated with LN, we screened autoantigens reacting with the sera of LN patients by using an N-terminal biotinylated protein library created from a wheat cell-free protein production system. We screened 17 proteins that showed higher positive signals in the active phase than in the inactive phase of SLE, and higher positive signals in the serum of SLE patient with nephritis than in that of patient without nephritis. Of these, two LN-associated autoantigens, ribosomal RNA-processing protein 8 (RRP8) and spermatid nuclear transition protein 1 (TNP1) were identified by immunoprecipitation and immunofluorescence of renal tissues. Circulating anti-RRP8 and anti-TNP1 autoantibodies were recognized and deposited as an immune complex (IC) in glomeruli. IC was deposited preferentially in glomeruli rather than in other organs in C57BL/6 mice injected with RRP8 or TNP1. ELISA analysis of sera from patients with various rheumatic diseases demonstrated reactivity for RRP8 and TNP1 in 20% and 14.7% of SLE patients, respectively, whereas there was little or no reactivity in patients with other rheumatic diseases. Among SLE patients, 63.6% and 45.5% of those with LN were positive for anti-RRP8 and anti-TNP1 antibodies, compared with 12.5% and 9.4% of SLE patients without nephritis, respectively. Both proteins are cationic, and their respective antibodies did not cross-react with dsDNA. These proteins released from apoptotic cells form ICs with each autoantibody, and their ICs may become trapped at anionic sites in the glomerular basement membrane, leading to deposition in glomeruli. These autoantibodies may be useful for prediction of LN in subsets of SLE patients who

  3. Ofatumumab treatment in lupus nephritis patients

    PubMed Central

    Haarhaus, Malena Loberg; Svenungsson, Elisabet; Gunnarsson, Iva

    2016-01-01

    Rituximab is frequently used in systemic lupus erythematosus; however, side effects such as infusion-related reactions limit its use. In this case report, we describe, for the first time, treatment with ofatumumab in four patients with lupus nephritis. The treatment was well tolerated in three of the patients, and a reduction of proteinuria was seen in all cases. This emphasizes the importance of alternative B-cell-depleting therapies in patients with an initial good response to rituximab, but who develop side effects. PMID:27478595

  4. Epidemiological studies on radiation carcinogenesis in human populations following acute exposure: nuclear explosions and medical radiation

    SciTech Connect

    Fabrikant, J.I.

    1982-08-01

    The present review provides an understanding of our current knowledge of the carcinogenic effect of low-dose radiation in man, and surveys the epidemiological studies of human populations exposed to nuclear explosions and medical radiation. Discussion centers on the contributions of quantitative epidemiology to present knowledge, the reliability of the dose-incidence data, and those relevant epidemiological studies that provide the most useful information for risk estimation of cancer-induction in man. Reference is made to dose-incidence relationships from laboratory animal experiments where they may obtain for problems and difficulties in extrapolation from data obtained at high doses to low doses, and from animal data to the human situation. The paper describes the methods of application of such epidemiological data for estimation of excess risk of radiation-induced cancer in exposed human populations, and discusses the strengths and limitations of epidemiology in guiding radiation protection philosophy and public health policy.

  5. Epidemiological studies on radiation carcinogenesis in human populations following acute exposure: nuclear explosions and medical radiation

    SciTech Connect

    Fabrikant, J.I.

    1981-05-01

    The current knowledge of the carcinogenic effect of radiation in man is considered. The discussion is restricted to dose-incidence data in humans, particularly to certain of those epidemiological studies of human populations that are used most frequently for risk estimation for low-dose radiation carcinogenesis in man. Emphasis is placed solely on those surveys concerned with nuclear explosions and medical exposures. (ACR)

  6. Development of Graphical User Interface for ARRBOD (Acute Radiation Risk and BRYNTRN Organ Dose Projection)

    NASA Technical Reports Server (NTRS)

    Kim, Myung-Hee; Hu, Shaowen; Nounu, Hatem N.; Cucinotta, Francis A.

    2010-01-01

    The space radiation environment, particularly solar particle events (SPEs), poses the risk of acute radiation sickness (ARS) to humans; and organ doses from SPE exposure may reach critical levels during extra vehicular activities (EVAs) or within lightly shielded spacecraft. NASA has developed an organ dose projection model using the BRYNTRN with SUMDOSE computer codes, and a probabilistic model of Acute Radiation Risk (ARR). The codes BRYNTRN and SUMDOSE, written in FORTRAN, are a Baryon transport code and an output data processing code, respectively. The ARR code is written in C. The risk projection models of organ doses and ARR take the output from BRYNTRN as an input to their calculations. BRYNTRN code operation requires extensive input preparation. With a graphical user interface (GUI) to handle input and output for BRYNTRN, the response models can be connected easily and correctly to BRYNTRN in friendly way. A GUI for the Acute Radiation Risk and BRYNTRN Organ Dose (ARRBOD) projection code provides seamless integration of input and output manipulations, which are required for operations of the ARRBOD modules: BRYNTRN, SUMDOSE, and the ARR probabilistic response model. The ARRBOD GUI is intended for mission planners, radiation shield designers, space operations in the mission operations directorate (MOD), and space biophysics researchers. The ARRBOD GUI will serve as a proof-of-concept example for future integration of other human space applications risk projection models. The current version of the ARRBOD GUI is a new self-contained product and will have follow-on versions, as options are added: 1) human geometries of MAX/FAX in addition to CAM/CAF; 2) shielding distributions for spacecraft, Mars surface and atmosphere; 3) various space environmental and biophysical models; and 4) other response models to be connected to the BRYNTRN. The major components of the overall system, the subsystem interconnections, and external interfaces are described in this

  7. A possible approach to large-scale laboratory testing for acute radiation sickness after a nuclear detonation.

    PubMed

    Adalja, Amesh A; Watson, Matthew; Wollner, Samuel; Toner, Eric

    2011-12-01

    After the detonation of an improvised nuclear device, several key actions will be necessary to save the greatest number of lives possible. Among these tasks, the identification of patients with impending acute radiation sickness is a critical problem that so far has lacked a clear solution in national planning. We present one possible solution: the formation of a public-private partnership to augment the capacity to identify those at risk for acute radiation sickness. PMID:21988186

  8. Radiation resistance of primary clonogenic blasts from children with acute lymphoblastic leukemia

    SciTech Connect

    Uckun, F.M. Childrens Cancer Group, Arcadia, CA ); Aeppli, D.; Song, C.W. )

    1993-11-15

    Detailed comparative analyses of the radiation sensitivity of primary clonogenic blasts from children with acute lymphoblastic leukemia (ALL) were performed to achieve a better understanding of clinical radiation resistance in ALL. The radiation sensitivity of primary clonogenic blasts from 74 children with newly diagnosed ALL was analyzed using leukemic progenitor cell (LPC) assays. Primary bone marrow blasts from all 74 patients were exposed to ionizing radiation and subsequently assayed for LPC-derived blast colony formation. Radiation survival curves of LPC were constructed for each of the newly diagnosed patients using computer programs for the single-hit multitarget as well as the linear quadratic models of cell survival. A marked interpatient variation in intrinsic radiation sensitivity was observed between LPC populations. The SF[sub 2] values ranged from 0.01 to 1.00. Patients were divided into groups according to their sex, age, WBC at diagnosis, cell cycle distribution of leukemic blasts, and immunophenotype. Only immunophenotype provided a significant correlation with the intrinsic radiation sensitivity of LPC. Patients with B-lineage ALL had higher SF[sub 2] and smaller [alpha] values than T-lineage ALL patients, consistent with greater intrinsic radiation resistance at the level of LPC. Notably, 43% of B-lineage ALL cases, but only 27% of T-lineage ALL cases had LPC with SF[sub 2] [ge] 0.5. Similarly, 66% of B-lineage ALL cases, but only 37% of T-lineage ALL cases had LPC with [alpha] values [le] 0.4 Gy[sup [minus]1]. Combining the two indicators of radiation resistance, they found that only 34% of the B-lineage ALL patients had none of the two parameters in the respective critical regions, while 63% of the T-lineage patients had none. In multivariate analyses, the immunophenotypic B-lineage affiliation was the only significant predictor of radiation resistance at the level of LPC. 42 refs., 1 fig., 2 tabs.

  9. Evidence Report: Risk of Acute Radiation Syndromes Due to Solar Particle Events

    NASA Technical Reports Server (NTRS)

    Carnell, Lisa; Blattnig, Steve; Hu, Shaowen; Huff, Janice; Kim, Myung-Hee; Norman, Ryan; Patel, Zarana; Simonsen, Lisa; Wu, Honglu

    2016-01-01

    Crew health and performance may be impacted by a major solar particle event (SPE), multiple SPEs, or the cumulative effect of galactic cosmic rays (GCR) and SPEs. Beyond low-Earth orbit, the protection of the Earth's magnetosphere is no longer available, such that increased shielding and protective mechanisms are necessary in order to prevent acute radiation sickness and impacts to mission success or crew survival. While operational monitoring and shielding are expected to minimize radiation exposures, there are EVA scenarios outside of low-Earth orbit where the risk of prodromal effects, including nausea, vomiting, anorexia, and fatigue, as well as skin injury and depletion of the blood-forming organs (BFO), may occur. There is a reasonable concern that a compromised immune system due to high skin doses from a SPE or due to synergistic space flight factors (e.g., microgravity) may lead to increased risk to the BFO. The primary data available at present are derived from analyses of medical patients and persons accidentally exposed to acute, high doses of low-linear energy transfer (LET) (or terrestrial) radiation. Data more specific to the space flight environment must be compiled to quantify the magnitude of increase of this risk and to develop appropriate protection strategies. In particular, information addressing the distinct differences between solar proton exposures and terrestrial exposure scenarios, including radiation quality, dose-rate effects, and non-uniform dose distributions, is required for accurate risk estimation.

  10. Association of Acute Radiation Syndrome and Rain after the Bombings in Atomic Bomb Survivors.

    PubMed

    Ozasa, K; Sakata, R; Cullings, H M; Grant, E J

    2016-06-01

    Acute radiation-induced symptoms reported in survivors after the atomic bombings in Hiroshima and Nagasaki have been suspected to be associated with rain that fell after the explosions, but this association has not been evaluated in an epidemiological study that considers the effects of the direct dose from the atomic bombs and other factors. The aim of this study was to evaluate this association using information from a fixed cohort, comprised of 93,741 members of the Life Span Study who were in the city at the time of the bombing. Information on acute symptoms and exposure to rain was collected in surveys conducted by interviewers, primarily in the 1950s. The proportion of survivors developing severe epilation was around 60% at levels of direct radiation doses of 3 Gy or higher and less than 0.2% at levels <0.005 Gy regardless of reported rain exposure status. The low prevalence of acute symptoms at low direct doses indicates that the reported fallout rain was not homogeneously radioactive at a level sufficient to cause a substantial probability of acute symptoms. We observed that the proportion of reported acute symptoms was slightly higher among those who reported rain exposure in some subgroups, however, suggestions that rain was the cause of these reported symptoms are not supported by analyses specific to the known areas of radioactive fallout. Misclassification of exposure and outcome, including symptoms due to other causes and recall bias, appears to be a more plausible explanation. However, the insufficient and retrospective nature of the available data limited our ability to quantify the attribution to those possible causes.

  11. Association of Acute Radiation Syndrome and Rain after the Bombings in Atomic Bomb Survivors.

    PubMed

    Ozasa, K; Sakata, R; Cullings, H M; Grant, E J

    2016-06-01

    Acute radiation-induced symptoms reported in survivors after the atomic bombings in Hiroshima and Nagasaki have been suspected to be associated with rain that fell after the explosions, but this association has not been evaluated in an epidemiological study that considers the effects of the direct dose from the atomic bombs and other factors. The aim of this study was to evaluate this association using information from a fixed cohort, comprised of 93,741 members of the Life Span Study who were in the city at the time of the bombing. Information on acute symptoms and exposure to rain was collected in surveys conducted by interviewers, primarily in the 1950s. The proportion of survivors developing severe epilation was around 60% at levels of direct radiation doses of 3 Gy or higher and less than 0.2% at levels <0.005 Gy regardless of reported rain exposure status. The low prevalence of acute symptoms at low direct doses indicates that the reported fallout rain was not homogeneously radioactive at a level sufficient to cause a substantial probability of acute symptoms. We observed that the proportion of reported acute symptoms was slightly higher among those who reported rain exposure in some subgroups, however, suggestions that rain was the cause of these reported symptoms are not supported by analyses specific to the known areas of radioactive fallout. Misclassification of exposure and outcome, including symptoms due to other causes and recall bias, appears to be a more plausible explanation. However, the insufficient and retrospective nature of the available data limited our ability to quantify the attribution to those possible causes. PMID:27223827

  12. Acute Radiation Risk and BRYNTRN Organ Dose Projection Graphical User Interface

    NASA Technical Reports Server (NTRS)

    Cucinotta, Francis A.; Hu, Shaowen; Nounu, Hateni N.; Kim, Myung-Hee

    2011-01-01

    The integration of human space applications risk projection models of organ dose and acute radiation risk has been a key problem. NASA has developed an organ dose projection model using the BRYNTRN with SUM DOSE computer codes, and a probabilistic model of Acute Radiation Risk (ARR). The codes BRYNTRN and SUM DOSE are a Baryon transport code and an output data processing code, respectively. The risk projection models of organ doses and ARR take the output from BRYNTRN as an input to their calculations. With a graphical user interface (GUI) to handle input and output for BRYNTRN, the response models can be connected easily and correctly to BRYNTRN. A GUI for the ARR and BRYNTRN Organ Dose (ARRBOD) projection code provides seamless integration of input and output manipulations, which are required for operations of the ARRBOD modules. The ARRBOD GUI is intended for mission planners, radiation shield designers, space operations in the mission operations directorate (MOD), and space biophysics researchers. BRYNTRN code operation requires extensive input preparation. Only a graphical user interface (GUI) can handle input and output for BRYNTRN to the response models easily and correctly. The purpose of the GUI development for ARRBOD is to provide seamless integration of input and output manipulations for the operations of projection modules (BRYNTRN, SLMDOSE, and the ARR probabilistic response model) in assessing the acute risk and the organ doses of significant Solar Particle Events (SPEs). The assessment of astronauts radiation risk from SPE is in support of mission design and operational planning to manage radiation risks in future space missions. The ARRBOD GUI can identify the proper shielding solutions using the gender-specific organ dose assessments in order to avoid ARR symptoms, and to stay within the current NASA short-term dose limits. The quantified evaluation of ARR severities based on any given shielding configuration and a specified EVA or other mission

  13. Treatment of young patients with lupus nephritis using calcineurin inhibitors

    PubMed Central

    Tanaka, Hiroshi; Tsuruga, Kazushi; Aizawa-Yashiro, Tomomi; Watanabe, Shojiro; Imaizumi, Tadaatsu

    2012-01-01

    Recent advances in the management of lupus nephritis, together with earlier renal biopsy and selective use of aggressive immunosuppressive therapy, have contributed to a favorable outcome in children and adolescents with systemic lupus erythematosus (SLE). Nevertheless, we believe that a more effective and less toxic treatment is needed to attain an optimal control of the activity of lupus nephritis. Recent published papers and our experiences regarding treatment of young patients with lupus nephritis using calcineurin inhibitors are reviewed. Although it has been reported that intermittent monthly pulses of intravenous cyclophosphamide (IVCY) are effective for preserving renal function in adult patients, CPA is a potent immunosuppressive agent that induces severe toxicity, including myelo- and gonadal toxicity, and increases the risk of secondary malignancy. Thus, treatment for controlling lupus nephritis activity, especially in children and adolescents, remains challenging. Cyclosporine A (CsA) and tacrolimus (Tac) are T-cell-specific calcineurin inhibitors that prevent the activation of helper T cells, thereby inhibiting the transcription of the early activation genes of interleukin (IL)-2 and suppressing T cell-induced activation of tumor necrosis factor-α, IL-1β and IL-6. Therefore, both drugs, which we believe may be less cytotoxic, are attractive therapeutic options for young patients with lupus nephritis. Recently, a multidrug regimen of prednisolone (PDN), Tac, and mycophenolate mofetile (MMF) has been found effective and relatively safe in adult lupus nephritis. Since the mechanisms of action of MMF and Tac are probably complementary, multidrug therapy for lupus nephritis may be useful. We propose as an alternative to IVCY, a multidrug therapy with mizoribine, which acts very similarly to MMF, and Tac, which has a different mode of action, combined with PDN for pediatric-onset lupus nephritis. We also believe that a multidrug therapy including CsA and

  14. Acute hematological effects of solar particle event proton radiation in the porcine model.

    PubMed

    Sanzari, J K; Wan, X S; Wroe, A J; Rightnar, S; Cengel, K A; Diffenderfer, E S; Krigsfeld, G S; Gridley, D S; Kennedy, A R

    2013-07-01

    Acute radiation sickness (ARS) is expected to occur in astronauts during large solar particle events (SPEs). One parameter associated with ARS is the hematopoietic syndrome, which can result from decreased numbers of circulating blood cells in those exposed to radiation. The peripheral blood cells are critical for an adequate immune response, and low blood cell counts can result in an increased susceptibility to infection. In this study, Yucatan minipigs were exposed to proton radiation within a range of skin dose levels expected for an SPE (estimated from previous SPEs). The proton-radiation exposure resulted in significant decreases in total white blood cell count (WBC) within 1 day of exposure, 60% below baseline control value or preirradiation values. At the lowest level of the blood cell counts, lymphocytes, neutrophils, monocytes and eosinophils were decreased up to 89.5%, 60.4%, 73.2% and 75.5%, respectively, from the preirradiation values. Monocytes and lymphocytes were decreased by an average of 70% (compared to preirradiation values) as early as 4 h after radiation exposure. Skin doses greater than 5 Gy resulted in decreased blood cell counts up to 90 days after exposure. The results reported here are similar to studies of ARS using the nonhuman primate model, supporting the use of the Yucatan minipig as an alternative. In addition, the high prevalence of hematologic abnormalities resulting from exposure to acute, whole-body SPE-like proton radiation warrants the development of appropriate countermeasures to prevent or treat ARS occurring in astronauts during space travel.

  15. Fatal suppurative nephritis caused by Pseudomonas in a chimpanzee

    USGS Publications Warehouse

    Migaki, G.; Asher, D.M.; Casey, H.W.; Locke, L.N.; Gibbs, C.J.; Gajdusek, C.

    1979-01-01

    Reports of nephritis in chimpanzees are relatively rare, compared with those in other nonhuman primates. McClure and Guilloud reported chronic pyelonephritis in a 35-year-old female chimpanzee; Schmidt and Butler reported glomerulonephritis in an 11-year-old female chimpanzee, and Kim reported on a 12-year-old male with subacute interstitial nephritis in a chimpanzee after the animal had recurrent hemolysis due to phenolic intoxication. The present report deals with supprative nephritis caused by Pseudomonas resulting in renal failure in a chimpanzee.

  16. Overview of Graphical User Interface for ARRBOD (Acute Radiation Risk and BRYNTRN Organ Dose Projection)

    NASA Astrophysics Data System (ADS)

    Kim, Myung-Hee Y.; Hu, Shaowen; Nounu, Hatem; Cucinotta, Francis A.

    Solar particle events (SPEs) pose the risk of acute radiation sickness (ARS) to astronauts be-cause organ doses from large SPEs may reach critical levels during extra vehicular activities (EVAs) or lightly shielded spacecraft. NASA has developed an organ dose projection model of Baryon transport code (BRYNTRN) with an output data processing module of SUMDOSE, and a probabilistic model of acute radiation risk (ARR). BRYNTRN code operation requires extensive input preparation, and the risk projection models of organ doses and ARR take the output from BRYNTRN as an input to their calculations. With a graphical user interface (GUI) to handle input and output for BRYNTRN, these response models can be connected easily and correctly to BRYNTRN in a user-friendly way. The GUI for the Acute Radiation Risk and BRYNTRN Organ Dose (ARRBOD) projection code provides seamless integration of input and output manipulations required for operations of the ARRBOD modules: BRYNTRN, SUMDOSE, and the ARR probabilistic response model. The ARRBOD GUI is intended for mission planners, radiation shield designers, space operations in the mission operations direc-torate (MOD), and space biophysics researchers. Assessment of astronauts' organ doses and ARS from the exposure to historically large SPEs is in support of mission design and opera-tion planning to avoid ARS and stay within the current NASA short-term dose limits. The ARRBOD GUI will serve as a proof-of-concept for future integration of other risk projection models for human space applications. We present an overview of the ARRBOD GUI prod-uct, which is a new self-contained product, for the major components of the overall system, subsystem interconnections, and external interfaces.

  17. Overview of Graphical User Interface for ARRBOD (Acute Radiation Risk and BRYNTRN Organ Dose Projection)

    NASA Technical Reports Server (NTRS)

    Kim, Myung-Hee Y.; Hu, Shaowen; Nounu, Hatem N.; Cucinotta, Francis A.

    2010-01-01

    Solar particle events (SPEs) pose the risk of acute radiation sickness (ARS) to astronauts, because organ doses from large SPEs may reach critical levels during extra vehicular activities (EVAs) or lightly shielded spacecraft. NASA has developed an organ dose projection model of Baryon transport code (BRYNTRN) with an output data processing module of SUMDOSE, and a probabilistic model of acute radiation risk (ARR). BRYNTRN code operation requires extensive input preparation, and the risk projection models of organ doses and ARR take the output from BRYNTRN as an input to their calculations. With a graphical user interface (GUI) to handle input and output for BRYNTRN, these response models can be connected easily and correctly to BRYNTRN in a user friendly way. The GUI for the Acute Radiation Risk and BRYNTRN Organ Dose (ARRBOD) projection code provides seamless integration of input and output manipulations required for operations of the ARRBOD modules: BRYNTRN, SUMDOSE, and the ARR probabilistic response model. The ARRBOD GUI is intended for mission planners, radiation shield designers, space operations in the mission operations directorate (MOD), and space biophysics researchers. Assessment of astronauts organ doses and ARS from the exposure to historically large SPEs is in support of mission design and operation planning to avoid ARS and stay within the current NASA short-term dose limits. The ARRBOD GUI will serve as a proof-of-concept for future integration of other risk projection models for human space applications. We present an overview of the ARRBOD GUI product, which is a new self-contained product, for the major components of the overall system, subsystem interconnections, and external interfaces.

  18. Chemical toxicity of uranium hexafluoride compared to acute effects of radiation

    SciTech Connect

    McGuire, S.A.

    1991-02-01

    The chemical effects from acute exposures to uranium hexafluoride are compared to the nonstochastic effects from acute radiation doses of 25 rems to the whole body and 300 rems to the thyroid. The analysis concludes that an intake of about 10 mg of uranium in soluble form is roughly comparable, in terms of early effects, to an acute whole body dose of 25 rems because both are just below the threshold for significant nonstochastic effects. Similarly, an exposure to hydrogen fluoride at a concentration of 25 mg/m{sup 3} for 30 minutes is roughly comparable because there would be no significant nonstochastic effects. For times t other than 30 minutes, the concentration C of hydrogen fluoride considered to have the same effect can be calculated using a quadratic equation: C = 25 mg/m{sup 3} (30 min/t). The purpose of these analyses is to provide information for developing design and siting guideline based on chemical toxicity for enrichment plants using uranium hexafluoride. These guidelines are to be similar, in terms of stochastic health effects, to criteria in NRC regulations of nuclear power plants, which are based on radiation doses. 26 refs., 1 fig., 5 tabs.

  19. Medical Management of Acute Radiation Syndromes : Comparison of Antiradiation Vaccine and Antioxidants radioprotection potency.

    NASA Astrophysics Data System (ADS)

    Maliev, Slava; Popov, Dmitri; Lisenkov, Nikolai

    Introduction: This experimental study of biological effects of the Antiradiation Vaccine and Antioxidants which were used for prophylaxis and treatment of the Acute Radiation Syndromes caused by high doses of the low-LET radiation. An important role of Reactive Oxyden Species (Singlet oxygen, hydroxyl radicals, superoxide anions and bio-radicals)in development of the Acute Radiation Syndromes could be defined as a "central dogma" of radiobiology. Oxida-tion and damages of lipids, proteins, DNA, and RNA are playing active role in development of postradiation apoptosis. However, the therapeutic role of antioxidants in modification of a postradiation injury caused by high doses of radiation remains controversial.Previous stud-ies had revealed that antioxidants did not increase a survival rate of mammals with severe forms of the Acute Radiation Syndromes caused by High Doses of the low-LET radiation. The Antiradiation Vaccine(ARV) contains toxoid forms of the Radiation Toxins(RT) from the Specific Radiation Determinants Group (SRD). The RT SRD has toxic and antigenic prop-erties at the same time and stimulates a specific antibody elaboration and humoral response form activated acquired immune system. The blocking antiradiation antibodies induce an im-munologically specific effect and have inhibiting effects on radiation induced neuro-toxicity, vascular-toxicity, gastrointestinal toxcity, hematopoietic toxicity, and radiation induced cytol-ysis of selected groups of cells that are sensitive to radiation. Methods and materials: Scheme of experiments: 1. Irradiated animals with development of Cerebrovascular ARS (Cv-ARS), Cardiovascular ARS (Cr-ARS) Gastrointestinal ARS(GI-ARS), Hematopoietic ARS (H-ARS) -control -were treated with placebo administration. 2. Irradiated animals were treated with antioxidants prophylaxisis and treatment of Cv-ARS, Cr-SRS, GI-ARS, Hp-ARS forms of the ARS. 3. irradiated animals were treated with radioprotection by Antiradiation Vaccine

  20. Dosimetric Predictors of Radiation-induced Acute Nausea and Vomiting in IMRT for Nasopharyngeal Cancer

    SciTech Connect

    Lee, Victor H.F.; Ng, Sherry C.Y.; Leung, T.W.; Au, Gordon K.H.; Kwong, Dora L.W.

    2012-09-01

    Purpose: We wanted to investigate dosimetric parameters that would predict radiation-induced acute nausea and vomiting in intensity-modulated radiation therapy (IMRT) for undifferentiated carcinoma of the nasopharynx (NPC). Methods and Materials: Forty-nine consecutive patients with newly diagnosed NPC were treated with IMRT alone in this prospective study. Patients receiving any form of chemotherapy were excluded. The dorsal vagal complex (DVC) as well as the left and right vestibules (VB-L and VB-R, respectively) were contoured on planning computed tomography images. A structure combining both the VB-L and the VB-R, named VB-T, was also generated. All structures were labeled organs at risk (OAR). A 3-mm three-dimensional margin was added to these structures and labeled DVC+3 mm, VB-L+3 mm, VB-R+3 mm, and VB-T+3 mm to account for physiological body motion and setup error. No weightings were given to these structures during optimization in treatment planning. Dosimetric parameters were recorded from dose-volume histograms. Statistical analysis of parameters' association with nausea and vomiting was performed using univariate and multivariate logistic regression. Results: Six patients (12.2%) reported Grade 1 nausea, and 8 patients (16.3%) reported Grade 2 nausea. Also, 4 patients (8.2%) complained of Grade 1 vomiting, and 4 patients (8.2%) experienced Grade 2 vomiting. No patients developed protracted nausea and vomiting after completion of IMRT. For radiation-induced acute nausea, V40 (percentage volume receiving at least 40Gy) to the VB-T and V40>=80% to the VB-T were predictors, using univariate analysis. On multivariate analysis, V40>=80% to the VB-T was the only predictor. There were no predictors of radiation-induced acute vomiting, as the number of events was too small for analysis. Conclusions: This is the first study demonstrating that a V40 to the VB-T is predictive of radiation-induced acute nausea. The vestibules should be labeled as sensitive OARs, and

  1. Pentraxin 3 Is Closely Associated With Tubulointerstitial Injury in Lupus Nephritis: A Large Multicenter Cross-Sectional Study.

    PubMed

    Pang, Yun; Tan, Ying; Li, Yongzhe; Zhang, Jianchun; Guo, Yongbing; Guo, Zhiling; Zhang, Chengying; Yu, Feng; Zhao, Ming-Hui

    2016-01-01

    Lupus nephritis always elicits immune inflammatory tissue damages in kidney. Pentraxin 3 (PTX3), mainly produced at inflammatory sites, is known to be involved in the regulation of the innate immunity system. The aim of this study was to investigate the serum and urine levels of PTX3, and the expression of PTX3 in renal tissues in lupus nephritis patients from a large Chinese cohort.The study used cross-sectional survey and 288 active lupus nephritis patients, including discovery cohort and validation cohort, 115 systemic lupus erythematosus (SLE) patients without clinical renal involvement and 46 healthy controls were enrolled. Serum and urine PTX3 were screened by enzyme-linked immunosorbent assay (ELISA). The renal deposition of PTX3 was detected by immunohistochemistry and immunofluorescence.The average level of serum PTX3 in the discovery cohort of lupus nephritis was significantly higher than that in nonrenal involvement SLE group and normal controls (P < 0.001, P < 0.001, respectively), which was confirmed by the validation cohort. Serum PTX3 levels of 15 lupus nephritis patients in remission decreased significantly compared with that in active phase. Serum PTX3 levels were significantly higher in patients with hematuria (P = 0.014), leucocyturia (P = 0.002), acute renal failure (P = 0.001), and nephrotic syndrome (P = 0.036). There were significant correlations between serum PTX3 levels and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores, serum creatinine value, renal pathological activity indices, and serum complement 3 (C3) in active lupus nephritis patients. The urinary PTX3 levels were significantly higher in active lupus nephritis patients compared with patients in remission and normal controls (P = 0.011, P = 0.008, respectively). There were significant associations between urinary PTX3 levels and multiple indices of tubulointerstitial lesions, including urinary KIM-1 (r = 0.368, P = 0

  2. Low-dose radiation modifies skin response to acute gamma-rays and protons.

    PubMed

    Mao, Xiao Wen; Pecaut, Michael J; Cao, Jeffrey D; Moldovan, Maria; Gridley, Daila S

    2013-01-01

    The goal of the present study was to obtain pilot data on the effects of protracted low-dose/low-dose-rate (LDR) γ-rays on the skin, both with and without acute gamma or proton irradiation (IR). Six groups of C57BL/6 mice were examined: a) 0 Gy control, b) LDR, c) Gamma, d) LDR+Gamma, e) Proton, and f) LDR+Proton. LDR radiation was delivered to a total dose of 0.01 Gy (0.03 cGy/h), whereas the Gamma and Proton groups received 2 Gy (0.9 Gy/min and 1.0 Gy/min, respectively). Assays were performed 56 days after exposure. Skin samples from all irradiated groups had activated caspase-3, indicative of apoptosis. The significant (p<0.05) increases in immunoreactivity in the Gamma and Proton groups were not present when LDR pre-exposure was included. However, the terminal deoxynucleotidyl transferase dUTP nick-end labeling assay for DNA fragmentation and histological examination of hematoxylin and eosin-stained sections revealed no significant differences among groups, regardless of radiation regimen. The data demonstrate that caspase-3 activation initially triggered by both forms of acute radiation was greatly elevated in the skin nearly two months after whole-body exposure. In addition, LDR γ-ray priming ameliorated this response.

  3. [Tubulointerstitial nephritis associated with treatment with selective Cox-2 inhibitors, celecoxib and rofecoxib].

    PubMed

    Ortiz, M; Mon, C; Fernández, M J; Sánchez, R; Mampaso, F; Alvarez Ude, F

    2005-01-01

    The nephrotoxic effect of nonselective nonsteroidal anti-inflamatory drugs (NSAIDS) has been widely described. The main benefit of the Cox-2 inhibitors in relation to the NSAIDS is the production of a very similar analgesic effect, but with fewer gastrointestinal side effects. However, their effects on renal function are little known as yet and their long-term safety is still pending definition. The use of selective Cox-2 inhibitors as anti-inflamatory analgesic is becoming more and more common in our environment. We report two cases of tubulointersticial nephritis confirmed by renal biopsy, associated with administration of the two Cox-2 inhibitors currently available on the market, celecoxib and rofecoxib. In both cases, we were talking about elderly women, with deterioration of the general condition and acute renal failure. In the former case, renal biopsy showed an acute tubulo-intersticial nephritis (TIN) so highly "variegated" in its histologic expression. In the second case, was associated with strong indications of chronicity. Treatment with steroid was initiated in both patients and improvement of renal function was observed.

  4. Intravenous Immunoglobulin in the Management of Lupus Nephritis

    PubMed Central

    Wenderfer, Scott E.; Thacker, Trisha

    2012-01-01

    The occurrence of nephritis in patients with systemic lupus erythematosus is associated with increased morbidity and mortality. The pathogenesis of lupus nephritis is complex, involving innate and adaptive cellular and humoral immune responses. Autoantibodies in particular have been shown to be critical in the initiation and progression of renal injury, via interactions with both Fc-receptors and complement. One approach in the management of patients with lupus nephritis has been the use of intravenous immunoglobulin. This therapy has shown benefit in the setting of many forms of autoantibody-mediated injury; however, the mechanisms of efficacy are not fully understood. In this paper, the data supporting the use of immunoglobulin therapy in lupus nephritis will be evaluated. In addition, the potential mechanisms of action will be discussed with respect to the known involvement of complement and Fc-receptors in the kidney parenchyma. Results are provocative and warrant additional clinical trials. PMID:23056926

  5. Intensity-Modulated Radiation Therapy Significantly Improves Acute Gastrointestinal Toxicity in Pancreatic and Ampullary Cancers

    SciTech Connect

    Yovino, Susannah; Poppe, Matthew; Jabbour, Salma; David, Vera; Garofalo, Michael; Pandya, Naimesh; Alexander, Richard; Hanna, Nader; Regine, William F.

    2011-01-01

    Purpose: Among patients with upper abdominal malignancies, intensity-modulated radiation therapy (IMRT) can improve dose distributions to critical dose-limiting structures near the target. Whether these improved dose distributions are associated with decreased toxicity when compared with conventional three-dimensional treatment remains a subject of investigation. Methods and Materials: 46 patients with pancreatic/ampullary cancer were treated with concurrent chemoradiation (CRT) using inverse-planned IMRT. All patients received CRT based on 5-fluorouracil in a schema similar to Radiation Therapy Oncology Group (RTOG) 97-04. Rates of acute gastrointestinal (GI) toxicity for this series of IMRT-treated patients were compared with those from RTOG 97-04, where all patients were treated with three-dimensional conformal techniques. Chi-square analysis was used to determine if there was a statistically different incidence in acute GI toxicity between these two groups of patients. Results: The overall incidence of Grade 3-4 acute GI toxicity was low in patients receiving IMRT-based CRT. When compared with patients who had three-dimensional treatment planning (RTOG 97-04), IMRT significantly reduced the incidence of Grade 3-4 nausea and vomiting (0% vs. 11%, p = 0.024) and diarrhea (3% vs. 18%, p = 0.017). There was no significant difference in the incidence of Grade 3-4 weight loss between the two groups of patients. Conclusions: IMRT is associated with a statistically significant decrease in acute upper and lower GI toxicity among patients treated with CRT for pancreatic/ampullary cancers. Future clinical trials plan to incorporate the use of IMRT, given that it remains a subject of active investigation.

  6. Renal glycosphingolipid metabolism is dysfunctional in lupus nephritis.

    PubMed

    Nowling, Tamara K; Mather, Andrew R; Thiyagarajan, Thirumagal; Hernández-Corbacho, María José; Powers, Thomas W; Jones, E Ellen; Snider, Ashley J; Oates, Jim C; Drake, Richard R; Siskind, Leah J

    2015-06-01

    Nearly one half of patients with lupus develop glomerulonephritis (GN), which often leads to renal failure. Although nephritis is diagnosed by the presence of proteinuria, the pathology of nephritis can fall into one of five classes defined by different forms of tissue injury, and the mechanisms involved in pathogenesis are not completely understood. Glycosphingolipids are abundant in the kidney, have roles in many cellular functions, and were shown to be involved in other renal diseases. Here, we show dysfunctional glycosphingolipid metabolism in patients with lupus nephritis and MRL/lpr lupus mice. Specifically, we found that glucosylceramide (GlcCer) and lactosylceramide (LacCer) levels are significantly higher in the kidneys of nephritic MRL/lpr lupus mice than the kidneys of non-nephritic lupus mice or healthy controls. This elevation may be, in part, caused by altered transcriptional regulation and/or activity of LacCer synthase (GalT5) and neuraminidase 1, enzymes that mediate glycosphingolipid metabolism. We show increased neuraminidase 1 activity early during the progression of nephritis (before significant elevation of GlcCer and LacCer in the kidney). Elevated levels of urinary LacCer were detected before proteinuria in lupus mice. Notably, LacCer levels were higher in the urine and kidneys of patients with lupus and nephritis than patients with lupus without nephritis or healthy controls. Together, these results show early and significant dysfunction of the glycosphingolipid metabolic pathway in the kidneys of lupus mice and patients with lupus nephritis and suggest that molecules in this pathway may serve as early markers in lupus nephritis.

  7. THE USE OF BASIC DIETS IN THE TREATMENT OF NEPHRITIS*

    PubMed Central

    Sansum, W. D.

    1922-01-01

    By the employment of what we are pleased to call a “basic diet,” the urinary acidity may be easily reduced to a pH of 7.00 or better. On such diets patients with chronic interstitial nephritis appear to improve, as evidenced by a decrease in blood pressure, albumin and casts in the urine and other symptoms of nephritis and arterial hypertension. PMID:18738737

  8. Amifostine ameliorates recognition memory defect in acute radiation syndrome caused by relatively low-dose of gamma radiation

    PubMed Central

    Lee, Hae-June; Kim, Joong-Sun; Song, Myoung-Sub; Seo, Heung-Sik; Yang, Miyoung; Kim, Jong Choon; Jo, Sung-Kee; Shin, Taekyun

    2010-01-01

    This study examined whether amifostine (WR-2721) could attenuate memory impairment and suppress hippocampal neurogenesis in adult mice with the relatively low-dose exposure of acute radiation syndrome (ARS). These were assessed using object recognition memory test, the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay, and immunohistochemical markers of neurogenesis [Ki-67 and doublecortin (DCX)]. Amifostine treatment (214 mg/kg, i.p.) prior to irradiation significantly attenuated the recognition memory defect in ARS, and markedly blocked the apoptotic death and decrease of Ki-67- and DCX-positive cells in ARS. Therefore, amifostine may attenuate recognition memory defect in a relatively low-dose exposure of ARS in adult mice, possibly by inhibiting a detrimental effect of irradiation on hippocampal neurogenesis. PMID:20195069

  9. Involvement of histamine released from mast cells in acute radiation dermatitis in mice.

    PubMed

    Moriyasu, Saiko; Yamamoto, Kouichi; Kureyama, Naoko; Okamura, Keita; Ikeda, Toshiji; Yamatodani, Atsushi

    2007-06-01

    A possible involvement of histamine in acute radiation dermatitis in mice was investigated. The dose of 40 Gy of gamma irradiation induced erythema and edema in C57BL/6 mice treated with vehicle. However, in C57BL/6 mice treated with chlorpheniramine and WBB6F1-W/Wv mice, erythema and edema were not observed. In all of these mice, epilation and dry desquamation were induced, but bepotastine significantly reduced the extent of these areas. These results suggest that gamma irradiation-induced erythema and edema were caused by histamine released from mast cells via histamine H1 receptor, and epilation was induced by other inflammatory mediators.

  10. The Mitogen-Activated Protein Kinase p38α Regulates Tubular Damage in Murine Anti-Glomerular Basement Membrane Nephritis

    PubMed Central

    Müller, Ralf; Daniel, Christoph; Hugo, Christian; Amann, Kerstin; Mielenz, Dirk; Endlich, Karlhans; Braun, Tobias; van der Veen, Betty; Heeringa, Peter; Schett, Georg; Zwerina, Jochen

    2013-01-01

    p38 mitogen-activated protein kinase (MAPK) is thought to play a central role in acute and chronic inflammatory responses. Whether p38MAPK plays a pathogenic role in crescentic GN (GN) and which of its four isoforms is preferentially involved in kidney inflammation is not definitely known. We thus examined expression and activation of p38MAPK isoforms during anti-glomerular basement membrane (GBM) nephritis. Therefore, p38α conditional knockout mice (MxCre-p38αΔ/Δ) were used to examine the role of p38α in anti-GBM induced nephritis. Both wild type and MxCre-p38αΔ/Δ mice developed acute renal failure over time. Histological examinations revealed a reduced monocyte influx and less tubular damage in MxCre-p38αΔ/Δ mice, whereas glomerular crescent formation and renal fibrosis was similar. Likewise, the levels of pro- and anti-inflammatory cytokines such as TNF, IL-1 and IL-10 were similar, but IL-8 was even up-regulated in MxCre-p38αΔ/Δ mice. In contrast, we could detect strong down-regulation of chemotactic cytokines such as CCL-2, -5 and -7, in the kidneys of MxCre-p38αΔ/Δ mice. In conclusion, p38α is the primary p38MAPK isoform expressed in anti-GBM nephritis and selectively affects inflammatory cell influx and tubular damage. Full protection from nephritis is however not achieved as renal failure and structural damage still occurs. PMID:23441175

  11. Lupus Nephritis: An Overview of Recent Findings

    PubMed Central

    de Zubiria Salgado, Alberto; Herrera-Diaz, Catalina

    2012-01-01

    Lupus nephritis (LN) is one of the most serious complications of systemic lupus erythematosus (SLE) since it is the major predictor of poor prognosis. In susceptible individuals suffering of SLE, in situ formation and deposit of immune complexes (ICs) from apoptotic bodies occur in the kidneys as a result of an amplified epitope immunological response. IC glomerular deposits generate release of proinflammatory cytokines and cell adhesion molecules causing inflammation. This leads to monocytes and polymorphonuclear cells chemotaxis. Subsequent release of proteases generates endothelial injury and mesangial proliferation. Presence of ICs promotes adaptive immune response and causes dendritic cells to release type I interferon. This induces maturation and activation of infiltrating T cells, and amplification of Th2, Th1 and Th17 lymphocytes. Each of them, amplify B cells and activates macrophages to release more proinflammatory molecules, generating effector cells that cannot be modulated promoting kidney epithelial proliferation and fibrosis. Herein immunopathological findings of LN are reviewed. PMID:22536486

  12. Prostate Hypofractionated Radiation Therapy With Injection of Hyaluronic Acid: Acute Toxicities in a Phase 2 Study

    SciTech Connect

    Chapet, Olivier; Decullier, Evelyne; Bin, Sylvie; Faix, Antoine; Ruffion, Alain; Jalade, Patrice; Fenoglietto, Pascal; Udrescu, Corina; Enachescu, Ciprian; Azria, David

    2015-03-15

    Purpose: Hypofractionated radiation therapy (RT) in prostate cancer can be developed only if the risk of rectal toxicity is controlled. In a multicenter phase 2 trial, hypofractionated irradiation was combined with an injection of hyaluronic acid (HA) to preserve the rectal wall. Tolerance of the injection and acute toxicity rates are reported. Methods and Materials: The study was designed to assess late grade 2 toxicity rates. The results described here correspond to the secondary objectives. Acute toxicity was defined as occurring during RT or within 3 months after RT and graded according to the Common Terminology Criteria for Adverse Events version 4.0. HA tolerance was evaluated with a visual analog scale during the injection and 30 minutes after injection and then by use of the Common Terminology Criteria at each visit. Results: From 2010 to 2012, 36 patients with low-risk to intermediate-risk prostate cancer were included. The HA injection induced a mean pain score of 4.6/10 ± 2.3. Thirty minutes after the injection, 2 patients still reported pain (2/10 and 3/10), which persisted after the intervention. Thirty-three patients experienced at least 1 acute genitourinary toxicity and 20 patients at least 1 acute gastrointestinal toxicity. Grade 2 toxicities were reported for 19 patients with urinary obstruction, frequency, or both and for 1 patient with proctitis. No grade 3 or 4 toxicities were reported. At the 3-month visit, 4 patients described grade 2 obstruction or frequency, and no patients had any grade 2 gastrointestinal toxicities. Conclusions: The injection of HA makes it possible to deliver hypofractionated irradiation over 4 weeks with a dose per fraction of > 3 Gy, with limited acute rectal toxicity.

  13. Lupus Nephritis: The Evolving Role of Novel Therapeutics

    PubMed Central

    Rovin, Brad H.; Parikh, Samir V.

    2014-01-01

    Immune complex accumulation in the kidney is the hallmark of lupus nephritis and triggers a series of events that result in kidney inflammation and injury. Cytotoxic agents and corticosteroids are standard of care for lupus nephritis treatment, but are associated with considerable morbidity and suboptimal outcomes. Recently, there has been interest in using novel biologic agents and small molecules to treat lupus nephritis. These therapies can be broadly categorized as anti-inflammatory (laquinamod, anti–tumor necrosis factor–like weak inducer of apotosis, anti-C5, and retinoids), antiautoimmunity (anti-CD20, anti–interferon α, and costimulatory blockers), or both (anti–interleukin 6 and proteasome inhibitors). Recent lupus nephritis clinical trials applied biologics or small molecules of any category to induction treatment, seeking short-term end points of complete renal response. These trials in general have not succeeded. When lupus nephritis comes to clinical attention during the inflammatory stage of the disease, the autoimmune stage leading to kidney inflammation will have been active for some time. The optimal approach for using novel therapies may be to initially target kidney inflammation to preserve renal parenchyma, followed by suppression of autoimmunity. In this review, we discuss novel lupus nephritis therapies and how they fit into a combinatorial treatment strategy based on the pathogenic stage. PMID:24411715

  14. Complement in Lupus Nephritis: New Perspectives

    PubMed Central

    Bao, Lihua; Cunningham, Patrick N.; Quigg, Richard J.

    2015-01-01

    Background Systemic lupus erythematosus (SLE) is an autoimmune disorder caused by loss of tolerance to self-antigens, the production of autoantibodies and deposition of complement-fixing immune complexes (ICs) in injured tissues. SLE is characterized by a wide range of clinical manifestations and targeted organs, with lupus nephritis being one of the most serious complications. The complement system consists of three pathways and is tightly controlled by a set of regulatory proteins to prevent injudicious complement activation on host tissue. The involvement of the complement system in the pathogenesis of SLE is well accepted; yet, its exact role is still not clear. Summary Complement plays dual roles in the pathogenesis of SLE. On the one hand, the complement system appears to have protective features in that hereditary homozygous deficiencies of classical pathway components, such as C1q and C4, are associated with an increased risk for SLE. On the other hand, IC-mediated activation of complement in affected tissues is clearly evident in both experimental and human SLE along with pathological features that are logical consequences of complement activation. Studies in genetically altered mice have shown that lack of complement inhibitors, such as complement factor H (CFH) or decay-accelerating factor (DAF) accelerates the development of experimental lupus nephritis, while treatment with recombinant protein inhibitors, such as Crry-Ig, CR2-Crry, CR2-DAF and CR2-CFH, ameliorates the disease development. Complement-targeted drugs, including soluble complement receptor 1 (TP10), C1 esterase inhibitor and a monoclonal anti-C5 antibody (eculizumab), have been shown to inhibit complement safely, and are now being investigated in a variety of clinical conditions. Key Messages SLE is an autoimmune disorder which targets multiple systems. Complement is centrally involved and plays dual roles in the pathogenesis of SLE. Studies from experimental lupus models and clinical

  15. Painful acute radiation thyroiditis induced by 131I treatment of Graves' disease.

    PubMed

    Shah, Kinjal K; Tarasova, Valentina; Davidian, Michael; Anderson, Robert J

    2015-01-01

    A 44-year-old woman, chronic smoker with Graves' disease was treated with radioactive iodine ablation (RAI). One week after the treatment, she presented with severe pain in the anterior neck with radiation to the angle of the jaw associated with fatigue, tremor and odynophagia. Physical examination demonstrated an asymmetric and exquisitely tender thyroid gland. There was no laboratory evidence of thyrotoxicosis. Acute radiation thyroiditis was diagnosed. Non-steroidal anti-inflammatory drugs and hydrocodone-acetaminophen started initially were ineffective for pain control. Prednisone provided relief and was continued for 1 month with a tapering dose. Symptoms completely resolved after 1 month at which time the thyroid remained diffusely enlarged and non-tender. Three months following RAI ablation she developed hypothyroid symptoms. Levothyroxine was initiated. The patient has remained asymptomatic on continued follow-up care. PMID:25576511

  16. Successful Mitigation of Delayed Intestinal Radiation Injury Using Pravastatin is not Associated with Acute Injury Improvement or Tumor Protection

    SciTech Connect

    Haydont, Valerie; Bourhis, Jean; Vozenin-Brotons, Marie-Catherine |. E-mail: vozenin@igr.fr

    2007-08-01

    Purpose: To investigate whether pravastatin mitigates delayed radiation-induced enteropathy in rats, by focusing on the effects of pravastatin on acute cell death and fibrosis according to connective tissue growth factor (CTGF) expression and collagen inhibition. Methods and Materials: Mitigation of delayed radiation-induced enteropathy was investigated in rats using pravastatin administered in drinking water (30 mg/kg/day) 3 days before and 14 days after irradiation. The ileum was irradiated locally after surgical exteriorization (X-rays, 19 Gy). Acute apoptosis, acute and late histologic alterations, and late CTGF and collagen deposition were monitored by semiquantitative immunohistochemistry and colorimetric staining (6 h, 3 days, 14 days, 15 weeks, and 26 weeks after irradiation). Pravastatin antitumor action was studied in HT-29, HeLa, and PC-3 cells by clonogenic cell survival assays and tumor growth delay experiments. Results: Pravastatin improved delayed radiation enteropathy in rats, whereas its benefit in acute and subacute injury remained limited (6 h, 3 days, and 14 days after irradiation). Delayed structural improvement was associated with decreased CTGF and collagen deposition but seemed unrelated to acute damage. Indeed, the early apoptotic index increased, and severe subacute structural damage occurred. Pravastatin elicited a differential effect, protecting normal intestine but not tumors from radiation injury. Conclusion: Pravastatin provides effective protection against delayed radiation enteropathy without interfering with the primary antitumor action of radiotherapy, suggesting that clinical transfer is feasible.

  17. Treatment of radiation-induced acute intestinal injury with bone marrow-derived mesenchymal stem cells

    PubMed Central

    ZHENG, KAI; WU, WEIZHEN; YANG, SHUNLIANG; HUANG, LIANGHU; CHEN, JIN; GONG, CHUNGUI; FU, ZHICHAO; LIN, RUOFEI; TAN, JIANMING

    2016-01-01

    The aim of the present study was to investigate the ability of bone marrow-derived mesenchymal stem cells (BMSCs) to repair radiation-induced acute intestinal injury, and to elucidate the underlying repair mechanism. Male Sprague-Dawley rats were subjected to whole abdominal irradiation using a single medical linear accelerator (12 Gy) and randomly assigned to two groups. Rats in the BMSC-treated group were injected with 1 ml BMSC suspension (2×106 cells/ml) via the tail vein, while the control group rats were injected with normal saline. BMSCs were identified by detecting the expression of CD29, CD90, CD34 and CD45 using flow cytometry. The expression of the cytokines stromal cell-derived factor 1 (SDF-1), prostaglandin E2 (PGE2) and interleukin (IL)-2 was detected using immunohistochemical techniques. Plasma citrulline concentrations were evaluated using an ELISA kit. Rat general conditions, including body weight, and changes in cellular morphology were also recorded. The results suggested that BMSCs exerted a protective effect on radiation-induced acute intestinal injury in rats. The histological damage was rapidly repaired in the BMSC-treated group. In addition, the BMSC-treated group showed significantly reduced radiation injury scores (P<0.01), mildly reduced body weight and plasma citrulline levels, significantly more rapid recovery (P<0.01), significantly reduced expression of the cytokines PGE2 and IL-2 (P<0.05) and significantly increased SDF-1 expression (P<0.01) compared with the control group. In summary, the present results indicate that BMSCs are able to effectively reduce inflammation and promote repair of the structure and function of intestinal tissues damaged by radiation exposure, suggesting that they may provide a promising therapeutic agent. PMID:27284330

  18. Combined Exposure to Simulated Microgravity and Acute or Chronic Radiation Reduces Neuronal Network Integrity and Survival

    PubMed Central

    Quintens, Roel; Samari, Nada; de Saint-Georges, Louis; van Oostveldt, Patrick; Baatout, Sarah; Benotmane, Mohammed Abderrafi

    2016-01-01

    During orbital or interplanetary space flights, astronauts are exposed to cosmic radiations and microgravity. However, most earth-based studies on the potential health risks of space conditions have investigated the effects of these two conditions separately. This study aimed at assessing the combined effect of radiation exposure and microgravity on neuronal morphology and survival in vitro. In particular, we investigated the effects of simulated microgravity after acute (X-rays) or during chronic (Californium-252) exposure to ionizing radiation using mouse mature neuron cultures. Acute exposure to low (0.1 Gy) doses of X-rays caused a delay in neurite outgrowth and a reduction in soma size, while only the high dose impaired neuronal survival. Of interest, the strongest effect on neuronal morphology and survival was evident in cells exposed to microgravity and in particular in cells exposed to both microgravity and radiation. Removal of neurons from simulated microgravity for a period of 24 h was not sufficient to recover neurite length, whereas the soma size showed a clear re-adaptation to normal ground conditions. Genome-wide gene expression analysis confirmed a modulation of genes involved in neurite extension, cell survival and synaptic communication, suggesting that these changes might be responsible for the observed morphological effects. In general, the observed synergistic changes in neuronal network integrity and cell survival induced by simulated space conditions might help to better evaluate the astronaut's health risks and underline the importance of investigating the central nervous system and long-term cognition during and after a space flight. PMID:27203085

  19. Combined Exposure to Simulated Microgravity and Acute or Chronic Radiation Reduces Neuronal Network Integrity and Survival.

    PubMed

    Pani, Giuseppe; Verslegers, Mieke; Quintens, Roel; Samari, Nada; de Saint-Georges, Louis; van Oostveldt, Patrick; Baatout, Sarah; Benotmane, Mohammed Abderrafi

    2016-01-01

    During orbital or interplanetary space flights, astronauts are exposed to cosmic radiations and microgravity. However, most earth-based studies on the potential health risks of space conditions have investigated the effects of these two conditions separately. This study aimed at assessing the combined effect of radiation exposure and microgravity on neuronal morphology and survival in vitro. In particular, we investigated the effects of simulated microgravity after acute (X-rays) or during chronic (Californium-252) exposure to ionizing radiation using mouse mature neuron cultures. Acute exposure to low (0.1 Gy) doses of X-rays caused a delay in neurite outgrowth and a reduction in soma size, while only the high dose impaired neuronal survival. Of interest, the strongest effect on neuronal morphology and survival was evident in cells exposed to microgravity and in particular in cells exposed to both microgravity and radiation. Removal of neurons from simulated microgravity for a period of 24 h was not sufficient to recover neurite length, whereas the soma size showed a clear re-adaptation to normal ground conditions. Genome-wide gene expression analysis confirmed a modulation of genes involved in neurite extension, cell survival and synaptic communication, suggesting that these changes might be responsible for the observed morphological effects. In general, the observed synergistic changes in neuronal network integrity and cell survival induced by simulated space conditions might help to better evaluate the astronaut's health risks and underline the importance of investigating the central nervous system and long-term cognition during and after a space flight. PMID:27203085

  20. Evidence Report: Risk of Acute and Late Central Nervous System Effects from Radiation Exposure

    NASA Technical Reports Server (NTRS)

    Nelson, Gregory A.; Simonsen, Lisa; Huff, Janice L.

    2016-01-01

    Possible acute and late risks to the central nervous system (CNS) from galactic cosmic rays (GCR) and solar particle events (SPE) are concerns for human exploration of space. Acute CNS risks may include: altered cognitive function, reduced motor function, and behavioral changes, all of which may affect performance and human health. Late CNS risks may include neurological disorders such as Alzheimer's disease (AD), dementia and premature aging. Although detrimental CNS changes are observed in humans treated with high-dose radiation (e.g., gamma rays and 9 protons) for cancer and are supported by experimental evidence showing neurocognitive and behavioral effects in animal models, the significance of these results on the morbidity to astronauts has not been elucidated. There is a lack of human epidemiology data on which to base CNS risk estimates; therefore, risk projection based on scaling to human data, as done for cancer risk, is not possible for CNS risks. Research specific to the spaceflight environment using animal and cell models must be compiled to quantify the magnitude of CNS changes in order to estimate this risk and to establish validity of the current permissible exposure limits (PELs). In addition, the impact of radiation exposure in combination with individual sensitivity or other space flight factors, as well as assessment of the need for biological/pharmaceutical countermeasures, will be considered after further definition of CNS risk occurs.

  1. Role of interleukin-1 in mesangial cell proliferation and matrix deposition in experimental mesangioproliferative nephritis.

    PubMed Central

    Tesch, G. H.; Lan, H. Y.; Atkins, R. C.; Nikolic-Paterson, D. J.

    1997-01-01

    We examined the functional role of interleukin (IL)-1 in mesangial cell proliferation during rat anti-Thy-1 nephritis by blocking its action with IL-1 receptor antagonist (IL-1ra). Anti-Thy-1 nephritis was induced by intravenous injection of 5 mg/kg OX-7 IgG (day 0) into inbred Wistar rats. Groups of animals (n = 9) were implanted with a micro-osmotic pump on day -1, which delivered 25 micrograms/hour human recombinant IL-1ra or saline continuously until the rats were killed at day 6, the peak of mesangial cell proliferation. Immunostaining showed that IL-1 was expressed by mesangial cells during disease. IL-1ra treatment did not affect the mild, but significant, proteinuria seen after OX-7 injection. Compared with saline treatment, IL-1ra treatment reduced mesangial cell proliferation (decreases 24% P < 0.05), glomerular hypercellularity (decreases 29%; P < 0.05), and glomerular macrophage accumulation (decreases 20%; P < 0.05). However, IL-1ra treatment had no effect on glomerular IL-1 beta mRNA expression and caused only a small reduction in the high levels of glomerular expression of platelet-derived growth factor-beta protein (decreases 6%; P < 0.05). IL-1ra caused a modest reduction in the marked up-regulation of glomerular transforming growth factor-beta 1 mRNA expression on day 6 (decreases 26%; P < 0.05), although urinary excretion of this factor was unaffected. Interestingly, IL-1ra treatment had relatively little effect upon glomerular deposition of laminin, fibronectin, and collagen type IV seen in this acute disease. In conclusion, this study has 1) demonstrated that IL-1 is expressed by mesangial cells in vivo, 2) demonstrated that IL-1 is a mesangial cell growth factor in experimental mesangioproliferative nephritis, and 3) suggests that IL-1 has little or no fibrogenic activity in mesangial matrix deposition. Images Figure 1 Figure 5 PMID:9212740

  2. Medical Management of Acute Radiation Syndromes : Comparison of Antiradiation Vaccine and Antioxidants radioprotection potency.

    NASA Astrophysics Data System (ADS)

    Maliev, Slava; Popov, Dmitri; Lisenkov, Nikolai

    Introduction: This experimental study of biological effects of the Antiradiation Vaccine and Antioxidants which were used for prophylaxis and treatment of the Acute Radiation Syndromes caused by high doses of the low-LET radiation. An important role of Reactive Oxyden Species (Singlet oxygen, hydroxyl radicals, superoxide anions and bio-radicals)in development of the Acute Radiation Syndromes could be defined as a "central dogma" of radiobiology. Oxida-tion and damages of lipids, proteins, DNA, and RNA are playing active role in development of postradiation apoptosis. However, the therapeutic role of antioxidants in modification of a postradiation injury caused by high doses of radiation remains controversial.Previous stud-ies had revealed that antioxidants did not increase a survival rate of mammals with severe forms of the Acute Radiation Syndromes caused by High Doses of the low-LET radiation. The Antiradiation Vaccine(ARV) contains toxoid forms of the Radiation Toxins(RT) from the Specific Radiation Determinants Group (SRD). The RT SRD has toxic and antigenic prop-erties at the same time and stimulates a specific antibody elaboration and humoral response form activated acquired immune system. The blocking antiradiation antibodies induce an im-munologically specific effect and have inhibiting effects on radiation induced neuro-toxicity, vascular-toxicity, gastrointestinal toxcity, hematopoietic toxicity, and radiation induced cytol-ysis of selected groups of cells that are sensitive to radiation. Methods and materials: Scheme of experiments: 1. Irradiated animals with development of Cerebrovascular ARS (Cv-ARS), Cardiovascular ARS (Cr-ARS) Gastrointestinal ARS(GI-ARS), Hematopoietic ARS (H-ARS) -control -were treated with placebo administration. 2. Irradiated animals were treated with antioxidants prophylaxisis and treatment of Cv-ARS, Cr-SRS, GI-ARS, Hp-ARS forms of the ARS. 3. irradiated animals were treated with radioprotection by Antiradiation Vaccine

  3. Countermeasure development : Specific Immunoprophylaxis and Immunotherapy of Combined Acute Radiation Syndromes.

    NASA Astrophysics Data System (ADS)

    Popov, Dmitri; Maliev, Slava

    Introduction: Combined Acute Radiation Syndromes (CARS) are extremely severe injuries. Combination of Radiation and Thermal factors induce development of the acute pathologi-cal processes in irradiated mammals: systemic inflammatory response syndrome (SIRS), toxic multiple organ injury (TMOI), toxic multiple organ dysfunction syndromes (TMOD), toxic multiple organ failure (TMOF). Also, high doses of Radiation and Thermal injury induce for-mation of following Toxin groups: A. Specific Radiation Toxins; B. Specific Thermal Toxins; C. Nonspecific Histiogenic Pro-inflammatory and Inflammatory Toxins (NHIT). Specific Radi-ation Toxins (SRT) include four major group of Toxins: Cerebrovascular Radiation Toxins (Cv RT), Cardiovascular Radiation Toxins (Cr RT), Gastrointestinal Radiation Toxins (Gi RT), and Hematopoietic Radiation Toxins (Hp RT). CvRT, Cr RT, Gi RT groups of toxins are defined as Neurotoxins and Hp RT group is defined as Hematotoxins. Specific Thermal Toxins (STT) were isolated from the burned skin (Voul S., Colker I. 1972). The group of Nonspecific Histio-genic Inflammatory Toxins (NHIT) includes high amount of tissue toxins which are peptides with medium molecular weight. This group of polypeptides can be a significant factor as a part of developing of the general inflammation reaction. However, NHIT toxins can't induce many reactions and changes which are specific for radiation. Specific Radiation Toxins (SRT) can induce specific processes and reactions such as clonogenic cell death -programmed apoptotic necrosis. Although besides high doses of radiation, other forms of cell death such as Pyroptosis or Oncosis should be considered. We postulate that NHIT toxins are similar for high doses of radiation and thermal injury. Specific Radiation Toxins (SRT) are induced by high doses of radiation. Specific Thermal Toxins (STT) toxins which formation is induced by a Thermal Factor are different from SRT. Administration of STT toxins or NHIT toxins (IV or IM) to

  4. Impact of Bone Marrow Radiation Dose on Acute Hematologic Toxicity in Cervical Cancer: Principal Component Analysis on High Dimensional Data

    SciTech Connect

    Yun Liang; Messer, Karen; Rose, Brent S.; Lewis, John H.; Jiang, Steve B.; Yashar, Catheryn M.; Mundt, Arno J.; Mell, Loren K.

    2010-11-01

    Purpose: To study the effects of increasing pelvic bone marrow (BM) radiation dose on acute hematologic toxicity in patients undergoing chemoradiotherapy, using a novel modeling approach to preserve the local spatial dose information. Methods and Materials: The study included 37 cervical cancer patients treated with concurrent weekly cisplatin and pelvic radiation therapy. The white blood cell count nadir during treatment was used as the indicator for acute hematologic toxicity. Pelvic BM radiation dose distributions were standardized across patients by registering the pelvic BM volumes to a common template, followed by dose remapping using deformable image registration, resulting in a dose array. Principal component (PC) analysis was applied to the dose array, and the significant eigenvectors were identified by linear regression on the PCs. The coefficients for PC regression and significant eigenvectors were represented in three dimensions to identify critical BM subregions where dose accumulation is associated with hematologic toxicity. Results: We identified five PCs associated with acute hematologic toxicity. PC analysis regression modeling explained a high proportion of the variation in acute hematologicity (adjusted R{sup 2}, 0.49). Three-dimensional rendering of a linear combination of the significant eigenvectors revealed patterns consistent with anatomical distributions of hematopoietically active BM. Conclusions: We have developed a novel approach that preserves spatial dose information to model effects of radiation dose on toxicity, which may be useful in optimizing radiation techniques to avoid critical subregions of normal tissues. Further validation of this approach in a large cohort is ongoing.

  5. Feasibility and Acute Toxicity of Hypofractionated Radiation in Large-breasted Patients

    SciTech Connect

    Dorn, Paige L.; Corbin, Kimberly S.; Al-Hallaq, Hania; Hasan, Yasmin; Chmura, Steven J.

    2012-05-01

    Purpose: To determine the feasibility of and acute toxicity associated with hypofractionated whole breast radiation (HypoRT) after breast-conserving surgery in patients excluded from or underrepresented in randomized trials comparing HypoRT with conventional fractionation schedules. Methods and Materials: A review was conducted of all patients consecutively treated with HypoRT at University of Chicago. All patients were treated to 42.56 Gy in 2.66 Gy daily fractions in either the prone or supine position. Planning was performed in most cases using wedges and large segments or a 'field-in-field' technique. Breast volume was estimated using volumetric measurements of the planning target volume (PTV). Dosimetric parameters of heterogeneity (V105, V107, V110, and maximum dose) were recorded for each treatment plan. Acute toxicity was scored for each treated breast. Results: Between 2006 and 2010, 78 patients were treated to 80 breasts using HypoRT. Most women were overweight or obese (78.7%), with a median body mass index of 29.2 kg/m{sup 2}. Median breast volume was 1,351 mL. Of the 80 treated breasts, the maximum acute skin toxicity was mild erythema or hyperpigmentation in 70.0% (56/80), dry desquamation in 21.25% (17/80), and focal moist desquamation in 8.75% (7/80). Maximum acute toxicity occurred after the completion of radiation in 31.9% of patients. Separation >25 cm was not associated with increased toxicity. Breast volume was the only patient factor significantly associated with moist desquamation on multivariable analysis (p = 0.01). Patients with breast volume >2,500 mL experienced focal moist desquamation in 27.2% of cases compared with 6.34% in patients with breast volume <2,500 mL (p = 0.03). Conclusions: HypoRT is feasible and safe in patients with separation >25 cm and in patients with large breast volume when employing modern planning and positioning techniques. We recommend counseling regarding expected increases in skin toxicity in women with a PTV

  6. Successful treatment of severe hantavirus nephritis with corticosteroids: a case report and literature review.

    PubMed

    Martinuč Bergoč, Maja; Lindič, Jelka; Kovač, Damjan; Ferluga, Dušan; Pajek, Jernej

    2013-08-01

    Hantaviruses can be associated with severe form of hemorrhagic fever with renal syndrome although there are only a few cases reporting chronic kidney disease after hantavirus infection. We report a severe nonresolving chronic renal failure after protracted Dobrava hantavirus infection successfully treated with corticosteroids. Ten days after working in a basement a 33-year-old man fell seriously ill, with high fever, chills, diffuse myalgia, headache and abdominal pain. After hospital admission a diagnosis of hemorrhagic fever with renal syndrome caused by Dobrava hantavirus was made. Acute oliguric kidney injury developed in the first 3 days after admission, in a few days diuresis restored and he became polyuric. Nevertheless renal failure persisted and he needed hemodialysis. Because of nonresolving kidney failure, nephrogenic diabetes insipidus and renoparenchymal arterial hypertension persisting 2 months after onset of symptoms, a kidney biopsy was performed, showing severe necrotizing tubulointerstitial nephritis. High dose methylprednisolone therapy was started and his renal function significantly improved. Two months later a second renal biopsy showed persisting elements of active necrotizing tubulointerstitial nephritis. We decided to stop corticosteroid treatment and introduced aldosterone antagonist eplerenon as anti-fibrotic agent, and his renal function further improved and remained stable. Nine months later his serum creatinine concentration was 227 μmol/L, proteinuria 0.156 g/day and well controlled nephrogenic diabetes insipidus. PMID:23931879

  7. Parasites alter the pathological phenotype of lupus nephritis

    PubMed Central

    Miyake, Katsuhisa; Adachi, Keishi; Watanabe, Maho; Sasatomi, Yoshie; Ogahara, Satoru; Abe, Yasuhiro; Ito, Kenji; Dan Justin, Yombo K.; Saito, Takao

    2014-01-01

    lpr Lupus nephritis is one of the most serious complications of systemic lupus erythematosus and manifests with considerable phenotypic and histological heterogeneity. In particular, diffuse proliferative lupus nephritis (DPLN) and membranous lupus nephritis (MLN) represent morphologic forms that are polar opposites. DPLN is associated with autoimmune responses dominated by Th1 immune response associated with high levels of interferon (IFN)-γ. In contrast, a Th2 cytokine response is associated with the pathogenesis of MLN. MRL/lpr mice develop human LN-like immune complex-associated nephritis and provide a suitable histological model for human DPLN. Infection with Schistosoma mansoni skewed a Th2-type immune response induction and IL-10 in MRL/lpr mice, drastically changing the pathophysiology of glomerulonephritis from DPLN to MLN accompanied by increased IgG1 and IgE in the sera. T cells in 32-week-old MRL/lpr mice infected with S. mansoni expressed significantly more IL-4 and IL-10 than T cells of uninfected mice; T cells with IFN-γ were comparable between infected and uninfected MR/lpr mice. Thus, the helminthic infection modified the cytokine microenvironment and altered the pathological phenotype of autoimmune nephritis. PMID:24957876

  8. [Lupus nephritis: up-to-date].

    PubMed

    Karras, A

    2015-02-01

    Renal involvement is frequent during natural history of systemic lupus erythematosus (SLE) and has a major prognostic value in this systemic disease. Screening for renal symptoms, such as proteinuria, micro-haematuria or renal failure must be performed at initial diagnosis and repeated during subsequent follow-ups. Any significant abnormality of these parameters may reveal active glomerulonephritis (GN) and should lead to a renal biopsy, which will significantly impact the therapeutic choices. Proliferative GN, defined as class III or IV by the actual histo-pathological classification, is the most severe form of SLE-associated nephropathy and can lead to end-stage renal disease (ESRD) in up to 60% of cases, according to ethnicity and follow-up duration. Standard induction treatment of active proliferative GN includes corticosteroids combined with an immunosuppressive drug, which can either be cyclophosphamide or mycophenolate mofetil (MMF). Even though, recent biotherapies have not yet proved their efficacy in the field of lupus nephritis, new protocols are expected, aiming higher remission rates and avoidance of high-dose corticosteroids regimens. When remission is achieved in proliferative GN, a maintenance therapy is required to decrease the risk of relapse, using either azathioprine or MMF. Immunosuppressive drugs are responsible for an increased risk of infectious or neoplastic complications but cardiovascular disease is actually one of the main causes of mortality among lupus patients, especially for patients with SLE-related kidney disease, well before reaching ESRD.

  9. Lupus nephritis: a nucleosome waste disposal defect?

    PubMed

    Berden, Jo H M; Grootscholten, Cecile; Jürgen, W C Dieker; van der Vlag, Johan

    2002-01-01

    Formation of anti-nuclear autoantibodies is a cardinal characteristic of systemic lupus erythematosus (SLE). In recent years the nucleosome has been identified as the major autoantigen, since nucleosome specific T cells have been identified, which also drive the formation of anti-dsDNA and anti-histone antibodies. Nucleosome specific autoantibodies are present in a large majority of SLE patients and lupus mice. Nucleosomes are formed during apoptosis by organized cleavage of chromatin. These nucleosomes together with other lupus autoantigens cluster in apoptotic bodies at the surface of apoptotic cells. Systemic release of these autoantigens is normally prevented by swift removal of apoptotic cels. However, if the rate of apoptosis overflows the removal capacity and/or the cleaning machinery is reduced, nucleosomes are released. Furthermore, during apoptosis autoantigens can be modified, which makes them more immunogenic. Nucleosomes also play a pivotal role in the evolution of tissue lesions, especially glomerulonephritis. In lupus nephritis nucleosomes, anti-nucleosome autoantibodies and nucleosome/Ig complexes have been identified in the glomerular immune deposits. Via their cationic histone part nucleosomes can bind to heparan sulfate, a strong anionic constituent of the glomerular basement membrane.

  10. [Clinical and experimental study on effects of man-shen-ling oral liquid in the treatment of 100 cases of chronic nephritis].

    PubMed

    Su, Z Z; He, Y Y; Chen, G

    1993-05-01

    A new Chinese herbal preparation, Man-Shen-Ling (MSL, consisted of medicinal herbs such as Astragalus and Rehmannia) in treating 100 cases of chronic nephritis. The effective rate was 91% in comparing to 66.7% in the control group, P < 0.001. It was markedly effective for proteinuria, hematuria, improvement and recovery of renal functions, edema, anemia, anorexia etc in comparing with the control group. It showed no adverse effects on functions of liver, kidney, heart and GI tract. Animal model of chronic nephritis was established and the effects of MSL were observed. The laboratory findings and histopathological investigation on kidney revealed and confirmed that MSL has therapeutic effects on chronic nephritis. Pharmacodynamically, MSL exhibited effects of anti-allergy, its immuno-suppressive effect corresponded to that of cyclophosphamide, with diuretic, hypotensive, proteinuria eliminating, anti-inflammatory, anti-coagulatory, renal blood flow and glomerular filtration enhancing, the excretion of urea-nitrogen, potassium and sodium promoting function; in addition, it also could promote and modulate the immunity. Acute and chronic toxicity tests on animal models neither showed toxic, mutagenic, teratogenic nor carcinogenic effects. It is a new preparation of Chinese medicinal herbs in treating chronic nephritis, it is safe and effective. PMID:8219675

  11. Th Cell Gene Expression and Function in Response to Low Dose and Acute Radiation

    SciTech Connect

    Daila S. Gridley, PhD

    2012-03-30

    FINAL TECHNICAL REPORT Supported by the Low Dose Radiation Research Program, Office of Science U.S. Department of Energy Grant No. DE-FG02-07ER64345 Project ID: 0012965 Award Register#: ER64345 Project Manager: Noelle F. Metting, Sc.D. Phone: 301-903-8309 Division SC-23.2 noelle.metting@science.doe.gov Submitted March 2012 To: https://www.osti.gov/elink/241.3.jsp Title: Th Cell Gene Expression and Function in Response to Low Dose and Acute Radiation PI: Daila S. Gridley, Ph.D. Human low dose radiation data have been derived primarily from studies of space and airline flight personnel, nuclear plant workers and others exposed occupationally, as well as victims in the vicinity of atomic bomb explosions. The findings remain inconclusive due to population inconsistencies and complex interactions among total dose, dose rate, radiation quality and age at exposure. Thus, safe limits for low dose occupational irradiation are currently based on data obtained with doses far exceeding the levels expected for the general population and health risks have been largely extrapolated using the linear-nonthreshold dose-response model. The overall working hypothesis of the present study is that priming with low dose, low-linear energy transfer (LET) radiation can ameliorate the response to acute high-dose radiation exposure. We also propose that the efficacy of low-dose induced protection will be dependent upon the form and regimen of the high-dose exposure: photons versus protons versus simulated solar particle event protons (sSPE). The emphasis has been on gene expression and function of CD4+ T helper (Th) lymphocytes harvested from spleens of whole-body irradiated C57BL/6 mice, a strain that provides the genetic background for many genetically engineered strains. Evaluations of the responses of other selected cells, tissues such as skin, and organs such as lung, liver and brain were also initiated (partially funded by other sources). The long-term goal is to provide information

  12. [Radiation-induced intracranial osteosarcoma after radiation for acute lymphocytic leukemia associated with Li-Fraumeni syndrome].

    PubMed

    Yoshimura, Junichi; Natsumeda, Manabu; Nishihira, Yasushi; Nishiyama, Kenichi; Saito, Akihiko; Okamoto, Kouichirou; Takahashi, Hitoshi; Fujii, Yukihiko

    2013-06-01

    A 28-year-old man presented with osteosarcoma of the occipital bone 16 years after 24 Gy of craniospinal irradiation for acute lymphocytic leukemia. The tumor had both intra- and extra-cranial components. However, the affected skull appeared to be normal on imaging because of permeative infiltration by the tumor. Subtotal resection was achieved and the tumor was verified histologically as an osteosarcoma. The residual tumor soon showed remarkable enlargement and disseminated to the spinal cord. Both of the enlarged and disseminated tumor masses were treated by surgical intervention and chemotherapy. However, the patient deteriorated due to the tumor regrowth and died 11 months after the initial diagnosis. This patient had previously developed a leukemia, a colon cancer, a rectal cancer and a hepatocellular carcinoma. His brother also died of leukemia. The patient had a heterozygous TP53 germ-line mutation of codon 248 in the exon 7. In conclusion, we consider the present tumor to be a rare example of radiation-induced skull osteosarcoma in a member of the cancer-prone family with TP53 germ-line mutation which is associated with Li-Fraumeni syndrome.

  13. Efficacy of Polaprezinc for Acute Radiation Proctitis in a Rat Model

    SciTech Connect

    Doi, Hiroshi; Kamikonya, Norihiko; Takada, Yasuhiro; Fujiwara, Masayuki; Tsuboi, Keita; Inoue, Hiroyuki; Tanooka, Masao; Nakamura, Takeshi; Shikata, Toshiyuki; Tsujimura, Tohru; Hirota, Shozo

    2011-07-01

    Purpose: The purpose of the present study was to standardize the experimental rat model of radiation proctitis and to examine the efficacy of polaprezinc on radiation proctitis. Methods and Materials: A total of 54 female Wistar rats (5 weeks old) were used. The rats were divided into three groups: those treated with polaprezinc (PZ+), those treated with base alone, exclusive of polaprezinc (PZ-), and those treated without any medication (control). All the rats were irradiated to the rectum. Polaprezinc was prepared as an ointment. The ointment was administered rectally each day after irradiation. All rats were killed on the 10th day after irradiation. The mucosal changes were evaluated endoscopically and pathologically. The results were graded from 0 to 4 and compared according to milder or more severe status, as applicable. Results: According to the endoscopic findings, the proportion of mild changes in the PZ+, PZ-, and control group was 71.4%, 25.0%, and 14.3% respectively. On pathologic examination, the proportion of low-grade findings in the PZ+, PZ-, and control group was 80.0%, 58.3%, and 42.9% for mucosal damage, 85.0%, 41.7%, and 42.9% for a mild degree of inflammation, and 50.0%, 33.3%, and 4.8% for a shallow depth of inflammation, respectively. The PZ+ group tended to have milder mucosal damage than the other groups, according to all criteria used. In addition, significant differences were observed between the PZ+ and control groups regarding the endoscopic findings, degree of inflammation, and depth of inflammation. Conclusions: This model was confirmed to be a useful experimental rat model for radiation proctitis. The results of the present study have demonstrated the efficacy of polaprezinc against acute radiation-induced rectal disorders using the rat model.

  14. γ-Tocotrienol as a Promising Countermeasure for Acute Radiation Syndrome: Current Status.

    PubMed

    Singh, Vijay K; Hauer-Jensen, Martin

    2016-01-01

    The hazard of ionizing radiation exposure due to nuclear accidents or terrorist attacks is ever increasing. Despite decades of research, still, there is a shortage of non-toxic, safe and effective medical countermeasures for radiological and nuclear emergency. To date, the U.S. Food and Drug Administration (U.S. FDA) has approved only two growth factors, Neupogen (granulocyte colony-stimulating factor (G-CSF), filgrastim) and Neulasta (PEGylated G-CSF, pegfilgrastim) for the treatment of hematopoietic acute radiation syndrome (H-ARS) following the Animal Efficacy Rule. Promising radioprotective efficacy results of γ-tocotrienol (GT3; a member of the vitamin E family) in the mouse model encouraged its further evaluation in the nonhuman primate (NHP) model. These studies demonstrated that GT3 significantly aided the recovery of radiation-induced neutropenia and thrombocytopenia compared to the vehicle controls; these results particularly significant after exposure to 5.8 or 6.5 Gray (Gy) whole body γ-irradiation. The stimulatory effect of GT3 on neutrophils and thrombocytes (platelets) was directly and positively correlated with dose; a 75 mg/kg dose was more effective compared to 37.5 mg/kg. GT3 was also effective against 6.5 Gy whole body γ-irradiation for improving neutrophils and thrombocytes. Moreover, a single administration of GT3 without any supportive care was equivalent, in terms of improving hematopoietic recovery, to multiple doses of Neupogen and two doses of Neulasta with full supportive care (including blood products) in the NHP model. GT3 may serve as an ultimate radioprotector for use in humans, particularly for military personnel and first responders. In brief, GT3 is a promising radiation countermeasure that ought to be further developed for U.S. FDA approval for the ARS indication. PMID:27153057

  15. γ-Tocotrienol as a Promising Countermeasure for Acute Radiation Syndrome: Current Status

    PubMed Central

    Singh, Vijay K.; Hauer-Jensen, Martin

    2016-01-01

    The hazard of ionizing radiation exposure due to nuclear accidents or terrorist attacks is ever increasing. Despite decades of research, still, there is a shortage of non-toxic, safe and effective medical countermeasures for radiological and nuclear emergency. To date, the U.S. Food and Drug Administration (U.S. FDA) has approved only two growth factors, Neupogen (granulocyte colony-stimulating factor (G-CSF), filgrastim) and Neulasta (PEGylated G-CSF, pegfilgrastim) for the treatment of hematopoietic acute radiation syndrome (H-ARS) following the Animal Efficacy Rule. Promising radioprotective efficacy results of γ-tocotrienol (GT3; a member of the vitamin E family) in the mouse model encouraged its further evaluation in the nonhuman primate (NHP) model. These studies demonstrated that GT3 significantly aided the recovery of radiation-induced neutropenia and thrombocytopenia compared to the vehicle controls; these results particularly significant after exposure to 5.8 or 6.5 Gray (Gy) whole body γ-irradiation. The stimulatory effect of GT3 on neutrophils and thrombocytes (platelets) was directly and positively correlated with dose; a 75 mg/kg dose was more effective compared to 37.5 mg/kg. GT3 was also effective against 6.5 Gy whole body γ-irradiation for improving neutrophils and thrombocytes. Moreover, a single administration of GT3 without any supportive care was equivalent, in terms of improving hematopoietic recovery, to multiple doses of Neupogen and two doses of Neulasta with full supportive care (including blood products) in the NHP model. GT3 may serve as an ultimate radioprotector for use in humans, particularly for military personnel and first responders. In brief, GT3 is a promising radiation countermeasure that ought to be further developed for U.S. FDA approval for the ARS indication. PMID:27153057

  16. Autologous bone marrow stromal cell transplantation as a treatment for acute radiation enteritis induced by a moderate dose of radiation in dogs.

    PubMed

    Xu, Wenda; Chen, Jiang; Liu, Xu; Li, Hongyu; Qi, Xingshun; Guo, Xiaozhong

    2016-05-01

    Radiation enteritis is one of the most common complications of cancer radiotherapy, and the development of new and effective measures for its prevention and treatment is of great importance. Adult bone marrow stromal stem cells (ABMSCs) are capable of self-renewal and exhibit low immunogenicity. In this study, we investigated ABMSC transplantation as a treatment for acute radiation enteritis. We developed a dog model of acute radiation enteritis using abdominal intensity-modulated radiation therapy in a single X-ray dose of 14 Gy. ABMSCs were cultured in vitro, identified via immunofluorescence and flow cytometry, and double labeled with CM-Dil and superparamagnetic iron oxide (SPIO) before transplantation, which took place 48 hours after abdominal irradiation in a single fraction. The dog model of acute radiation enteritis was transplanted with cultured ABMSCs labeled with CM-Dil and SPIO into the mesenteric artery through the femoral artery. Compared with untreated control groups, dogs treated with ABMSCs exhibited substantially longer survival time and improved relief of clinical symptoms. ABMSC transplantation induced the regeneration of the intestinal epithelium and the recovery of intestinal function. Furthermore, ABMSC transplantation resulted in elevated serum levels of the anti-inflammatory cytokine interleukin-11 (IL10) and intestinal radioprotective factors, such as keratinocyte growth factor, basic fibroblast growth factor-2, and platelet-derived growth factor-B while reducing the serum level of the inflammatory cytokine IL17. ABMSCs induced the regeneration of the intestinal epithelium and regulated the secretion of serum cytokines and the expression of radioprotective proteins and thus could be beneficial in the development of novel and effective mitigators of and protectors against acute radiation enteritis. PMID:26763584

  17. Autologous bone marrow stromal cell transplantation as a treatment for acute radiation enteritis induced by a moderate dose of radiation in dogs.

    PubMed

    Xu, Wenda; Chen, Jiang; Liu, Xu; Li, Hongyu; Qi, Xingshun; Guo, Xiaozhong

    2016-05-01

    Radiation enteritis is one of the most common complications of cancer radiotherapy, and the development of new and effective measures for its prevention and treatment is of great importance. Adult bone marrow stromal stem cells (ABMSCs) are capable of self-renewal and exhibit low immunogenicity. In this study, we investigated ABMSC transplantation as a treatment for acute radiation enteritis. We developed a dog model of acute radiation enteritis using abdominal intensity-modulated radiation therapy in a single X-ray dose of 14 Gy. ABMSCs were cultured in vitro, identified via immunofluorescence and flow cytometry, and double labeled with CM-Dil and superparamagnetic iron oxide (SPIO) before transplantation, which took place 48 hours after abdominal irradiation in a single fraction. The dog model of acute radiation enteritis was transplanted with cultured ABMSCs labeled with CM-Dil and SPIO into the mesenteric artery through the femoral artery. Compared with untreated control groups, dogs treated with ABMSCs exhibited substantially longer survival time and improved relief of clinical symptoms. ABMSC transplantation induced the regeneration of the intestinal epithelium and the recovery of intestinal function. Furthermore, ABMSC transplantation resulted in elevated serum levels of the anti-inflammatory cytokine interleukin-11 (IL10) and intestinal radioprotective factors, such as keratinocyte growth factor, basic fibroblast growth factor-2, and platelet-derived growth factor-B while reducing the serum level of the inflammatory cytokine IL17. ABMSCs induced the regeneration of the intestinal epithelium and regulated the secretion of serum cytokines and the expression of radioprotective proteins and thus could be beneficial in the development of novel and effective mitigators of and protectors against acute radiation enteritis.

  18. Assessment of acute and late effects to high-LET radiation

    SciTech Connect

    Blakely, E.A.; Castro, J.R. |

    1994-11-01

    We have begun to reassess late tissue effects available from the Charged Particle Cancer Radiotherapy program at Berkeley. Our quantitative approach is limited in the analysis of these Phase I/II studies by not having equivalent patient numbers for each of the particle beams studied, by not having completely comparable follow-up times, by variations in the sizes of the fields compared, by variations in the skin scoring photographic documentation available from the patient charts, and by variations in the fractionation sizes, numbers and schedules. Despite these limitations, preliminary evidence demonstrates acute skin reactions with a shift to increasing lower dose per fraction per field for the maximum skin reactions of helium, carbon and neon ions compared to electrons. Comparisons with skin reactions from low-energy neutrons indicate that Bragg peak carbon ions (initial energy 308 MeV/nucleon) are slightly less effective than 7.5 MeV neutrons. Bragg peak neon ions (initial energy 670 MeV/nucleon) corrected for differences in reference radiation are slightly more effective than 7.5 MeV neutrons. Bragg peak silicon (initial energy 670 MeV/nucleon) result in an enhanced acute skin reaction, and a premature appearance of late effects that may indicate a significantly different mechanism of damage and/or repair.

  19. Acute DNA damage activates the tumour suppressor p53 to promote radiation-induced lymphoma

    PubMed Central

    Lee, Chang-Lung; Castle, Katherine D.; Moding, Everett J.; Blum, Jordan M.; Williams, Nerissa; Luo, Lixia; Ma, Yan; Borst, Luke B.; Kim, Yongbaek; Kirsch, David G.

    2015-01-01

    Genotoxic cancer therapies, such as chemoradiation, cause haematological toxicity primarily by activating the tumour suppressor p53. While inhibiting p53-mediated cell death during cancer therapy ameliorates haematologic toxicity, whether it also impacts carcinogenesis remains unclear. Here we utilize a mouse model of inducible p53 short hairpin RNA (shRNA) to show that temporarily blocking p53 during total-body irradiation (TBI) not only ameliorates acute toxicity, but also improves long-term survival by preventing lymphoma development. Using KrasLA1 mice, we show that TBI promotes the expansion of a rare population of thymocytes that express oncogenic KrasG12D. However, blocking p53 during TBI significantly suppresses the expansion of KrasG12D-expressing thymocytes. Mechanistically, bone marrow transplant experiments demonstrate that TBI activates p53 to decrease the ability of bone marrow cells to suppress lymphoma development through a non-cell-autonomous mechanism. Together, our results demonstrate that the p53 response to acute DNA damage promotes the development of radiation-induced lymphoma. PMID:26399548

  20. 2013 Space Radiation Standing Review Panel Status Review for: The Risk of Acute and Late Central Nervous System Effects from Radiation Exposure, The Risk of Acute Radiation Syndromes Due to Solar Particle Events (SPEs), The Risk Of Degenerative Tissue Or Other Health Effects From Radiation Exposure, and The Risk of Radiation Carcinogenesis

    NASA Technical Reports Server (NTRS)

    2014-01-01

    The Space Radiation Standing Review Panel (from here on referred to as the SRP) was impressed with the strong research program presented by the scientists and staff associated with NASA's Space Radiation Program Element and National Space Biomedical Research Institute (NSBRI). The presentations given on-site and the reports of ongoing research that were provided in advance indicated the potential Risk of Acute and Late Central Nervous System Effects from Radiation Exposure (CNS) and were extensively discussed by the SRP. This new data leads the SRP to recommend that a higher priority should be placed on research designed to identify and understand these risks at the mechanistic level. To support this effort the SRP feels that a shift of emphasis from Acute Radiation Syndromes (ARS) and carcinogenesis to CNS-related endpoints is justified at this point. However, these research efforts need to focus on mechanisms, should follow pace with advances in the field of CNS in general and should consider the specific comments and suggestions made by the SRP as outlined below. The SRP further recommends that the Space Radiation Program Element continue with its efforts to fill the vacant positions (Element Scientist, CNS Risk Discipline Lead) as soon as possible. The SRP also strongly recommends that NASA should continue the NASA Space Radiation Summer School. In addition to these broad recommendations, there are specific comments/recommendations noted for each risk, described in detail below.

  1. Do we still need renal biopsy in lupus nephritis?

    PubMed

    Haładyj, Ewa; Cervera, Ricard

    2016-01-01

    The natural course of systemic lupus erythematosus (SLE) is characterized by periods of disease activity and remissions. Prolonged disease activity results in cumulative organ damage. Lupus nephritis is one of the most common and devastating manifestations of SLE. In the era of changing therapy to less toxic regimens, some authors have stated that if mycophenolate mofetil can be used for the induction and maintenance treatment in all histological classes of lupus nephritis, renal biopsy can be omitted. This article aims to answer the question of what brings the bigger risk: renal biopsy or its abandonment.

  2. Do we still need renal biopsy in lupus nephritis?

    PubMed Central

    Cervera, Ricard

    2016-01-01

    The natural course of systemic lupus erythematosus (SLE) is characterized by periods of disease activity and remissions. Prolonged disease activity results in cumulative organ damage. Lupus nephritis is one of the most common and devastating manifestations of SLE. In the era of changing therapy to less toxic regimens, some authors have stated that if mycophenolate mofetil can be used for the induction and maintenance treatment in all histological classes of lupus nephritis, renal biopsy can be omitted. This article aims to answer the question of what brings the bigger risk: renal biopsy or its abandonment. PMID:27407281

  3. Dietary sugar beet fiber ameliorates diarrhea as an acute gamma-radiation injury in rats.

    PubMed

    Ishizuka, S; Ito, S; Kasai, T; Hara, H

    2000-09-01

    Gamma radiation induces diarrhea as an acute injury. We have studied whether ingestion of sugar beet fiber influences radiation-induced diarrhea. Abdominal irradiation with gamma rays induced diarrhea in male Wistar/ST rats from 2 to 7 days after a single sublethal dose. The body weight of the irradiated rats was decreased temporarily at 4 days after irradiation regardless of the ingestion of sugar beet fiber. At day 8, it returned to almost the same level as that of unirradiated rats. A change in daily food intake resulted in a pattern similar to that for body weight. Dietary sugar beet fiber had little significant effect on the changes in body weight and daily food intake, and its ingestion significantly decreased gamma-ray-induced diarrhea. Changes in biochemical and histological parameters in intestinal mucosa (small intestine, cecum and colon) were not greatly influenced by the ingestion of sugar beet fiber through the periods of diarrhea. It was concluded that dietary sugar beet fiber ameliorated the diarrhea induced by abdominal irradiation. We suggest that the inhibitory effect of the ingestion of sugar beet fiber is due to its effects on the luminal environment, such as support for bacterial function in the luminal contents in the colon of animals that ingest sugar beet fiber.

  4. Intrarectal amifostine suspension may protect against acute proctitis during radiation therapy for prostate cancer: A pilot study

    SciTech Connect

    Singh, Anurag K.; Menard, Cynthia; Guion, Peter . E-mail: guionp@mail.nih.gov; Simone, Nicole L.; Smith, Sharon; Crouse, Nancy Sears; Godette, Denise J.; Cooley-Zgela, Theresa; Sciuto, Linda C.; Camphausen, Kevin; Coleman, C. Norman; Coleman, Jonathan; Pinto, Peter; Albert, Paul S.

    2006-07-15

    Purpose: Our goal was to test the ability of intrarectal amifostine to limit symptoms of radiation proctitis. Methods and Materials: The first 18 patients received 1 g of intrarectal amifostine suspension placed 30-45 min before each radiation treatment. The following 12 patients received 2 g of amifostine. Total dose prescribed ranged from 66 to 76 Gy. All patients were treated with three-dimensional conformal radiation therapy. The suspension remained intrarectal during treatment and was expelled after treatment. For gastrointestinal symptoms, during treatment and follow-up, all patients had a Radiation Therapy Oncology Group (RTOG) grade recorded. Results: Median follow-up was 18 months (range, 6-24 months). With 2 g vs. 1 g amifostine, there was a nearly significant decrease in RTOG Grade 2 acute rectal toxicity. Seven weeks after the start of radiation therapy, the incidence of Grade 2 toxicity was 33% in the 1-g group (6/18) compared with 0% (0/12) in the 2-g group (p = 0.06). No Grade 3 toxicity or greater occurred in this study. Conclusion: This trial suggests greater rectal radioprotection from acute effects with 2 g vs. 1 g amifostine suspension. Further studies should be conducted in populations at higher risk for developing symptomatic acute and late proctitis.

  5. A potential trigger of nephritogenic anti-DNA antibodies in lupus nephritis.

    PubMed

    Hirabayashi, Y; Oka, Y; Tada, M; Takahashi, R; Ishii, T

    2007-06-01

    Anti-DNA antibodies play an essential role in the pathogenesis of lupus nephritis. Mammalian DNA alone, however, is poorly immunogenic. We speculated that the antigenic trigger for the production of human nephritogenic anti-DNA antibodies is a non-DNA substance. The cDNA library from peripheral blood lymphocytes (PBLs) of a patient with active lupus nephritis was screened using the single-chain Fv of a human monoclonal nephritogenic O-81 anti-DNA antibody in a two-hybrid system. A clone containing the gene of an endoplasmic reticulum (ER) stress-inducible protein, Herp, was obtained: The O-81 antibody bound to recombinant Herp protein synthesized by Escherichia coli. Immunization with Herp elicited both anti-double-stranded DNA (anti-dsDNA) and anti-single-stranded (anti-ssDNA) antibodies in BALB/c mice and formed deposits of IgG in renal glomeruli. Anti-DNA antibodies purified from SLE sera bound to Herp. Moreover, anti-Herp antibodies showed specific binding to DNA. Herp was spontaneously expressed in PBLs of patients with active SLE, but not in PBLs of healthy subjects. These results imply that an inducible intracellular self-protein represents a candidate trigger for human nephritogenic anti-DNA autoantibodies. Any cell stress causing ER stress, such as viral infection, ultraviolet radiation, and chemicals, might be responsible for anti-DNA antibody production via Herp.

  6. [Computer tomography in acute pyelonephritis].

    PubMed

    Triller, J; Scheidegger, J; Terrier, F

    1983-07-01

    Computer tomography of the kidneys was performed on 30 patients with acute renal infections (acute suppurative pyelonephritis, acute renal abscess, infected cyst, pyelonephrosis, calculus perforation, retroperitoneal abscess). Computer tomography provided more accurate information concerning the extent of the renal and extra-renal inflammatory process than did the urogram or sonogram. This may significantly affect the choice of treatment, particularly concerning the use of drugs or of surgery. Angiography and retrograde pyelography may be used in selected cases, especially where there is a suspicion of acute bacterial nephritis, renal vein thrombosis or ureteric obstruction.

  7. Protracted Oxidative Alterations in the Mechanism of Hematopoietic Acute Radiation Syndrome

    PubMed Central

    Gorbunov, Nikolai V.; Sharma, Pushpa

    2015-01-01

    The biological effects of high-dose total body ionizing irradiation [(thereafter, irradiation (IR)] are attributed to primary oxidative breakage of biomolecule targets, mitotic, apoptotic and necrotic cell death in the dose-limiting tissues, clastogenic and epigenetic effects, and cascades of functional and reactive responses leading to radiation sickness defined as the acute radiation syndrome (ARS). The range of remaining and protracted injuries at any given radiation dose as well as the dynamics of post-IR alterations is tissue-specific. Therefore, functional integrity of the homeostatic tissue barriers may decline gradually within weeks in the post-IR period culminating with sepsis and failure of organs and systems. Multiple organ failure (MOF) leading to moribundity is a common sequela of the hemotapoietic form of ARS (hARS). Onset of MOF in hARS can be presented as “two-hit phenomenon” where the “first hit” is the underlying consequences of the IR-induced radiolysis in cells and biofluids, non-septic inflammation, metabolic up-regulation of pro-oxidative metabolic reactions, suppression of the radiosensitive hematopoietic and lymphoid tissues and the damage to gut mucosa and vascular endothelium. While the “second hit” derives from bacterial translocation and spread of the bacterial pathogens and inflammagens through the vascular system leading to septic inflammatory, metabolic responses and a cascade of redox pro-oxidative and adaptive reactions. This sequence of events can create a ground for development of prolonged metabolic, inflammatory, oxidative, nitrative, and carbonyl, electrophilic stress in crucial tissues and thus exacerbate the hARS outcomes. With this perspective, the redox mechanisms, which can mediate the IR-induced protracted oxidative post-translational modification of proteins, oxidation of lipids and carbohydrates and their countermeasures in hARS are subjects of the current review. Potential role of ubiquitous, radioresistant

  8. Combined Hydration and Antibiotics with Lisinopril to Mitigate Acute and Delayed High-dose Radiation Injuries to Multiple Organs.

    PubMed

    Fish, Brian L; Gao, Feng; Narayanan, Jayashree; Bergom, Carmen; Jacobs, Elizabeth R; Cohen, Eric P; Moulder, John E; Orschell, Christie M; Medhora, Meetha

    2016-11-01

    The NIAID Radiation and Nuclear Countermeasures Program is developing medical agents to mitigate the acute and delayed effects of radiation that may occur from a radionuclear attack or accident. To date, most such medical countermeasures have been developed for single organ injuries. Angiotensin converting enzyme (ACE) inhibitors have been used to mitigate radiation-induced lung, skin, brain, and renal injuries in rats. ACE inhibitors have also been reported to decrease normal tissue complication in radiation oncology patients. In the current study, the authors have developed a rat partial-body irradiation (leg-out PBI) model with minimal bone marrow sparing (one leg shielded) that results in acute and late injuries to multiple organs. In this model, the ACE inhibitor lisinopril (at ~24 mg m d started orally in the drinking water at 7 d after irradiation and continued to ≥150 d) mitigated late effects in the lungs and kidneys after 12.5-Gy leg-out PBI. Also in this model, a short course of saline hydration and antibiotics mitigated acute radiation syndrome following doses as high as 13 Gy. Combining this supportive care with the lisinopril regimen mitigated overall morbidity for up to 150 d after 13-Gy leg-out PBI. Furthermore, lisinopril was an effective mitigator in the presence of the growth factor G-CSF (100 μg kg d from days 1-14), which is FDA-approved for use in a radionuclear event. In summary, by combining lisinopril (FDA-approved for other indications) with hydration and antibiotics, acute and delayed radiation injuries in multiple organs were mitigated. PMID:27682899

  9. Combined Hydration and Antibiotics with Lisinopril to Mitigate Acute and Delayed High-dose Radiation Injuries to Multiple Organs.

    PubMed

    Fish, Brian L; Gao, Feng; Narayanan, Jayashree; Bergom, Carmen; Jacobs, Elizabeth R; Cohen, Eric P; Moulder, John E; Orschell, Christie M; Medhora, Meetha

    2016-11-01

    The NIAID Radiation and Nuclear Countermeasures Program is developing medical agents to mitigate the acute and delayed effects of radiation that may occur from a radionuclear attack or accident. To date, most such medical countermeasures have been developed for single organ injuries. Angiotensin converting enzyme (ACE) inhibitors have been used to mitigate radiation-induced lung, skin, brain, and renal injuries in rats. ACE inhibitors have also been reported to decrease normal tissue complication in radiation oncology patients. In the current study, the authors have developed a rat partial-body irradiation (leg-out PBI) model with minimal bone marrow sparing (one leg shielded) that results in acute and late injuries to multiple organs. In this model, the ACE inhibitor lisinopril (at ~24 mg m d started orally in the drinking water at 7 d after irradiation and continued to ≥150 d) mitigated late effects in the lungs and kidneys after 12.5-Gy leg-out PBI. Also in this model, a short course of saline hydration and antibiotics mitigated acute radiation syndrome following doses as high as 13 Gy. Combining this supportive care with the lisinopril regimen mitigated overall morbidity for up to 150 d after 13-Gy leg-out PBI. Furthermore, lisinopril was an effective mitigator in the presence of the growth factor G-CSF (100 μg kg d from days 1-14), which is FDA-approved for use in a radionuclear event. In summary, by combining lisinopril (FDA-approved for other indications) with hydration and antibiotics, acute and delayed radiation injuries in multiple organs were mitigated.

  10. Decay-Accelerating Factor 1 Deficiency Exacerbates Leptospiral-Induced Murine Chronic Nephritis and Renal Fibrosis

    PubMed Central

    Ferrer, María F.; Scharrig, Emilia; Alberdi, Lucrecia; Cedola, Maia; Pretre, Gabriela; Drut, Ricardo; Song, Wen-Chao; Gomez, Ricardo M.

    2014-01-01

    Leptospirosis is a global zoonosis caused by pathogenic Leptospira, which can colonize the proximal renal tubules and persist for long periods in the kidneys of infected hosts. Here, we characterized the infection of C57BL/6J wild-type and Daf1−/− mice, which have an enhanced host response, with a virulent Leptospira interrogans strain at 14 days post-infection, its persistence in the kidney, and its link to kidney fibrosis at 90 days post-infection. We found that Leptospira interrogans can induce acute moderate nephritis in wild-type mice and is able to persist in some animals, inducing fibrosis in the absence of mortality. In contrast, Daf1−/− mice showed acute mortality, with a higher bacterial burden. At the chronic stage, Daf1−/− mice showed greater inflammation and fibrosis than at 14 days post-infection and higher levels at all times than the wild-type counterpart. Compared with uninfected mice, infected wild-type mice showed higher levels of IL-4, IL-10 and IL-13, with similar levels of α-smooth muscle actin, galectin-3, TGF-β1, IL-17, IFN-γ, and lower IL-12 levels at 90 days post-infection. In contrast, fibrosis in Daf1−/− mice was accompanied by high expression of α-smooth muscle actin, galectin-3, IL-10, IL-13, and IFN-γ, similar levels of TGF-β1, IL-12, and IL-17 and lower IL-4 levels. This study demonstrates the link between Leptospira-induced murine chronic nephritis with renal fibrosis and shows a protective role of Daf1. PMID:25032961

  11. Decay-accelerating factor 1 deficiency exacerbates leptospiral-induced murine chronic nephritis and renal fibrosis.

    PubMed

    Ferrer, María F; Scharrig, Emilia; Alberdi, Lucrecia; Cedola, Maia; Pretre, Gabriela; Drut, Ricardo; Song, Wen-Chao; Gomez, Ricardo M

    2014-01-01

    Leptospirosis is a global zoonosis caused by pathogenic Leptospira, which can colonize the proximal renal tubules and persist for long periods in the kidneys of infected hosts. Here, we characterized the infection of C57BL/6J wild-type and Daf1-/- mice, which have an enhanced host response, with a virulent Leptospira interrogans strain at 14 days post-infection, its persistence in the kidney, and its link to kidney fibrosis at 90 days post-infection. We found that Leptospira interrogans can induce acute moderate nephritis in wild-type mice and is able to persist in some animals, inducing fibrosis in the absence of mortality. In contrast, Daf1-/- mice showed acute mortality, with a higher bacterial burden. At the chronic stage, Daf1-/- mice showed greater inflammation and fibrosis than at 14 days post-infection and higher levels at all times than the wild-type counterpart. Compared with uninfected mice, infected wild-type mice showed higher levels of IL-4, IL-10 and IL-13, with similar levels of α-smooth muscle actin, galectin-3, TGF-β1, IL-17, IFN-γ, and lower IL-12 levels at 90 days post-infection. In contrast, fibrosis in Daf1-/- mice was accompanied by high expression of α-smooth muscle actin, galectin-3, IL-10, IL-13, and IFN-γ, similar levels of TGF-β1, IL-12, and IL-17 and lower IL-4 levels. This study demonstrates the link between Leptospira-induced murine chronic nephritis with renal fibrosis and shows a protective role of Daf1.

  12. Combined mitigation of the gastrointestinal and hematopoietic acute radiation syndromes by an LPA2 receptor-specific nonlipid agonist.

    PubMed

    Patil, Renukadevi; Szabó, Erzsébet; Fells, James I; Balogh, Andrea; Lim, Keng G; Fujiwara, Yuko; Norman, Derek D; Lee, Sue-Chin; Balazs, Louisa; Thomas, Fridtjof; Patil, Shivaputra; Emmons-Thompson, Karin; Boler, Alyssa; Strobos, Jur; McCool, Shannon W; Yates, C Ryan; Stabenow, Jennifer; Byrne, Gerrald I; Miller, Duane D; Tigyi, Gábor J

    2015-02-19

    Pharmacological mitigation of injuries caused by high-dose ionizing radiation is an unsolved medical problem. A specific nonlipid agonist of the type 2 G protein coupled receptor for lysophosphatidic acid (LPA2) 2-[4-(1,3-dioxo-1H,3H-benzoisoquinolin-2-yl)butylsulfamoyl]benzoic acid (DBIBB) when administered with a postirradiation delay of up to 72 hr reduced mortality of C57BL/6 mice but not LPA2 knockout mice. DBIBB mitigated the gastrointestinal radiation syndrome, increased intestinal crypt survival and enterocyte proliferation, and reduced apoptosis. DBIBB enhanced DNA repair by augmenting the resolution of γ-H2AX foci, increased clonogenic survival of irradiated IEC-6 cells, attenuated the radiation-induced death of human CD34(+) hematopoietic progenitors and enhanced the survival of the granulocyte/macrophage lineage. DBIBB also increased the survival of mice suffering from the hematopoietic acute radiation syndrome after total-body irradiation. DBIBB represents a drug candidate capable of mitigating acute radiation syndrome caused by high-dose γ-radiation to the hematopoietic and gastrointestinal system. PMID:25619933

  13. Pathogenetic role of glomerular CXCL13 expression in lupus nephritis

    PubMed Central

    Worthmann, K; Gueler, F; von Vietinghoff, S; Davalos-Mißlitz, A; Wiehler, F; Davidson, A; Witte, T; Haller, H; Schiffer, M; Falk, C S; Schiffer, L

    2014-01-01

    Podocytes maintain the structure and function of the glomerular filtration barrier. However, podocytes have recently been implicated in the innate immune response, and their function as non-haematopoietic antigen-presenting cells was highlighted. We have shown previously that excessive expression of the chemokine CXCL13 is a distinctive early event for nephritis in a murine model of systemic lupus erythematosus (SLE). Furthermore, we found that CXCL13 is elevated significantly in the serum of patients with SLE-nephritis. In this study, we were able to show for the first time that (i) CXCL13 is expressed locally in glomeruli in a model for SLE-nephritis in mice and that (ii) incubation of human podocytes with CXCL13 induces receptor stimulation of CXCR5 with activation of signalling pathways, resulting in (iii) secretion of proinflammatory cytokines and chemokines in culture supernatant. This cytokine/chemokine cocktail can lead to (iv) a neutrophil respiratory burst in isolated human granulocytes. Taken together, our results provide further evidence that CXCL13 is involved in the pathogenesis of glomerulonephritis and that podocytes can play an active role in local proinflammatory immune responses. Thus, CXCL13 could be a direct target for the therapy of glomerulonephritis in general and for SLE-nephritis in particular. PMID:24827905

  14. Diagnosis and treatment of lupus nephritis flares--an update.

    PubMed

    Sprangers, Ben; Monahan, Marianne; Appel, Gerald B

    2012-12-01

    Relapses or flares of systemic lupus erythematosus (SLE) are frequent and observed in 27-66% of patients. SLE flares are defined as an increase in disease activity, in general, requiring alternative treatment or intensification of therapy. A renal flare is indicated by an increase in proteinuria and/or serum creatinine concentration, abnormal urine sediment or a reduction in creatinine clearance rate as a result of active disease. The morbidity associated with renal flares is derived from both the kidney damage due to lupus nephritis and treatment-related toxic effects. Current induction treatment protocols achieve remission in the majority of patients with lupus nephritis; however, few studies focus on treatment interventions for renal flares in these patients. The available data, however, suggest that remission can be induced again in a substantial percentage of patients experiencing a lupus nephritis flare. Lupus nephritis flares are independently associated with an increased risk of deterioration in renal function; prevention of renal flares might, therefore, also decrease long-term morbidity and mortality. Appropriate immunosuppressive maintenance therapy might lead to a decrease in the occurrence of renal and extrarenal flares in patients with SLE, and monitoring for the early detection and treatment of renal flares could improve their outcomes.

  15. Predictors of Severe Acute and Late Toxicities in Patients With Localized Head-and-Neck Cancer Treated With Radiation Therapy

    SciTech Connect

    Meyer, Francois; Fortin, Andre; Wang, Chang Shu; Liu, Geoffrey

    2012-03-15

    Purpose: Radiation therapy (RT) causes acute and late toxicities that affect various organs and functions. In a large cohort of patients treated with RT for localized head and neck cancer (HNC), we prospectively assessed the occurrence of RT-induced acute and late toxicities and identified characteristics that predicted these toxicities. Methods and Materials: We conducted a randomized trial among 540 patients treated with RT for localized HNC to assess whether vitamin E supplementation could improve disease outcomes. Adverse effects of RT were assessed using the Radiation Therapy Oncology Group Acute Radiation Morbidity Criteria during RT and one month after RT, and the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer Late Radiation Morbidity Scoring Scheme at six and 12 months after RT. The most severe adverse effect among the organs/tissues was selected as an overall measure of either acute or late toxicity. Grade 3 and 4 toxicities were considered as severe. Stepwise multivariate logistic regression models were used to identify all independent predictors (p < 0.05) of acute or late toxicity and to estimate odds ratios (OR) for severe toxicity with their 95% confidence intervals (CI). Results: Grade 3 or 4 toxicity was observed in 23% and 4% of patients, respectively, for acute and late toxicity. Four independent predictors of severe acute toxicity were identified: sex (female vs. male: OR = 1.72, 95% confidence interval [CI]: 1.06-2.80), Karnofsky Performance Status (OR = 0.67 for a 10-point increment, 95% CI: 0.52-0.88), body mass index (above 25 vs. below: OR = 1.88, 95% CI: 1.22-2.90), TNM stage (Stage II vs. I: OR = 1.91, 95% CI: 1.25-2.92). Two independent predictors were found for severe late toxicity: female sex (OR = 3.96, 95% CI: 1.41-11.08) and weight loss during RT (OR = 1.26 for a 1 kg increment, 95% CI: 1.12-1.41). Conclusions: Knowledge of these predictors easily collected in a clinical setting could help

  16. Transplantation of Endothelial Cells to Mitigate Acute and Chronic Radiation Injury to Vital Organs.

    PubMed

    Rafii, Shahin; Ginsberg, Michael; Scandura, Joseph; Butler, Jason M; Ding, Bi-Sen

    2016-08-01

    Current therapeutic approaches for treatment of exposure to radiation involve the use of antioxidants, chelating agents, recombinant growth factors and transplantation of stem cells (e.g., hematopoietic stem cell transplantation). However, exposure to high-dose radiation is associated with severe damage to the vasculature of vital organs, often leading to impaired healing, tissue necrosis, thrombosis and defective regeneration caused by aberrant fibrosis. It is very unlikely that infusion of protective chemicals will reverse severe damage to the vascular endothelial cells (ECs). The role of irradiated vasculature in mediating acute and chronic radiation syndromes has not been fully appreciated or well studied. New approaches are necessary to replace and reconstitute ECs in organs that are irreversibly damaged by radiation. We have set forth the novel concept that ECs provide paracrine signals, also known as angiocrine signals, which not only promote healing of irradiated tissue but also direct organ regeneration without provoking fibrosis. We have developed innovative technologies that enable manufacturing and banking of human GMP-grade ECs. These ECs can be transplanted intravenously to home to and engraft to injured tissues where they augment organ repair, while preventing maladaptive fibrosis. In the past, therapeutic transplantation of ECs was not possible due to a shortage of availability of suitable donor cell sources and preclinical models, a lack of understanding of the immune privilege of ECs, and inadequate methodologies for expansion and banking of engraftable ECs. Recent advances made by our group as well as other laboratories have breached the most significant of these obstacles with the development of technologies to manufacture clinical-scale quantities of GMP-grade and human ECs in culture, including genetically diverse reprogrammed human amniotic cells into vascular ECs (rAC-VECs) or human pluripotent stem cells into vascular ECs (iVECs). This

  17. Literature Review and Global Consensus on Management of Acute Radiation Syndrome Affecting Nonhematopoietic Organ Systems

    PubMed Central

    Dainiak, Nicholas; Gent, Robert Nicolas; Carr, Zhanat; Schneider, Rita; Bader, Judith; Buglova, Elena; Chao, Nelson; Coleman, C. Norman; Ganser, Arnold; Gorin, Claude; Hauer-Jensen, Martin; Huff, L. Andrew; Lillis-Hearne, Patricia; Maekawa, Kazuhiko; Nemhauser, Jeffrey; Powles, Ray; Schünemann, Holger; Shapiro, Alla; Stenke, Leif; Valverde, Nelson; Weinstock, David; White, Douglas; Albanese, Joseph; Meineke, Viktor

    2013-01-01

    Objectives The World Health Organization convened a panel of experts to rank the evidence for medical countermeasures for management of acute radiation syndrome (ARS) in a hypothetical scenario involving the hospitalization of 100 to 200 victims. The goal of this panel was to achieve consensus on optimal management of ARS affecting nonhematopoietic organ systems based upon evidence in the published literature. Methods English-language articles were identified in MEDLINE and PubMed. Reference lists of retrieved articles were distributed to conferees in advance of and updated during the meeting. Published case series and case reports of ARS, publications of randomized controlled trials of relevant interventions used to treat nonirradiated individuals, reports of studies in irradiated animals, and prior recommendations of subject matter experts were selected. Studies were extracted using the Grading of Recommendations Assessment Development and Evaluation system. In cases in which data were limited or incomplete, a narrative review of the observations was made. Results No randomized controlled trials of medical countermeasures have been completed for individuals with ARS. Reports of countermeasures were often incompletely described, making it necessary to rely on data generated in nonirradiated humans and in experimental animals. A strong recommendation is made for the administration of a serotonin-receptor antagonist prophylactically when the suspected exposure is >2 Gy and topical steroids, antibiotics, and antihistamines for radiation burns, ulcers, or blisters; excision and grafting of radiation ulcers or necrosis with intractable pain; provision of supportive care to individuals with neurovascular syndrome; and administration of electrolyte replacement therapy and sedatives to individuals with significant burns, hypovolemia, and/ orshock. A strong recommendation is made against the use of systemic steroids in the absence of a specific indication. A weak

  18. Transplantation of Endothelial Cells to Mitigate Acute and Chronic Radiation Injury to Vital Organs

    PubMed Central

    Rafii, Shahin; Ginsberg, Michael; Scandura, Joseph; Butler, Jason M.; Ding, Bi-Sen

    2016-01-01

    Current therapeutic approaches for treatment of exposure to radiation involve the use of antioxidants, chelating agents, recombinant growth factors and transplantation of stem cells (e.g., hematopoietic stem cell transplantation). However, exposure to high-dose radiation is associated with severe damage to the vasculature of vital organs, often leading to impaired healing, tissue necrosis, thrombosis and defective regeneration caused by aberrant fibrosis. It is very unlikely that infusion of protective chemicals will reverse severe damage to the vascular endothelial cells (ECs). The role of irradiated vasculature in mediating acute and chronic radiation syndromes has not been fully appreciated or well studied. New approaches are necessary to replace and reconstitute ECs in organs that are irreversibly damaged by radiation. We have set forth the novel concept that ECs provide paracrine signals, also known as angiocrine signals, which not only promote healing of irradiated tissue but also direct organ regeneration without provoking fibrosis. We have developed innovative technologies that enable manufacturing and banking of human GMP-grade ECs. These ECs can be transplanted intravenously to home to and engraft to injured tissues where they augment organ repair, while preventing maladaptive fibrosis. In the past, therapeutic transplantation of ECs was not possible due to a shortage of availability of suitable donor cell sources and preclinical models, a lack of understanding of the immune privilege of ECs, and inadequate methodologies for expansion and banking of engraftable ECs. Recent advances made by our group as well as other laboratories have breached the most significant of these obstacles with the development of technologies to manufacture clinical-scale quantities of GMP-grade and human ECs in culture, including genetically diverse reprogrammed human amniotic cells into vascular ECs (rAC-VECs) or human pluripotent stem cells into vascular ECs (iVECs). This

  19. Molecular and cellular profiling of acute responses to total body radiation exposure in ovariectomized female cynomolgus macaques

    PubMed Central

    DeBo, Ryne J.; Register, Thomas C.; Caudell, David L.; Sempowski, Gregory D.; Dugan, Gregory; Gray, Shauna; Owzar, Kouros; Jiang, Chen; Bourland, J. Daniel; Chao, Nelson J.; Cline, J. Mark

    2015-01-01

    Purpose The threat of radiation exposure requires a mechanistic understanding of radiation-induced immune injury and recovery. The study objective was to evaluate responses to ionizing radiation in ovariectomized (surgically post-menopausal) female cynomolgus macaques. Materials and methods Animals received a single total-body irradiation (TBI) exposure at doses of 0, 2 or 5 Gy with scheduled necropsies at 5 days, 8 weeks and 24 weeks post-exposure. Blood and lymphoid tissues were evaluated for morphologic, cellular, and molecular responses. Results Irradiated animals developed symptoms of acute hematopoietic syndrome, and reductions in thymus weight, thymopoiesis, and bone marrow cellularity. Acute, transient increases in plasma monocyte chemoattractant protein 1 (MCP-1) were observed in 5 Gy animals along with dose-dependent alterations in messenger ribonucleic acid (mRNA) signatures in thymus, spleen, and lymph node. Expression of T cell markers was lower in thymus and spleen, while expression of macrophage marker CD68 (cluster of differentiation 68) was relatively elevated in lymphoid tissues from irradiated animals. Conclusions Ovariectomized female macaques exposed to moderate doses of radiation experienced increased morbidity, including acute, dose-dependent alterations in systemic and tissue-specific biomarkers, and increased macrophage/T cell ratios. The effects on mortality exceeded expectations based on previous studies in males, warranting further investigation. PMID:25786585

  20. Mortality from nephritis and nephrosis in the fibreglass manufacturing industry

    PubMed Central

    Chiazze, L.; Watkins, D. K.; Fryar, C.; Fayerweather, W.; Bender, J. R.; Chiazze, M.

    1999-01-01

    OBJECTIVES: To investigate the question of whether there is an association between exposure to silica or respirable glass fibre and mortality from nephritis or nephrosis among workers in fibrous glass wool manufacturing facilities. METHODS: A case-control study with cases and controls derived from the Owens Corning mortality surveillance system. Two case-control analyses were carried out, one where the cases are defined with nephritis or nephrosis as the underlying cause of death and one where cases are defined as those where nephritis or nephrosis is either the underlying or a contributing cause of death. RESULTS: There is no consistent relation between respirable fibres or respirable silica and nephritis or nephrosis when the analysis is based either on underlying cause only or on underlying plus contributing cause of death. None of the sociodemographic variables considered suggests an increased risk when considering both underlying and contributing cause of death. CONCLUSIONS: These data would seem to support the contention that the most accurate picture of renal disease will be gained from the use of all information on the death certificate and not only the underlying cause. For these data, all odds ratios (ORs) for respirable fibres and silica based on both underlying and contributing cause of death are < 1 with the exception of the highest exposure to silica which is slightly > 1 (OR = 1.04). Although these results do not prove that there is no association between nephritis and nephrosis and exposure to fibreglass or silica in the fibreglass manufacturing environment, they do not support the assertion that such an association exists.   PMID:10448324

  1. Establishing a murine model of the Hematopoietic Syndrome of the Acute Radiation Syndrome

    PubMed Central

    Plett, P. Artur; Sampson, Carol H.; Chua, Hui Lin; Joshi, Mandar; Booth, Catherine; Gough, Alec; Johnson, Cynthia S.; Katz, Barry P.; Farese, Ann M.; Parker, Jeffrey; MacVittie, Thomas J.; Orschell, Christie M.

    2012-01-01

    We have developed a murine model of the Hematopoietic Syndrome of the Acute Radiation Syndrome (H-ARS) for efficacy testing of medical countermeasures (MCM) against radiation according to the FDA Animal Rule. Ten to 12 week old male and female C57BL/6 mice were exposed to the LD50/30-LD70/30 dose of total body irradiation (TBI, 137Cs, 0.62-0.67 Gy min-1) in the morning hours when mice were determined to be most radiosensitive, and assessed for 30 day survival and mean survival time (MST). Antibiotics were delivered in the drinking water on days 4-30 post-TBI at a concentration based on the amount of water that lethally-irradiated mice were found to consume. The fluoroquinolones, ciprofloxacin and levofloxacin, and the tetracycline doxycycline and aminoglycoside neomycin, all significantly increased MST of decedent mice, while ciprofloxacin (p=0.061) and doxycycline + neomycin (p=0.005) showed at least some efficacy to increase 30 day survival. Blood sampling (30uL/mouse every 5th day) was found to negatively impact 30 day survival. Histopathology of tissues harvested from non-moribund mice showed expected effects of lethal irradiation, while moribund mice were largely septicemic with a preponderance of enteric organisms. Kinetics of loss and recovery of peripheral blood cells in untreated mice and those treated with two MCM, granulocyte-colony stimulating factor and Amifostine, further characterized and validated our model for use in screening studies and pivotal efficacy studies of candidate MCM for licensure to treat irradiated individuals suffering from H-ARS. PMID:22929467

  2. Acute Esophagus Toxicity in Lung Cancer Patients After Intensity Modulated Radiation Therapy and Concurrent Chemotherapy

    SciTech Connect

    Kwint, Margriet; Uyterlinde, Wilma; Nijkamp, Jasper; Chen, Chun; Bois, Josien de; Sonke, Jan-Jakob; Heuvel, Michel van den; Knegjens, Joost; Herk, Marcel van; Belderbos, Jose

    2012-10-01

    Purpose: The purpose of this study was to investigate the dose-effect relation between acute esophageal toxicity (AET) and the dose-volume parameters of the esophagus after intensity modulated radiation therapy (IMRT) and concurrent chemotherapy for patients with non-small cell lung cancer (NSCLC). Patients and Methods: One hundred thirty-nine patients with inoperable NSCLC treated with IMRT and concurrent chemotherapy were prospectively analyzed. The fractionation scheme was 66 Gy in 24 fractions. All patients received concurrently a daily dose of cisplatin (6 mg/m Superscript-Two ). Maximum AET was scored according to Common Toxicity Criteria 3.0. Dose-volume parameters V5 to V70, D{sub mean} and D{sub max} of the esophagus were calculated. A logistic regression analysis was performed to analyze the dose-effect relation between these parameters and grade {>=}2 and grade {>=}3 AET. The outcome was compared with the clinically used esophagus V35 prediction model for grade {>=}2 after radical 3-dimensional conformal radiation therapy (3DCRT) treatment. Results: In our patient group, 9% did not experience AET, and 31% experienced grade 1 AET, 38% grade 2 AET, and 22% grade 3 AET. The incidence of grade 2 and grade 3 AET was not different from that in patients treated with CCRT using 3DCRT. The V50 turned out to be the most significant dosimetric predictor for grade {>=}3 AET (P=.012). The derived V50 model was shown to predict grade {>=}2 AET significantly better than the clinical V35 model (P<.001). Conclusions: For NSCLC patients treated with IMRT and concurrent chemotherapy, the V50 was identified as most accurate predictor of grade {>=}3 AET. There was no difference in the incidence of grade {>=}2 AET between 3DCRT and IMRT in patients treated with concurrent chemoradiation therapy.

  3. The Hematopoietic Syndrome of the Acute Radiation Syndrome in Rhesus Macaques: A Systematic Review of the Lethal Dose Response Relationship.

    PubMed

    MacVittie, Thomas J; Farese, Ann M; Jackson, William

    2015-11-01

    Well characterized animal models that mimic the human response to potentially lethal doses of radiation are required to assess the efficacy of medical countermeasures under the criteria of the U.S. Food and Drug Administration "animal rule." Development of a model requires the determination of the radiation dose response relationship and time course of mortality and morbidity across the hematopoietic acute radiation syndrome. The nonhuman primate, rhesus macaque, is a relevant animal model that may be used to determine the efficacy of medical countermeasures to mitigate major signs of morbidity and mortality at selected lethal doses of total body irradiation. A systematic review of relevant studies that determined the dose response relationship for the hematopoietic acute radiation syndrome in the rhesus macaque relative to radiation quality, dose rate, and exposure uniformity has never been performed. The selection of data cohorts was made from the following sources: Ovid Medline (1957-present), PubMed (1954-present), AGRICOLA (1976-present), Web of Science (1954-present), and U.S. HHS REPORT (2002 to present). The following terms were used: Rhesus, total body-irradiation, total body x irradiation, TBI, irradiation, gamma radiation, hematopoiesis, LD50/60, Macaca mulatta, whole-body irradiation, nonhuman primate, NHP, monkey, primates, hematopoietic radiation syndrome, mortality, and nuclear radiation. The reference lists of all studies, published and unpublished, were reviewed for additional studies. The total number of hits across all search sites was 3,001. There were a number of referenced, unpublished, non-peer reviewed government reports that were unavailable for review. Fifteen studies, 11 primary (n = 863) and four secondary (n = 153) studies [n = 1,016 total nonhuman primates (NHP), rhesus Macaca mulatta] were evaluated to provide an informative and consistent review. The dose response relationships (DRRs) were determined for uniform or non-uniform total

  4. Chronomodulation of topotecan or X-radiation treatment increases treatment efficacy without enhancing acute toxicity

    SciTech Connect

    Mullins, Dana; Proulx, Denise; Saoudi, A.; Ng, Cheng E. . E-mail: cng@ohri.ca

    2005-05-01

    Purpose: Topotecan (TPT), a camptothecin analog, is currently used to treat human ovarian and small-cell lung cancer and is in clinical trials for other tumor sites. However, it is unknown whether chronomodulation of TPT treatment is beneficial. We examined the effects of administering TPT or X-radiation (XR) alone at different times of the day or night. Methods: We treated mice bearing human colorectal tumor xenografts at four different times representing the early rest period (9 AM or 3 HALO [hours after light onset]), late rest period (3 PM or 9 HALO), early active period (9 PM or 15 HALO), and late active period (3 AM or 21 HALO) of the mice. We gave either TPT (12 mg/kg, injected i.p.) or XR (4 Gy, directed to the tumor) twice weekly on Days 0, 4, 7, 10 within 2 weeks. Results: Treatment with either TPT or XR at 3 AM demonstrated the greatest efficacy (measured by a tumor regrowth assay) without significantly increasing acute toxicity (assessed by a decrease in leukocyte counts or body weight). Conversely, treatment at 3 PM, in particular, showed increased toxicity without any enhanced efficacy. Conclusions: Our study provided the first evidence that chronomodulation of TPT treatments, consistent with the findings of other camptothecin analogs, is potentially clinically beneficial. Additionally, our findings suggest that chronomodulation of fractionated XR treatments is also potentially clinically beneficial.

  5. Effects of cranial radiation on hearing in children with acute lymphocytic leukemia

    SciTech Connect

    Thibadoux, G.M.; Pereira, W.V.; Hodges, J.M.; Aur, R.J.

    1980-03-01

    The hearing sensitivity of 61 children with acute lymphocytic leukemia who were admitted to our Total Therapy IX study between December 1975 and July 1977 was studied. Their treatment included combined chemotherapy, 2400 rads of cranial radiation, and intrathecal methotrexate. Subjects initially received an otologic examination and middle ear function testing. Audiometric testing was not done until ears were free of outer or middle ear pathology. If the child had no outer or middle ear disease, audiometric thresholds were obtained for the test frequencies: 500, 1000, 2000, 4000, 6000, and 8000 Hz. Pure-tone thresholds were obtained before irradiation (61 patients) and at 6, 12, and 36 months thereafter (49, 46, and 22 patients, respectively). The median age of time of baseline testing was 10 years, 2 months. A paired sample test based on group data was used to test whether there were any significant changes from the threshold values at 6, 12, and 36 months after irradiation. Thresholds were not significantly affected for any test frequency at any test time. Assessments of individual audiograms indicated that none of the children had any significant reductions in hearing levels at the end of the third year after cranial irradiation.

  6. The healing effect of bone marrow-derived stem cells in acute radiation syndrome

    PubMed Central

    Mortazavi, Seyed Mohammad Javad; Shekoohi-Shooli, Fatemeh; Aghamir, Seyed Mahmood Reza; Mehrabani, Davood; Dehghanian, Amirreza; Zare, Shahrokh; Mosleh-Shirazi, Mohammad Amin

    2016-01-01

    Objectives: To determine the effect of bone marrow-derived mesenchymal stem cells (BMSCs) on regeneration of bone marrow and intestinal tissue and survival rate in experimental mice with acute radiation syndrome (ARS). Methods: Forty mice were randomly divided into two equal groups of A receiving no BMSC transplantation and B receiving BMSCs. BMSCs were isolated from the bone marrow and cultured in DMEM media. Both groups were irradiated with 10 Gy (dose rate 0.28 Gy/ min) 60CO during 35 minutes with a field size of 35×35 for all the body area. Twenty-four hours after γ irradiation, 150×103 cells of passage 5 in 150 µl medium were injected intravenously into the tail. Animals were euthanized one and two weeks after cell transplantation. They were evaluated histologically for any changes in bone marrow and intestinal tissues. The survival rate in mice were also determined. Results: A significant increase for bone marrow cell count and survival rate were observed in group B in comparison to group A. Histological findings denoted to a healing in sample tissues. Conclusion: BMSCs could significantly reduce the side effects of ARS and increase the survival rate and healing in injured tissue. As such their transplantation may open a window in treatment of patients with ARS. PMID:27375707

  7. [The individual prognosis of the gravity and of the outcome of acute radiation disease based on immunological indexes].

    PubMed

    Mal'tsev, V N; Ivanov, A A; Mikhaĭlov, V F; Mazurik, V K

    2006-01-01

    The information significance of the immunological indexes for the prognosis of gravity of course and of outcome of an acute radiation disease for the people after the exposure of ionizing radiation in clinically significant doses is studied. The value of indexes of the C-reactive protein contents, of the complement contents and of the titer of haemagglutinins in serum of a blood of 147 patients damaged at Chernobyl NPP accident as a result of external radiation gamma-exposure in combination with internal irradiation from the incorporation in an organism predominantly beta-emitting radionuclides were compared to the weight of acute radiation disease and its outcome (survival or loss). Was determined, that indexes of the contents of C-reactive protein in a peripheral blood during primary reactions on the irradiation (1-2 day after irradiation) and in latent period of disease (3-9 day after irradiation), and also titer of a complement on 3-9 day after irradiation can serve a source of information for the prognosis of probable gravity of a radiation injury and its outcome at irradiation of the man in clinically significant doses.

  8. Tubulointerstitial Nephritis and Uveitis Syndrome with non caseating granuloma in bone marrow biopsy.

    PubMed

    Fraga, Maria; Nunes da Silva, Maria João; Lucas, Margarida; Victorino, Rui M

    2014-01-01

    The Tubulointerstitial Nephritis and Uveitis syndrome is a very rare condition, probably under-diagnosed in clinical practice. It is characterized by the combination of an interstitial nephritis and uveitis, and is an exclusion diagnosis. Tissue non caseating granuloma can be rarely present, with only 6 cases reported on bone marrow. We present a case of a 55 year old female with a 3-month history of asthenia and weight loss. Blood tests showed anemia and renal insufficiency. Renal biopsy revealed interstitial nephritis and the bone marrow biopsy showed caseating granuloma. One month later anterior uveitis of the left eye appeared. An extensive exclusion of all possible causes allowed a diagnosis of Tubulointerstitial Nephritis and Uveitis syndrome with caseating granuloma in bone marrow. As ocular and renal manifestations may not occur simultaneously, Tubulointerstitial Nephritis and Uveitis Syndrome should be systematically considered in cases of interstitial nephritis and/or uveitis, and tissue granulomas can be part of this rare syndrome.

  9. 38 CFR 4.115 - Nephritis.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ..., nor will the presence of transient albumin and casts following acute febrile illness be taken as... clear up entirely or progress to a chronic condition. The nephrosclerotic type, originating in... event that chronic renal disease has progressed to the point where regular dialysis is required,...

  10. 38 CFR 4.115 - Nephritis.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ..., nor will the presence of transient albumin and casts following acute febrile illness be taken as... clear up entirely or progress to a chronic condition. The nephrosclerotic type, originating in... event that chronic renal disease has progressed to the point where regular dialysis is required,...

  11. 38 CFR 4.115 - Nephritis.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ..., nor will the presence of transient albumin and casts following acute febrile illness be taken as... clear up entirely or progress to a chronic condition. The nephrosclerotic type, originating in... event that chronic renal disease has progressed to the point where regular dialysis is required,...

  12. 38 CFR 4.115 - Nephritis.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ..., nor will the presence of transient albumin and casts following acute febrile illness be taken as... clear up entirely or progress to a chronic condition. The nephrosclerotic type, originating in... event that chronic renal disease has progressed to the point where regular dialysis is required,...

  13. 38 CFR 4.115 - Nephritis.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ..., nor will the presence of transient albumin and casts following acute febrile illness be taken as... clear up entirely or progress to a chronic condition. The nephrosclerotic type, originating in... event that chronic renal disease has progressed to the point where regular dialysis is required,...

  14. A phase III randomized, placebo-controlled, double-blind study of misoprostol rectal suppositories to prevent acute radiation proctitis in patients with prostate cancer

    SciTech Connect

    Hille, Andrea . E-mail: ahille@med.uni-goettingen.de; Schmidberger, Heinz; Hermann, Robert M.; Christiansen, Hans; Saile, Bernhard; Pradier, Olivier; Hess, Clemens F.

    2005-12-01

    Purpose: Acute radiation proctitis is the most relevant complication of pelvic radiation and is still mainly treated supportively. Considering the negative impact of acute proctitis symptoms on patients' daily activities and the potential relationship between the severity of acute radiation injury and late damage, misoprostol was tested in the prevention of acute radiation-induced proctitis. Methods and Materials: A total of 100 patients who underwent radiotherapy for prostate cancer were entered into this phase III randomized, placebo-controlled, double-blind study with misoprostol or placebo suppositories. Radiation-induced toxicity was evaluated weekly during radiotherapy using the Common Toxicity Criteria. Results: Between the placebo and the misoprostol groups, no significant differences in proctitis symptoms occurred: 76% of patients in each group had Grade 1 toxicity, and 26% in the placebo group and 36% in the misoprostol group had Grade 2 toxicity. No differences were found in onset or symptom duration. Comparing the peak incidence of patients' toxicity symptoms, significantly more patients experienced rectal bleeding in the misoprostol group (p = 0.03). Conclusion: Misoprostol given as a once-daily suppository did not decrease the incidence and severity of radiation-induced acute proctitis and may increase the incidence of acute bleeding.

  15. Interstitial nephritis caused by HIV infection by itself: a case report

    PubMed Central

    Doi, Asako; Iwata, Kentaro; Hara, Shigeo; Imai, Yukihiro; Hasuike, Toshikazu; Nishioka, Hiroaki

    2016-01-01

    Interstitial nephritis is a common cause of renal dysfunction. It is primarily caused by drugs, infections, or autoimmune disorders. Patients with human immunodeficiency virus (HIV) infection can develop interstitial nephritis, although it typically occurs because of the aforementioned etiologies and not as a direct consequence of HIV infection. Interstitial lesions may occur in patients with HIV-associated nephropathy (HIVAN). However, interstitial nephritis without the glomerular injuries characteristic of HIVAN, and without the risk factors described earlier, is very rare. Here, we describe a rare case of interstitial nephritis that was likely caused directly by HIV infection and not by other etiologies. PMID:27621665

  16. Interstitial nephritis caused by HIV infection by itself: a case report

    PubMed Central

    Doi, Asako; Iwata, Kentaro; Hara, Shigeo; Imai, Yukihiro; Hasuike, Toshikazu; Nishioka, Hiroaki

    2016-01-01

    Interstitial nephritis is a common cause of renal dysfunction. It is primarily caused by drugs, infections, or autoimmune disorders. Patients with human immunodeficiency virus (HIV) infection can develop interstitial nephritis, although it typically occurs because of the aforementioned etiologies and not as a direct consequence of HIV infection. Interstitial lesions may occur in patients with HIV-associated nephropathy (HIVAN). However, interstitial nephritis without the glomerular injuries characteristic of HIVAN, and without the risk factors described earlier, is very rare. Here, we describe a rare case of interstitial nephritis that was likely caused directly by HIV infection and not by other etiologies.

  17. Interstitial nephritis caused by HIV infection by itself: a case report.

    PubMed

    Doi, Asako; Iwata, Kentaro; Hara, Shigeo; Imai, Yukihiro; Hasuike, Toshikazu; Nishioka, Hiroaki

    2016-01-01

    Interstitial nephritis is a common cause of renal dysfunction. It is primarily caused by drugs, infections, or autoimmune disorders. Patients with human immunodeficiency virus (HIV) infection can develop interstitial nephritis, although it typically occurs because of the aforementioned etiologies and not as a direct consequence of HIV infection. Interstitial lesions may occur in patients with HIV-associated nephropathy (HIVAN). However, interstitial nephritis without the glomerular injuries characteristic of HIVAN, and without the risk factors described earlier, is very rare. Here, we describe a rare case of interstitial nephritis that was likely caused directly by HIV infection and not by other etiologies. PMID:27621665

  18. Curcumin protects against radiation-induced acute and chronic cutaneous toxicity in mice and decreases mRNA expression of inflammatory and fibrogenic cytokines

    SciTech Connect

    Okunieff, Paul . E-mail: paul_okunieff@urmc.rochester.edu; Xu Jianhua; Hu Dongping; Liu Weimin; Zhang Lurong; Morrow, Gary; Pentland, Alice; Ryan, Julie L.; Ding, Ivan M.D.

    2006-07-01

    Purpose: To determine whether curcumin ameliorates acute and chronic radiation skin toxicity and to examine the expression of inflammatory cytokines (interleukin [IL]-1, IL-6, IL-18, IL-1Ra, tumor necrosis factor [TNF]-{alpha}, and lymphotoxin-{beta}) or fibrogenic cytokines (transforming growth factor [TGF]-{beta}) during the same acute and chronic phases. Methods and Materials: Curcumin was given intragastrically or intraperitoneally to C3H/HeN mice either: 5 days before radiation; 5 days after radiation; or both 5 days before and 5 days after radiation. The cutaneous damage was assessed at 15-21 days (acute) and 90 days (chronic) after a single 50 Gy radiation dose was given to the hind leg. Skin and muscle tissues were collected for measurement of cytokine mRNA. Results: Curcumin, administered before or after radiation, markedly reduced acute and chronic skin toxicity in mice (p < 0.05). Additionally, curcumin significantly decreased mRNA expression of early responding cytokines (IL-1 IL-6, IL-18, TNF-{alpha}, and lymphotoxin-{beta}) and the fibrogenic cytokine, TGF-{beta}, in cutaneous tissues at 21 days postradiation. Conclusion: Curcumin has a protective effect on radiation-induced cutaneous damage in mice, which is characterized by a downregulation of both inflammatory and fibrogenic cytokines in irradiated skin and muscle, particularly in the early phase after radiation. These results may provide the molecular basis for the application of curcumin in clinical radiation therapy.

  19. Mapping similarities in mTOR pathway perturbations in mouse lupus nephritis models and human lupus nephritis

    PubMed Central

    Reddy, Padmalatha S; Legault, Holly M; Sypek, Joseph P; Collins, Mark J; Goad, Elizabeth; Goldman, Samuel J; Liu, Wei; Murray, Stuart; Dorner, Andrew J; O'Toole, Margot

    2008-01-01

    Introduction Treatment with sirolimus, a mammalian target of rapamycin (mTOR) inhibitor, has been shown to be efficacious in the MRL/lpr and NZB × NZW F1 mouse models of lupus nephritis, indicating a critical role for the mTOR pathway in both models. This type of demonstration of efficacy in animal models is usually a pre-requisite for advancement into clinical development. However, efficacy in an animal model often has not translated to the desired activity in the clinic. Therefore, a more profound understanding of the mechanistic similarities and differences between various animal models and human diseases is highly desirable. Methods Transcriptional profiling was performed on kidneys from mice with lupus nephritis; from mice who had efficacious drug treatment; and from mice before they developed nephritis. Analysis of variance with false discovery rate adjusted to p < 0.05 and an average fold change of two or more was used to identify transcripts significantly associated with disease and response to therapy. Pathway analyses (using various bioinformatics tools) were carried out to understand the basis for drug efficacy in the mouse model. The relevance in human lupus of the pathways identified in the mouse model was explored using information from several databases derived from the published literature. Results We identified a set of nephritis-associated genes in mouse kidney. Expression of the majority of these returned to asymptomatic levels on sirolimus treatment, confirming the correlation between expression levels and symptoms of nephritis. Network analysis showed that many of these nephritis genes are known to interact with the mTOR pathway. This led us to ask what human diseases are linked to the mTOR pathway. We constructed the mTOR pathway interactome consisting of proteins that interact with members of the mTOR pathway and identified a strong association between mTOR pathway genes and genes reported in the literature as being involved in human lupus

  20. Lupus nephritis: clinicopathological study of 162 cases in Thailand.

    PubMed Central

    Parichatikanond, P; Francis, N D; Malasit, P; Laohapand, T; Nimmannit, S; Singchoovong, L; Nilwarangkur, S; Chrirawong, P; Vanichakarn, S

    1986-01-01

    One hundred and sixty two cases of lupus nephritis biopsied over three years in Thailand were studied. A pattern of clinical and histological renal disease very similar to that seen in the United States or Europe emerged. The predominant histological type was World Health Organisation class IV (diffuse proliferative; 58.6%). Patients with renal insufficiency (creatinine greater than or equal to 2 mg/100 ml) or hypertension at the time of biopsy had a considerably worse three year survival. Certain features such as sclerotic glomeruli, tubular atrophy, and an interstitial mononuclear cell infiltrate were significantly associated with a worse outcome (0.05 greater than p greater than 0.01), and patients who died with poor renal function had significantly higher chronicity scores than those in other groups (p less than 0.05). These findings emphasise the importance of chronic renal damage in the morbidity and mortality of patients with lupus nephritis. PMID:3485117

  1. Detection of avian nephritis virus in Australian chicken flocks.

    PubMed

    Hewson, Kylie A; O'Rourke, Denise; Noormohammadi, Amir H

    2010-09-01

    Avian nephritis virus (ANV) is thought to infect poultry flocks worldwide, but no confirmed case has been reported in Australia. The first such case is described in this study. Cases of young chickens with clinical signs of dehydration and diarrhea were submitted to our laboratory and histopathology detected interstitial nephritis. Vaccine strains of infectious bronchitis virus were detected in some of these cases but were not considered to be the causative agent. A total of seven fresh submissions from broiler chicken flocks were collected at 8-11 days of age. Degenerate PCR primers were designed based on published ANV polymerase gene sequences and used to analyze historic cases as well as the fresh submissions. Six of the seven fresh submissions, and one historic case, were positive for ANV with nucleotide sequencing confirming these results. These results establish ANV as an infectious pathogen circulating in Australian poultry.

  2. An Animal Model Using Metallic Ions to Produce Autoimmune Nephritis.

    PubMed

    Ramírez-Sandoval, Roxana; Luévano-Rodríguez, Nayeli; Rodríguez-Rodríguez, Mayra; Pérez-Pérez, María Elena; Saldívar-Elias, Sergio; Gurrola-Carlos, Reinaldo; Avalos-Díaz, Esperanza; Bollain-y-Goytia, Juan José; Herrera-Esparza, Rafael

    2015-01-01

    Autoimmune nephritis triggered by metallic ions was assessed in a Long-Evans rat model. The parameters evaluated included antinuclear autoantibody production, kidney damage mediated by immune complexes detected by immunofluorescence, and renal function tested by retention of nitrogen waste products and proteinuria. To accomplish our goal, the animals were treated with the following ionic metals: HgCl2, CuSO4, AgNO3, and Pb(NO3)2. A group without ionic metals was used as the control. The results of the present investigation demonstrated that metallic ions triggered antinuclear antibody production in 60% of animals, some of them with anti-DNA specificity. Furthermore, all animals treated with heavy metals developed toxic glomerulonephritis with immune complex deposition along the mesangium and membranes. These phenomena were accompanied by proteinuria and increased concentrations of urea. Based on these results, we conclude that metallic ions may induce experimental autoimmune nephritis.

  3. Immunologic findings, thrombocytopenia and disease activity in lupus nephritis.

    PubMed Central

    Clark, W. F.; Linton, A. L.; Cordy, P. E.; Keown, P. E.; Lohmann, R. C.; Lindsay, R. M.

    1978-01-01

    Twenty patients with nephritis due to systemic lupus erythematosus were followed up for a mean of 34 months after renal biopsy with serial determinations of total serum complement and C3 and C4 concentrations, binding of deoxyribonucleic acid (DNA), antinuclear antibody pattern and platelet count. There were 25 episodes of nonhematologic observed disease activity in 16 of the 20 patients; elevated DNA binding and thrombocytopenia correlated well with these episodes. The mean platelet count during episodes of observed disease activity was 96 +/- 42 X 10(9)/L, which was significantly different from the mean count of 248 +/- 90 X 10(9)/L during disease quiescence. The proportion of false-positive results with the immunologic tests varied from 25% to 67% and with platelet counts it was 11%. It is suggested that thrombocytopenia may be a simple and accurate index of disease activity in lupus nephritis. PMID:350367

  4. Granulomatous Nephritis Consistent with Malakoplakia in a Cynomolgus Monkey

    PubMed Central

    Taketa, Yoshikazu; Inomata, Akira; Sonoda, Jiro; Hayakawa, Kazuhiro; Nakano-Ito, Kyoko; Ohta, Etsuko; Seki, Yuki; Goto, Aya; Hosokawa, Satoru

    2013-01-01

    Malakoplakia is a rare form of chronic granulomatous inflammation in mammals, and usually affects the urinary tract in humans. In this report, we present a case of granulomatous nephritis consistent with malakoplakia in a 4-year-old male cynomolgus monkey. Gross examination showed that the kidney was markedly enlarged and adhered to the surrounding organs. Histology showed that there was diffuse interstitial infiltration of histiocytes with abundant foamy eosinophilic cytoplasm resembling von Hansemann cells, PAS-positive granular cytoplasm and occasional PAS- and iron-positive intracellular small inclusion bodies. Electron microscopy showed that these histiocytes contained abundant lysosomes and phagolysosomes but no obvious Michaelis-Gutmann bodies. Based on these findings, a diagnosis of granulomatous nephritis consistent with early malakoplakia was made. This is the first report in a monkey of a renal lesion consistent with malakoplakia. PMID:24526815

  5. An Animal Model Using Metallic Ions to Produce Autoimmune Nephritis

    PubMed Central

    Ramírez-Sandoval, Roxana; Luévano-Rodríguez, Nayeli; Rodríguez-Rodríguez, Mayra; Pérez-Pérez, María Elena; Saldívar-Elias, Sergio; Gurrola-Carlos, Reinaldo; Avalos-Díaz, Esperanza; Bollain-y-Goytia, Juan José

    2015-01-01

    Autoimmune nephritis triggered by metallic ions was assessed in a Long-Evans rat model. The parameters evaluated included antinuclear autoantibody production, kidney damage mediated by immune complexes detected by immunofluorescence, and renal function tested by retention of nitrogen waste products and proteinuria. To accomplish our goal, the animals were treated with the following ionic metals: HgCl2, CuSO4, AgNO3, and Pb(NO3)2. A group without ionic metals was used as the control. The results of the present investigation demonstrated that metallic ions triggered antinuclear antibody production in 60% of animals, some of them with anti-DNA specificity. Furthermore, all animals treated with heavy metals developed toxic glomerulonephritis with immune complex deposition along the mesangium and membranes. These phenomena were accompanied by proteinuria and increased concentrations of urea. Based on these results, we conclude that metallic ions may induce experimental autoimmune nephritis. PMID:26064998

  6. Interstitial Nephritis in a Patient with Inflammatory Bowel Disease

    PubMed Central

    Vasanth, Payaswini; Parmley, Michelle; Torrealba, Jose

    2016-01-01

    Tubulointerstitial nephritis in patients with inflammatory bowel disease has been linked to the use of 5-ASA derivatives. Various aspects of this theory have been challenged with a potential role for the underlying autoimmune disorder. Steroids are the mainstay of treatment and mycophenolate mofetil might be an effective alternative. We report a patient who responded well to mycophenolate despite continuing mesalamine, the suspected offending agent. PMID:27703822

  7. Macrophage depletion ameliorates nephritis induced by pathogenic antibodies.

    PubMed

    Chalmers, Samantha A; Chitu, Violeta; Herlitz, Leal C; Sahu, Ranjit; Stanley, E Richard; Putterman, Chaim

    2015-02-01

    Kidney involvement affects 40-60% of patients with lupus, and is responsible for significant morbidity and mortality. Using depletion approaches, several studies have suggested that macrophages may play a key role in the pathogenesis of lupus nephritis. However, "off target" effects of macrophage depletion, such as altered hematopoiesis or enhanced autoantibody production, impeded the determination of a conclusive relationship. In this study, we investigated the role of macrophages in mice receiving rabbit anti-glomerular antibodies, or nephrotoxic serum (NTS), an experimental model which closely mimics the immune complex mediated disease seen in murine and human lupus nephritis. GW2580, a selective inhibitor of the colony stimulating factor-1 (CSF-1) receptor kinase, was used for macrophage depletion. We found that GW2580-treated, NTS challenged mice did not develop the increased levels of proteinuria, serum creatinine, and BUN seen in control-treated, NTS challenged mice. NTS challenged mice exhibited significantly increased kidney expression of inflammatory cytokines including RANTES, IP-10, VCAM-1 and iNOS, whereas GW2580-treated mice were protected from the robust expression of these inflammatory cytokines that are associated with lupus nephritis. Quantification of macrophage related gene expression, flow cytometry analysis of kidney single cell suspensions, and immunofluorescence staining confirmed the depletion of macrophages in GW2580-treated mice, specifically within renal glomeruli. Our results strongly implicate a specific and necessary role for macrophages in the development of immune glomerulonephritis mediated by pathogenic antibodies, and support the development of macrophage targeting approaches for the treatment of lupus nephritis. PMID:25554644

  8. Outcomes in African Americans and Hispanics with lupus nephritis.

    PubMed

    Contreras, G; Lenz, O; Pardo, V; Borja, E; Cely, C; Iqbal, K; Nahar, N; de La Cuesta, C; Hurtado, A; Fornoni, A; Beltran-Garcia, L; Asif, A; Young, L; Diego, J; Zachariah, M; Smith-Norwood, B

    2006-05-01

    Poor outcomes have been reported in African Americans and Hispanics compared to Caucasians with lupus nephritis. The purpose of this retrospective analysis was to identify independent predictors of outcomes in African Americans and Hispanics with lupus nephritis. In total, 93 African Americans, 100 Hispanics, and 20 Caucasians with a mean age of 28 +/- 13 years and an annual household income of 32.9 +/- 17.3 (in 1000 US dollars) were studied. World Health Organization (WHO) lupus nephritis classes II, III, IV, and V were seen in 9, 13, 52, and 26%, respectively. Important baseline differences were higher mean arterial pressure (MAP) in African Americans compared to Hispanics and Caucasians (107 +/- 19, 102 +/- 15, and 99 +/- 13 mmHg, P < 0.05), and higher serum creatinine (1.66 +/- 1.3, 1.25 +/- 1.0, and 1.31 +/- 1.0 mg/dl, P < 0.025). African Americans had lower hematocrit compared to Hispanics and Caucasians (29 +/- 5, and 31 +/- 6, and 32 +/- 7%, P < 0.05), and lower annual household income (30.8 +/- 14.9, 33.1 +/- 15.9, and 42.2 +/- 29.3 in 1000 US dollars; P < 0.05). Lower prevalence of WHO class IV was seen in Caucasians (30%) compared to Hispanics (57%, P = 0.03) and African Americans (51%, P = 0.09). Development of doubling creatinine or end-stage renal disease was higher in African Americans and Hispanics than in Caucasians (31, 18, and 10%; P < 0.05), as was the development of renal events or death (34, 20, and 10%; P < 0.025). Our results suggest that both biological factors indicating an aggressive disease and low household income are common in African Americans and Hispanics with lupus nephritis, and outcomes in these groups are worse than in Caucasians.

  9. Renal biopsy in the management of lupus nephritis during pregnancy.

    PubMed

    Chen, T K; Gelber, A C; Witter, F R; Petri, M; Fine, D M

    2015-02-01

    The differential diagnosis of proteinuria and hematuria in pregnancy is broad and includes active lupus nephritis. Identification of the correct diagnosis often has a profound therapeutic impact on not only the mother but also the fetus. To date, relatively few reports exist on the role of renal biopsy during pregnancy among women with systemic lupus erythematosus (SLE). We present a case series of 11 pregnant women with SLE who underwent a renal biopsy to evaluate a presumptive flare of lupus nephritis. The electronic medical record was retrospectively analyzed for pre-biopsy serum creatinine, proteinuria, hematuria, antinuclear antibodies (ANA), and antibodies to double-stranded DNA (anti-dsDNA); histologic findings on renal biopsy; and the clinical course of each mother and fetus. From 2001 to 2012, 11 pregnant women with SLE flares during pregnancy underwent a renal biopsy at an academic tertiary medical center. At the time of biopsy, median gestational age was 16 weeks (range 9 to 27), median serum creatinine was 0.6 mg/dl (interquartile range 0.5 to 0.9), six (55%) had hematuria, and all had proteinuria >500 mg/24 hours. Proliferative lupus nephritis was found in 10 (91%) of 11 biopsies (five with ISN/RPS Class III; five with ISN/RPS Class IV). All but one individual underwent a change in management guided by information gleaned from renal biopsy. No apparent biopsy-related complications occurred to mother or fetus. Three women elected to terminate their pregnancy; although many factors were involved, the findings on renal biopsy informed the decision-making process. Among the remaining cases, there were three pre-term deliveries, one fetus with complete heart block, one in utero demise, and one maternal death. Renal biopsy is helpful at informing the management of patients with lupus nephritis during pregnancy.

  10. Mycophenolate Mofetil versus Cyclophosphamide for Induction Treatment of Lupus Nephritis

    PubMed Central

    Appel, Gerald B.; Contreras, Gabriel; Dooley, Mary Anne; Ginzler, Ellen M.; Isenberg, David; Jayne, David; Li, Lei-Shi; Mysler, Eduardo; Sánchez-Guerrero, Jorge; Solomons, Neil; Wofsy, David

    2009-01-01

    Recent studies have suggested that mycophenolate mofetil (MMF) may offer advantages over intravenous cyclophosphamide (IVC) for the treatment of lupus nephritis, but these therapies have not been compared in an international randomized, controlled trial. Here, we report the comparison of MMF and IVC as induction treatment for active lupus nephritis in a multinational, two-phase (induction and maintenance) study. We randomly assigned 370 patients with classes III through V lupus nephritis to open-label MMF (target dosage 3 g/d) or IVC (0.5 to 1.0 g/m2 in monthly pulses) in a 24-wk induction study. Both groups received prednisone, tapered from a maximum starting dosage of 60 mg/d. The primary end point was a prespecified decrease in urine protein/creatinine ratio and stabilization or improvement in serum creatinine. Secondary end points included complete renal remission, systemic disease activity and damage, and safety. Overall, we did not detect a significantly different response rate between the two groups: 104 (56.2%) of 185 patients responded to MMF compared with 98 (53.0%) of 185 to IVC. Secondary end points were also similar between treatment groups. There were nine deaths in the MMF group and five in the IVC group. We did not detect significant differences between the MMF and IVC groups with regard to rates of adverse events, serious adverse events, or infections. Although most patients in both treatment groups experienced clinical improvement, the study did not meet its primary objective of showing that MMF was superior to IVC as induction treatment for lupus nephritis. PMID:19369404

  11. Immunomodulatory effects of high-protein diet with resveratrol supplementation on radiation-induced acute-phase inflammation in rats.

    PubMed

    Kim, Kyoung-Ok; Park, HyunJin; Chun, Mison; Kim, Hyun-Sook

    2014-09-01

    We hypothesized that a high-protein diet and/or resveratrol supplementation will improve acute inflammatory responses in rats after receiving experimental abdominal radiation treatment (ART). Based on our previous study, the period of 10 days after ART was used as an acute inflammation model. Rats were exposed to a radiation dose of 17.5 Gy and were supplied with a control (C), 30% high-protein diet (HP), resveratrol supplementation (RES), or HP with RES diet ([HP+RES]). At day 10 after ART, we measured profiles of lipids, proteins, and immune cells in blood. The levels of clusters of differentiating 4(+) (CD4(+)) cells and regulatory T cells, serum proinflammatory cytokines, and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in urine were also measured. ART caused significant disturbances of lipid profiles by increasing triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C), and decreasing high-density lipoprotein cholesterol. The proinflammatroy cytokine levels were also increased by ART. All the experimental diets (HP, RES, and [HP+RES]) significantly decreased levels of TG, monocytes, proinflammatory cytokines, and 8-OHdG, whereas the platelet counts were increased. In addition, the HP and [HP+RES] diets decreased the concentrations of plasma LDL-C and total cholesterol. Also, the HP and RES diets decreased regulatory T cells compared with those of the control diet in ART group. Further, the HP diet led to a significant recovery of white blood cell counts, as well as increased percentages of lymphocyte and decreased percentages of neutrophils. In summary, RES appeared to be significantly effective in minimizing radiation-induced damage to lipid metabolism and immune responses. Our study also demonstrated the importance of dietary protein intake in recovering from acute inflammation by radiation.

  12. Appraisal of lupus nephritis by renal imaging with gallium-67

    SciTech Connect

    Bakir, A.A.; Lopez-Majano, V.; Hryhorczuk, D.O.; Rhee, H.L.; Dunea, G.

    1985-08-01

    To assess the activity of lupus nephritis, 43 patients with systemic lupus erythematosus (SLE) were studied by gallium imaging. Delayed renal visualization 48 hours after the gallium injection, a positive result, was noted in 25 of 48 scans. Active renal disease was defined by the presence of hematuria, pyuria (10 or more red blood cells or white blood cells per high-power field), proteinuria (1 g or more per 24 hours), a rising serum creatinine level, or a recent biopsy specimen showing proliferative and/or necrotizing lesions involving more than 20 percent of glomeruli. Renal disease was active in 18 instances, inactive in 23, and undetermined in seven (a total of 48 scans). Sixteen of the 18 scans (89 percent) in patients with active renal disease showed positive findings, as compared with only four of 23 scans (17 percent) in patients with inactive renal disease (p less than 0.001). Patients with positive scanning results had a higher rate of hypertension (p = 0.02), nephrotic proteinuria (p = 0.01), and progressive renal failure (p = 0.02). Mild mesangial nephritis (World Health Organization classes I and II) was noted only in the patients with negative scanning results (p = 0.02) who, however, showed a higher incidence of severe extrarenal SLE (p = 0.04). It is concluded that gallium imaging is a useful tool in evaluating the activity of lupus nephritis.

  13. Longitudinal study of circulating immune complexes in a patient with Staphylococcus albus-induced shunt nephritis.

    PubMed

    Harkiss, G D; Brown, D L; Evans, D B

    1979-08-01

    The direct measurement and partial characterization of circulating immune complexes has been performed in a longitudinal study of a patient with Staphylococcus albus-induced shunt nephritis. The high levels of immune complexes were associated with cryoglobulinaemia and hypocomplementaemia. The activation of complement was found to be via the classical pathway, but the functioning of the alternative pathway may have been impaired in vivo due to very low levels of C3. The host response to the infection was also characterized by the production of a marked macroglobulinaemia, high titres of rheumatoid factor and a typical acute phase increase in the C-reactive protein level. Immune complex levels were persistently elevated many months after the removal of the focus of the infection. A possible explanation for this surprising finding may lie in the nature of the antigens in the immune complexes. It was found that the immune complexes contained both antibodies to and antigens from Staphlococcus albus. In particular, glycerol teichoic acid and staphylococcal nuclease were identified as components of the immune complexes present during the acute phase. Glycerol teichoic acid was also identified in the immune complexes found later although other Staphylococcus albus antigens as yet unidentified were also present and persisted in the circulation for several months.

  14. Clozapine-induced interstitial nephritis - a rare but important complication: a case report

    PubMed Central

    2009-01-01

    Introduction Given the limited range of effective drug treatments for patients with schizophrenia, increasing numbers of patients, often termed 'treatment-resistant' are prescribed clozapine. While the induction of neutropenia or agranulocytosis by clozapine is well appreciated, other rare potentially fatal adverse reactions may also occur including acute interstitial nephritis as reported in this case. Case presentation A 57-year-old Caucasian woman with treatment-resistant chronic schizophrenia developed acute renal failure following initiation of treatment with clozapine. The adverse reaction occurred after only four doses of the drug had been administered (titrated from 12.5 to 25 mg per day). After clozapine had been withdrawn, the patient's renal function returned to normal with no other changes to medication. The patient had been exposed to clozapine about 4 years previously when she had developed a similar reaction. Conclusion Renal reactions to clozapine are extremely rare but, if not recognized promptly, may prove fatal. Psychiatrists need to be aware of this possible complication when clozapine is initiated. PMID:20126316

  15. Henoch-Schönlein nephritis associated with streptococcal infection and persistent hypocomplementemia: a case report

    PubMed Central

    2010-01-01

    Introduction Henoch-Schönlein purpura is a systemic disease with frequent renal involvement, characterized by IgA mesangial deposits. Streptococcal infection can induce an abnormal IgA immune response like Henoch-Schönlein purpura, quite similar to typical acute post-infectious glomerulonephritis. Indeed, hypocomplementemia that is typical of acute glomerulonephritis has also been described in Henoch-Schönlein purpura. Case presentation We describe a 14-year-old Caucasian Spanish girl who developed urinary abnormalities and cutaneous purpura after streptococcal infection. Renal biopsy showed typical findings from Henoch-Schönlein purpura nephritis. In addition, she had low serum levels of complement (C4 fraction) that persisted during follow-up, in spite of her clinical evolution. She responded to treatment with enalapril and steroids. Conclusion The case described has, at least, three points of interest in Henoch-Schönlein purpura: 1) Initial presentation was preceded by streptococcal infection; 2) There was a persistence of low serum levels of complement; and 3) There was response to steroids and angiotensin-converting enzyme inhibitor in the presence of nephrotic syndrome. There are not many cases described in the literature with these characteristics. We conclude that Henoch-Schönlein purpura could appear after streptococcal infection in patients with abnormal complement levels, and that steroids and angiotensin-converting enzyme inhibitor could be successful treatment for the disease. PMID:20181224

  16. Radiation carcinogenesis and acute radiation mortality in the rat as produced by 2.2 GeV protons

    NASA Technical Reports Server (NTRS)

    Shellabarger, C. J.; Straub, R. F.; Jesseph, J. E.; Montour, J. L.

    1972-01-01

    Biological studies, proton carcinogenesis, the interaction of protons and gamma-rays on carcinogenesis, proton-induced acute mortality, and chemical protection against proton-induced acute mortality were studied in the rat and these proton-produced responses were compared to similar responses produced by gamma-rays or X-rays. Litter-mate mice were assigned to each experimental and control group so that approximately equal numbers of litter mates were placed in each group. Animals to be studied for mammary neoplasia were handled for 365 days post-exposure when all animals alive were killed. All animals were examined frequently for mammary tumors and as these were found, they were removed, sectioned and given a pathologic classification.

  17. A case-referent study on acute myeloid leukemia, background radiation and exposure to solvents and other agents.

    PubMed

    Flodin, U; Andersson, L; Anjou, C G; Palm, U B; Vikrot, O; Axelson, O

    1981-09-01

    The effect of potential risk factors for acute myeloid leukemia was evaluated in a case-referent study encompassing 42 cases and 244 referents, all deceased. Information on exposure was obtained with questionnaires mailed to the next of kin. Particularly the effect of background radiation was evaluated, as assessed with a gamma radiation index weighing the time spent outdoors and indoors and considering the building material (stone, wood, etc.) in the homes and the workplaces of the subjects. Especially between the ages of 20 and 49 a, to some extent also between 50 and 69 a but not above 70, there seemed to be an effect from background radiation and a trend suggesting an exposure-effect relationship. There was also about a sixfold increase in the rate ratio with regard to solvent exposure, which also seemed to modify the effect of background radiation. Other exposures were associated with relatively modest increases in the rate ratios and/or very small numbers of exposed individuals. It would be worthwhile to undertake further cancer epidemiologic studies of background radiation in which effective study designs are applied and a variety of potential confounders and modifiers of effect are identified and accounted for. PMID:20120581

  18. The impact of microbial immune enteral nutrition on the patients with acute radiation enteritis in bowel function and immune status.

    PubMed

    Shao, Feng; Xin, Fu-Ze; Yang, Cheng-Gang; Yang, Dao-Gui; Mi, Yue-Tang; Yu, Jun-Xiu; Li, Guo-Yong

    2014-06-01

    The aim of the study was to investigate the effect of microbial immune enteral nutrition by microecopharmaceutics and deep sea fish oil and glutamine and Peptisorb on the patients with acute radiation enteritis in bowel function and immune status. From June 2010 to January 2013, 46 acute radiation enteritis patients in Liaocheng People's Hospital were randomized into the microbial immune enteral nutrition group and the control group: 24 patients in treatment group and 22 patients in control group. The immune microbial nutrition was given to the study group, but not to the control group. The concentration of serum albumin and prealbumin and the number of CD3 (+) T cell, CD4 (+) T cell, CD8 (+) T cell, CD4 (+)/CD8 (+) and natural killer cell of the two groups were detected on the 1, 7 and 14 days after treatment. The arm muscle circumference and triceps skinfold thickness (TSF) were recorded, and the tolerance of the two groups for enteral nutrition and intestinal symptoms was collected and then comparing the two indicators and get results. The tolerance of microbial immune enteral nutrition group about abdominal pain, bloating and diarrhea was better than the control group (P values were 0.018, 0.04 and 0.008 after 7 days; P values were 0.018, 0.015 and 0.002 after 14 days); and the cellular immune parameters were better than the control group((△) P = 0.008,([Symbol: see text]) P = 0.039, (☆) P = 0.032); No difference was found in nutrition indicators. To the patients with acute radiation enteritis, microbial immune enteral nutrition could improve the patient's immune status, and the tolerance of enteral nutrition could be better for the bowel function and the patients' rehabilitation.

  19. Preclinical acute toxicity, biodistribution, pharmacokinetics, radiation dosimetry and microPET imaging studies of [(18)F]fluorocholine in mice.

    PubMed

    Silveira, Marina B; Ferreira, Soraya M Z M D; Nascimento, Leonardo T C; Costa, Flávia M; Mendes, Bruno M; Ferreira, Andrea V; Malamut, Carlos; Silva, Juliana B; Mamede, Marcelo

    2016-10-01

    [(18)F]Fluorocholine ([(18)F]FCH) has been proven to be effective in prostate cancer. Since [(18)F]FCH is classified as a new radiopharmaceutical in Brazil, preclinical safety and efficacy data are required to support clinical trials and to obtain its approval. The aim of this work was to perform acute toxicity, biodistribution, pharmacokinetics, radiation dosimetry and microPET imaging studies of [(18)F]FCH. The results could support its use in nuclear medicine as an important piece of work for regulatory in Brazil.

  20. Preclinical acute toxicity, biodistribution, pharmacokinetics, radiation dosimetry and microPET imaging studies of [(18)F]fluorocholine in mice.

    PubMed

    Silveira, Marina B; Ferreira, Soraya M Z M D; Nascimento, Leonardo T C; Costa, Flávia M; Mendes, Bruno M; Ferreira, Andrea V; Malamut, Carlos; Silva, Juliana B; Mamede, Marcelo

    2016-10-01

    [(18)F]Fluorocholine ([(18)F]FCH) has been proven to be effective in prostate cancer. Since [(18)F]FCH is classified as a new radiopharmaceutical in Brazil, preclinical safety and efficacy data are required to support clinical trials and to obtain its approval. The aim of this work was to perform acute toxicity, biodistribution, pharmacokinetics, radiation dosimetry and microPET imaging studies of [(18)F]FCH. The results could support its use in nuclear medicine as an important piece of work for regulatory in Brazil. PMID:27509594

  1. Diffuse Optical Spectroscopy for the Quantitative Assessment of Acute Ionizing Radiation Induced Skin Toxicity Using a Mouse Model

    PubMed Central

    Chin, Lee; Korpela, Elina; Kim, Anthony; Yohan, Darren; Niu, Carolyn; Wilson, Brian C.; Liu, Stanley K.

    2016-01-01

    Acute skin toxicities from ionizing radiation (IR) are a common side effect from therapeutic courses of external beam radiation therapy (RT) and negatively impact patient quality of life and long term survival. Advances in the understanding of the biological pathways associated with normal tissue toxicities have allowed for the development of interventional drugs, however, current response studies are limited by a lack of quantitative metrics for assessing the severity of skin reactions. Here we present a diffuse optical spectroscopic (DOS) approach that provides quantitative optical biomarkers of skin response to radiation. We describe the instrumentation design of the DOS system as well as the inversion algorithm for extracting the optical parameters. Finally, to demonstrate clinical utility, we present representative data from a pre-clinical mouse model of radiation induced erythema and compare the results with a commonly employed visual scoring. The described DOS method offers an objective, high through-put evaluation of skin toxicity via functional response that is translatable to the clinical setting. PMID:27284926

  2. Acute effects of radiation therapy on indium-111-labeled leukocyte uptake in bone marrow

    SciTech Connect

    Palestro, C.J.; Kim, C.K.; Vega, A.; Goldsmith, S.J. )

    1989-11-01

    We recently performed ({sup 99m}Tc)MDP bone and {sup 111}In-labeled leukocyte scintigraphy on a patient receiving radiation therapy to the lower cervical and upper thoracic spine. While the bone images revealed only minimally increased activity in the radiation port, leukocyte images revealed diffuse, intensely increased uptake in this same region. Radiation therapy should be included in the differential diagnosis of increased bone marrow activity on {sup 111}In leukocyte images.

  3. Prophylactic Treatment with Adlay Bran Extract Reduces the Risk of Severe Acute Radiation Dermatitis: A Prospective, Randomized, Double-Blind Study

    PubMed Central

    Huang, Chih-Jen; Hou, Ming-Feng; Kan, Jung-Yu; Juan, Chiung-Hui; Yuan, Shyng-Shiou F.; Luo, Kuei-Hau; Chuang, Hung-Yi; Hu, Stephen Chu-Sung

    2015-01-01

    Acute radiation dermatitis is a frequent adverse effect in patients with breast cancer undergoing radiotherapy, but there are only a small number of studies providing evidence-based interventions for this clinical condition. Adlay is a cereal crop that has been previously shown to have anti-inflammatory and antioxidant properties. In this study, we seek to evaluate the effectiveness of oral prophylactic treatment with adlay bran extract in reducing the risk of severe acute radiation dermatitis. A total of 110 patients with breast cancer undergoing radiotherapy were analyzed. Using a prospective, randomized, double-blind design, 73 patients received oral treatment with adlay bran extract and 37 patients received olive oil (placebo). Treatment was started at the beginning of radiation therapy and continued until the termination of radiation treatment. Our results showed that the occurrence of severe acute radiation dermatitis (RTOG grade 2 or higher) was significantly lower in patients treated with oral adlay bran extract compared to placebo (45.2% versus 75.7%, adjusted odds ratio 0.24). No serious adverse effects from adlay bran treatment were noted. In conclusion, prophylactic oral treatment with adlay bran extract reduces the risk of severe acute radiation dermatitis and may have potential use in patients with breast cancer undergoing radiotherapy. PMID:26495009

  4. Acceleration of atherogenesis in ApoE-/- mice exposed to acute or low-dose-rate ionizing radiation.

    PubMed

    Mancuso, Mariateresa; Pasquali, Emanuela; Braga-Tanaka, Ignacia; Tanaka, Satoshi; Pannicelli, Alessandro; Giardullo, Paola; Pazzaglia, Simonetta; Tapio, Soile; Atkinson, Michael J; Saran, Anna

    2015-10-13

    There is epidemiological evidence for increased non-cancer mortality, primarily due to circulatory diseases after radiation exposure above 0.5 Sv. We evaluated the effects of chronic low-dose rate versus acute exposures in a murine model of spontaneous atherogenesis. Female ApoE-/- mice (60 days) were chronically irradiated for 300 days with gamma rays at two different dose rates (1 mGy/day; 20 mGy/day), with total accumulated doses of 0.3 or 6 Gy. For comparison, age-matched ApoE-/- females were acutely exposed to the same doses and sacrificed 300 days post-irradiation. Mice acutely exposed to 0.3 or 6 Gy showed increased atherogenesis compared to age-matched controls, and this effect was persistent. When the same doses were delivered at low dose rate over 300 days, we again observed a significant impact on global development of atherosclerosis, although at 0.3 Gy effects were limited to the descending thoracic aorta. Our data suggest that a moderate dose of 0.3 Gy can have persistent detrimental effects on the cardiovascular system, and that a high dose of 6 Gy poses high risks at both high and low dose rates. Our results were clearly nonlinear with dose, suggesting that lower doses may be more damaging than predicted by a linear dose response. PMID:26359350

  5. Acceleration of atherogenesis in ApoE−/− mice exposed to acute or low-dose-rate ionizing radiation

    PubMed Central

    Mancuso, Mariateresa; Pasquali, Emanuela; Braga-Tanaka, Ignacia; Tanaka, Satoshi; Pannicelli, Alessandro; Giardullo, Paola; Pazzaglia, Simonetta; Tapio, Soile; Atkinson, Michael J.; Saran, Anna

    2015-01-01

    There is epidemiological evidence for increased non-cancer mortality, primarily due to circulatory diseases after radiation exposure above 0.5 Sv. We evaluated the effects of chronic low-dose rate versus acute exposures in a murine model of spontaneous atherogenesis. Female ApoE−/− mice (60 days) were chronically irradiated for 300 days with gamma rays at two different dose rates (1 mGy/day; 20 mGy/day), with total accumulated doses of 0.3 or 6 Gy. For comparison, age-matched ApoE−/− females were acutely exposed to the same doses and sacrificed 300 days post-irradiation. Mice acutely exposed to 0.3 or 6 Gy showed increased atherogenesis compared to age-matched controls, and this effect was persistent. When the same doses were delivered at low dose rate over 300 days, we again observed a significant impact on global development of atherosclerosis, although at 0.3 Gy effects were limited to the descending thoracic aorta. Our data suggest that a moderate dose of 0.3 Gy can have persistent detrimental effects on the cardiovascular system, and that a high dose of 6 Gy poses high risks at both high and low dose rates. Our results were clearly nonlinear with dose, suggesting that lower doses may be more damaging than predicted by a linear dose response. PMID:26359350

  6. Macrophage depletion ameliorates nephritis induced by pathogenic antibodies

    PubMed Central

    Chalmers, Samantha A.; Chitu, Violeta; Herlitz, Leal C.; Sahu, Ranjit; Stanley, E. Richard; Putterman, Chaim

    2014-01-01

    Objective Kidney involvement affects 40–60% of patients with lupus and is responsible for significant morbidity and mortality. Using depletion approaches, several studies have suggested that macrophages may play a key role in the pathogenesis of lupus nephritis. However, “off target” effects of macrophage depletion, such as altered hematopoiesis or enhanced autoantibody production, impeded the determination of a conclusive relationship. Methods In this study, we investigated the role of macrophages in mice receiving rabbit anti-glomerular antibodies, or nephrotoxic serum (NTS), an experimental model which closely mimics the immune complex mediated disease seen in murine and human lupus nephritis. GW2580, a selective inhibitor of the colony stimulating factor-1 (CSF-1) receptor kinase, was used for macrophage depletion. Results We found that GW2580-treated, NTS challenged mice did not develop the increased levels of proteinuria, serum creatinine, or serum urea seen in control-treated, NTS challenged mice. NTS challenged mice exhibited significantly increased kidney expression of inflammatory cytokines including RANTES, IP-10, VCAM-1 and iNOS, whereas GW2580-treated mice were protected from the robust expression of these inflammatory cytokines that are associated with LN. Quantification of macrophage related gene expression, flow cytometry analysis of kidney single cell suspensions, and immunofluorescence staining confirmed the depletion of macrophages in GW2580-treated mice, specifically within renal glomeruli. Conclusions Our results strongly implicate a specific and necessary role for macrophages in the development of immune glomerulonephritis mediated by pathogenic antibodies, and support the development of macrophage targeting approaches for the treatment of lupus nephritis. PMID:25554644

  7. Vascular Access Port Implantation and Serial Blood Sampling in a Gottingen Minipig (Sus scrofa domestica) Model of Acute Radiation Injury

    PubMed Central

    Moroni, Maria; Coolbaugh, Thea V; Mitchell, Jennifer M; Lombardini, Eric; Moccia, Krinon D; Shelton, Larry J; Nagy, Vitaly; Whitnall, Mark H

    2011-01-01

    Threats of nuclear and other radiologic exposures have been increasing, but no countermeasure for acute radiation syndrome has been approved by regulatory authorities. Because of their similarity to humans in regard to physiology and anatomy, we are characterizing Gottingen minipigs as a model to aid the development of radiation countermeasures. Irradiated minipigs exhibit immunosuppression, severe thrombocytopenia, vascular leakage, and acute inflammation. These complications render serial acquisition of blood samples problematic. Vascular access ports (VAP) facilitate serial sampling, but their use often is complicated by infections and fibrin deposition. We demonstrate here the successful use of VAP for multiple blood samplings in irradiated minipigs. Device design and limited postoperative prophylactic antimicrobial therapy before irradiation were key to obtaining serial sampling, reducing swelling, and eliminating infection and skin necrosis at the implantation site. Modifications of previous protocols included the use of polydioxanone sutures instead of silk; eliminating chronic port access; single-use, sterile, antireflux prefilled syringes for flushing; strict aseptic weekly maintenance of the device, and acclimating animals to reduce stress. VAP remained functional in 19 of 20 irradiated animals for as long as 3 mo. The remaining VAP failed due to a small leak in the catheter, leading to clot formation. VAP-related sepsis occurred in 2 minipigs. Blood sampling did not cause detectable stress in nonanesthetized sham-irradiated animals, according to leukograms and clinical signs. PMID:21333166

  8. Comparative proteomic profiling and possible toxicological mechanism of acute injury induced by carbon ion radiation in pubertal mice testes

    NASA Astrophysics Data System (ADS)

    Zhang, Hong

    2016-07-01

    We investigated potential mechanisms of acute injury in pubertal mice testes after exposure to carbon ion radiation (CIR). Serum testosterone was measured following whole-body irradiation with a 2Gy carbon ion beam. Comparative proteomic profiling and Western blotting were applied to identify potential biomarkers and measure protein expression, and terminal dUTP nick end-labeling (TUNEL) was performed to detect apoptotic cells. Immunohistochemistry and immunofluorescence were used to investigate protein localization. Serum testosterone was lowest at 24h after CIR, and 10 differentially expressed proteins were identified at this time point that included eIF4E, an important regulator of initiation that combines with mTOR and 4EBP1 to control protein synthesis via the mTOR signalling pathway during proliferation and apoptosis. Protein expression and localization studies confirmed their association with acute injury following exposure to CIR. These three proteins may be useful molecular markers for detecting abnormal spermatogenesis following exposure to environmental and cosmic radiation

  9. Chemokines and Chemokine Receptors in the Development of Lupus Nephritis

    PubMed Central

    2016-01-01

    Lupus nephritis (LN) is a major cause of morbidity and mortality in the patients with systemic lupus erythematosus (SLE), an autoimmune disease with damage to multiple organs. Leukocyte recruitment into the inflamed kidney is a critical step to promote LN progression, and the chemokine/chemokine receptor system is necessary for leukocyte recruitment. In this review, we summarize recent studies on the roles of chemokines and chemokine receptors in the development of LN and discuss the potential and hurdles of developing novel, chemokine-based drugs to treat LN. PMID:27403037

  10. Ataxia Telangiectasia–Mutated Gene Polymorphisms and Acute Normal Tissue Injuries in Cancer Patients After Radiation Therapy: A Systematic Review and Meta-analysis

    SciTech Connect

    Dong, Lihua; Cui, Jingkun; Tang, Fengjiao; Cong, Xiaofeng; Han, Fujun

    2015-04-01

    Purpose: Studies of the association between ataxia telangiectasia–mutated (ATM) gene polymorphisms and acute radiation injuries are often small in sample size, and the results are inconsistent. We conducted the first meta-analysis to provide a systematic review of published findings. Methods and Materials: Publications were identified by searching PubMed up to April 25, 2014. Primary meta-analysis was performed for all acute radiation injuries, and subgroup meta-analyses were based on clinical endpoint. The influence of sample size and radiation injury incidence on genetic effects was estimated in sensitivity analyses. Power calculations were also conducted. Results: The meta-analysis was conducted on the ATM polymorphism rs1801516, including 5 studies with 1588 participants. For all studies, the cut-off for differentiating cases from controls was grade 2 acute radiation injuries. The primary meta-analysis showed a significant association with overall acute radiation injuries (allelic model: odds ratio = 1.33, 95% confidence interval: 1.04-1.71). Subgroup analyses detected an association between the rs1801516 polymorphism and a significant increase in urinary and lower gastrointestinal injuries and an increase in skin injury that was not statistically significant. There was no between-study heterogeneity in any meta-analyses. In the sensitivity analyses, small studies did not show larger effects than large studies. In addition, studies with high incidence of acute radiation injuries showed larger effects than studies with low incidence. Power calculations revealed that the statistical power of the primary meta-analysis was borderline, whereas there was adequate power for the subgroup analysis of studies with high incidence of acute radiation injuries. Conclusions: Our meta-analysis showed a consistency of the results from the overall and subgroup analyses. We also showed that the genetic effect of the rs1801516 polymorphism on acute radiation injuries was

  11. Treatment of acute pancreatitis with mexidol and low-intensity laser radiation

    NASA Astrophysics Data System (ADS)

    Parzyan, G. R.; Geinits, A. V.

    2001-04-01

    This article presents the results of treatment of 54 patients with acute pancreatitis. The patients were divided into two groups according to the method of treatment. The control group (26 patients) received a conventional therapy, whereas the experimental group (28 patients) received mexidol in combination with the intravenous laser irradiation of blood. Clinical and laboratory tests confirmed a high efficiency of the combined therapy based on the administration of mexidol antioxidant and low-intensity (lambda) equals 0.63 micrometers diode laser irradiation of blood. This therapeutic technique produced an influence on the basic pathogenetic mechanisms of acute pancreatitis. The application of this method of treatment improved the course and prognosis of acute pancreatitis.

  12. Skin infections and immunoglobulin A in serum, sweat, and saliva of patients recovered from poststreptococcal acute glomerulonephritis or acute rheumatic fever and their siblings.

    PubMed

    Potter, E V; Vincente, J B; Mayon-WHite, R T; Shaughnessy, M A; Poon-King, T; Earle, D P

    1982-06-01

    Differences in hygienic habits and base-line secretory immunoglobulin (Ig) A which might have contributed to the prevalence of skin infections and/or absence of increased serum IgA values were sought in patients with poststreptococcal acute glomerulonephritis (nephritis) in contrast to patients with acute rheumatic fever in Trinidad by studying patients and their siblings after the patients had recovered from these diseases. The overall history of skin infections was similar at this time in all groups, although they had been much more common in patients with nephritis and their families at the time of acute illness. The recovered nephritis patients bathed slightly less often than the other individuals, used a cream or lotion after bathing rather than coconut oil, and tended to sweat less than the others, but none of these differences was statistically significant. Neither were significant differences demonstrated in amounts of IgA and IgG in serum and saliva of recovered nephritis patients and their siblings compared to recovered rheumatic fever patients and their siblings, while only small amounts of IgA and IgG were present in any sweat, and probably had been transuded rather than secreted. These studies suggest that the lower serum IgA titers in patients with nephritis compared to patients with rheumatic fever in Trinidad do not reflect basic differences in serum IgA or secretory IgA as measured in saliva, and that IgA is not secreted by the eccrine glands.

  13. Acute adverse effects of radiation therapy on HIV-positive patients in Japan: study of 31 cases at Tokyo Metropolitan Komagome Hospital.

    PubMed

    Kaminuma, Takuya; Karasawa, Katsuyuki; Hanyu, Nahoko; Chang, Ta-Chen; Kuga, Gencho; Okano, Naoko; Kubo, Nobuteru; Okuma, Yusuke; Nagata, Yasunobu; Maeda, Yoshiharu; Ajisawa, Atsushi

    2010-01-01

    Recently, the number of human immunodeficiency virus (HIV) -positive patients has increased in Japan. HIV-positive patients are at a higher risk of cancer than the general population. This paper retrospectively reports the acute adverse effects of radiation therapy on HIV-positive patients who were treated at Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital (TMCICK). Thirty-one cases involving 24 HIV-positive cancer patients who were treated at TMCICK from January 1997 to March 2009 were included in this study. All acute adverse effects of radiation therapy were examined during, and one month after, the last radiation therapy session. Acute adverse effects were classified according to the site of radiation therapy treatment and analyzed using the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. Grade 3 acute adverse effects were seen in 17% of cases, and Grade 2 toxicities were found in 23% of patients. Damage to the skin and mucosa, including stomatitis or diarrhea, tended to occur after low-dose radiation therapy; however, no severe acute adverse effects were seen in other organs, such as the brain, lung, and bone. Acute adverse effects tended to occur earlier in HIV-positive patients and became severe more frequently than in the general population. In particular, disorders of the mucosa, such as those of the oral cavity, pharynx, and intestine, tended to occur rapidly. It was shown that radiation therapy is safe when treatment is performed carefully and that it is a very useful treatment for cancer in HIV-positive patients.

  14. Acute Hematological Effects in Mice Exposed to the Expected Doses, Dose-rates, and Energies of Solar Particle Event-like Proton Radiation

    PubMed Central

    Sanzari, Jenine K.; Cengel, Keith A.; Wan, X. Steven; Rusek, Adam; Kennedy, Ann R.

    2014-01-01

    NASA has funded several projects that have provided evidence for the radiation risk in space. One radiation concern arises from solar particle event (SPE) radiation, which is composed of energetic electrons, protons, alpha particles and heavier particles. SPEs are unpredictable and the accompanying SPE radiation can place astronauts at risk of blood cell death, contributing to a weakened immune system and increased susceptibility to infection. The doses, dose rates, and energies of the proton radiation expected to occur during a SPE have been simulated at the NASA Space Radiation Laboratory, Brookhaven National Laboratory, delivering total body doses to mice. Hematological values were evaluated at acute time points, up to 24 hrs. post-radiation exposure. PMID:25202654

  15. Therapeutics interventions with anti-inflammatory creams in post radiation acute skin reactions: a systematic review of most important clinical trials.

    PubMed

    Koukourakis, Georgios V; Kelekis, Nikolaos; Kouvaris, John; Beli, Ivelina K; Kouloulias, Vassilios E

    2010-06-01

    The majority of cancer patients will receive radiation therapy treatment at some stage during their malignancy. An acute skin reaction represents a common post radiation side effect with different grade of severity. In order to investigate the optimal methods to prevent and manage acute skin reactions related to radiation therapy we have conducted a systematic review on this topic. It seems that skin washing, including gentle washing with water alone with or without mild soap, should be permitted in patients receiving radiation therapy, to prevent acute skin reaction. In addition, a low dose (i.e., 1%) corticosteroid cream may be beneficial in the reduction of itching and irritation. We have concluded that there is insufficient evidence to support or refute specific topical or oral agents for the prevention or management of acute skin reaction. There is a need for further research to review treatments that have produced promising results in the reviewed research studies and to evaluate other commonly recommended topical treatments. The purpose of this patent and literature review is to advocate the current management of acute skin reaction.

  16. Combined exposure to simulated microgravity and acute or chronic radiation reduces neuronal network integrity and cell survival

    NASA Astrophysics Data System (ADS)

    Benotmane, Rafi

    During orbital or interplanetary space flights, astronauts are exposed to cosmic radiations and microgravity. This study aimed at assessing the effect of these combined conditions on neuronal network density, cell morphology and survival, using well-connected mouse cortical neuron cultures. To this end, neurons were exposed to acute low and high doses of low LET (X-rays) radiation or to chronic low dose-rate of high LET neutron irradiation (Californium-252), under the simulated microgravity generated by the Random Positioning Machine (RPM, Dutch space). High content image analysis of cortical neurons positive for the neuronal marker βIII-tubulin unveiled a reduced neuronal network integrity and connectivity, and an altered cell morphology after exposure to acute/chronic radiation or to simulated microgravity. Additionally, in both conditions, a defect in DNA-repair efficiency was revealed by an increased number of γH2AX-positive foci, as well as an increased number of Annexin V-positive apoptotic neurons. Of interest, when combining both simulated space conditions, we noted a synergistic effect on neuronal network density, neuronal morphology, cell survival and DNA repair. Furthermore, these observations are in agreement with preliminary gene expression data, revealing modulations in cytoskeletal and apoptosis-related genes after exposure to simulated microgravity. In conclusion, the observed in vitro changes in neuronal network integrity and cell survival induced by space simulated conditions provide us with mechanistic understanding to evaluate health risks and the development of countermeasures to prevent neurological disorders in astronauts over long-term space travels. Acknowledgements: This work is supported partly by the EU-FP7 projects CEREBRAD (n° 295552)

  17. Glomerular, tubular and interstitial nephritis associated with non-steroidal antiinflammatory drugs. Evidence of a common mechanism

    PubMed Central

    Ravnskov, Uffe

    1999-01-01

    Aims To study the mechanisms behind NSAID-associated nephropathy. Methods Analysis of published case reports satisfying strict criteria for NSAID nephropathy. Results Ninety-seven cases with acute nephritis (AN; 19 patients), minimal change nephropathy (MC; 38 patients), membranous glomerulonephritis (MGN; 19 patients), focal sclerosis (FS; 13 patients) and other glomerulonephritis subgroups (8 patients) were identified. Hypersensitivity reactions were seen in all groups, most often in AN. Proteinuria was more severe in MC and FS than in MGN and unrelated to amount of glomerular deposits. The mean NSAID treatment time was 1.7 months in AN, 8.2 months in MC and 39 months in MGN and associated with amount of glomerular deposits, fusion of podocytes and proteinuria, and inversely associated with hypersensitivity, interstitial damage and renal failure. Rheumatic diseases were common in MGN. At follow-up 68 of 72 patients who had discontinued NSAID treatment had improved, 57 with normal renal function. Conclusions NSAID nephropathy may be caused by hypersensitivity. The reaction is milder than in drug-induced acute tubulointerstitial nephritis, probably because the offending drug inhibits the inflammatory reaction it has started itself. Heavy proteinuria is probably due to lymphokines produced as a result of the immunological response. If the allergic reaction is strong, AN is produced rapidly with severe renal failure but little proteinuria; if it is less violent, immunocompetent cells may develop to produce lymphokines and proteinuria. Immune complexes may be formed eventually, secondary to the increased glomerular permeability, more easily in patients with a hyperactive immune system and with little consequence for renal function. PMID:10190656

  18. Acute Radiation-Induced Nocturia in Prostate Cancer Patients Is Associated With Pretreatment Symptoms, Radical Prostatectomy, and Genetic Markers in the TGF{beta}1 Gene

    SciTech Connect

    De Langhe, Sofie; De Ruyck, Kim; Ost, Piet; Fonteyne, Valerie; Werbrouck, Joke; De Meerleer, Gert; De Neve, Wilfried; Thierens, Hubert

    2013-02-01

    Purpose: After radiation therapy for prostate cancer, approximately 50% of the patients experience acute genitourinary symptoms, mostly nocturia. This may be highly bothersome with a major impact on the patient's quality of life. In the past, nocturia is seldom reported as a single, physiologically distinct endpoint, and little is known about its etiology. It is assumed that in addition to dose-volume parameters and patient- and therapy-related factors, a genetic component contributes to the development of radiation-induced damage. In this study, we investigated the association among dosimetric, clinical, and TGF{beta}1 polymorphisms and the development of acute radiation-induced nocturia in prostate cancer patients. Methods and Materials: Data were available for 322 prostate cancer patients treated with primary or postoperative intensity modulated radiation therapy (IMRT). Five genetic markers in the TGF{beta}1 gene (-800 G>A, -509 C>T, codon 10 T>C, codon 25 G>C, g.10780 T>G), and a high number of clinical and dosimetric parameters were considered. Toxicity was scored using an symptom scale developed in-house. Results: Radical prostatectomy (P<.001) and the presence of pretreatment nocturia (P<.001) are significantly associated with the occurrence of radiation-induced acute toxicity. The -509 CT/TT (P=.010) and codon 10 TC/CC (P=.005) genotypes are significantly associated with an increased risk for radiation-induced acute nocturia. Conclusions: Radical prostatectomy, the presence of pretreatment nocturia symptoms, and the variant alleles of TGF{beta}1 -509 C>T and codon 10 T>C are identified as factors involved in the development of acute radiation-induced nocturia. These findings may contribute to the research on prediction of late nocturia after IMRT for prostate cancer.

  19. Pathological Significance of a Panel of Urinary Biomarkers in Patients with Drug-Induced Tubulointerstitial Nephritis

    PubMed Central

    Wu, Yu; Yang, Li; Su, Tao; Wang, Chen; Liu, Gang

    2010-01-01

    Background and objectives: Although a renal biopsy is indispensable for depicting the severity of pathologic lesions in drug-induced tubulointerstitial nephritis (DTIN), it is not acceptable in some cases and cannot be performed serially because of its invasive nature. Therefore, the discovery of noninvasive markers that are closely related to the pathology of DTIN is of great value. Design, setting, participants, & measurements: In this study, the urinary levels of monocyte chemotactic peptide-1 (MCP-1), neutrophil gelatinase-associated lipocalin (NGAL), N-acetyl-β-d-glucosaminidase, and α1-microglobulin were measured in 40 DTIN subjects, and the performances of these parameters for distinguishing different pathologic lesions were compared. Results: Linear correlation and receiver operating characteristic curve analyses showed that urinary MCP-1 levels were able to identify serious interstitial edema and inflammatory infiltration with greater accuracy than the other biomarkers (r = 0.501, P < 0.001 and r = 0.768, P < 0.001, respectively), whereas urinary NGAL levels showed the highest correlation coefficient with tubular atrophy (r = 0.692, P < 0.001). Conclusions: These results suggest that these biomarker levels were higher in patients with DTIN than in controls. Urinary MCP-1 levels correlated and were predictive of the gradated severity of acute lesions in DTIN, whereas the roles of NGAL and α1-microglobulin in chronic alterations require further study. PMID:20813857

  20. Rifampin-associated tubulointersititial nephritis and Fanconi syndrome presenting as hypokalemic paralysis

    PubMed Central

    2013-01-01

    Background Rifampin is one of the most important drugs in first-line therapies for tuberculosis. The renal toxicity of rifampin has been reported sporadically and acute tubulointerstitial nephritis (ATIN) is a frequent histological finding. We describe for the first time a case of ATIN and Fanconi syndrome presenting as hypokalemic paralysis, associated with the use of rifampin. Case presentation A 42-year-old man was admitted with sudden-onset lower extremity paralysis and mild renal insufficiency. He had been treated for pulmonary tuberculosis with isoniazid, rifampin, and ethambutol for 2 months. Laboratory tests revealed proteinuria, profound hypokalemia, hyperchloremic metabolic acidosis with a normal anion gap, positive urine anion gap, hypophosphatemia with hyperphosphaturia, hypouricemia with hyperuricosuria, glycosuria with normal serum glucose level, generalized aminoaciduria, and β2-microglobulinuria. A kidney biopsy revealed findings typical of ATIN and focal granular deposits of immunoglubulin A and complement 3 in the glomeruli and tubules. Electron microscopy showed epithelial foot process effacement and electron-dense deposits in the subendothelial and mesangial spaces. Cessation of rifampin resolved the patient’s clinical presentation of Fanconi syndrome, and improved his renal function and proteinuria. Conclusion This case demonstrates that rifampin therapy can be associated with Fanconi syndrome presenting as hypokalemic paralysis, which is a manifestation of ATIN. Kidney function and the markers of proximal tubular injury should be carefully monitored in patients receiving rifampin. PMID:23320835

  1. Treatment of intractable lupus nephritis with total lymphoid irradiation

    SciTech Connect

    Strober, S.; Field, E.; Hoppe, R.T.; Kotzin, B.L.; Shemesh, O.; Engleman, E.; Ross, J.C.; Myers, B.D.

    1985-04-01

    Ten patients with lupus nephritis and marked proteinuria (3.9 g or more/d) that did not respond adequately to treatment with prednisone alone or prednisone in combination with azathioprine were treated with total lymphoid irradiation in an uncontrolled feasibility study. Within 6 weeks after the start of total lymphoid irradiation, the serum albumin level rose in all patients in association with a reduction in the serum level of anti-DNA antibodies, an increase in the serum complement level, or both. Improvement in these variables persisted in eight patients followed for more than 1 year, with the stabilization or reduction of the serum creatinine level. Urinary leakage of albumin was substantially reduced in all patients. Side effects associated with radiotherapy included transient constitutional complaints in ten patients, transient blood element depressions in three, localized viral and bacterial infections in four, and ovarian failure in one. The results suggest that total lymphoid irradiation may provide an alternative to cytotoxic drugs in the treatment of lupus nephritis.

  2. Lupus nephritis reoccurs following transplantation in the lupus prone mouse.

    PubMed

    Hamar, P; Wang, M; Godo, M; Kokeny, G; Rosivall, L; Ouyang, N; Heemann, U

    2010-02-01

    The incidence and pathomechanism of recurrent lupus nephritis (RLN) after transplantation is not clearly understood. Burning out of the autoimmune process or local immunoregulatory mechanisms in the kidney may be responsible for the low incidence of recurrence. These mechanisms cannot be investigated in human subjects, due to post-transplant immunosuppression. To investigate the pathomechanisms of RLN, male and female kidneys were transplanted from FAS deficient lupus prone (LPR) or control (FAS intact) MRL mice into either LPR or MRL recipients. Urinary protein and blood urea were assessed. Double negative (DN) lymphocyte proliferation was determined by flow cytometry. Two months after transplantation inflammatory infiltration of the glomerular, vascular and interstitial compartments were determined. Renal function as demonstrated by blood urea levels was normal in MRL recipients, but elevated in LPR recipients, independent of the donor strain. Paralleling functional results, inflammatory infiltration was mild or absent in MRL recipients of MRL grafts, and mild to moderate in MRL recipients of LPR grafts, suggesting that kidney removal from the autoimmune (LPR) environment significantly reduced inflammation. Graft infiltration was most severe in LPR recipients: grafts were similarly inflamed independent of the donor. All LPR recipients had significantly less CD4+ Th cells versus MRL mice. Transplantation of LPR grafts into MRL recipients reduced CD4+ Th cell percentage, accompanied by a slight induction of lupus autoantibody production. Our results demonstrate that lupus nephritis is not kidney specific in the LPR model with recurrence after transplantation in the absence of immunosuppression.

  3. Comprehensive Evaluation of Personal, Clinical, and Radiation Dosimetric Parameters for Acute Skin Reaction during Whole Breast Radiotherapy

    PubMed Central

    Yang, Dae Sik; Lee, Jung Ae; Lee, Nam Kwon; Park, Young Je; Lee, Suk; Kim, Chul Yong; Son, Gil Soo

    2016-01-01

    Skin reaction is major problem during whole breast radiotherapy. To identify factors related to skin reactions during whole breast radiotherapy, various personal, clinical, and radiation dosimetric parameters were evaluated. From January 2012 to December 2013, a total of 125 patients who underwent breast conserving surgery and adjuvant whole breast irradiation were retrospectively reviewed. All patients had both whole breast irradiation and boost to the tumour bed. Skin reaction was measured on the first day of boost therapy based on photography of the radiation field and medical records. For each area of axilla and inferior fold, the intensity score of erythema (score 1 to 5) and extent (score 0 to 1) were summed. The relationship of various parameters to skin reaction was evaluated using chi-square and linear regression tests. The V100 (volume receiving 100% of prescribed radiation dose, p < 0.001, both axilla and inferior fold) and age (p = 0.039 for axilla and 0.026 for inferior fold) were significant parameters in multivariate analyses. The calculated axilla dose (p = 0.003) and breast separation (p = 0.036) were also risk factors for axilla and inferior fold, respectively. Young age and large V100 are significant factors for acute skin reaction that can be simply and cost-effectively measured. PMID:27579310

  4. Comprehensive Evaluation of Personal, Clinical, and Radiation Dosimetric Parameters for Acute Skin Reaction during Whole Breast Radiotherapy.

    PubMed

    Yang, Dae Sik; Lee, Jung Ae; Yoon, Won Sup; Lee, Nam Kwon; Park, Young Je; Lee, Suk; Kim, Chul Yong; Son, Gil Soo

    2016-01-01

    Skin reaction is major problem during whole breast radiotherapy. To identify factors related to skin reactions during whole breast radiotherapy, various personal, clinical, and radiation dosimetric parameters were evaluated. From January 2012 to December 2013, a total of 125 patients who underwent breast conserving surgery and adjuvant whole breast irradiation were retrospectively reviewed. All patients had both whole breast irradiation and boost to the tumour bed. Skin reaction was measured on the first day of boost therapy based on photography of the radiation field and medical records. For each area of axilla and inferior fold, the intensity score of erythema (score 1 to 5) and extent (score 0 to 1) were summed. The relationship of various parameters to skin reaction was evaluated using chi-square and linear regression tests. The V 100 (volume receiving 100% of prescribed radiation dose, p < 0.001, both axilla and inferior fold) and age (p = 0.039 for axilla and 0.026 for inferior fold) were significant parameters in multivariate analyses. The calculated axilla dose (p = 0.003) and breast separation (p = 0.036) were also risk factors for axilla and inferior fold, respectively. Young age and large V 100 are significant factors for acute skin reaction that can be simply and cost-effectively measured. PMID:27579310

  5. Collective radiation biodosimetry for dose reconstruction of acute accidental exposures: a review.

    PubMed Central

    Pass, B

    1997-01-01

    Quantification of the biologically relevant dose is required to establish cause and effect between radiation detriment or burden and important biological outcomes. Most epidemiologic studies of unanticipated radiation exposure fail to establish cause and effect because researchers have not been able to construct a valid quantification of dose for the exposed population. However, no one biodosimetric technique (biophysical or biological) meets all the requirements of an ideal dosimeter. This paper reviews how the collection of biodosimetric data for victims of radiation accidents can be used to create a dosimetric "gold standard." Particular emphasis is placed on the use of electron spin resonance, a standard for radiation accident dosimetry. As an example of this technique, a review will be presented of a previously reported study of an individual exposed to a 60Co sterilization source. PMID:9467051

  6. The effect of acute dose charge particle radiation on expression of DNA repair genes in mice.

    PubMed

    Tariq, Muhammad Akram; Soedipe, Ayodotun; Ramesh, Govindarajan; Wu, Honglu; Zhang, Ye; Shishodia, Shishir; Gridley, Daila S; Pourmand, Nader; Jejelowo, Olufisayo

    2011-03-01

    The space radiation environment consists of trapped particle radiation, solar particle radiation, and galactic cosmic radiation (GCR), in which protons are the most abundant particle type. During missions to the moon or to Mars, the constant exposure to GCR and occasional exposure to particles emitted from solar particle events (SPE) are major health concerns for astronauts. Therefore, in order to determine health risks during space missions, an understanding of cellular responses to proton exposure is of primary importance. The expression of DNA repair genes in response to ionizing radiation (X-rays and gamma rays) has been studied, but data on DNA repair in response to protons is lacking. Using qPCR analysis, we investigated changes in gene expression induced by positively charged particles (protons) in four categories (0, 0.1, 1.0, and 2.0 Gy) in nine different DNA repair genes isolated from the testes of irradiated mice. DNA repair genes were selected on the basis of their known functions. These genes include ERCC1 (5' incision subunit, DNA strand break repair), ERCC2/NER (opening DNA around the damage, Nucleotide Excision Repair), XRCC1 (5' incision subunit, DNA strand break repair), XRCC3 (DNA break and cross-link repair), XPA (binds damaged DNA in preincision complex), XPC (damage recognition), ATA or ATM (activates checkpoint signaling upon double strand breaks), MLH1 (post-replicative DNA mismatch repair), and PARP1 (base excision repair). Our results demonstrate that ERCC1, PARP1, and XPA genes showed no change at 0.1 Gy radiation, up-regulation at 1.0 Gy radiation (1.09 fold, 7.32 fold, 0.75 fold, respectively), and a remarkable increase in gene expression at 2.0 Gy radiation (4.83 fold, 57.58 fold and 87.58 fold, respectively). Expression of other genes, including ATM and XRCC3, was unchanged at 0.1 and 1.0 Gy radiation but showed up-regulation at 2.0 Gy radiation (2.64 fold and 2.86 fold, respectively). We were unable to detect gene expression for the

  7. Emetic mechanism in acute radiation sickness. Technical report, 1 December 1982-30 November 1986

    SciTech Connect

    Borison, H.L.

    1987-08-20

    A dose-response relationship was established in normal cats for the evocation of vomiting within 24 h after whole-body exposure to /sup 60/Co radiation with doses ranging from 7.5 to 60 Gy delivered at 1.0 Gy/min. Vomiting was recorded oscillographically. Radiation-induced vomiting was elicited unabatedly at the optimal dose of 45 Gy in chronically postremectomized cats. Radioemetic susceptibility was evaluated in normal cats after each of two doses of radiation, from 7.5 to 60 Gy, given on successive days. Occurrence of radioemetic protection against the second irradiation was manifested in direct relation to the magnitude of the first exposure, and complete protection for 24 h resulted after second radiation exposure at the highest dose level. Postremectomized cats were also fully protected against the radioemetic effect of a second exposure at 45 Gy. All normal cats vomited in response to an emetic drug injection during the state of radioemetic refractoriness after the second irradiation at 45 Gy. A neural origin of emetic signal generated by first radiation exposure was examined in postrema-intact cats.

  8. Effects of acute low doses of gamma-radiation on erythrocytes membrane.

    PubMed

    Mahmoud, Sherif S; El-Sakhawy, Eman; Abdel-Fatah, Eman S; Kelany, Adel M; Rizk, Rizk M

    2011-03-01

    It is believed that any dose of ionizing radiation may damage cells and that the mutated cells could develop into cancer cells. Additionally, results of research performed over the past century on the effects of low doses of ionizing radiation on biological organisms show beneficial health effects, called hormesis. Much less is known about the cellular response to low doses of ionizing radiation, such as those typical for medical diagnostic procedures, normal occupational exposures or cosmic-ray exposures at flight altitudes. Extrapolating from the effects observed at higher doses to predict changes in cells after low-dose exposure is problematic. We examined the biological effects of low doses (0.01-0.3 Gy) of γ-radiation on the membrane characteristics of erythrocytes of albino rats and carried out osmotic fragility tests and Fourier transform infrared spectroscopy (FTIR). Our results indicate that the lowest three doses in the investigated radiation range, i.e., 0.01, 0.025 and 0.05 Gy, resulted in positive effects on the erythrocyte membranes, while a dose of 0.1 Gy appeared to represent the limiting threshold dose of those positive effects. Doses higher than 0.1 Gy were associated with the denaturation of erythrocyte proteins. PMID:20865271

  9. Genetic predictors of acute toxicities related to radiation therapy following lumpectomy for breast cancer: a case-series study

    PubMed Central

    Ambrosone, Christine B; Tian, Chunqiao; Ahn, Jiyoung; Kropp, Silke; Helmbold, Irmgard; von Fournier, Dietrich; Haase, Wulf; Sautter-Bihl, Marie Luise; Wenz, Frederik; Chang-Claude, Jenny

    2006-01-01

    Introduction The cytotoxic effects of radiation therapy are mediated primarily through increased formation of hydroxyl radicals and reactive oxygen species, which can damage cells, proteins and DNA; the glutathione S-transferases (GSTs) function to protect against oxidative stress. We hypothesized that polymorphisms encoding reduced or absent activity in the GSTs might result in greater risk for radiation-associated toxicity. Methods Women receiving therapy in radiation units in Germany following lumpectomy for breast cancer (1998–2001) provided a blood sample and completed an epidemiological questionnaire (n = 446). Genotypes were determined using Sequonom MALDI-TOF (GSTA1, GSTP1) and Masscode (GSTM1, GSTT1). Biologically effective radiotherapy dose (BED) was calculated, accounting for differences in fractionation and overall treatment time. Side effects considered were grade 2c and above, as classified using the modified Common Toxicity Criteria. Predictors of toxicity were modelled using Cox regression models in relation to BED, with adjustment for treating clinic, photon field, beam energy and boost method, and potential confounding variables. Results Low activity GSTP1 genotypes were associated with a greater than twofold increase in risk for acute skin toxicities (adjusted hazard ratio 2.28, 95% confidence interval 1.04–4.99). No associations were noted for the other GST genotypes. Conclusion These data indicate that GSTP1 plays an important role in protecting normal cells from damage associated with radiation therapy. Studies examining the effects of GSTP1 polymorphisms on toxicity, recurrence and survival will further inform individualized therapeutics based on genotypes. PMID:16848913

  10. Symptomatology of acute radiation effects in humans after exposure to doses of 0. 5-30 Gy

    SciTech Connect

    Anno, G.H.; Baum, S.J.; Withers, H.R.; Young, R.W. )

    1989-06-01

    This article distills from available data descriptions of typical human symptoms in reaction to prompt total-body ionizing radiation in the dose range 0.5 to 30 Gy midline body tissue. The symptoms are correlated with dose and time over the acute postexposure period of 6 wk. The purpose is to provide a symptomatology basis for assessing early functional impairment of individuals who may be involved in civil defense, emergency medical care and various military activities in the event of a nuclear attack. The dose range is divided into eight subranges associated with important pathophysiological events. For each subrange, signs and symptoms are designated including estimates of symptom onset, severity, duration and incidence.

  11. Mitigation of the Hematopoietic and Gastrointestinal Acute Radiation Syndrome by Octadecenyl Thiophosphate, a Small Molecule Mimic of Lysophosphatidic Acid

    PubMed Central

    Deng, Wenlin; Kimura, Yasuhiro; Gududuru, Veeresh; Wu, Wenjie; Balogh, Andrea; Szabo, Erzsebet; Thompson, Karin Emmons; Yates, C. Ryan; Balazs, Louisa; Johnson, Leonard R.; Miller, Duane D.; Strobos, Jur; McCool, W. Shannon; Tigyi, Gabor J.

    2015-01-01

    We have previously demonstrated that the small molecule octadecenyl thiophosphate (OTP), a synthetic mimic of the growth factor-like mediator lysophosphatidic acid (LPA), showed radioprotective activity in a mouse model of total-body irradiation (TBI) when given orally or intraperitoneally 30 min before exposure to 9 Gy γ radiation. In the current study, we evaluated the effects of OTP, delivered subcutaneously, for radioprotection or radiomitigation from −24 h before to up to +72 h postirradiation using a mouse TBI model with therapeutic doses at around 1 mg/kg. OTP was injected at 10 mg/kg without observable toxic side effects in mice, providing a comfortable safety margin. Treatment of C57BL/6 mice with a single dose of OTP over the time period from −12 h before to +26 h after a lethal dose of TBI reduced mortality by 50%. When administered at +48 h to +72 h postirradiation (LD50/30 to LD100/30), OTP reduced mortality by ≥34%. OTP administered at +24 h postirradiation significantly elevated peripheral white blood cell and platelet counts, increased crypt survival in the jejunum, enhanced intestinal glucose absorption and reduced endotoxin seepage into the blood. In the 6.4–8.6 Gy TBI range using LD50/10 as the end point, OTP yielded a dose modification factor of 1.2. The current data indicate that OTP is a potent radioprotector and radiomitigator ameliorating the mortality and tissue injury of acute hematopoietic as well as acute gastrointestinal radiation syndrome. PMID:25807318

  12. BM-16INCREASED ACUTE RADIATION EFFECT (ARE) WITH IPILUMUMAB AND RADIOSURGERY IN PATIENTS WITH MELANOMA BRAIN METASTASES

    PubMed Central

    Khoja, Leila; Kurtz, Goldie; Zadeh, Gelareh; Laperriere, Normand; Menard, Cynthia; Millar, Barbara-Ann; Bernstein, Mark; Kongkham, Paul; Joshua, Anthony; Hogg, David; Butler, Marcus; Chung, Caroline

    2014-01-01

    BACKGROUND: Ipilumumab (Ipi), an antibody that enhances T-cell activation, has been shown to improve survival in patients with metastatic melanoma. Ipilumumab may have synergistic effects with radiotherapy but this may result in increased toxicity. This study investigated the incidence of acute radiation effect (ARE) in patients with melanoma brain metastases treated with Ipi and radiosurgery (SRS) or whole brain radiotherapy (WBRT). METHODOLOGY: This retrospective study included metastatic melanoma patients treated at our institution from 2008-2013 who received SRS or WBRT for brain metastases within 4 months of Ipi treatment. We evaluated the incidence, timing and factors associated with acute radiation effect (ARE). RESULTS: From 159 patients treated with Ipi, 22 patients also received brain RT within 4 months of treatment. Three patients were excluded for lack of follow-up brain imaging, thus 19 were analysed: 14 males and 5 females, with median age 58 years (range 24-82). Ten were treated with SRS, 7 with WBRT, and 2 with SRS plus WBRT. Median dose for SRS was 21 Gy (range: 15-24 Gy). Five of 13 patients treated with SRS (38%) experienced symptomatic edema requiring steroids within 1 month of starting Ipi, and within 4 months of RT. One patient had a haemorrhage and 1 required surgical resection, which demonstrated viable disease. Therefore 3 patients (23%) treated with SRS developed isolated ARE. These metastases had volumes less than 4.2 cm3 and were treated within 4 months of Ipi to a median dose of 19.5 Gy (range 15-21 Gy). No patients with WBRT alone developed ARE. CONCLUSIONS: Following SRS for brain mets and Ipi, ARE was seen in 23% of patients within 4 months of starting Ipi treatment. This is greater than the commonly reported 10% risk of ARE after SRS alone for brain metastasis. No increased toxicity was seen with WBRT and Ipi.

  13. Quantitative analysis of contrast-enhanced ultrasonography in acute radiation-induced liver injury: An animal model

    PubMed Central

    FENG, JUN; CHEN, SHU-BO; WU, SHU-JUN; SUN, PING; XIN, TIAN-YOU; CHEN, YING-ZHEN

    2015-01-01

    The aim of the present study was to examine and assess contrast-enhanced ultrasound in the early diagnosis of acute radiation-induced liver injury in a rat model. Sixty female rats were used, with 50 rats being utilized to produce an animal model of liver injury with a single dose of stereotactic X-ray irradiation of 20 Gy. Ten rats from the injury group and 2 rats from the control group were randomly selected on days 3, 7, 14, 21 and 28, and examined by contrast-enhanced ultrasound and histopathology of liver specimens. The rats were divided into four groups: the normal control group, mild, moderate, and severe radioactive liver injury groups based on the histopathological examination results. Hepatic artery arriving time (HAAT) and hepatic vein arriving time (HVAT) were recorded, and hepatic artery to vein transit time (HA-HVTT) was calculated. The time-intensity curve of liver parenchyma, the time to peak (TTP) and peak intensity (PI) were also obtained. Significant differences were observed between liver injury and control groups for PI and HA-HVTT (P<0.05). PI and HA-HVTT were shorter in the severe liver injury group compared to the mild and moderate liver injury groups (P<0.05). Compared to the control group, higher TTP was recorded in all the liver injury groups (P<0.05), and the highest TTP level was observed in the severe liver injury group compared to the mild or moderate group (P<0.05). However, no significant difference was observed between the mild and moderate groups for PI, HA-HVTT and TTP. In conclusion, the results showed that contrast-enhanced ultrasonography is useful for an earlier diagnosis in a rat model of acute radiation-induced liver injury. PMID:26640553

  14. Effect of corticosteroid treatment on cell recovery by lung lavage in acute radiation-induced lung injury

    SciTech Connect

    Wesselius, L.J.; Floreani, A.A.; Kimler, B.F.; Papasian, C.J.; Dixon, A.Y. )

    1989-11-01

    The purpose of this study was to quantitate cell populations recovered by lung lavage up to 6 weeks following thoracic irradiation (24 Gy) as an index of the acute inflammatory response within lung structures. Additionally, rats were treated five times weekly with intraperitoneal saline (0.3 cc) or methylprednisolone (7.5 mg/kg/week). Lung lavage of irradiated rats recovered increased numbers of total cells compared to controls beginning 3 weeks after irradiation (P less than 0.05). The initial increase in number of cells recovered was attributable to an influx of neutrophils (P less than 0.05), and further increases at 4 and 6 weeks were associated with increased numbers of recovered macrophages (P less than 0.05). Lung lavage of steroid-treated rats at 6 weeks after irradiation recovered increased numbers of all cell populations compared to controls (P less than 0.05); however, numbers of recovered total cells, macrophages, neutrophils, and lymphocytes were all significantly decreased compared to saline-treated rats (P less than 0.05). The number of inflammatory cells recovered by lung lavage during acute radiation-induced lung injury is significantly diminished by corticosteroid treatment. Changes in cells recovered by lung lavage can also be correlated with alteration in body weight and respiration rate subsequent to treatment with thoracic irradiation and/or corticosteroids.

  15. Severe nephrotoxic nephritis following conditional and kidney-specific knockdown of stanniocalcin-1

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Inflammation is the hallmark of nephrotoxic nephritis. Stanniocalcin-1 (STC1), a pro-survival factor, inhibits macrophages, stabilizes endothelial barrier function, and diminishes trans-endothelial migration of leukocytes; consistently, transgenic (Tg) overexpression of STC1 protects from nephrotoxi...

  16. Acute effects of exposure to space radiation on CNS function and cognitive performance

    Technology Transfer Automated Retrieval System (TEKTRAN)

    On exploratory class missions, such as a mission to Mars, astronauts will be exposed to types and doses of radiation (cosmic rays) that are not experienced in low earth orbit where the Space Shuttle and International Space Station operate. Exposure to cosmic rays produces changes in neuronal functi...

  17. Management of radiation and chemotherapy related acute toxicity in gastrointestinal cancer.

    PubMed

    Grabenbauer, Gerhard G; Holger, Göbel

    2016-08-01

    Possible toxic effects following radiation and chemotherapy of gastrointestinal tumours may cause a depletion of the mucosal barrier within the radiation volumes with severe mucositis. Diarrhoea, nausea, emesis and severe malabsorption followed by infections with dehydration and electrolyte disorders have to be encountered. For prevention and treatment of oropharyngeal mucositis an oral care protocol, oral cryotherapy together with benzydamine mouthwash may be recommended. Lower gastrointestinal diarrhoea is best treated by Octreotide (>100 μg s.c. bid) if loperamide is ineffective and amifostine (340 mg/m(2) IV) to prevent radiation proctitis. Enteral nutrition may be necessary with severe malnutrition or no enteral food intake for >7days or insufficient intake (<60%) for >10 days. With severe generalized mucositis or severe radiation induced enteritis parenteral nutrition will be initiated. Following the application of highly emetogenic chemotherapy regimen, 5-HT3 antagonists, dexamethasone and aprepitant, whereas in moderate risk levels 5-HT3 antagonist plus dexamethasone may be sufficient. PMID:27644912

  18. Hereditary nephritis (with unusual renal histology): report of a first case from the West Indies.

    PubMed

    Hayes, J S; Jankey, N

    1976-11-01

    A 21-year-old Grenadian girl undergoing investigation in Trinidad for anaemia was diagnosed as a case of hereditary nephritis. She had the clinical features of a nephropathy, nerve deafness and an ocular defect. Renal histology was exceptional in that in addition to the typical findings of a hereditary nephritis, cystic areas generally associated with medullary cystic disease were noted. Several members of the patient's maternal family were afflicted with either deafness visual distrubances or renal disease.

  19. TNFSF10/TRAIL regulates human T4 effector memory lymphocyte radiosensitivity and predicts radiation-induced acute and subacute dermatitis

    PubMed Central

    Baijer, Jan; Déchamps, Nathalie; Perdry, Hervé; Morales, Pablo; Kerns, Sarah; Vasilescu, Alexandre; Baulande, Sylvain; Azria, David; Roméo, Paul Henri; Schmitz, Annette

    2016-01-01

    Sensitivity of T4 effector-memory (T4EM) lymphocytes to radiation-induced apoptosis shows heritability compatible with a Mendelian mode of transmission. Using gene expression studies and flow cytometry, we show a higher TNF-Related Apoptosis Inducing Ligand (TRAIL/TNFSF10) mRNA level and a higher level of membrane bound TRAIL (mTRAIL) on radiosensitive compared to radioresistant T4EM lymphocytes. Functionally, we show that mTRAIL mediates a pro-apoptotic autocrine signaling after irradiation of T4EM lymphocytes linking mTRAIL expression to T4EM radiosensitivity. Using single marker and multimarker Family-Based Association Testing, we identified 3 SNPs in the TRAIL gene that are significantly associated with T4EM lymphocytes radiosensitivity. Among these 3 SNPs, two are also associated with acute and subacute dermatitis after radiotherapy in breast cancer indicating that T4EM lymphocytes radiosensitivity may be used to predict response to radiotherapy. Altogether, these results show that mTRAIL level regulates the response of T4EM lymphocytes to ionizing radiation and suggest that TRAIL/TNFSF10 genetic variants hold promise as markers of individual radiosensitivity. PMID:26982083

  20. Minimal change disease: a variant of lupus nephritis.

    PubMed

    Moysés-Neto, Miguel; Costa, Roberto S; Rodrigues, Fernanda F; Vieira Neto, Osvaldo M; Reis, Marlene A; Louzada Júnior, Paulo; Romão, Elen A; Dantas, Márcio

    2011-02-01

    Some patients with systemic lupus erythematosus (SLE) present with nephrotic syndrome due to minimal change disease (MCD). Histopathological diagnosis of patients with SLE and nephrotic-range proteinuria has shown that these patients present with diffuse proliferative glomerulonephritis and membranous glomerulonephritis, World Health Organization (WHO) classes IV and V, respectively, more frequently than the other classes. In the present study, we reported a case of nephrotic syndrome and renal biopsy-proven MCD associated with SLE. A complete remission occurred after steroid treatment, which was followed by a relapse 15 months later with a concomitant reactivation of SLE. A second biopsy showed WHO class IIb lupus nephritis. Prednisone treatment was restarted, and the patient went into complete remission again. The association of MCD and SLE may not be a coincidence, and MCD should be considered as an associated SLE nephropathy.

  1. Development of FET-type albumin sensor for diagnosing nephritis.

    PubMed

    Park, Keun-Yong; Sohn, Young-Soo; Kim, Chang-Kyu; Kim, Hong-Seok; Bae, Young-Seuk; Choi, Sie-Young

    2008-07-15

    An albumin biosensor based on a potentiometric measurement using Biofield-effect-transistor (BioFET) has been designed and fabricated, and its characteristics were investigated. The BioFET was fabricated using semiconductor integrated circuit (IC) technology. The gate surface of the BioFET was chemically modified by newly developed self-assembled monolayer (SAM) synthesized by a thiazole benzo crown ether ethylamine (TBCEA)-thioctic acid to immobilize anti-albumin. SAM formation, antibody immobilization, and antigen-antibody interaction were verified using surface plasmon resonance (SPR). The output voltage changes of the BioFET with respect to various albumin concentrations were obtained. Quasi-reference electrode (QRE) and reference FET (ReFET) has been integrated with the BioFET, and its output characteristic was investigated. The results demonstrate the feasibility of the BioFET as the albumin sensor for diagnosing nephritis.

  2. IL-17-producing T cells in lupus nephritis.

    PubMed

    Apostolidis, S A; Crispín, J C; Tsokos, G C

    2011-02-01

    Significant evidence implicates interleukin-17 (IL-17) in the pathogenesis of systemic lupus erythematosus (SLE), particularly in the development of tissue damage. IL-17 production and IL-17-producing CD4+ and CD3 + CD4-CD8- cells are increased in patients with SLE. IL-17-producing cells are present in the inflamed kidney tissues from patients with lupus nephritis. In lupus-prone mice, IL-17 production appears to be involved in the expression of disease pathology and pharmacologic or genetic manipulation of its production results in suppression of the disease. It becomes obvious that the use of biologics including humanized anti-IL-17 antibodies or decoy IL-17 receptors deserve clinical consideration. Similarly, the development of drugs that suppress the production of IL-17 is in order.

  3. Acute Toxicity After Image-Guided Intensity Modulated Radiation Therapy Compared to 3D Conformal Radiation Therapy in Prostate Cancer Patients

    SciTech Connect

    Wortel, Ruud C.; Incrocci, Luca; Pos, Floris J.; Lebesque, Joos V.; Witte, Marnix G.; Heide, Uulke A. van der; Herk, Marcel van; Heemsbergen, Wilma D.

    2015-03-15

    Purpose: Image-guided intensity modulated radiation therapy (IG-IMRT) allows significant dose reductions to organs at risk in prostate cancer patients. However, clinical data identifying the benefits of IG-IMRT in daily practice are scarce. The purpose of this study was to compare dose distributions to organs at risk and acute gastrointestinal (GI) and genitourinary (GU) toxicity levels of patients treated to 78 Gy with either IG-IMRT or 3D-CRT. Methods and Materials: Patients treated with 3D-CRT (n=215) and IG-IMRT (n=260) receiving 78 Gy in 39 fractions within 2 randomized trials were selected. Dose surface histograms of anorectum, anal canal, and bladder were calculated. Identical toxicity questionnaires were distributed at baseline, prior to fraction 20 and 30 and at 90 days after treatment. Radiation Therapy Oncology Group (RTOG) grade ≥1, ≥2, and ≥3 endpoints were derived directly from questionnaires. Univariate and multivariate binary logistic regression analyses were applied. Results: The median volumes receiving 5 to 75 Gy were significantly lower (all P<.001) with IG-IMRT for anorectum, anal canal, and bladder. The mean dose to the anorectum was 34.4 Gy versus 47.3 Gy (P<.001), 23.6 Gy versus 44.6 Gy for the anal canal (P<.001), and 33.1 Gy versus 43.2 Gy for the bladder (P<.001). Significantly lower grade ≥2 toxicity was observed for proctitis, stool frequency ≥6/day, and urinary frequency ≥12/day. IG-IMRT resulted in significantly lower overall RTOG grade ≥2 GI toxicity (29% vs 49%, respectively, P=.002) and overall GU grade ≥2 toxicity (38% vs 48%, respectively, P=.009). Conclusions: A clinically meaningful reduction in dose to organs at risk and acute toxicity levels was observed in IG-IMRT patients, as a result of improved technique and tighter margins. Therefore reduced late toxicity levels can be expected as well; additional research is needed to quantify such reductions.

  4. Clinicopathologic characteristics, treatment, and outcomes of tubulointerstitial nephritis and uveitis syndrome in adults

    PubMed Central

    Legendre, Mathieu; Devilliers, Hervé; Perard, Laurent; Groh, Matthieu; Nefti, Habdelamid; Dussol, Bertrand; Trad, Salim; Touré, Fatouma; Abad, Sébastien; Boffa, Jean-Jacques; Frimat, Luc; Torner, Stéphane; Seidowsky, Alexandre; Massy, Ziad André; Saadoun, David; Rieu, Virginie; Schoindre, Yoland; Heron, Emmanuel; Frouget, Thierry; Lionet, Arnaud; Glowacki, François; Arnaud, Laurent; Mousson, Christiane; Besancenot, Jean-François; Rebibou, Jean-Michel; Bielefeld, Philip

    2016-01-01

    Abstract Tubulointerstitial nephritis and uveitis (TINU) syndrome is a rare disease, defined by the association of idiopathic acute TINU. The aim of our work was to determine the characteristics of adult TINU syndrome in France, and to assess factors (including treatment) influencing medium-term prognosis. We conducted a nationwide study including 20 French hospitals. Clinical, laboratory, and renal histopathologic data of 41 biopsy-proven TINU syndromes were retrospectively collected. The patients were diagnosed between January 1, 1999 and December 1, 2015. Twenty-five females and 16 males were included (F/M ratio: 1.6:1). The median age at disease onset was 46.8 years (range 16.8–77.4) with a median serum creatinine level at 207 μmol/L (range 100–1687) and a median estimated glomerular filtration rate (eGFR) at 27 mL/min per 1.73 m2 (range 2–73). Twenty-nine patients (71%) had a bilateral anterior uveitis and 24 (59%) had deterioration in general health at presentation. Moderate proteinuria was found in 32 patients (78%) (median proteinuria 0.52 g/24 h; range 0.10–2.10), aseptic leukocyturia in 25/36 patients (70%). The evaluation of renal biopsies revealed 41 patients (100%) with an acute tubulointerstitial nephritis, 19/39 patients (49%) with light to moderate fibrosis and 5 patients (12%) with an acute tubular necrosis. Thirty-six patients (88%) were treated with oral corticosteroids. After 1 year of follow-up, the median eGFR was 76 mL/min per 1.73 m2 (range 17–119) and 32% of the patients suffered from moderate to severe chronic kidney disease. Serum creatinine (P < 0.001, r = −0.54), serum bicarbonate and phosphate levels (respectively, P = 0.01, r = 0.53; and P = 0.04, r = 0.46), and age (P = 0.03, r = −0.37) at the 1st symptoms were associated with eGFR after 1 year. During the 1st year 40% of patients had uveitis relapses. The use of oral corticosteroids was not associated with a better kidney function but was associated

  5. High-mobility Group Box-1 Protein Promotes Granulomatous Nephritis in Adenine-induced nephropathy

    PubMed Central

    Oyama, Yoko; Hashiguchi, Teruto; Taniguchi, Noboru; Tancharoen, Salunya; Uchimura, Tomonori; Biswas, Kamal K.; Kawahara, Ko-ichi; Nitanda, Takao; Umekita, Yoshihisa; Lotz, Martin; Maruyama, Ikuro

    2011-01-01

    Granulomatous nephritis can be triggered by diverse factors and results in kidney failure. However, despite accumulating data about granulomatous inflammation, pathogenetic mechanisms in nephritis remain unclear. The DNA-binding high-mobility group box-1 protein (HMGB1) initiates and propagates inflammation when released by activated macrophages, functions as an “alarm cytokine” signaling tissue damage. In this study, we demonstrated elevated HMGB1 expression in renal granulomas in rats with crystal-induced granulomatous nephritis caused by feeding an adenine-rich diet. HMGB1 levels were also raised in urine and serum, as well as monocyte chemoattractant protein-1 (MCP-1), a mediator of granulomatous inflammation. Injection of HMGB1 worsened renal function and upregulated MCP-1 in rats with crystal-induced granulomatous nephritis. HMGB1 also induced MCP-1 secretion through mitogen-activated protein kinase (MAPK) and phosphoinositide-3-kinase (PI3K) pathways in rat renal tubular epithelial cells in vitro. Hmgb1+/− mice with crystal-induced nephritis displayed reduced MCP-1 expression in the kidneys and in urine and the number of macrophages in the kidneys was significantly decreased. We conclude that HMGB1 is a new mediator involved in crystal-induced nephritis that amplifies granulomatous inflammation in a cycle where MCP-1 attracts activated macrophages, resulting in excessive and sustained HMGB1 release. HMGB1 could be a novel target for inhibiting chronic granulomatous diseases. PMID:20231821

  6. Renal haemodynamic characteristics in patients with lupus nephritis

    PubMed Central

    Nakano, M.; Ueno, M.; Hasegawa, H.; Watanabe, T.; Kuroda, T.; Ito, S.; Arakawa, M.

    1998-01-01

    OBJECTIVE—To clarify the characteristics of renal haemodynamics in patients with lupus nephritis (LN).
METHODS—The glomerular filtration rate (GFR) and renal plasma flow (RPF) of 37 patients with active LN were studied longitudinally over an interval of 8 to 144 weeks during treatment with corticosteroids or cytotoxic drugs, or both. All patients had clinical renal disorders and underwent renal biopsies.
RESULTS—Analysis of renal biopsy specimens showed that 31 patients had class IV LN. Class II, III, and V LN were present in two patients each. The average GFR increased significantly from 65.4 (SD 33.0) in the pretreatment stage to 86.6 (31.6) ml/min in the post-treatment stage, accompanied by an improvement in urinary or immunological abnormalities, or both. On the other hand, RPF decreased significantly from 625.2 (243.0) to 519.8 (179.0) ml/min. Therefore, the filtration fraction (FF) increased significantly from 10.7 (4.3)% to 16.8 (3.7)%. Low FF was recognised predominantly in patients with class IV LN, but was also observed in patients with other classes. The FF returned towards normal irrespective of the degree of GFR recovery. No significant changes were observed in the levels of blood pressure.
CONCLUSION—A reduction in GFR out of proportion to the reduction in RPF as demonstrated by the low FF values was related to the severity of LN or disease activity, or both. Therefore, relative evaluation of GFR and RPF, namely the determination of FF, may be a useful clinical parameter to determine the status of LN.

 Keywords: systemic lupus erythematosus; lupus nephritis; renal haemodynamics; filtration fraction PMID:9709179

  7. Effects of proton and gamma radiation on lymphocyte populations and acute response to antigen

    NASA Technical Reports Server (NTRS)

    Kajioka, E. H.; Gheorghe, C.; Andres, M. L.; Abell, G. A.; Folz-Holbeck, J.; Slater, J. M.; Nelson, G. A.; Gridley, D. S.

    1999-01-01

    BACKGROUND: The clinical use of proton radiation in the management of cancer, as well as benign disorders, is rapidly increasing. The major goal of this study was to compare the effects of proton and gamma (60Co) radiation on cell-mediated and humoral immunological parameters. MATERIALS AND METHODS: C57BL/6 mice were exposed to a single dose of 3 Gray (Gy) protons or gamma-rays and intraperitoneally injected 1 day later with sheep red blood cells (sRBC). On 4, 10, 15, and 29 days after exposure, subsets from each group were euthanised; nonirradiated controls (with and without sRBC injection) were included. Body and relative spleen weights, leukocyte counts, spontaneous blastogenesis, lymphocyte populations, and anti-sRBC titers were evaluated. RESULTS: The data showed significant depression (p < 0.05) in nearly all assays on days 4 and 10 after irradiation. B lymphocytes (CD19+) were the most radiosensitive, although reconstitution back to normal levels was observed by day 15. T cell (CD3+) and T helper cell (CD4+) recovery was evident by day 29, whereas the T cytotoxic cell (CD8+) count remained significantly below normal. Natural killer cells (NK1.1+) were relatively radioresistant. Anti-sRBC antibody production was slow and low titers were obtained after irradiation. No significant differences were noted between the two types of radiation. CONCLUSIONS: Taken together, the data show that whole-body irradiation with protons or gamma-rays, at the dose employed, results in marked, but transient, immunosuppression. However, at the time points of testing and with the assays used, little or no differences were found between the two forms of radiation.

  8. Delayed Effects of Acute Radiation Exposure in a Murine Model of the H-ARS: Multiple-Organ Injury Consequent to <10 Gy Total Body Irradiation.

    PubMed

    Unthank, Joseph L; Miller, Steven J; Quickery, Ariel K; Ferguson, Ethan L; Wang, Meijing; Sampson, Carol H; Chua, Hui Lin; DiStasi, Matthew R; Feng, Hailin; Fisher, Alexa; Katz, Barry P; Plett, P Artur; Sandusky, George E; Sellamuthu, Rajendran; Vemula, Sasidhar; Cohen, Eric P; MacVittie, Thomas J; Orschell, Christie M

    2015-11-01

    The threat of radiation exposure from warfare or radiation accidents raises the need for appropriate animal models to study the acute and chronic effects of high dose rate radiation exposure. The goal of this study was to assess the late development of fibrosis in multiple organs (kidney, heart, and lung) in survivors of the C57BL/6 mouse model of the hematopoietic-acute radiation syndrome (H-ARS). Separate groups of mice for histological and functional studies were exposed to a single uniform total body dose between 8.53 and 8.72 Gy of gamma radiation from a Cs radiation source and studied 1-21 mo later. Blood urea nitrogen levels were elevated significantly in the irradiated mice at 9 and 21 mo (from ∼22 to 34 ± 3.8 and 69 ± 6.0 mg dL, p < 0.01 vs. non-irradiated controls) and correlated with glomerosclerosis (29 ± 1.8% vs. 64 ± 9.7% of total glomeruli, p < 0.01 vs. non-irradiated controls). Glomerular tubularization and hypertrophy and tubular atrophy were also observed at 21 mo post-total body irradiation (TBI). An increase in interstitial, perivascular, pericardial and peribronchial fibrosis/collagen deposition was observed from ∼9-21 mo post-TBI in kidney, heart, and lung of irradiated mice relative to age-matched controls. Echocardiography suggested decreased ventricular volumes with a compensatory increase in the left ventricular ejection fraction. The results indicate that significant delayed effects of acute radiation exposure occur in kidney, heart, and lung in survivors of the murine H-ARS TBI model, which mirrors pathology detected in larger species and humans at higher radiation doses focused on specific organs.

  9. Deficient Innate Immunity, Thymopoiesis, and Gene Expression Response to Radiation in Survivors of Childhood Acute Lymphoblastic Leukemia

    PubMed Central

    Leung, Wing; Neale, Geoffrey; Behm, Fred; Iyengar, Rekha; Finkelstein, David; Kastan, Michael B.; Pui, Ching-Hon

    2010-01-01

    Background Survivors of childhood acute lymphoblastic leukemia (ALL) are at an increased risk of developing secondary malignant neoplasms. Radiation and chemotherapy can cause mutations and cytogenetic abnormalities and induce genomic instability. Host immunity and appropriate DNA damage responses are critical inhibitors of carcinogenesis. Therefore, we sought to determine the long-term effects of ALL treatment on immune function and response to DNA damage. Methods Comparative studies on 14 survivors in first complete remission and 16 siblings were conducted. Results In comparison to siblings on the cells that were involved in adaptive immunity, the patients had either higher numbers (CD19+ B cells and CD4+CD25+ T regulatory cells) or similar numbers (αβT cells and CD45RO+/RA− memory T cells) in the blood. In contrast, patients had lower numbers of all lymphocyte subsets involved in innate immunity (γδT cells and all NK subsets, including KIR2DL1+ cells, KIR2DL2/L3+ cells, and CD16+ cells), and lower natural cytotoxicity against K562 leukemia cells. Thymopoiesis was lower in patients, as demonstrated by less CD45RO−/RA+ Naïve T cell and less SjTREC levels in the blood, whereas the Vβ spectratype complexity score was similar. Array of gene expression response to low-dose radiation showed that about 70% of the probesets had a reduced response in patients. One of these genes, SCHIP-1, was also among the top-ranked single nucleotide polymorphisms (SNPs) during the whole genome scanning by SNP microarray analysis. Conclusion ALL survivors were deficient in innate immunity, thymopoiesis, and DNA damage responses to radiation. These defects may contribute to their increased likelihood of second malignancy. PMID:20413363

  10. Flaxseed Mitigates Acute Oxidative Lung Damage in a Mouse Model of Repeated Radiation and Hyperoxia Exposure Associated with Space Exploration

    PubMed Central

    Pietrofesa, Ralph A.; Solomides, Charalambos C.; Christofidou-Solomidou, Melpo

    2015-01-01

    Background Spaceflight missions may require crewmembers to conduct extravehicular activities (EVA). Pre-breathe protocols in preparation for an EVA entail 100% hyperoxia exposure that may last for a few hours and be repeated 2-3 times weekly. Each EVA is associated with additional challenges such as low levels of total body cosmic/galactic radiation exposure that may present a threat to crewmember health. We have developed a mouse model of total body radiation and hyperoxia exposure and identified acute damage of lung tissues. In the current study we evaluated the usefulness of dietary flaxseed (FS) as a countermeasure agent for such double-hit exposures. Methods We evaluated lung tissue changes 2 weeks post-initiation of exposure challenges. Mouse cohorts (n=5/group) were pre-fed diets containing either 0% FS or 10% FS for 3 weeks and exposed to: a) normoxia (Untreated); b) >95% O2 (O2); c) 0.25Gy single fraction gamma radiation (IR); or d) a combination of O2 and IR (O2+IR) 3 times per week for 2 consecutive weeks, where 8-hour hyperoxia treatments were spanned by normoxic intervals. Results At 2 weeks post challenge, while control-diet fed mice developed significant lung injury and inflammation across all challenges, FS protected lung tissues by decreasing bronchoalveolar lavage fluid (BALF) neutrophils (p<0.003) and protein levels, oxidative tissue damage, as determined by levels of malondialdehyde (MDA) (p<0.008) and nitrosative stress as determined by nitrite levels. Lung hydroxyproline levels, a measure of lung fibrosis, were significantly elevated in mice fed 0% FS (p<0.01) and exposed to hyperoxia/radiation or the combination treatment, but not in FS-fed mice. FS also decreased levels of a pro-inflammatory, pro-fibrogenic cytokine (TGF-β1) gene expression levels in lung. Conclusion Flaxseed mitigated adverse effects in lung of repeat exposures to radiation/hyperoxia. This data will provide useful information in the design of countermeasures to early

  11. Pregnancy and patients with preexisting lupus nephritis: 15 years of experience at a single center in Korea.

    PubMed

    Koh, J H; Ko, H S; Lee, J; Jung, S M; Kwok, S-K; Ju, J H; Park, S-H

    2015-06-01

    We investigated obstetric outcomes and comorbidities during pregnancy in females with preexisting lupus nephritis (LN) and identified predictors for renal flare. In cases of renal flare during pregnancy, we assessed the long-term post-delivery renal outcome. We performed a retrospective analysis of 183 systemic lupus erythematosus (SLE) pregnancies including blood chemistry, urinalysis, urinary protein, and disease activity recorded at prepregnancy, during pregnancy, and at one month, six months, and one year post-delivery. Pregnancies with preexisting LN had a greater frequency of adverse obstetric outcomes and maternal comorbidity. Renal flares occurred in 50.7% of pregnancies with preexisting LN, 89.2% of which were reactivations. Renal flare among pregnancies with SLE was predicted based on preexisting lupus nephritis (OR 17.73; 95% CI, 5.770-54.484), an active disease prior to pregnancy (OR 2.743; 95% CI, 1.074-7.004), and prepregnancy eGFR < 90 ml/min/1.73 m(2) (OR 11.151; 95% CI, 3.292-37.768). Persistent LN one year after delivery was observed in 33.3% of pregnancies. The median follow-up time after delivery was 5.9 (3.1-9.7) years and chronic kidney disease (CKD) occurred in 21.4% of pregnancies with renal flare. In patients with renal flare, failing to achieve a ≥ 50% reduction in urine protein levels within six months, longer total duration of renal flare, and acute kidney injury at renal flare was associated with CKD development. Females with preexisting LN should achieve remission before pregnancy. When patients experience renal flares during pregnancy, it is important to reduce the proteinuria level by >50% within six months and to achieve early remission for excellent long-term renal outcomes.

  12. Successful Pregnancy and Delivery After Radiation With Ovarian Shielding for Acute Lymphocytic Leukemia Before Menarche.

    PubMed

    Ishibashi, Naoya; Maebayashi, Toshiya; Aizawa, Takuya; Sakaguchi, Masakuni; Abe, Osamu; Saito, Tsutomu; Tanaka, Yoshiaki; Chin, Motoaki; Mugishima, Hideo

    2015-07-01

    Total body irradiation is performed as a preconditioning regimen to inhibit graft-versus-host disease after bone marrow transplantation and to eradicate remaining tumor cells. However, these regimens result in delayed secondary sex characteristics and failure of ovarian function recovery, leading to amenorrhea and infertility. Herein, we report a case of an 11-year-old girl diagnosed with acute lymphocytic leukemia who received induction chemotherapy and prophylactic cranial irradiation. For bone marrow transplantation, she received total body irradiation of 12 Gy with uterine and ovarian shielding at 13 years of age. The patient remained in remission and menarche began at 14 years of age. At 23, she became pregnant and delivered a baby naturally with no abnormalities.

  13. Acute effect of exposure of mollusk single neuron to 900-MHz mobile phone radiation.

    PubMed

    Partsvania, B; Sulaberidze, T; Shoshiashvili, L; Modebadze, Z

    2011-09-01

    The goal of the present work was to explore the influence of commercially available cell phone irradiation on the single neuron excitability and memory processes. A Transverse Electromagnetic Cell (TEM Cell) was used to expose single neurons of mollusk to the electromagnetic field. Finite-Difference Time-Domain (FDTD) method was used for modeling the TEM Cell and the electromagnetic field interactions with living nerve ganglion and neurons. Neuron electrophysiology was investigated using standard microelectrode technique. The specific absorption rate (SAR) deposited into the single neuron was calculated to be 0.63 W/kg with a temperature increment of 0.1°C. After acute exposure, average firing threshold of the action potentials was not changed. However, the average latent period was significantly decreased. This indicates that together with latent period the threshold and the time of habituation might be altered during exposure. However, these alterations are transient and only latent period remains on the changed level.

  14. Insights into the epidemiology and management of lupus nephritis from the US rheumatologist's perspective.

    PubMed

    Hoover, Paul J; Costenbader, Karen H

    2016-09-01

    Lupus nephritis is a common and severe manifestation of systemic lupus erythematosus that disproportionately affects nonwhites and those in lower socioeconomic groups. This review discusses recent data on the incidence, prevalence, and outcomes of patients with lupus nephritis with a focus on low-income US Medicaid patients. We also review recent guidelines on diagnosis, treatment, and screening for new onset and relapses of lupus nephritis. Finally, we discuss the management of lupus nephritis from a rheumatologist's perspective, including vigilance for the common adverse events related to disease and treatment, and we review prevention and new treatment strategies. PMID:27344205

  15. Prospects for management of gastrointestinal injury associated with the acute radiation syndrome

    SciTech Connect

    Dubois, A.; Walker, R.I.

    1988-08-01

    The effect of total-body ionizing radiation on the digestive tract is dose-dependent and time-dependent. At low doses (1.5 Gy), one observes only a short prodromal syndrome consisting of nausea, vomiting, and gastric suppression. At doses greater than 6 Gy, the prodromal syndrome is more marked, and it is followed after a 2-5-day remission period by a subacute syndrome, characterized by diarrhea and hematochezia. This gastrointestinal syndrome is superimposed onto a radiation-induced bone marrow suppression. The combination of intestinal and hemopoietic syndromes results in dehydration, anemia, and infection, leading eventually to irreversible shock and death. The treatment of prodromal symptoms is based on the administration of antiemetics and gastrokinetics, although an effective treatment devoid of side effects is not yet available for human therapy. The treatment of the gastrointestinal subacute syndrome remains difficult and unsuccessful after exposure to total body doses greater than 8-10 Gy. Supportive therapy to prevent infection and dehydration may be effective if restoration or repopulation of the intestinal and bone marrow stem cells does occur. In addition, bone marrow transplantation may improve the prospect of treating the hemopoietic syndrome, although the experience gained in Chernobyl suggests that this treatment is difficult to apply in the case of nuclear accidents. Administration of radioprotectants before irradiation decreases damage to healthy cells, while not protecting cancerous tissues. In the future, stimulation of gastrointestinal and hemopoietic progenitor cells may be possible using cell growth regulators, but much remains to be done to improve the treatment of radiation damage to the gastrointestinal tract. 77 references.

  16. Prospects for management of gastrointestinal injury associated with the acute radiation syndrome

    SciTech Connect

    Dubois, A.; Walker, R.I.

    1988-08-01

    The effect of total-body ionizing radiation on the digestive tract is dose-dependent and time-dependent. At low doses (1.5 Gy), one observes only a short prodromal syndrome consisting of nausea, vomiting, and gastric suppression. At doses>6 Gy, the prodromal syndrome is more marked, and it is followed after a 2-5-day remission period by a subacute syndrome, characterized by diarrhea and hematochezia. This gastrointestinal syndrome is superimposed onto a radiation-induced bone marrow suppression. The combination of intestinal and hemopoietic syndromes results in dehydration, anemia, and infection, leading eventually to irreversible shock and death. The treatment of prodromal symptoms is based on the administration of antiemetics and gastrokinetics, although an effective treatment devoid of side effects is not yet available for human therapy. The treatment of the gastrointestinal subacute syndrome remains difficult and unsuccessful after exposure to total-body doses >8-10 Gy. Supportive therapy to prevent infection and dehydration may be effective if restoration or repopulation of the intestinal and bone marrow stem cells does occur. In addition, bone marrow transplantation may improve the prospect of treating the hemopoietic syndrome, although the experience gained in Chernobyl suggests that this treatment is difficult to apply in the case of nuclear accidents. Administration of radioprotectants before irradiation decreases damage to healthy cells, while not protecting cancerous tissues. In the future, stimulation of gastrointestinal and hemopoietic progenitor cells may be possible using cell growth regulators, but much remains to be done to improve the treatment of radiation damage to the gastrointestinal tract.

  17. Combined Mitigation of the Gastrointestinal and Hematopoietic Acute Radiation Syndromes by a Novel LPA2 Receptor-specific Non-lipid Agonist

    PubMed Central

    Patil, Renukadevi; Szabó, Erzsébet; Fells, James I.; Balogh, Andrea; Lim, Keng G.; Fujiwara, Yuko; Norman, Derek B.; Lee, Sue-Chin; Balazs, Louisa; Thomas, Fridtjof; Patil, Shivaputra; Emmons-Thompson, Karin; Boler, Alyssa; Strobos, Jur; McCool, Shannon W.; Yates, C. Ryan; Stabenow, Jennifer; Byrne, Gerrald I.; Miller, Duane D.; Tigyi, Gábor J.

    2015-01-01

    Pharmacological mitigation of injuries caused by high-dose ionizing radiation is an unsolved medical problem. A specific nonlipid agonists of the type 2 GPCR for lysophosphatidic acid (LPA2) 2-[4-(1,3-Dioxo-1H,3H-benzoisoquinolin-2-yl)butylsulfamoyl]benzoic acid (DBIBB) when administered with a postirradiation delay up to 72 hours reduced mortality of C57BL/6 mice but not in LPA2 KO mice. DBIBB mitigated the gastrointestinal radiation syndrome, increased intestinal crypt survival and enterocyte proliferation, and reduced apoptosis. DBIBB enhanced DNA repair by augmenting the resolution of γ–H2AX foci, increased clonogenic survival of irradiated IEC-6 cells, attenuated the radiation-induced death of human CD34+ hematopoietic progenitors and enhanced the survival of the granulocyte/macrophage lineage. DBIBB also increased the survival of mice suffering of the hematopoietic acute radiation syndrome after total body irradiation. DBIBB represents the first drug candidate capable of mitigating acute radiation syndrome caused by high-dose γ-radiation to the hematopoietic and gastrointestinal system. PMID:25619933

  18. The long-term effects of acute exposure to ionising radiation on survival and fertility in Daphnia magna.

    PubMed

    Sarapultseva, Elena I; Dubrova, Yuri E

    2016-10-01

    The results of recent studies have provided strong evidence for the transgenerational effects of parental exposure to ionising radiation and chemical mutagens. However, the transgenerational effects of parental exposure on survival and fertility remain poorly understood. To establish whether parental irradiation can affect the survival and fertility of directly exposed organisms and their offspring, crustacean Daphnia magna were given 10, 100, 1000 and 10,000mGy of acute γ-rays. Exposure to 1000 and 10,000mGy significantly compromised the viability of irradiated Daphnia and their first-generation progeny, but did not affect the second-generation progeny. The fertility of F0 and F1Daphnia gradually declined with the dose of parental exposure and significantly decreased at dose of 100mGy and at higher doses. The effects of parental irradiation on the number of broods were only observed among the F0Daphnia exposed to 1000 and 10,000mGy, whereas the brood size was equally affected in the two consecutive generations. In contrast, the F2 total fertility was compromised only among progeny of parents that received the highest dose of 10,000mGy. We propose that the decreased fertility observed among the F2 progeny of parents exposed to 10,000mGy is attributed to transgenerational effects of parental irradiation. Our results also indicate a substantial recovery of the F2 progeny of irradiated F0Daphnia exposed to the lower doses of acute γ-rays.

  19. The long-term effects of acute exposure to ionising radiation on survival and fertility in Daphnia magna.

    PubMed

    Sarapultseva, Elena I; Dubrova, Yuri E

    2016-10-01

    The results of recent studies have provided strong evidence for the transgenerational effects of parental exposure to ionising radiation and chemical mutagens. However, the transgenerational effects of parental exposure on survival and fertility remain poorly understood. To establish whether parental irradiation can affect the survival and fertility of directly exposed organisms and their offspring, crustacean Daphnia magna were given 10, 100, 1000 and 10,000mGy of acute γ-rays. Exposure to 1000 and 10,000mGy significantly compromised the viability of irradiated Daphnia and their first-generation progeny, but did not affect the second-generation progeny. The fertility of F0 and F1Daphnia gradually declined with the dose of parental exposure and significantly decreased at dose of 100mGy and at higher doses. The effects of parental irradiation on the number of broods were only observed among the F0Daphnia exposed to 1000 and 10,000mGy, whereas the brood size was equally affected in the two consecutive generations. In contrast, the F2 total fertility was compromised only among progeny of parents that received the highest dose of 10,000mGy. We propose that the decreased fertility observed among the F2 progeny of parents exposed to 10,000mGy is attributed to transgenerational effects of parental irradiation. Our results also indicate a substantial recovery of the F2 progeny of irradiated F0Daphnia exposed to the lower doses of acute γ-rays. PMID:27288911

  20. Acute skin lesions following psoralen plus ultraviolet A radiation investigated by optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Liu, Z. M.; Zhong, H. Q.; Zhai, J.; Wang, C. X.; Xiong, H. L.; Guo, Z. Y.

    2013-08-01

    Psoralen plus ultraviolet A radiation (PUVA) therapy is a very important clinical treatment of skin diseases such as vitiligo and psoriasis, but associated with an increased risk of skin photodamage, especially photoaging. In this work, optical coherence tomography (OCT), a novel non-invasive imaging technology, was introduced to investigate in vivo the photodamage induced by PUVA qualitatively and quantitatively. Balb/c mouse dorsal skin was treated with 8-methoxypsoralen (8-MOP), and then exposed to UVA radiation. OCT images of the tissues were obtained by an OCT system with a 1310 nm central wavelength. Skin thickness and the attenuation coefficient were extracted from the OCT images to analyze the degree of injury to mouse skin. The results demonstrated that PUVA-treated skin showed an increase in skin thickness, and a reduction of attenuation coefficient in the OCT signal compared with the control groups. The data also showed good correlation with the results observed in histological sections using hematoxylin and eosin staining. In conclusion, OCT is a promising tool for photobiological studies aimed at assessing the effect of PUVA therapy in vivo.

  1. The Impact of Pretreatment Prostate Volume on Severe Acute Genitourinary Toxicity in Prostate Cancer Patients Treated With Intensity-Modulated Radiation Therapy

    SciTech Connect

    Aizer, Ayal A.; Anderson, Nicole S.; Oh, Steven C.; Yu, James B.; McKeon, Anne M.; Decker, Roy H.; Peschel, Richard E.

    2011-02-01

    Purpose: To assess the impact of pretreatment prostate volume on the development of severe acute genitourinary toxicity in patients undergoing intensity-modulated radiation therapy (IMRT) for prostate cancer. Methods and Materials: Between 2004 and 2007, a consecutive sample of 214 patients who underwent IMRT (75.6 Gy) for prostate cancer at two referral centers was analyzed. Prostate volumes were obtained from computed tomography scans taken during treatment simulation. Genitourinary toxicity was defined using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 guidelines. Acute toxicity was defined as any toxicity originating within 90 days of the completion of radiation therapy. Patients were characterized as having a small or large prostate depending on whether their prostate volume was less than or greater than 50 cm{sup 3}, respectively. Genitourinary toxicity was compared in these groups using the chi-square or Fisher's exact test, as appropriate. Bivariate and multivariate logistic regression analysis was performed to further assess the impact of prostate volume on severe (Grade 3) acute genitourinary toxicity. Results: Patients with large prostates (>50 cm{sup 3}) had a higher rate of acute Grade 3 genitourinary toxicity (p = .02). Prostate volume was predictive of the likelihood of developing acute Grade 3 genitourinary toxicity on bivariate (p = .004) and multivariate (p = .006) logistic regression. Every 27.0 cm{sup 3} increase in prostate volume doubled the likelihood of acute Grade 3 genitourinary toxicity. Conclusions: Patients with larger prostates are at higher risk for the development of severe acute genitourinary toxicity when treated with IMRT for prostate cancer.

  2. Comparison of Acute and Late Toxicities for Three Modern High-Dose Radiation Treatment Techniques for Localized Prostate Cancer

    SciTech Connect

    Mohammed, Nasiruddin; Kestin, Larry; Ghilezan, Mihai; Krauss, Daniel; Vicini, Frank; Brabbins, Donald; Gustafson, Gary; Ye Hong; Martinez, Alavaro

    2012-01-01

    Purpose: We compared acute and late genitourinary (GU) and gastrointestinal (GI) toxicities in prostate cancer patients treated with three different high-dose radiation techniques. Methods and Materials: A total of 1,903 patients with localized prostate cancer were treated with definitive RT at William Beaumont Hospital from 1992 to 2006: 22% with brachytherapy alone (BT), 55% with image-guided external beam (EB-IGRT), and 23% external beam with high-dose-rate brachytherapy boost (EBRT+HDR). Median dose with BT was 120 Gy for LDR and 38 Gy for HDR (9.5 Gy Multiplication-Sign 4). Median dose with EB-IGRT was 75.6 Gy (PTV) to prostate with or without seminal vesicles. For EBRT+HDR, the pelvis was treated to 46 Gy with an additional 19 Gy (9.5 Gy Multiplication-Sign 2) delivered via HDR. GI and GU toxicity was evaluated utilizing the NCI-CTC criteria (v.3.0). Median follow-up was 4.8 years. Results: The incidences of any acute {>=} Grade 2 GI or GU toxicities were 35%, 49%, and 55% for BT, EB-IGRT, and EBRT+HDR (p < 0.001). Any late GU toxicities {>=} Grade 2 were present in 22%, 21%, and 28% for BT, EB-IGRT, and EBRT+HDR (p = 0.01), respectively. Patients receiving EBRT+HDR had a higher incidence of urethral stricture and retention, whereas dysuria was most common in patients receiving BT. Any Grade {>=}2 late GI toxicities were 2%, 20%, and 9% for BT, EB-IGRT, and EBRT+HDR (p < 0.001). Differences were most pronounced for rectal bleeding, with 3-year rates of 0.9%, 20%, and 6% (p < 0.001) for BT, EB-IGRT, and EBRT+HDR respectively. Conclusions: Each of the three modern high-dose radiation techniques for localized prostate cancer offers a different toxicity profile. These data can help patients and physicians to make informed decisions regarding radiotherapy for prostate andenocarcinoma.

  3. Statistical Prediction of Solar Particle Event Frequency Based on the Measurements of Recent Solar Cycles for Acute Radiation Risk Analysis

    NASA Technical Reports Server (NTRS)

    Myung-Hee, Y. Kim; Shaowen, Hu; Cucinotta, Francis A.

    2009-01-01

    Large solar particle events (SPEs) present significant acute radiation risks to the crew members during extra-vehicular activities (EVAs) or in lightly shielded space vehicles for space missions beyond the protection of the Earth's magnetic field. Acute radiation sickness (ARS) can impair performance and result in failure of the mission. Improved forecasting capability and/or early-warning systems and proper shielding solutions are required to stay within NASA's short-term dose limits. Exactly how to make use of observations of SPEs for predicting occurrence and size is a great challenge, because SPE occurrences themselves are random in nature even though the expected frequency of SPEs is strongly influenced by the time position within the solar activity cycle. Therefore, we developed a probabilistic model approach, where a cumulative expected occurrence curve of SPEs for a typical solar cycle was formed from a non-homogeneous Poisson process model fitted to a database of proton fluence measurements of SPEs that occurred during the past 5 solar cycles (19 - 23) and those of large SPEs identified from impulsive nitrate enhancements in polar ice. From the fitted model, the expected frequency of SPEs was estimated at any given proton fluence threshold (Phi(sub E)) with energy (E) >30 MeV during a defined space mission period. Corresponding Phi(sub E) (E=30, 60, and 100 MeV) fluence distributions were simulated with a random draw from a gamma distribution, and applied for SPE ARS risk analysis for a specific mission period. It has been found that the accurate prediction of deep-seated organ doses was more precisely predicted at high energies, Phi(sub 100), than at lower energies such as Phi(sub 30) or Phi(sub 60), because of the high penetration depth of high energy protons. Estimates of ARS are then described for 90th and 95th percentile events for several mission lengths and for several likely organ dose-rates. The ability to accurately measure high energy protons

  4. Evaluation of continuous low dose rate versus acute single high dose rate radiation combined with oncolytic viral therapy for prostate cancer

    PubMed Central

    LIU, CHUNYAN; ZHANG, YONGGANG; LIU, MINZHI MAGGIE; ZHOU, HAOMING; CHOWDHURY, WASIM H.; LUPOLD, SHAWN E.; DEWEESE, TED L.; RODRIGUEZ, RONALD

    2011-01-01

    Purpose Conditionally Replicative Adenovirus (CRAd) has been previously demonstrated to augment the activity of radiation, resulting in synergy of cell kill. However, previous models combining radiation with CRAd have not focused on the methods of radiation delivery. Materials and methods We model the combination of a novel prostate-specific CRAd, Ad5 PSE/PBN E1A-AR (Ad5: adenovirus 5; PSE: prostate-specific enhancer; PBN: rat probasin promoter; E1A: early region 1A; AR: androgen receptor), with radiation delivered both acutely and continuously, in an effort to better mimic the potential clinical modes of prostate cancer radiotherapy. Results We demonstrate that pre-treatment of cells with acute single high dose rate (HDR) radiation 24 hours prior to viral infection results in significantly enhanced viral replication and virus-mediated cell death. In addition, this combination causes increased level of γ-H2AX (Phosphorylated histone protein H2AX on serine 139), a marker of double-stranded DNA damage and an indirect measure of nuclear fragmentation. In contrast, continuous low dose rate (LDR) radiation immediately following infection of the same CRAd results in no enhancement of viral replication, and only additive effects in virus-mediated cell death. Conclusions These data provide the first direct assessment of the real-time impact of radiation on viral replication and the first comparison of the effect of radiation delivery on the efficacy of CRAd virotherapy. Our data demonstrate substantial differences in CRAd efficacy based on the mode of radiation delivery. PMID:20201650

  5. Hematopoietic stem cell compartment: Acute and late effects of radiation therapy an chemotherapy

    SciTech Connect

    Mauch, P.; Constine, L.; Greenberger, J.

    1995-03-30

    The bone marrow is an important dose-limiting cell renewal tissue for chemotherapy, wide-field irradiation, and autologous bone marrow transplantion. Over the past 5-10 years a great deal has been discovered about the hematopoietic stem cell compartment. Although the toxicity associated with prolonged myelosuppression continue to limit the wider use of chemotherapy and irradiation, ways are being discovered to circumvent this toxicity such as with the increasing use of cytokines. This review describes what is known of how chemotherapy and irradiation damage stem cells and the microenvironment, how cytokines protect hematopoietic cells from radiation damage and speed marrow recovery after chemotherapy or marrow transplantation, and how various types of blood marrow cells contribute to engraftment and long-term hematopoiesis after high doses of cytotoxic agents and/or total body irradiation. 167 refs., 7 figs., 6 tabs.

  6. Clinical and Laboratory Predictors of Distinct Histopathogical Features of Lupus Nephritis

    PubMed Central

    Mavragani, Clio P.; Fragoulis, George E.; Somarakis, George; Drosos, Alexandros; Tzioufas, Athanasios G.; Moutsopoulos, Haralampos M.

    2015-01-01

    Abstract The authors aimed to explore whether distinct clinical, serological, and urinalysis findings are associated with specific histological classes of lupus nephritis. Clinical and laboratory features were recorded at the time of clinical diagnosis from 297 consecutive patients with biopsy-confirmed lupus nephritis. Univariate and logistic regression analyses were performed and a risk score was developed to estimate the risk for developing different classes of lupus nephritis. Variables independently associated with class II included absence of malar rash, negative anti-dsDNA, and ≤5 urine leucocytes/high power field (hpf); with III/IV: age at nephritis diagnosis ≤32 years old, presence of musculoskeletal features, new-onset hypertension, positive anti-dsDNA, >5 urine leucocytes/hpf, creatinine >1.2 mg/dL, cellular casts >1/hpf, and absence of nephrotic range proteinuria; with V: age at nephritis diagnosis >32 years, malar rash, absence of musculoskeletal complaints or serum C3 hypocomplementemia, nephrotic range proteinuria, and ≤9 urine erythrocytes/hpf. A risk predictive score of specific histological classes was calculated for each patient. Associations between 2, 3 or more risk factors with specific histological classes were also revealed [Odds ratios (95% confidence interval) (≥2 risk factors) was 6.7 (2.8–17.4) for class II nephritis, 15.6 (5.1–47.8), and 8.2 (3.6–19.0) for classes III/IV and for class V, respectively (≥3 risk factors)]. The identification of independent factors associated with specific classes of lupus nephritis can provide guidance in selecting specific therapeutic modalities, particularly in cases in which renal biopsy is contraindicated. PMID:26020385

  7. Association of Hematological Nadirs and Survival in a Nonhuman Primate Model of Hematopoietic Syndrome of Acute Radiation Syndrome.

    PubMed

    Gluzman-Poltorak, Zoya; Vainstein, Vladimir; Basile, Lena A

    2015-08-01

    Recombinant human interleukin-12 (rHuIL-12) mitigates the hematopoietic subsyndrome of acute radiation syndrome (HSARS) after total body irradiation (TBI) in a nonhuman primate (NHP) model of HSARS. The mechanism for this effect appears to involve multiple effects of rHuIL-12 on hematopoiesis. We conducted a meta-analysis to examine hematological nadirs and survival across our three NHP completed studies. Animals were irradiated (700 cGy) and treated with a single subcutaneous injection of vehicle (n = 64) or rHuIL-12 (50-500 ng/kg; n = 108) 24-25 h after irradiation, or with daily subcutaneous injections of granulocyte-colony stimulating factor (G-CSF; 10 μg/kg/day) for 18 days starting 24-25 h after exposure (n = 26). Blood samples were obtained at various time points up to day 60 after TBI. Lymphocytes, neutrophils and platelets were significantly lower in nonsurvivors than in survivors in the overall sample and in each treatment group (P < 0.001 for each comparison, Wilcoxon rank-sum test). Lymphocyte nadir was the strongest and most consistent predictor of death by Spearman's rank correlation. Receiver operating characteristic (ROC) curve analysis of death and threshold hematologic nadir values (where nadir values less than or equal the threshold are predictive of death) showed that a threshold of 0.08 × 10(9)/L for lymphocytes had the largest positive predictive value of death (97.2% and 92.5% for the control and rHuIL-12 groups, respectively) and high sensitivity (76.1% and 62.7%, respectively), consistent with human radiation victims data. The current findings suggest that enhanced early bone marrow regeneration resulting in increases in nadir values for all major blood cell types may be the main mechanism of action by which rHuIL-12 mitigates the lethality of HSARS.

  8. Clinical and Dosimetric Predictors of Acute Severe Lymphopenia During Radiation Therapy and Concurrent Temozolomide for High-Grade Glioma

    SciTech Connect

    Huang, Jiayi; DeWees, Todd A.; Badiyan, Shahed N.; Speirs, Christina K.; Mullen, Daniel F.; Fergus, Sandra; Tran, David D.; Linette, Gerry; Campian, Jian L.; Chicoine, Michael R.; Kim, Albert H.; Dunn, Gavin; Simpson, Joseph R.; Robinson, Clifford G.

    2015-08-01

    Purpose: Acute severe lymphopenia (ASL) frequently develops during radiation therapy (RT) and concurrent temozolomide (TMZ) for high-grade glioma (HGG) and is associated with decreased survival. The current study was designed to identify potential predictors of ASL, with a focus on actionable RT-specific dosimetric parameters. Methods and Materials: From January 2007 to December 2012, 183 patients with HGG were treated with RT+TMZ and had available data including total lymphocyte count (TLC) and radiation dose-volume histogram parameters. ASL was defined as TLC of <500/μL within the first 3 months from the start of RT. Stepwise logistic regression analysis was used to determine the most important predictors of ASL. Results: Fifty-three patients (29%) developed ASL. Patients with ASL had significantly worse overall survival than those without (median: 12.5 vs 20.2 months, respectively, P<.001). Stepwise logistic regression analysis identified female sex (odds ratio [OR]: 5.30; 95% confidence interval [CI]: 2.46-11.41), older age (OR: 1.05; 95% CI: 1.02-1.09), lower baseline TLC (OR: 0.92; 95% CI: 0.87-0.98), and higher brain volume receiving 25 Gy (V{sub 25Gy}) (OR: 1.03; 95% CI: 1.003-1.05) as the most significant predictors for ASL. Brain V{sub 25Gy} <56% appeared to be the optimal threshold (OR: 2.36; 95% CI: 1.11-5.01), with an ASL rate of 38% versus 20% above and below this threshold, respectively (P=.006). Conclusions: Female sex, older age, lower baseline TLC, and higher brain V{sub 25Gy} are significant predictors of ASL during RT+TMZ therapy for HGG. Maintaining the V{sub 25Gy} of brain below 56% may reduce the risk of ASL.

  9. Influence of Double-Strand Break Repair on Radiation Therapy-Induced Acute Skin Reactions in Breast Cancer Patients

    SciTech Connect

    Mumbrekar, Kamalesh Dattaram; Fernandes, Donald Jerard; Goutham, Hassan Venkatesh; Sharan, Krishna; Vadhiraja, Bejadi Manjunath; Satyamoorthy, Kapaettu; Bola Sadashiva, Satish Rao

    2014-03-01

    Purpose: Curative radiation therapy (RT)-induced toxicity poses strong limitations for efficient RT and worsens the quality of life. The parameter that explains when and to what extent normal tissue toxicity in RT evolves would be of clinical relevance because of its predictive value and may provide an opportunity for personalized treatment approach. Methods and Materials: DNA double-strand breaks and repair were analyzed by microscopic γ-H2AX foci analysis in peripheral lymphocytes from 38 healthy donors and 80 breast cancer patients before RT, a 2 Gy challenge dose of x-ray exposed in vitro. Results: The actual damage (AD) at 0.25, 3, and 6 hours and percentage residual damage (PRD) at 3 and 6 hours were used as parameters to measure cellular radiosensitivity and correlated with RT-induced acute skin reactions in patients stratified as non-overresponders (NOR) (Radiation Therapy Oncology Group [RTOG] grade <2) and overresponders (OR) (RTOG grade ≥2). The results indicated that the basal and induced (at 0.25 and 3 hours) γ-H2AX foci numbers were nonsignificant (P>.05) between healthy control donors and the NOR and OR groups, whereas it was significant between ORs and healthy donors at 6 hours (P<.001). There was a significantly higher PRD in OR versus NOR (P<.05), OR versus healthy donors (P<.001) and NOR versus healthy donors (P<.01), supported further by the trend analysis (r=.2392; P=.0326 at 6 hours). Conclusions: Our findings strongly suggest that the measurement of PRD by performing γ-H2AX foci analysis has the potential to be developed into a clinically useful predictive assay.

  10. [RBE of neutrons from the BR-10 reactor based on their antitumor effect and on acute radiation reactions of the skin].

    PubMed

    Kuznetsova, M N; Ul'ianenko, S E

    1989-05-01

    The paper is concerned with the results of investigation of antitumor effectiveness (rats, sarcoma M-1) of neutron radiation of a BR-10 reactor with the mean energy of 0.85 MeV, correlated with the effect of 60Co gamma radiation (Luch-1). RBE in single local tumor radiation with neutrons was 4.5, being higher than RBE based on acute skin radiation reactions over a tumor (4.0). For this case FTA is over I (1.13) but slightly lower than after dose fractionated irradiation (1.18). Experimental data indicate the necessity of extending the clinical use of reactor neutrons and a profound study of the effects after neutron irradiation, particularly in dose-fractionated regimens.

  11. Acute Radiation Effects on Cardiac Function Detected by Strain Rate Imaging in Breast Cancer Patients

    SciTech Connect

    Erven, Katrien; Jurcut, Ruxandra; Weltens, Caroline; Giusca, Sorin; Ector, Joris; Wildiers, Hans; Van den Bogaert, Walter; Voigt, Jens-Uwe

    2011-04-01

    Purpose: To investigate the occurrence of early radiation-induced changes in regional cardiac function using strain rate imaging (SRI) by tissue Doppler echocardiography. Methods and Materials: We included 20 left-sided and 10 right-sided breast cancer patients receiving radiotherapy (RT) to the breast or chest wall. Standard echocardiography and SRI were performed before RT (baseline), immediately after RT (post-RT), and at 2 months follow-up (FUP) after RT. Regional strain (S) and strain rate (SR) values were obtained from all 18 left ventricular (LV) segments. Data were compared to the regional radiation dose. Results: A reduction in S was observed post-RT and at FUP in left-sided patients (S{sub post-RT}: -17.6 {+-} 1.5%, and S{sub FUP}: -17.4 {+-} 2.3%, vs. S{sub baseline}: -19.5 {+-} 2.1%, p < 0.001) but not in right-sided patients. Within the left-sided patient group, S and SR were significantly reduced after RT in apical LV segments (S{sub post-RT}: -15.3 {+-} 2.5%, and S{sub FUP}: -14.3 {+-} 3.7%, vs. S{sub baseline}: -19.3 {+-} 3.0%, p < 0.01; and SR{sub post-RT}: -1.06 {+-} 0.15 s {sup -1}, and SR{sub FUP}: -1.16 {+-} 0.28 s {sup -1}, vs. SR{sub baseline}: -1.29 {+-} 0.27s {sup -1}, p = 0.01), but not in mid- or basal segments. Furthermore, we observed that segments exposed to more than 3 Gy showed a significant decrease in S after RT (S{sub post-RT}: -16.1 {+-} 1.6%, and S{sub FUP}: -15.8 {+-} 3.4%, vs. S{sub baseline}: -18.9 {+-} 2.6%, p < 0.001). This could not be observed in segments receiving less than 3 Gy. Conclusions: SRI shows a dose-related regional decrease in myocardial function after RT. It might be a useful tool in the evaluation of modern RT techniques, with respect to cardiac toxicity.

  12. Mitigation Effect of an FGF-2 Peptide on Acute Gastrointestinal Syndrome After High-Dose Ionizing Radiation

    SciTech Connect

    Zhang Lurong; Sun Weimin; Wang Jianjun; Zhang Mei; Yang Shanmin; Tian Yeping; Vidyasagar, Sadasivan; Pena, Louis A.; Zhang Kunzhong; Cao Yongbing; Yin Liangjie; Wang Wei; Zhang Lei; Schaefer, Katherine L.; Saubermann, Lawrence J.; Swarts, Steven G.; Fenton, Bruce M.; Keng, Peter C.; Okunieff, Paul

    2010-05-01

    Purpose: Acute gastrointestinal syndrome (AGS) resulting from ionizing radiation causes death within 7 days. Currently, no satisfactory agent exists for mitigation of AGS. A peptide derived from the receptor binding domain of fibroblast growth factor 2 (FGF-P) was synthesized and its mitigation effect on AGS was examined. Methods and Materials: A subtotal body irradiation (sub-TBI) model was created to induce gastrointestinal (GI) death while avoiding bone marrow death. After 10.5 to 16 Gy sub-TBI, mice received an intramuscular injection of FGF-P (10 mg/kg/day) or saline (0.2 ml/day) for 5 days; survival (frequency and duration) was measured. Crypt cells and their proliferation were assessed by hematoxylin, eosin, and BrdU staining. In addition, GI hemoccult score, stool formation, and plasma levels of endotoxin, insulin, amylase, interleukin (IL)-6, keratinocyte-derived chemokine (KC) monocyte chemoattractant protein 1 (MCP-1) and tumor necrosis factor (TNF)-alpha were evaluated. Results: Treatment with FGF-P rescued a significant fraction of four strains of mice (33-50%) exposed to a lethal dose of sub-TBI. Use of FGF-P improved crypt survival and repopulation and partially preserved or restored GI function. Furthermore, whereas sub-TBI increased plasma endotoxin levels and several pro-inflammation cytokines (IL-6, KC, MCP-1, and TNF-alpha), FGF-P reduced these adverse responses. Conclusions: The study data support pursuing FGF-P as a mitigator for AGS.

  13. Prediction of Renal Allograft Acute Rejection Using a Novel Non-Invasive Model Based on Acoustic Radiation Force Impulse.

    PubMed

    Yang, Cheng; Jin, Yunjie; Wu, Shengdi; Li, Long; Hu, Mushuang; Xu, Ming; Rong, Ruiming; Zhu, Tongyu; He, Wanyuan

    2016-09-01

    Point shear wave elastography based on acoustic radiation force impulse is a novel technology used to quantify tissue stiffness by measuring shear wave speed. A total of 115 kidney transplantation recipients were consecutively enrolled in this prospective study. The patients were subdivided into two groups using 1 mo post-transplantation as the cutoff time for determining the development of acute rejection (AR). Shear wave speed was significantly higher in the AR group than in the non-AR group. We created a model called SEV, comprising shear wave speed, estimated glomerular filtration rate and kidney volume change, that could successfully discriminate patients with or without AR. The area under the receiver operating characteristic curve of SEV was 0.89, which was higher than values for other variables; it was even better in patients within 1 mo post-transplantation (0.954), but was lower than the estimated glomerular filtration rate in patients after 1 mo post-transplantation. Therefore, the SEV model may predict AR after renal transplantation with a high degree of accuracy, and it may be more useful in the early post-operative stage after renal transplantation. PMID:27267289

  14. Effect of acute nutritional deprivation on immune function in mice. II. Response to sublethal radiation

    SciTech Connect

    Wing, E.J.; Barczynski, L.K.

    1984-03-01

    Previous studies from this laboratory indicated that mice starved for 48 or 72 hr were resistant to the intracellular pathogen, Listeria monocytogenes. In the present experiments, we investigated the possibility that rapidly proliferating monocytes were responsible for the early protective effect observed in these mice. Confirming previous studies, the numbers of L. monocytogenes in livers and spleens of starved mice were 2-3 logs lower than those of fed mice 72 hr after inoculation of bacteria. The early protective effect of starvation could be eliminated completely by nonlethal doses of radiation (200-900 rads). Organ bacterial counts in starved-irradiated mice were similar to those of fed mice. Correlative histopathologic studies were carried out on all three groups of mice. Seventy-two hours after challenge with L. monocytogenes, the livers of fed mice had multiple microabscesses with cental necrosis and a poor mononuclear response. In contrast, livers of starved mice had fewer infectious foci, less necrosis, and a more prominent monocyte/macrophage inflammatory response. Similar to fed mice, the livers of starved-irradiated mice had marked necrosis and few monocytes/macrophages. In addition, the number of peripheral blood monocytes in starved mice was increased 72 hr after inoculation compared to fed and starved-irradiated mice. The data from these experiments suggest that a proliferating population of monocytes is responsible for resistance of starved mice against L. monocytogenes.

  15. The effects of PTK787/ZK222584, an inhibitor of VEGFR and PDGFRβ pathways, on intussusceptive angiogenesis and glomerular recovery from Thy1.1 nephritis.

    PubMed

    Wnuk, Monika; Hlushchuk, Ruslan; Tuffin, Gérald; Huynh-Do, Uyen; Djonov, Valentin

    2011-04-01

    The aim of our study was to investigate the phenomenon of intussusceptive angiogenesis with a focus on its molecular regulation by vascular endothelial growth factor receptor (VEGFR)/platelet-derived growth factor receptor β (PDGFRβ) pathways and biological significance for glomerular recovery after acute injury. Glomerular healing by intussusception was examined in a particular setting of Thy1.1 nephritis, where the lysis of mesangial cells results in an initial collapse and successive rebuilding of glomerular capillary structure. Restoration of capillary structure after induction of Thy1.1 nephritis occurred by intussusceptive angiogenesis resulting in i) rapid expansion of the capillary plexus with reinstatement of the glomerular filtration surface and ii) restoration of the archetypical glomerular vascular pattern. Glomerular capillaries of nephritic rats after combined VEGFR2 and PDGFRβ inhibition by PTK787/ZK222584 (PTK/ZK) were tortuous and irregular. However, the onset of intussusceptive angiogenesis was influenced only after long-term PTK/ZK treatment, providing an important insight into differential molecular regulation between sprouting and intussusceptive angiogenesis. PTK/ZK treatment abolished α-smooth muscle actin and tensin expression by injured mesangial cells, impaired glomerular filtration of microspheres, and led to the reduction of glomerular volume and the presence of multiple hemorrhages detectable in the tubular system. Collectively, treatment of nephritic patients with PTK/ZK compound is not recommended. PMID:21435466

  16. Acute and fractionated exposure to high-LET (56)Fe HZE-particle radiation both result in similar long-term deficits in adult hippocampal neurogenesis.

    PubMed

    Rivera, Phillip D; Shih, Hung-Ying; Leblanc, Junie A; Cole, Mara G; Amaral, Wellington Z; Mukherjee, Shibani; Zhang, Shichuan; Lucero, Melanie J; Decarolis, Nathan A; Chen, Benjamin P C; Eisch, Amelia J

    2013-12-01

    Astronauts on multi-year interplanetary missions will be exposed to a low, chronic dose of high-energy, high-charge particles. Studies in rodents show acute, nonfractionated exposure to these particles causes brain changes such as fewer adult-generated hippocampal neurons and stem cells that may be detrimental to cognition and mood regulation and thus compromise mission success. However, the influence of a low, chronic dose of these particles on neurogenesis and stem cells is unknown. To examine the influence of galactic cosmic radiation on neurogenesis, adult-generated stem and progenitor cells in Nestin-CreER(T2)/R26R-YFP transgenic mice were inducibly labeled to allow fate tracking. Mice were then sham exposed or given one acute 100 cGy (56)Fe-particle exposure or five fractionated 20 cGy (56)Fe-particle exposures. Adult-generated hippocampal neurons and stem cells were quantified 24 h or 3 months later. Both acute and fractionated exposure decreased the amount of proliferating cells and immature neurons relative to sham exposure. Unexpectedly, neither acute nor fractionated exposure decreased the number of adult neural stem cells relative to sham expsoure. Our findings show that single and fractionated exposures of (56)Fe-particle irradiation are similarly detrimental to adult-generated neurons. Implications for future missions and ground-based studies in space radiation are discussed. PMID:24320054

  17. Acute and Fractionated Exposure to High-LET 56Fe HZE-Particle Radiation Both Result in Similar Long-Term Deficits in Adult Hippocampal Neurogenesis

    PubMed Central

    Rivera, Phillip D.; Shih, Hung-Ying; LeBlanc, Junie A.; Cole, Mara G.; Amaral, Wellington Z.; Mukherjee, Shibani; Zhang, Shichuan; Lucero, Melanie J.; DeCarolis, Nathan A.; Chen, Benjamin P. C.; Eisch, Amelia J.

    2014-01-01

    Astronauts on multi-year interplanetary missions will be exposed to a low, chronic dose of high-energy, high-charge particles. Studies in rodents show acute, nonfractionated exposure to these particles causes brain changes such as fewer adult-generated hippocampal neurons and stem cells that may be detrimental to cognition and mood regulation and thus compromise mission success. However, the influence of a low, chronic dose of these particles on neurogenesis and stem cells is unknown. To examine the influence of galactic cosmic radiation on neurogenesis, adult-generated stem and progenitor cells in Nestin-CreERT2/R26R-YFP transgenic mice were inducibly labeled to allow fate tracking. Mice were then sham exposed or given one acute 100 cGy 56Fe-particle exposure or five fractionated 20 cGy 56Fe-particle exposures. Adult-generated hippocampal neurons and stem cells were quantified 24 h or 3 months later. Both acute and fractionated exposure decreased the amount of proliferating cells and immature neurons relative to sham exposure. Unexpectedly, neither acute nor fractionated exposure decreased the number of adult neural stem cells relative to sham expsoure. Our findings show that single and fractionated exposures of 56Fe-particle irradiation are similarly detrimental to adult-generated neurons. Implications for future missions and ground-based studies in space radiation are discussed. PMID:24320054

  18. Murine and Human Lupus Nephritis: Pathogenic Mechanisms and Theoretical Strategies for Therapy.

    PubMed

    Pedersen, Hege Lynum; Horvei, Kjersti Daae; Thiyagarajan, Dhivya; Seredkina, Natalya; Rekvig, Ole Petter

    2015-09-01

    Lupus nephritis is one of the most serious manifestations of systemic lupus erythematosus, and represents one of the criteria implemented to classify systemic lupus erythematosus. Although studied for decades, no consensus has been reached related to the basic cellular, molecular, and immunologic mechanism(s) responsible for lupus nephritis. No causal treatments have been developed; therapy is approached mainly with nonspecific immunosuppressive medications. More detailed insight into disease mechanisms therefore is indispensable to develop new therapeutic strategies. In this review, contemporary knowledge on the pathogenic mechanisms of lupus nephritis is discussed based on recent data in murine and human lupus nephritis. Specific focus is given to the effect of anti-double-stranded DNA/antinucleosome antibodies in the kidneys and whether they bind exposed chromatin fragments in glomeruli or whether they bind inherent glomerular structures by cross-recognition. Overall, the data presented here favor the exposed chromatin model because we did not find any indication to substantiate the anti-double-stranded DNA antibody cross-reacting model. At the end of this review we present data on why chromatin fragments are expressed in the glomeruli of patients with lupus nephritis, and discuss how this knowledge can be used to direct the development of future therapies.

  19. Efficacy of novel monoclonal antibody belimumab in the treatment of lupus nephritis

    PubMed Central

    Frieri, Marianne; Heuser, William; Bliss, Joshua

    2015-01-01

    Recently introduced into the market, belimumab (Benlysta) is a monoclonal antibody that has potential clinically efficacious applications for the treatment of lupus nephritis. Lupus nephritis is a major complication of systemic lupus erythematosus (SLE) that can lead to significant illness or even death without proper intervention and treatment. With vast implications through a novel mechanism, belimumab offers a new standard of treatment for physicians in the complications associated with SLE, specifically lupus nephritis. By targeting B cell signaling and maturation, belimumab is able to mitigate the underlying pathological complications surrounding SLE. Phase 3 clinical trials with belimumab have depicted clinically efficacious applications, suggesting belimumab as a revolutionary breakthrough in the treatment armamentarium for practicing clinicians. This article explains the precise mechanism of action of belimumab on the soluble protein BlyS that plays a major role in the pathogenesis of lupus nephritis. In addition, the extensive pharmacokinetics and clinical implications are exemplified in this review with belimumab's comparison with standard therapeutic guidelines for the treatment of lupus nephritis. PMID:25969652

  20. An Unusual Initial Presentation of Lupus Nephritis as a Renal Mass

    PubMed Central

    Royal, Virginie

    2015-01-01

    Lupus nephritis is a frequent manifestation of systemic lupus erythematous. Lupus nephritis usually presents with abnormal urinalysis, proteinuria, and/or renal insufficiency. We report a case of a 48-year-old woman who underwent partial nephrectomy for a fortuitously discovered solid enhancing left kidney mass. No neoplastic cells were found in the biopsy specimen; however, the pathology findings were compatible with immune complex glomerulonephritis with a predominantly membranous distribution, a pattern suggestive of lupus nephritis. The mass effect was apparently due to a dense interstitial lymphocytic infiltrate resulting in a pseudotumor. Further investigation revealed microscopic hematuria with a normal kidney function and no significant proteinuria. Antinuclear antibodies were negative, although anti-DNA and anti-SSA/Rho antibodies were positive. A diagnosis of probable silent lupus nephritis was made and the patient was followed up without immunosuppressive treatment. After two years of follow-up, she did not progress to overt disease. To our knowledge, this represents the first case of lupus nephritis with an initial presentation as a renal mass. PMID:25649369

  1. Mechanisms of Kidney Injury in Lupus Nephritis – the Role of Anti-dsDNA Antibodies

    PubMed Central

    Yung, Susan; Chan, Tak Mao

    2015-01-01

    Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by a breakdown of self-tolerance, production of auto-antibodies and immune-mediated injury, resulting in damage accrual in multiple organs. Kidney involvement, termed lupus nephritis, is a major cause of morbidity and mortality that affects over half of the SLE population during the course of disease. The etiology of lupus nephritis is multifactorial and remains to be fully elucidated. Accumulating evidence suggests that in addition to forming immune complexes and triggering complement activation, anti-dsDNA antibodies contribute to the pathogenesis of lupus nephritis through binding, either directly or indirectly, to cross-reactive antigens or chromatin materials, respectively, to resident renal cells and/or extracellular matrix components, thereby triggering downstream cellular activation and proliferation as well as inflammatory and fibrotic processes. Several cross-reactive antigens that mediate anti-dsDNA antibody binding have been identified, such as annexin II and alpha-actinin. This review discusses the mechanisms through which anti-dsDNA antibodies contribute to immunopathogenesis in lupus nephritis. Corticosteroids combined with either mycophenolic acid (MPA) or cyclophosphamide is the current standard of care immunosuppressive therapy for severe lupus nephritis. This review also discusses recent data showing distinct effects of MPA and cyclophosphamide on inflammatory and fibrotic processes in resident renal cells. PMID:26441980

  2. The prevalence of interstitial nephritis and leptospirosis in 283 raccoons (Procyon lotor) from 5 different sites in the United States.

    PubMed Central

    Hamir, A N; Hanlon, C A; Niezgoda, M; Rupprecht, C E

    2001-01-01

    A retrospective histopathological study was carried out on tissues of 283 raccoons from 5 different geographical locations for presence of interstitial nephritis and renal leptospirosis. Results of this study indicate that although interstitial nephritis was common in raccoons from all locations, the presence of renal leptospiral spirochetes was not. PMID:11708206

  3. Value of repeat biopsy in lupus nephritis flares

    PubMed Central

    Greloni, G; Scolnik, M; Marin, J; Lancioni, E; Quiroz, C; Zacariaz, J; De la Iglesia Niveyro, P; Christiansen, S; Pierangelo, M A; Varela, C F; Rosa-Diez, G J; Catoggio, L J; Soriano, E R

    2014-01-01

    Objectives Renal flares are common in lupus nephritis (LN), and class switch is thought to be characteristic. There is no agreement on indications for performing a repeat renal biopsy. Our objective was to retrospectively review patients who had more than one renal biopsy performed on clinical indications, and analyse clinical, pathological and treatment changes after successive biopsies. Methods Forty-five patients with LN and one or more repeat renal biopsies were included, with a total of 116 biopsies. Results Of the 71 repeat biopsies, pathological transition occurred in 39 (54.9%). When having a previous biopsy with a proliferative lesion, class switch occurred in 55.6%, with 24.4% evolving into non-proliferative classes. When previous biopsy was class V, transition to other classes occurred in 58.3% and changes were all into proliferative classes. Conversion from one pure proliferative form to another (class III to class IV or vice versa) happened in 11.3% of the rebiopsies, with 62 rebiopsies (87.3%) leading to a change in the treatment regimen. Conclusions Histological transformations were common, and they occurred when the previous biopsy had non-proliferative lesions as well as when lesions were proliferative. Treatments were modified after repeat renal biopsy in the majority of patients. In this experience, kidney repeat biopsies were useful in guiding treatment of LN flares. PMID:25396056

  4. Epidermal injury promotes nephritis flare in lupus-prone mice.

    PubMed

    Clark, Kaitlyn L; Reed, Tamra J; Wolf, Sonya J; Lowe, Lori; Hodgin, Jeffrey B; Kahlenberg, J Michelle

    2015-12-01

    Systemic lupus erythematosus is clinically characterized by episodes of flare and remission. In patients, cutaneous exposure to ultraviolet light has been proposed as a flare trigger. However, induction of flare secondary to cutaneous exposure has been difficult to emulate in many murine lupus models. Here, we describe a system in which epidermal injury is able to trigger the development of a lupus nephritis flare in New Zealand Mixed (NZM) 2328 mice. 20-week old NZM2328 female mice underwent removal of the stratum corneum via duct tape, which resulted in rapid onset of proteinuria and death when compared to sham-stripped littermate control NZM2328 mice. This was coupled with a drop in serum C3 concentrations and dsDNA antibody levels and enhanced immune complex deposition in the glomeruli. Recruitment of CD11b(+)CD11c(+)F4/80(high) macrophages and CD11b(+)CD11c(+)F4/80(low) dendritic cells was noted prior to the onset of proteinuria in injured mice. Transcriptional changes within the kidney suggest a burst of type I IFN-mediated and inflammatory signaling which is followed by upregulation of CXCL13 following epidermal injury. Thus, we propose that tape stripping of lupus-prone NZM2328 mice is a novel model of lupus flare induction that will allow for the study of the role of cutaneous inflammation in lupus development and how crosstalk between dermal and systemic immune systems can lead to lupus flare.

  5. Henoch-Schonlein purpura nephritis: pathophysiology, treatment, and future strategy.

    PubMed

    Davin, Jean-Claude

    2011-03-01

    Henoch-Schönlein purpura nephritis is a rare kidney disease leading to chronic kidney disease in a non-negligible percentage of patients. Although retrospective studies suggest beneficial effects of some therapies, prospective randomized clinical trials proving treatment efficacy are still lacking. The dilemma of spontaneous recovery even in patients with severe clinical and histologic presentation and of late evolution to chronic kidney disease in patients with mild initial symptoms renders it difficult for clinicians to expose patients to treatment protocols that are not evidence-based. A better understanding of the pathophysiology of progression to chronic kidney disease in Henoch-Schönlein purpura patients could be achieved by designing prospective international multicenter studies looking at determinants of clinical and histopathological evolution as well as possible circulating and urinary markers of progression. Such studies should be supported by a database available on the web and a new histologic classification of kidney lesions. This paper reports clinical, pathologic, and experimental data to be used for this strategy and to assist clinicians and clinical trial designers to reach therapeutic decisions.

  6. Space Radiation

    NASA Technical Reports Server (NTRS)

    Wu, Honglu

    2006-01-01

    Astronauts receive the highest occupational radiation exposure. Effective protections are needed to ensure the safety of astronauts on long duration space missions. Increased cancer morbidity or mortality risk in astronauts may be caused by occupational radiation exposure. Acute and late radiation damage to the central nervous system (CNS) may lead to changes in motor function and behavior, or neurological disorders. Radiation exposure may result in degenerative tissue diseases (non-cancer or non-CNS) such as cardiac, circulatory, or digestive diseases, as well as cataracts. Acute radiation syndromes may occur due to occupational radiation exposure.

  7. Kallikrein genes are associated with lupus and glomerular basement membrane–specific antibody–induced nephritis in mice and humans

    PubMed Central

    Liu, Kui; Li, Quan-Zhen; Delgado-Vega, Angelica M.; Abelson, Anna-Karin; Sánchez, Elena; Kelly, Jennifer A.; Li, Li; Liu, Yang; Zhou, Jinchun; Yan, Mei; Ye, Qiu; Liu, Shenxi; Xie, Chun; Zhou, Xin J.; Chung, Sharon A.; Pons-Estel, Bernardo; Witte, Torsten; de Ramón, Enrique; Bae, Sang-Cheol; Barizzone, Nadia; Sebastiani, Gian Domenico; Merrill, Joan T.; Gregersen, Peter K.; Gilkeson, Gary G.; Kimberly, Robert P.; Vyse, Timothy J.; Kim, Il; D’Alfonso, Sandra; Martin, Javier; Harley, John B.; Criswell, Lindsey A.; Wakeland, Edward K.; Alarcón-Riquelme, Marta E.; Mohan, Chandra

    2009-01-01

    Immune-mediated nephritis contributes to disease in systemic lupus erythematosus, Goodpasture syndrome (caused by antibodies specific for glomerular basement membrane [anti-GBM antibodies]), and spontaneous lupus nephritis. Inbred mouse strains differ in susceptibility to anti-GBM antibody–induced and spontaneous lupus nephritis. This study sought to clarify the genetic and molecular factors that may be responsible for enhanced immune-mediated renal disease in these models. When the kidneys of 3 mouse strains sensitive to anti-GBM antibody–induced nephritis were compared with those of 2 control strains using microarray analysis, one-fifth of the underexpressed genes belonged to the kallikrein gene family, which encodes serine esterases. Mouse strains that upregulated renal and urinary kallikreins exhibited less evidence of disease. Antagonizing the kallikrein pathway augmented disease, while agonists dampened the severity of anti-GBM antibody–induced nephritis. In addition, nephritis-sensitive mouse strains had kallikrein haplotypes that were distinct from those of control strains, including several regulatory polymorphisms, some of which were associated with functional consequences. Indeed, increased susceptibility to anti-GBM antibody–induced nephritis and spontaneous lupus nephritis was achieved by breeding mice with a genetic interval harboring the kallikrein genes onto a disease-resistant background. Finally, both human SLE and spontaneous lupus nephritis were found to be associated with kallikrein genes, particularly KLK1 and the KLK3 promoter, when DNA SNPs from independent cohorts of SLE patients and controls were compared. Collectively, these studies suggest that kallikreins are protective disease-associated genes in anti-GBM antibody–induced nephritis and lupus. PMID:19307730

  8. No evidence for an independent role of anti-heparan sulphate reactivity apart from anti-DNA in lupus nephritis.

    PubMed Central

    Hylkema, M N; Zwet, I V; Kramers, C; Van Bruggen, M C; Swaak, A J; Berden, J H; Smeenk, R J

    1995-01-01

    The presence of anti-heparan sulphate (HS) reactivity in serum is closely related to the occurrence of nephritis in patients with systemic lupus erythematosus (SLE). Since patients with lupus nephritis in general also have high titres of anti-DNA antibodies, we wanted to clarify the relationship between anti-HS and anti-DNA reactivity in serum. Therefore, we studied longitudinally six patients with lupus nephritis who experienced 12 exacerbations of their disease, and five SLE patients without nephritis experiencing 10 periods of non-renal disease exacerbations. In addition, we tested single serum samples of another 24 patients obtained during a renal disease exacerbation and 22 sera of patients without nephritis. The sera of all patients were tested for anti-DNA (Farr assay) and anti-HS reactivity (ELISA). We confirmed that SLE patients during renal exacerbations have a significantly higher anti-HS reactivity than patients without nephritis (P < 0.003). In addition, patients with nephritis also had higher titres of anti-DNA antibodies during renal exacerbations than during non-renal exacerbations (P < 0.01). A correlation between anti-DNA and anti-HS reactivity was observed (r = 0.40, P < 0.02), which in itself explains the correlation between nephritis and anti-HS reactivity. Comparing sera from nephritis and non-nephritis patients matched for anti-DNA titre, we found no difference in anti-HS reactivity, and therefore must conclude that the anti-HS reactivity is a direct reflection of anti-DNA reactivity. PMID:7621592

  9. The renal metallothionein expression profile is altered in human lupus nephritis

    PubMed Central

    Faurschou, Mikkel; Penkowa, Milena; Andersen, Claus Bøgelund; Starklint, Henrik; Jacobsen, Søren

    2008-01-01

    Introduction Metallothionein (MT) isoforms I + II are polypeptides with potent antioxidative and anti-inflammatory properties. In healthy kidneys, MT-I+II have been described as intracellular proteins of proximal tubular cells. The aim of the present study was to investigate whether the renal MT-I+II expression profile is altered during lupus nephritis. Methods Immunohistochemistry was performed on renal biopsies from 37 patients with lupus nephritis. Four specimens of healthy renal tissue served as controls. Clinicopathological correlation studies and renal survival analyses were performed by means of standard statistical methods. Results Proximal tubules displaying epithelial cell MT-I+II depletion in combination with luminal MT-I+II expression were observed in 31 out of 37 of the lupus nephritis specimens, but not in any of the control sections (P = 0.006). The tubular MT score, defined as the median number of proximal tubules displaying this MT expression pattern per high-power microscope field (40× magnification), was positively correlated to the creatinine clearance in the lupus nephritis cohort (P = 0.01). Furthermore, a tubular MT score below the median value of the cohort emerged as a significant predictor of a poor renal outcome in renal survival analyses. Thus, patients with a tubular MT score < 1.0 had a 6.2-times higher risk of developing end-stage renal disease than patients with a tubular MT score ≥ 1.0 (P = 0.03). Conclusion Lupus nephritis is associated with significant alterations in renal MT-I+II expression. Our data indicate that important prognostic information can be deduced from the renal MT-I+II expression profile in systemic lupus erythematosus patients with nephritis. PMID:18601746

  10. Identification of unique microRNA signature associated with lupus nephritis.

    PubMed

    Te, Jeannie L; Dozmorov, Igor M; Guthridge, Joel M; Nguyen, Kim L; Cavett, Joshua W; Kelly, Jennifer A; Bruner, Gail R; Harley, John B; Ojwang, Joshua O

    2010-05-11

    MicroRNAs (miRNA) have emerged as an important new class of modulators of gene expression. In this study we investigated miRNA that are differentially expressed in lupus nephritis. Microarray technology was used to investigate differentially expressed miRNA in peripheral blood mononuclear cells (PBMCs) and Epstein-Barr Virus (EBV)-transformed cell lines obtained from lupus nephritis affected patients and unaffected controls. TaqMan-based stem-loop real-time polymerase chain reaction was used for validation. Microarray analysis of miRNA expressed in both African American (AA) and European American (EA) derived lupus nephritis samples revealed 29 and 50 differentially expressed miRNA, respectively, of 850 tested. There were 18 miRNA that were differentially expressed in both racial groups. When samples from both racial groups and different specimen types were considered, there were 5 primary miRNA that were differentially expressed. We have identified 5 miRNA; hsa-miR-371-5P, hsa-miR-423-5P, hsa-miR-638, hsa-miR-1224-3P and hsa-miR-663 that were differentially expressed in lupus nephritis across different racial groups and all specimen types tested. Hsa-miR-371-5P, hsa-miR-1224-3P and hsa-miR-423-5P, are reported here for the first time to be associated with lupus nephritis. Our work establishes EBV-transformed B cell lines as a useful model for the discovery of miRNA as biomarkers for SLE. Based on these findings, we postulate that these differentially expressed miRNA may be potential novel biomarkers for SLE as well as help elucidate pathogenic mechanisms of lupus nephritis. The investigation of miRNA profiles in SLE may lead to the discovery and development of novel methods to diagnosis, treat and prevent SLE.

  11. Lung texture in serial thoracic CT scans: correlation with radiologist-defined severity of acute changes following radiation therapy

    NASA Astrophysics Data System (ADS)

    Cunliffe, Alexandra R.; Armato, Samuel G., III; Straus, Christopher; Malik, Renuka; Al-Hallaq, Hania A.

    2014-09-01

    This study examines the correlation between the radiologist-defined severity of normal tissue damage following radiation therapy (RT) for lung cancer treatment and a set of mathematical descriptors of computed tomography (CT) scan texture (‘texture features’). A pre-therapy CT scan and a post-therapy CT scan were retrospectively collected under IRB approval for each of the 25 patients who underwent definitive RT (median dose: 66 Gy). Sixty regions of interest (ROIs) were automatically identified in the non-cancerous lung tissue of each post-therapy scan. A radiologist compared post-therapy scan ROIs with pre-therapy scans and categorized each as containing no abnormality, mild abnormality, moderate abnormality, or severe abnormality. Twenty texture features that characterize gray-level intensity, region morphology, and gray-level distribution were calculated in post-therapy scan ROIs and compared with anatomically matched ROIs in the pre-therapy scan. Linear regression and receiver operating characteristic (ROC) analysis were used to compare the percent feature value change (ΔFV) between ROIs at each category of visible radiation damage. Most ROIs contained no (65%) or mild abnormality (30%). ROIs with moderate (3%) or severe (2%) abnormalities were observed in 9 patients. For 19 of 20 features, ΔFV was significantly different among severity levels. For 12 features, significant differences were observed at every level. Compared with regions with no abnormalities, ΔFV for these 12 features increased, on average, by 1.5%, 12%, and 30%, respectively, for mild, moderate, and severe abnormalitites. Area under the ROC curve was largest when comparing ΔFV in the highest severity level with the remaining three categories (mean AUC across features: 0.84). In conclusion, 19 features that characterized the severity of radiologic changes from pre-therapy scans were identified. These features may be used in future studies to quantify acute normal lung tissue damage

  12. Comparison of Radiation-Induced Bystander Effect in QU-DB Cells after Acute and Fractionated Irradiation: An In Vitro Study

    PubMed Central

    Soleymanifard, Shokouhozaman; Bahreyni Toossi, Mohammad Taghi; Kamran Samani, Roghayeh; Mohebbi, Shokoufeh

    2016-01-01

    Objective Radiation effects induced in non-irradiated cells are termed radiation-induced bystander effects (RIBE). The present study intends to examine the RIBE response of QU-DB bystander cells to first, second and third radiation fractions and compare their cumulative outcome with an equal, single acute dose. Materials and Methods This experimental study irradiated three groups of target cells for one, two and three times with60Co gamma rays. One hour after irradiation, we transferred their culture media to non-irradiated (bystander) cells. We used the cytokinesis block micronucleus assay to evaluate RIBE response in the bystander cells. The numbers of micronuclei generated in bystander cells were determined. Results RIBE response to single acute doses increased up to 4 Gy, then decreased, and finally at the 8 Gy dose disappeared. The second and third fractions induced RIBE in bystander cells, except when RIBE reached to the maximum level at the first fraction. We split the 4 Gy acute dose into two fractions, which decreased the RIBE response. However, fractionation of 6 Gy (into two fractions of 3 Gy or three fractions of 2 Gy) had no effect on RIBE response. When we split the 8 Gy acute dose into two fractions we observed RIBE, which had disappeared following the single 8 Gy dose. Conclusion The impact of dose fractionation on RIBE induced in QU-DB cells de- pended on the RIBE dose-response relationship. Where RIBE increased proportion- ally with the dose, fractionation reduced the RIBE response. In contrast, at high dos- es where RIBE decreased proportionally with the dose, fractionation either did not change RIBE (at 6 Gy) or increased it (at 8 Gy).

  13. Comparison of Radiation-Induced Bystander Effect in QU-DB Cells after Acute and Fractionated Irradiation: An In Vitro Study

    PubMed Central

    Soleymanifard, Shokouhozaman; Bahreyni Toossi, Mohammad Taghi; Kamran Samani, Roghayeh; Mohebbi, Shokoufeh

    2016-01-01

    Objective Radiation effects induced in non-irradiated cells are termed radiation-induced bystander effects (RIBE). The present study intends to examine the RIBE response of QU-DB bystander cells to first, second and third radiation fractions and compare their cumulative outcome with an equal, single acute dose. Materials and Methods This experimental study irradiated three groups of target cells for one, two and three times with60Co gamma rays. One hour after irradiation, we transferred their culture media to non-irradiated (bystander) cells. We used the cytokinesis block micronucleus assay to evaluate RIBE response in the bystander cells. The numbers of micronuclei generated in bystander cells were determined. Results RIBE response to single acute doses increased up to 4 Gy, then decreased, and finally at the 8 Gy dose disappeared. The second and third fractions induced RIBE in bystander cells, except when RIBE reached to the maximum level at the first fraction. We split the 4 Gy acute dose into two fractions, which decreased the RIBE response. However, fractionation of 6 Gy (into two fractions of 3 Gy or three fractions of 2 Gy) had no effect on RIBE response. When we split the 8 Gy acute dose into two fractions we observed RIBE, which had disappeared following the single 8 Gy dose. Conclusion The impact of dose fractionation on RIBE induced in QU-DB cells de- pended on the RIBE dose-response relationship. Where RIBE increased proportion- ally with the dose, fractionation reduced the RIBE response. In contrast, at high dos- es where RIBE decreased proportionally with the dose, fractionation either did not change RIBE (at 6 Gy) or increased it (at 8 Gy). PMID:27602316

  14. Effects and mechanism of Tripterygium wilfordii on chronic glomerulo nephritis.

    PubMed

    Pei, W Y; Yang, C H; Zhang, X L

    2016-02-05

    The objective of this study was to investigate the clinical effects of Tripterygium wilfordii on chronic glomerulo nephritis (CGN) and its mechanisms. Eighty-two cases of CGN treated in our hospital were randomly divided into observation and control groups. The control group was treated with conventional western medicine, and the observation group was treated with conventional western medicine and orally-administered T. wilfordii pills for three courses of treatment, each consisting of 4 weeks. Changes in serum reatinine, blood urea nitrogen, blood total cholesterol, blood albumin, and 24-h urine protein were observed. The levels of peripheral tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were determined with enzyme-linked immunosorbent assay. The curative effects of both groups were evaluated respectively. Both groups had significantly improved serum creatinine, blood urea nitrogen, blood total cholesterol, blood albumin, and 24-h urine protein (P < 0.05), and the observation group exhibited a more significant improvement (P < 0.05). TNF-α and IL-6 levels in both groups obviously decreased (P < 0.05), and the observation group exhibited remarkable changes (P < 0.05). After treatment, the total efficiency of the observation group was 90.24%, which was significantly higher than the 73.17% of the control group (P < 0.05). In conclusion, T. wilfordii can significantly improve kidney function and clinical symptoms in CGN patients, and the mechanism is possibly related to its inhibition of the secretion of TNF-α and IL-6.

  15. Serum Renalase Levels Correlate with Disease Activity in Lupus Nephritis

    PubMed Central

    Zhang, Minfang; Shao, Xinghua; Chang, Xinbei; Fan, Zhuping; Cao, Qin; Mou, Shan; Wang, Qin; Yan, Yucheng; Desir, Gary; Ni, Zhaohui

    2015-01-01

    Introduction Lupus nephritis (LN) is among the most serious complications of systemic lupus erythematosus (SLE), which causes significant morbidity and mortality. Renalase is a novel, kidney-secreted cytokine-like protein that promotes cell survival. Here, we aimed to investigate the relationship of serum renalase levels with LN and its role in the disease progression of LN. Methods For this cross-sectional study, 67 LN patients and 35 healthy controls were enrolled. Seventeen active LN patients who received standard therapies were followed up for six months. Disease activity was determined by the SLE Disease Activity–2000 (SLEDAI-2K) scoring system and serum renalase amounts were determined by ELISA. Predictive value of renalase for disease activity was assessed. Furthermore, the expression of renalase in the kidneys of patients and macrophage infiltration was assessed by immunohistochemistry. Results Serum renalase amounts were significantly higher in LN patients than in healthy controls. Moreover, patients with proliferative LN had more elevated serum renalase levels than Class V LN patients. In proliferative LN patients, serum renalase levels were significantly higher in patients with active LN than those with inactive LN. Serum renalase levels were positively correlated with SLEDAI-2K, 24-h urine protein excretion, ds-DNA and ESR but inversely correlated with serum albumin and C3. Renalase amounts decreased significantly after six-months of standard therapy. The performance of renalase as a marker for diagnosis of active LN was 0.906 with a cutoff value of 66.67 μg/ml. We also observed that the amount of renalase was significantly higher in glomerular of proliferative LN along with the co-expression of macrophages. Conclusion Serum renalase levels were correlated with disease activity in LN. Serum renalase might serve as a potential indicator for disease activity in LN. The marked increase of glomerular renalase and its association with macrophages suggest

  16. Capsid protein sequence diversity of avian nephritis virus.

    PubMed

    Todd, D; Trudgett, J; Smyth, V J; Donnelly, B; McBride, N; Welsh, M D

    2011-06-01

    The capsid gene sequences of 25 avian nephritis viruses (ANVs), collected in the UK, Germany and Belgium from the 1980s to 2008, were determined and compared with those of serotype 1 (ANV-1) and serotype 2 (ANV-2) ANV isolates. Amino acid identities as low as 51% were determined. Pairwise comparisons supported by phylogenetic analysis identified six ANVs, including ANV-1 and ANV-2, which shared<80% amino acid identities with one another, and which were selected to be representative of six groups. The ANVs were not distributed according to geographical location or year of sampling, and the detection of ANVs from five different groups in 11 samples sourced from six flocks belonging to the same UK organization within a 4-month period indicated that sequence-diverse ANVs were co-circulating. Amino acid alignments demonstrated the existence of variable regions throughout the capsid protein, nine of which were selected for detailed comparisons. With most ANVs, the variable region sequences were similar to those of one of the six representative ANVs, but some ANV capsids displayed novel variable region profiles, in which variable regions that were characteristic of more than one representative ANV were present. Phylogenetic analysis based on C-terminal sequences of approximately 260 amino acids and SimPlot analysis provided evidence that RNA recombination events located in the 1250 to 1350 nucleotide region resulted in new combinations of the N-terminal and C-terminal capsid regions. The high level of capsid sequence diversity observed in the present study has important implications for both the control and diagnosis of ANV infections.

  17. Etiological diagnosis of granulomatous tubulointerstitial nephritis in the tropics

    PubMed Central

    Agrawal, Vinita; Kaul, Anupama; Prasad, Narayan; Sharma, Kusum; Agarwal, Vikas

    2015-01-01

    Background Granulomatous tubulointerstitial nephritis (GIN) is common due to infections, drugs or sarcoidosis. However, the cause is often difficult to establish and the studies are limited. We studied the etiology of GIN and compared the clinical and histological features and outcome in different etiologies at a tertiary care center in North India. Methods Renaö biopsies from GIN cases diagnosed from January 2004 to April 2014 were retrieved. Stain for acid fast bacilli was performed in all biopsies. Etiological diagnosis was based on clinical features, extra-renal manifestations, radiology, history of drug intake and demonstration of infective agent. Tissue PCR for tubercular DNA was performed in seven biopsies. Results Seventeen GIN patients [mean age 35 ± 15 years; males 11] were identified. Tuberculosis was the commonest etiology followed by idiopathic, sarcoidosis and fungal. Both tuberculosis and sarcoidosis patients presented with subnephrotic proteinuria and raised serum creatinine. Acid fast bacilli were demonstrated in 1/9 and necrosis was demonstrated in 3/9 granulomas in tuberculosis. Tissue PCR for tubercular DNA was positive in six TB patients and negative in one sarcoidosis patient. Patients responded well to appropriate therapy. Conclusion Etiological diagnosis of GIN is essential for timely and appropriate therapy. Tuberculosis is the commonest etiology (53%) in the tropics. Necrosis in granuloma, demonstration of acid fast bacilli, blood interferon gamma release assay and urine culture is not sensitive for the diagnosis of tuberculosis in GIN. Our findings suggest that tissue PCR for tuberculosis performed in an appropriate clinical setting is useful in the diagnostic evaluation of GIN. PMID:26413276

  18. Radiation

    NASA Video Gallery

    Outside the protective cocoon of Earth's atmosphere, the universe is full of harmful radiation. Astronauts who live and work in space are exposed not only to ultraviolet rays but also to space radi...

  19. A prolonged course of Group A streptococcus-associated nephritis: a mild case of dense deposit disease (DDD)?

    PubMed

    Sawanobori, E; Umino, A; Kanai, H; Matsushita, K; Iwasa, S; Kitamura, H; Oda, T; Yoshizawa, N; Sugita, K; Higashida, K

    2009-06-01

    We herein report the case of a 12-year-old boy with dense deposit disease (DDD) evoked by streptococcal infection. He had been diagnosed to have asymptomatic hematuria syndrome at the age of 6 during school screening. At 12 years of age, he was found to have macrohematuria and overt proteinuria with hypocomplementemia 2 months after streptococcal pharyngitis. Renal biopsy showed endocapillary proliferative glomerulonephritis with double contours of the glomerular basement membrane. Hypocomplementemia and proteinuria were sustained for over 8 weeks. He was suspected to have dense deposit disease due to intramembranous deposits in the first and the second biopsies. 1 month after treatment with methylprednisolone pulse therapy, proteinuria decreased to a normal level. Microscopic hematuria disappeared 2 years later, but mild hypocomplementemia persisted for more than 7 years. Nephritis-associated plasmin receptor (NAPlr), a nephritic antigen for acute poststreptococcal glomerulonephritis, was found to be positive in the glomeruli for more than 8 weeks. DDD is suggested to be caused by dysgeneration of the alternative pathway due to C3NeF and impaired Factor H activity. A persistent deposition of NAPlr might be one of the factors which lead to complement dysgeneration. A close relationship was suggested to exist between the streptococcal infection and dense deposit disease in this case.

  20. Pauci-Immune Necrotizing and Crescentic Glomerulonephritis with Membranous Lupus Nephritis, Fifteen Years after Initial Diagnosis of Secondary Membranous Nephropathy

    PubMed Central

    Burkhart, Ryan; Shah, Nina; Abel, Michael; Oliver, James D.; Lewin, Matthew

    2015-01-01

    Renal involvement in systemic lupus erythematosus (SLE) is usually immune complex mediated and may have multiple different presentations. Pauci-immune necrotizing and crescentic glomerulonephritis (NCGN) refers to extensive glomerular inflammation with few or no immune deposits that may result in rapid decline in renal function. We report a case of a 79-year-old Hispanic male with a history of secondary membranous nephropathy (diagnosed by renal biopsy 15 years previously) who was admitted with acute kidney injury and active urinary sediment. P-ANCA titers and anti-myeloperoxidase antibodies were positive. The renal biopsy was diagnostic for NCGN superimposed on a secondary membranous nephropathy. A previous diagnosis of SLE based on American College of Rheumatology criteria was discovered via Veteran's Administration records review after the completion of treatment for pauci-immune NCGN. ANCAs are detected in 20–31% of patients with SLE. There may be an association between SLE and ANCA seropositivity. In patients with lupus nephritis and biopsy findings of necrotizing and crescentic glomerulonephritis, without significant immune complex deposition, ANCA testing should be performed. In patients with secondary membranous nephropathy SLE should be excluded. PMID:26558120

  1. Granulomatous nephritis and dermatitis in a patient with BRAF V600E mutant metastatic melanoma treated with dabrafenib and trametinib.

    PubMed

    Jansen, Yanina J; Janssens, Peter; Hoorens, Anne; Schreuer, Max S; Seremet, Teofila; Wilgenhof, Sofie; Neyns, Bart

    2015-12-01

    A 61-year-old man was diagnosed with stage IIIB BRAF V600E mutant melanoma in October 2012. He was treated with a combination therapy of dabrafenib and trametinib. He remained in complete remission for 18 months and the treatment was well tolerated after dose reduction because of pyrexia. In March 2013, he developed bilateral pitting edema of the legs with an erythematous, slightly infiltrated rash on his back and upper arms. His face was edematous, with a heliotrope rash-like aspect. Eye examination showed bilateral blepharitis. Additional blood test showed inflammation and acute kidney injury Rifle category failure. A skin and kidney biopsy indicated a granulomatous inflammation. A complete workup for other causes of granulomatous inflammation was negative. Treatment with dabrafenib and trametinib was stopped and corticosteroids were initiated, with a rapid beneficial effect on both the kidney function and skin rash. When corticosteroids were halted after 1 month, a rapid decline in the kidney function was observed. After reintroduction of corticosteroids, kidney function normalized and steroids could be tapered gradually over 6 months. To our knowledge, interstitial nephritis has not been described in patients on BRAF-targeted nor MEK-targeted therapy for melanoma, although it has been described in a melanoma patient treated with the immune checkpoint inhibitor, ipilimumab. Currently, the patient has no sign of local or distal recurrence of melanoma, notwithstanding that treatment with dabrafenib and trametinib has been stopped for 10 months and no other antimelanoma therapy was initiated.

  2. Granulomatous nephritis and dermatitis in a patient with BRAF V600E mutant metastatic melanoma treated with dabrafenib and trametinib.

    PubMed

    Jansen, Yanina J; Janssens, Peter; Hoorens, Anne; Schreuer, Max S; Seremet, Teofila; Wilgenhof, Sofie; Neyns, Bart

    2015-12-01

    A 61-year-old man was diagnosed with stage IIIB BRAF V600E mutant melanoma in October 2012. He was treated with a combination therapy of dabrafenib and trametinib. He remained in complete remission for 18 months and the treatment was well tolerated after dose reduction because of pyrexia. In March 2013, he developed bilateral pitting edema of the legs with an erythematous, slightly infiltrated rash on his back and upper arms. His face was edematous, with a heliotrope rash-like aspect. Eye examination showed bilateral blepharitis. Additional blood test showed inflammation and acute kidney injury Rifle category failure. A skin and kidney biopsy indicated a granulomatous inflammation. A complete workup for other causes of granulomatous inflammation was negative. Treatment with dabrafenib and trametinib was stopped and corticosteroids were initiated, with a rapid beneficial effect on both the kidney function and skin rash. When corticosteroids were halted after 1 month, a rapid decline in the kidney function was observed. After reintroduction of corticosteroids, kidney function normalized and steroids could be tapered gradually over 6 months. To our knowledge, interstitial nephritis has not been described in patients on BRAF-targeted nor MEK-targeted therapy for melanoma, although it has been described in a melanoma patient treated with the immune checkpoint inhibitor, ipilimumab. Currently, the patient has no sign of local or distal recurrence of melanoma, notwithstanding that treatment with dabrafenib and trametinib has been stopped for 10 months and no other antimelanoma therapy was initiated. PMID:26512791

  3. Anti-dsDNA negative and anti-Ro positive lupus nephritis: a report of a rare case.

    PubMed

    Jain, D; Aggarwal, H K; Kaverappa, V; Dhayia, S; Jain, P; Yadav, S

    2014-03-17

    Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease, characterized by an autoantibody response to various nuclear and cytoplasmic antigens. Renal disease in SLE occurs in 40-75% of patients, most often within five years of onset of disease, and is one of the strongest predictors of a poor outcome. A hallmark of glomerular involvement in lupus nephritis is the presence of autoantibodies against double-stranded DNA (dsDNA). Its level usually correlates with disease activity. Our patient presented with a rash resembling malar rash and features of nephrotic syndrome. On investigating, patient was found to have pancytopenia, raised erythrocyte sedimentation rate and depressed serum C3 levels with positivity of antinuclear antibodies and anti- Ro antibodies. However, most of the markers of lupus nephritis including anti dsDNA antibody were negative. Renal biopsy showed features of lupus nephritis (class-IV). Differential item functioning studies showed a full house immunoflourescence staining pattern characteristic of lupus nephritis. Association of Anti-Ro antibody alone with lupus nephritis is less known in literature. Negativity of anti-dsDNA antibody, which is usually considered to be diagnostic of lupus nephritis, poses a diagnostic dilemma short of renal biopsy. Till date only very few cases of non-drug induced lupus nephritis with negative dsDNA antibodies have been reported. In this report we wish to highlight a case of lupus nephritis which was negative for its specific anti dsDNA antibodies and with possible role of anti-Ro antibodies in the pathogenesis of lupus nephritis although the underlying mechanism is incompletely understood.

  4. Life-span exposure to sinusoidal-50 Hz magnetic field and acute low-dose γ radiation induce carcinogenic effects in Sprague-Dawley rats.

    PubMed

    Soffritti, Morando; Tibaldi, Eva; Padovani, Michela; Hoel, David G; Giuliani, Livio; Bua, Luciano; Lauriola, Michelina; Falcioni, Laura; Manservigi, Marco; Manservisi, Fabiana; Panzacchi, Simona; Belpoggi, Fiorella

    2016-01-01

    Background In 2002 the International Agency for Research on Cancer classified extremely low frequency magnetic fields (ELFMF) as a possible carcinogen on the basis of epidemiological evidence. Experimental bioassays on rats and mice performed up to now on ELFMF alone or in association with known carcinogens have failed to provide conclusive confirmation. Objectives To study the carcinogenic effects of combined exposure to sinusoidal-50 Hz (S-50 Hz) magnetic fields and acute γ radiation in Sprague-Dawley rats. Methods We studied groups of male and female Sprague-Dawley rats exposed from prenatal life until natural death to 20 or 1000 μT S-50 Hz MF and also to 0.1 Gy γ radiation delivered as a single acute exposure at 6 weeks of age. Results The results of the study showed significant carcinogenic effects for the mammary gland in males and females and a significant increased incidence of malignant schwannomas of the heart as well as increased incidence of lymphomas/leukemias in males. Conclusions These results call for a re-evaluation of the safety of non-ionizing radiation. PMID:26894944

  5. Efficacy of Synbiotics to Reduce Acute Radiation Proctitis Symptoms and Improve Quality of Life: A Randomized, Double-Blind, Placebo-Controlled Pilot Trial

    SciTech Connect

    Nascimento, Mariana; Aguilar-Nascimento, José Eduardo; Caporossi, Cervantes; Castro-Barcellos, Heloisa Michelon; Motta, Rodrigo Teixeira

    2014-10-01

    Purpose: To evaluate whether the daily intake of synbiotics interferes in radiation-induced acute proctitis symptoms and in quality of life in patients with prostate cancer. Methods and Materials: Twenty patients who underwent 3-dimensional conformal radiation therapy for prostate cancer were randomized to intake either a synbiotic powder containing Lactobacillus reuteri 10{sup 8} colony-forming units and 4.3 g of soluble fiber (Nestlé) or placebo. The questionnaire EORTC QLQ-PRT23 was applied before the beginning of radiation therapy and in every week for the first 4 weeks of treatment. The sum of both the complete (proctitis symptoms plus quality of life) and partial (proctitis symptoms) scores of the EORTC QLQ-PRT23 (European Organization for Research and Treatment of Cancer Quality of Life Module for Proctitis–23 items) questionnaire were the main endpoints. Results: This pilot study showed that the complete questionnaire score (median [range]) was higher in the second (23 [21-30] vs 26.5 [22-34], P<.05) and third (23 [21-32] vs 27.5 [24-33], P<.01) weeks in the placebo group. Proctitis symptoms were highest scored in the placebo group in both the second (19.5 [16-25]) and third (19 [17-24]) weeks than in the synbiotic group (week 2: 16.5 [15-20], P<.05; week 3: 17 [15-23], P<.01). In both scores the placebo group had a significantly higher result (P<.01) than the synbiotic group (repeated-measures analysis of variance). Conclusions: Synbiotics reduce proctitis symptoms and improve quality of life in radiation-induced acute proctitis during radiation therapy for prostate cancer.

  6. Steroid-dependent nephrotic syndrome in lupus nephritis. Response to chlorambucil.

    PubMed

    Abuelo, J G; Esparza, A R; Garella, S

    1984-12-01

    Nephrotic syndrome associated with mesangial lupus nephritis developed in a young woman. The heavy proteinuria exhibited a striking steroid-dependent course during a three-year period of time, with ten relapses occurring whenever attempts were made to withdraw prednisone therapy. A prolonged remission was induced by the administration of chlorambucil.

  7. 75 FR 35492 - Guidance for Industry on Lupus Nephritis Caused By Systemic Lupus Erythematosus-Developing...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-22

    ... Federal Register of March 29, 2005 (70 FR 15868), FDA announced the availability of a draft guidance... HUMAN SERVICES Food and Drug Administration Guidance for Industry on Lupus Nephritis Caused By Systemic Lupus Erythematosus--Developing Medical Products for Treatment; Availability AGENCY: Food and...

  8. 77 FR 38305 - Guidance for Industry on Lupus Nephritis Caused by Systemic Lupus Erythematosus-Developing...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-27

    ... a notice published in the Federal Register of June 22, 2010 (75 FR 35492), FDA announced the... HUMAN SERVICES Food and Drug Administration Guidance for Industry on Lupus Nephritis Caused by Systemic Lupus Erythematosus--Developing Medical Products for Treatment; Withdrawal of Guidance AGENCY: Food...

  9. Karyomegalic Interstitial Nephritis: A Case Report and Review of the Literature.

    PubMed

    Isnard, Pierre; Rabant, Marion; Labaye, Jacques; Antignac, Corinne; Knebelmann, Bertrand; Zaidan, Mohamad

    2016-05-01

    Karyomegalic interstitial nephritis is a rare cause of hereditary chronic interstitial nephritis, described for the first time over 40 years ago.A 36-year-old woman, of Turkish origin, presented with chronic kidney disease and high blood pressure. She had a history of recurrent upper respiratory tract infections but no familial history of nephropathy. Physical examination was unremarkable. Laboratory tests showed serum creatinine at 2.3 mg/dL with an estimated glomerular filtration rate of 26 mL/min/1.73m, and gamma-glutamyl transpeptidase and alkaline phosphatase at 3 and 1.5 times the upper normal limit. Urinalysis showed 0.8 g/day of nonselective proteinuria, microscopic hematuria, and aseptic leukocyturia. Immunological tests and tests for human immunodeficiency and hepatitis B and C viruses were negative. Complement level and serum proteins electrophoresis were normal. Analysis of the renal biopsy showed severe interstitial fibrosis and tubular atrophy. Numerous tubular cells had nuclear enlargement with irregular outlines, hyperchromatic aspect, and prominent nucleoli. These findings were highly suggestive of karyomegalic interstitial nephritis, which was further confirmed by exome sequencing of FAN1 gene showing an identified homozygous frameshift mutation due to a one-base-pair deletion in exon 12 (c.2616delA).The present case illustrates a rare but severe cause of hereditary interstitial nephritis, sometimes accompanied by subtle extrarenal manifestations. Identification of mutations in FAN1 gene underscores recent insights linking inadequate DNA repair and susceptibility to chronic kidney disease. PMID:27196444

  10. Blockade of CD354 (TREM-1) Ameliorates Anti-GBM-Induced Nephritis.

    PubMed

    Du, Yong; Wu, Tianfu; Zhou, Xin J; Davis, Laurie S; Mohan, Chandra

    2016-06-01

    CD354, Triggering Receptor of Myeloid Cells-1 (TREM-1), is a potent amplifier of myeloid immune responses. Our goal was to determine the expression and function of TREM-1 in immune-mediated nephritis. An anti-glomerular basement membrane antibody (anti-GBM)-induced nephritis model was employed, where mice were sensitized with rabbit IgG followed by anti-GBM serum to induce disease. Anti-GBM-treated 129x1/svJ mice developed severe nephritis whereas C57BL/6 (B6) mice were resistant to disease. Anti-GBM disease resulted in elevated renal TREM-1 messenger RNA (mRNA) and protein levels and increased urine TREM-1 levels in 129x1/svJ. TREM-1 blockade with an inhibitory peptide, LP17, inhibited proteinuria and renal disease as measured by glomerulonephritis class, severity of tubulointerstitial disease, crescent formation, and inflammatory cell infiltrates. In sum, TREM-1 is upregulated in renal inflammation and plays a vital role in driving disease. Thus, TREM-1 blockade emerges as a potential therapeutic avenue for immune-mediated renal diseases such as lupus nephritis. PMID:27083877

  11. Ethylenediaminetetraacetic acid-dependent pseudothrombocytopenia in a patient with systemic lupus erythematosus and lupus nephritis

    PubMed Central

    Akyol, Lütfi; Önem, Soner; Özgen, Metin; Sayarlıoğlu, Mehmet

    2016-01-01

    Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by several immunological abnormalities. We wish to communicate the case of a patient with SLE and lupus nephritis (LN) who developed pseudothrombocytopenia. Pseudothrombocytopenia can occur in patients with SLE and LN and should be considered when diagnosing patients with thrombocytopenia without bleeding.

  12. Regulatory T Cells Contribute to the Inhibition of Radiation-Induced Acute Lung Inflammation via Bee Venom Phospholipase A2 in Mice

    PubMed Central

    Shin, Dasom; Lee, Gihyun; Sohn, Sung-Hwa; Park, Soojin; Jung, Kyung-Hwa; Lee, Ji Min; Yang, Jieun; Cho, Jaeho; Bae, Hyunsu

    2016-01-01

    Bee venom has long been used to treat various inflammatory diseases, such as rheumatoid arthritis and multiple sclerosis. Previously, we reported that bee venom phospholipase A2 (bvPLA2) has an anti-inflammatory effect through the induction of regulatory T cells. Radiotherapy is a common anti-cancer method, but often causes adverse effects, such as inflammation. This study was conducted to evaluate the protective effects of bvPLA2 in radiation-induced acute lung inflammation. Mice were focally irradiated with 75 Gy of X-rays in the lung and administered bvPLA2 six times after radiation. To evaluate the level of inflammation, the number of immune cells, mRNA level of inflammatory cytokine, and histological changes in the lung were measured. BvPLA2 treatment reduced the accumulation of immune cells, such as macrophages, neutrophils, lymphocytes, and eosinophils. In addition, bvPLA2 treatment decreased inflammasome-, chemokine-, cytokine- and fibrosis-related genes’ mRNA expression. The histological results also demonstrated the attenuating effect of bvPLA2 on radiation-induced lung inflammation. Furthermore, regulatory T cell depletion abolished the therapeutic effects of bvPLA2 in radiation-induced pneumonitis, implicating the anti-inflammatory effects of bvPLA2 are dependent upon regulatory T cells. These results support the therapeutic potential of bvPLA2 in radiation pneumonitis and fibrosis treatments. PMID:27144583

  13. The Role of Anti-DNA Antibodies in the Development of Lupus Nephritis: A Complementary, or Alternative, Viewpoint?

    PubMed

    Goilav, Beatrice; Putterman, Chaim

    2015-09-01

    Kidney disease, or lupus nephritis, is the organ involvement that is most closely associated with specific autoantibodies in patients with SLE. The concept of anti-DNA antibodies being instrumental in the pathogenesis of lupus nephritis emerged ~50 years ago, and has been a topic of debate ever since. This article focuses on the description of the renal sub-cellular targets of nephritogenic autoantibodies and offers a counter-point opinion to the article by Pedersen et al. In addition, we provide an overview of some of the mechanisms by which anti-DNA antibodies bind to their renal targets and the pathogenic relevance to clinical nephritis.

  14. Risk factors of radiation-induced acute esophagitis in non-small cell lung cancer patients treated with concomitant chemoradiotherapy

    PubMed Central

    2014-01-01

    Background To analyze the clinical and dosimetric risk factors of acute esophagitis (AE) in non-small-cell lung cancer (NSCLC) patients treated with concomitant chemoradiotherapy. Methods Seventy-six NSCLC patients treated with concomitant chemoradiotherapy were retrospectively analyzed. Forty-one patients received concomitant chemoradiotherapy with vinorelbine/cisplatin (VC), 35 with docetaxel/cisplatin (DC). AE was graded according to criteria of the Radiation Therapy Oncology Group (RTOG). The following clinical and dosimetric parameters were analyzed: gender, age, clinical stage, Karnofsky performance status (KPS), pretreatment weight loss, concomitant chemotherapy agents (CCA) (VC vs. DC), percentage of esophagus volume treated to ≥20 (V20), ≥30 (V30), ≥40 (V40), ≥50 (V50) and ≥60 Gy (V60), and the maximum (Dmax) and mean doses (Dmean) delivered to esophagus. Univariate and multivariate logistic regression analysis were used to test the association between the different factors and AE. Results Seventy patients developed AE (Grade 1, 19 patients; Grade 2, 36 patients; and Grade 3, 15 patients). By multivariate logistic regression analysis, V40 was the only statistically significant factor associated with Grade ≥2 AE (p<0.001, OR = 1.159). A V40 of <23% had a 33.3% (10/30) risk of Grade ≥2 AE, which increased to 89.1% (41/46) with a V40 of ≥23% (p<0.001). CCA (p =0.01; OR = 9.686) and V50 (p<0.001; OR = 1.122) were most significantly correlated with grade 3 AE. A V50 of <26.5% had a 6.7% (3/45) risk of Grade 3 AE, which increased to 38.7% (12/31) with a V50 of ≥26.5% (p = 0.001). On the linear regression analysis, V50 and CCA were significant independent factors affecting AE duration. Patients who received concomitant chemotherapy with VC had a decreased risk of grade 3 AE and shorter duration compared with DC. Conclusions Concomitant chemotherapy agents have potential influence on AE. Concomitant chemotherapy with VC led to

  15. Lupus nephritis in children: a longitudinal study of prognostic factors and therapy.

    PubMed

    Baqi, N; Moazami, S; Singh, A; Ahmad, H; Balachandra, S; Tejani, A

    1996-06-01

    There are only a few studies in the pediatric literature that have analyzed risk factors for renal failure in childhood lupus nephritis. This study reviewed the outcome of 56 children (4 to 18 yr of age) with lupus nephritis seen at the authors' institution over a 27-yr period (1965 to 1992), in relation to risk factors and therapy. All children underwent percutaneous renal biopsy before the institution of therapy. From 1965 to 1987, treatment for Class III and IV lupus nephritis consisted of high-dose pulse methylprednisolone, 500 mg daily for 10 days, followed by oral prednisone. From 1987 to 1992, IV cyclophosphamide was given monthly for 6 months and then every 3 months for a period of 3 yr for patients with Class III and Class IV disease. Of 56 children, 42% had Class IV and 21% had Class III histology at onset. The mean follow-up period was 4 yr and ranged from 0.5 to 20.3 yr. Life-table analysis showed that the cumulative proportion of patients surviving was 82.8% at 5 yr and 67.7% at 10 yr. Renal survival was 44.4% at 5 yr and 29% at 10 yr, after the initial diagnosis of lupus nephritis was made. Age at diagnosis, race, sex, initial serum creatinine level, and the presence of proteinuria, hypertension, and DNA antibody titers were reviewed with respect to disease progression, as was the histological class at diagnosis. The effect of the different therapies was also examined. Univariate analysis revealed a significant association of progression to ESRD with an elevated serum creatinine level (P = 0.021), decreased C3 complement (P = 0.024), hypertension (P = 0.053), and histological classification of Class IV lupus nephritis (P = 0.031). Multivariate analysis demonstrated that progression to ESRD was independently associated with an initial Class IV histology (relative risk, 1.78; P < 0.003), hypertension at presentation (relative risk, 1.67; P < 0.003), and a low C3 complement level in conjuction with a high creatinine level (relative risk, 1.52; P < 0

  16. Reconstruction of the Radiation Emergency Medical System From the Acute to the Sub-acute Phases After the Fukushima Nuclear Power Plant Crisis.

    PubMed

    Ojino, Mayo; Ishii, Masami

    2014-02-01

    The radiation emergency medical system in Japan ceased to function as a result of the accident at the Fukushima Daiichi Nuclear Power Plant, which has commonly become known as the "Fukushima Accident." In this paper, we review the reconstruction processes of the radiation emergency medical system in order of events and examine the ongoing challenges to overcoming deficiencies and reinforcing the system by reviewing relevant literature, including the official documents of the investigation committees of the National Diet of Japan, the Japanese government, and the Tokyo Electric Power Company, as well as technical papers written by the doctors involved in radiation emergency medical activities in Fukushima. Our review has revealed that the reconstruction was achieved in 6 stages from March 11 to July 1, 2011: (1) Re-establishment of an off-site center (March 13), (2) Re-establishment of a secondary radiation emergency hospital (March 14), (3) Reconstruction of the initial response system for radiation emergency care (April 2), (4) Reinforcement of the off-site center and stationing of disaster medical advisors at the off-site center (April 4), (5) Reinforcement of the medical care system and an increase in the number of hospitals for non-contaminated patients (From April 2 to June 23), and (6) Enhancement of the medical care system in the Fukushima Nuclear Power Plant and the construction of a new medical care system, involving both industrial medicine and emergency medicine (July 1). Medical resources such as voluntary efforts, academic societies, a local community medical system and university hospitals involved in medical care activities on 6 stages originally had not planned. In the future, radiation emergency medical systems should be evaluated with these 6 stages as a basis, in order to reinforce and enrich both the existing and backup systems so that minimal harm will come to nuclear power plant workers or evacuees and that they will receive proper care. This

  17. Assessment of lupus nephritis activity using urinary retinol-binding protein.

    PubMed

    Sesso, R; Rettori, R; Nishida, S; Sato, E; Ajzen, H; Pereira, A B

    1994-01-01

    We evaluated the presence of proximal renal tubular dysfunction as measured by urinary retinol-binding protein (RBP) in 70 patients with systemic lupus erythematosus. Renal disease activity was assessed using the British Isles Lupus Assessment Group (BILAG) index. This is a clinical-laboratory score based on the principle of the physician's intention to treat. Increased urinary RBP (> 400 micrograms/l) was detected in 17 of 22 (77%) patients with active nephritis, six of 18 (33%) patients with probably active nephritis, one of nine (12%) cases with stable renal disease, and one of 21 (5%) cases without apparent renal disease (P < 0.01). Compared to initial values, mean urinary RBP decreased significantly in six patients evaluated after improvement of the exacerbation of renal disease. There was a positive correlation between urinary RBP and 24-h proteinuria (r = 0.40, P < 0.01), and an inverse correlation between urinary RBP and creatinine clearance (r = -0.60, P < 0.01). In a multivariate analysis adjusting for duration of disease, blood pressure, 24-h proteinuria, and creatinine clearance, mean urinary RBP continued to be significantly and progressively greater for patients with no renal disease, stable renal disease, probably active and active nephritis. Proximal tubular dysfunction is frequent in patients with active lupus nephritis. This association cannot be completely explained by the effects of increased total proteinuria, reduced glomerular filtration rate, and systemic hypertension. Urinary RBP seems to be a marker of renal disease activity. This test may be clinically useful to differentiate patients with active lupus nephritis from those with stable or absent renal disease. PMID:8084448

  18. Acute renal failure in a young weight lifter taking multiple food supplements, including creatine monohydrate.

    PubMed

    Thorsteinsdottir, Bjorg; Grande, Joseph P; Garovic, Vesna D

    2006-10-01

    We report a case of a healthy 24-year-old man who presented with acute renal failure and proteinuria while taking creatine and multiple other supplements for bodybuilding purposes. A renal biopsy showed acute interstitial nephritis. The patient recovered completely after he stopped taking the supplements. Creatine is a performance-enhancing substance that has gained widespread popularity among professional as well as amateur athletes. It is legal and considered relatively safe. Recently there have been case reports of renal dysfunction, including acute interstitial nephritis, associated with its use. Further studies are needed to evaluate the safety of creatine supplementation. It may be prudent to include a warning of this possible side effect in the product insert.

  19. Identification of urinary metabolites that distinguish membranous lupus nephritis from proliferative lupus nephritis and focal segmental glomerulosclerosis

    PubMed Central

    2011-01-01

    Introduction Systemic lupus erythematosus (SLE or lupus) is a chronic autoimmune disease, and kidney involvement with SLE, a.k.a. lupus nephritis (LN), is a frequent and severe complication of SLE that increases patient morbidity and mortality. About 50% of patients with SLE encounter renal abnormalities which, if left untreated, can lead to end-stage renal disease. Kidney biopsy is considered the criterion standard for diagnosis and staging of LN using the International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification, which was developed to help predict renal outcomes and assist with medical decision-making. However, kidney biopsy-based classification of LN is highly invasive and impractical for real-time monitoring of LN status. Here, nuclear magnetic resonance (NMR) spectroscopy-based metabolic profiling was used to identify urinary metabolites that discriminated between proliferative and pure membranous LN as defined by the ISN/RPS classification, and between LN and primary focal segmental glomerulosclerosis (FSGS). Methods Metabolic profiling was conducted using urine samples of patients with proliferative LN without membranous features (Class III/IV; n = 7) or pure membranous LN (Class V; n = 7). Patients with primary FSGS and proteinuria (n = 10) served as disease controls. For each patient, demographic information and clinical data was obtained and a random urine sample collected to measure NMR spectra. Data and sample collection for patients with LN occurred around the time of kidney biopsy. Metabolic profiling analysis was done by visual inspection and principal component analysis. Results Urinary citrate levels were 8-fold lower in Class V LN compared to Class III/IV patients, who had normal levels of urinary citrate (P < 0.05). Class III/IV LN patients had > 10-fold lower levels of urinary taurine compared to Class V patients, who had mostly normal levels (P < 0.01). Class V LN patients had normal urinary hippurate levels compared

  20. Reconstruction of the Radiation Emergency Medical System From the Acute to the Sub-acute Phases After the Fukushima Nuclear Power Plant Crisis.

    PubMed

    Ojino, Mayo; Ishii, Masami

    2014-02-01

    The radiation emergency medical system in Japan ceased to function as a result of the accident at the Fukushima Daiichi Nuclear Power Plant, which has commonly become known as the "Fukushima Accident." In this paper, we review the reconstruction processes of the radiation emergency medical system in order of events and examine the ongoing challenges to overcoming deficiencies and reinforcing the system by reviewing relevant literature, including the official documents of the investigation committees of the National Diet of Japan, the Japanese government, and the Tokyo Electric Power Company, as well as technical papers written by the doctors involved in radiation emergency medical activities in Fukushima. Our review has revealed that the reconstruction was achieved in 6 stages from March 11 to July 1, 2011: (1) Re-establishment of an off-site center (March 13), (2) Re-establishment of a secondary radiation emergency hospital (March 14), (3) Reconstruction of the initial response system for radiation emergency care (April 2), (4) Reinforcement of the off-site center and stationing of disaster medical advisors at the off-site center (April 4), (5) Reinforcement of the medical care system and an increase in the number of hospitals for non-contaminated patients (From April 2 to June 23), and (6) Enhancement of the medical care system in the Fukushima Nuclear Power Plant and the construction of a new medical care system, involving both industrial medicine and emergency medicine (July 1). Medical resources such as voluntary efforts, academic societies, a local community medical system and university hospitals involved in medical care activities on 6 stages originally had not planned. In the future, radiation emergency medical systems should be evaluated with these 6 stages as a basis, in order to reinforce and enrich both the existing and backup systems so that minimal harm will come to nuclear power plant workers or evacuees and that they will receive proper care. This

  1. Reconstruction of the Radiation Emergency Medical System From the Acute to the Sub-acute Phases After the Fukushima Nuclear Power Plant Crisis

    PubMed Central

    OJINO, Mayo; ISHII, Masami

    2014-01-01

    The radiation emergency medical system in Japan ceased to function as a result of the accident at the Fukushima Daiichi Nuclear Power Plant, which has commonly become known as the “Fukushima Accident.” In this paper, we review the reconstruction processes of the radiation emergency medical system in order of events and examine the ongoing challenges to overcoming deficiencies and reinforcing the system by reviewing relevant literature, including the official documents of the investigation committees of the National Diet of Japan, the Japanese government, and the Tokyo Electric Power Company, as well as technical papers written by the doctors involved in radiation emergency medical activities in Fukushima. Our review has revealed that the reconstruction was achieved in 6 stages from March 11 to July 1, 2011: (1) Re-establishment of an off-site center (March 13), (2) Re-establishment of a secondary radiation emergency hospital (March 14), (3) Reconstruction of the initial response system for radiation emergency care (April 2), (4) Reinforcement of the off-site center and stationing of disaster medical advisors at the off-site center (April 4), (5) Reinforcement of the medical care system and an increase in the number of hospitals for non-contaminated patients (From April 2 to June 23), and (6) Enhancement of the medical care system in the Fukushima Nuclear Power Plant and the construction of a new medical care system, involving both industrial medicine and emergency medicine (July 1). Medical resources such as voluntary efforts, academic societies, a local community medical system and university hospitals involved in medical care activities on 6 stages originally had not planned. In the future, radiation emergency medical systems should be evaluated with these 6 stages as a basis, in order to reinforce and enrich both the existing and backup systems so that minimal harm will come to nuclear power plant workers or evacuees and that they will receive proper care

  2. [Clinical guideline for the treatment of lupus nephritis and single-centre results of mycofenolate mofetil among patients with lupus nephritis in the National Institute of Rheumatology and Physiotherapy, Budapest].

    PubMed

    Szabó, Melinda Zsuzsanna; Kiss, Emese

    2016-08-01

    The authors present the latest guideline for the treatment of lupus nephritis and their own single-centre results with mycofenolate mofetil treated lupus nephritis. Lupus nephritis and mainly its proliferative form is a frequent and potentially life-threatening manifestation of systemic lupus erythematosus that can lead to end-stage renal disease. The treatment of lupus nephritis greatly improved in the last decades; mycofenolate mofetil has become an alternative of cyclophosphamide both in remission induction and as a maintenance regimen as well in the treatment of Class III and IV glomerulonephritis. The authors ordered mycofenolate mofetil for 25 patients with lupus nephritis so far. Histologically most of them had Class III (A/C) or IV (A) glomerulonephritis (30-30%), and only 16% of the patients had renal impairment at that time. Mycofenolate mofetil given after glucocorticoid and cyclophosphamide induction therapy reduced the daily proteinuria from 3.18 grs to 1.06 grs. Complete remission could be achieved in 24% and partial remission in 48% of the patients. The authors conclude that mycofenolate mofetil is effective in the therapy of lupus nephritis. Orv. Hetil., 2016, 157(35), 1385-1393. PMID:27569461

  3. Colony-stimulating factors for the treatment of the hematopoietic component of the acute radiation syndrome (H-ARS): a review.

    PubMed

    Singh, Vijay K; Newman, Victoria L; Seed, Thomas M

    2015-01-01

    One of the greatest national security threats to the United States is the detonation of an improvised nuclear device or a radiological dispersal device in a heavily populated area. As such, this type of security threat is considered to be of relatively low risk, but one that would have an extraordinary high impact on health and well-being of the US citizenry. Psychological counseling and medical assessments would be necessary for all those significantly impacted by the nuclear/radiological event. Direct medical interventions would be necessary for all those individuals who had received substantial radiation exposures (e.g., >1 Gy). Although no drugs or products have yet been specifically approved by the United States Food and Drug Administration (US FDA) to treat the effects of acute radiation syndrome (ARS), granulocyte colony-stimulating factor (G-CSF), granulocyte macrophage colony-stimulating factor (GM-CSF), and pegylated G-CSF have been used off label for treating radiation accident victims. Recent threats of terrorist attacks using nuclear or radiologic devices makes it imperative that the medical community have up-to-date information and a clear understanding of treatment protocols using therapeutically effective recombinant growth factors and cytokines such as G-CSF and GM-CSF for patients exposed to injurious doses of ionizing radiation. Based on limited human studies with underlying biology, we see that the recombinants, G-CSF and GM-CSF appear to have modest, but significant medicinal value in treating radiation accident victims. In the near future, the US FDA may approve G-CSF and GM-CSF as ‘Emergency Use Authorization’ (EUA) for managing radiation-induced aplasia, an ARS-related pathology. In this article, we review the status of growth factors for the treatment of radiological/nuclear accident victims. PMID:25215458

  4. LAPping up dead cells to prevent lupus nephritis: a novel role for noncanonical autophagy in autoimmunity.

    PubMed

    Leventhal, Jeremy S; Ross, Michael J

    2016-08-01

    The mechanisms underlying the development of systemic lupus erythematosus and lupus nephritis remain poorly understood. A recent study demonstrates that deficiencies in the immune system's ability to degrade scavenged dead cells via noncanonical autophagy is sufficient to break immune tolerance and produce features commonly seen in lupus, including circulating autoantibodies, inflammatory cytokines, and nephritis. This work provides a possible mechanism for the association of polymorphisms in autophagy genes with the risk of lupus. PMID:27418084

  5. LAPping up dead cells to prevent lupus nephritis: a novel role for noncanonical autophagy in autoimmunity.

    PubMed

    Leventhal, Jeremy S; Ross, Michael J

    2016-08-01

    The mechanisms underlying the development of systemic lupus erythematosus and lupus nephritis remain poorly understood. A recent study demonstrates that deficiencies in the immune system's ability to degrade scavenged dead cells via noncanonical autophagy is sufficient to break immune tolerance and produce features commonly seen in lupus, including circulating autoantibodies, inflammatory cytokines, and nephritis. This work provides a possible mechanism for the association of polymorphisms in autophagy genes with the risk of lupus.

  6. First Generation Gene Expression Signature for Early Prediction of Late Occurring Hematological Acute Radiation Syndrome in Baboons.

    PubMed

    Port, M; Herodin, F; Valente, M; Drouet, M; Lamkowski, A; Majewski, M; Abend, M

    2016-07-01

    We implemented a two-stage study to predict late occurring hematologic acute radiation syndrome (HARS) in a baboon model based on gene expression changes measured in peripheral blood within the first two days after irradiation. Eighteen baboons were irradiated to simulate different patterns of partial-body and total-body exposure, which corresponded to an equivalent dose of 2.5 or 5 Gy. According to changes in blood cell counts the surviving baboons (n = 17) exhibited mild (H1-2, n = 4) or more severe (H2-3, n = 13) HARS. Blood samples taken before irradiation served as unexposed control (H0, n = 17). For stage I of this study, a whole genome screen (mRNA microarrays) was performed using a portion of the samples (H0, n = 5; H1-2, n = 4; H2-3, n = 5). For stage II, using the remaining samples and the more sensitive methodology, qRT-PCR, validation was performed on candidate genes that were differentially up- or down-regulated during the first two days after irradiation. Differential gene expression was defined as significant (P < 0.05) and greater than or equal to a twofold difference above a H0 classification. From approximately 20,000 genes, on average 46% appeared to be expressed. On day 1 postirradiation for H2-3, approximately 2-3 times more genes appeared up-regulated (1,418 vs. 550) or down-regulated (1,603 vs. 735) compared to H1-2. This pattern became more pronounced at day 2 while the number of differentially expressed genes decreased. The specific genes showed an enrichment of biological processes coding for immune system processes, natural killer cell activation and immune response (P = 1 × E-06 up to 9 × E-14). Based on the P values, magnitude and sustained differential gene expression over time, we selected 89 candidate genes for validation using qRT-PCR. Ultimately, 22 genes were confirmed for identification of H1-3 classifications and seven genes for identification of H2-3 classifications using qRT-PCR. For H1-3 classifications, most genes were

  7. A Comparison of Acute and Chronic Toxicity for Men With Low-Risk Prostate Cancer Treated With Intensity-Modulated Radiation Therapy or {sup 125}I Permanent Implant

    SciTech Connect

    Eade, Thomas N.; Horwitz, Eric M. Ruth, Karen; Buyyounouski, Mark K.; D'Ambrosio, David J.; Feigenberg, Steven J.; Chen, David Y.T.; Pollack, Alan

    2008-06-01

    Purpose: To compare the toxicity and biochemical outcomes of intensity-modulated radiation therapy (IMRT) and {sup 125}I transperineal permanent prostate seed implant ({sup 125}I) for patients with low-risk prostate cancer. Methods and Materials: Between 1998 and 2004, a total of 374 low-risk patients (prostate-specific antigen < 10 ng/ml, T1c-T2b, Gleason score of 6 or less, and no neoadjuvant hormones) were treated at Fox Chase Cancer Center (216 IMRT and 158 {sup 125}I patients). Median follow-up was 43 months for IMRT and 48 months for {sup 125}I. The IMRT prescription dose ranged from 74-78 Gy, and {sup 125}I prescription was 145 Gy. Acute and late gastrointestinal (GI) and genitourinary (GU) toxicity was recorded by using a modified Radiation Therapy Oncology Group scale. Freedom from biochemical failure was defined by using the Phoenix definition (prostate-specific antigen nadir + 2.0 ng/ml). Results: Patients treated by using IMRT were more likely to be older and have a higher baseline American Urological Association symptom index score, history of previous transurethral resection of the prostate, and larger prostate volumes. On multivariate analysis, IMRT was an independent predictor of lower acute and late Grade 2 or higher GU toxicity and late Grade 2 or higher GI toxicity. Three-year actuarial estimates of late Grade 2 or higher toxicity were 2.4% for GI and 3.5% for GU by using IMRT compared with 7.7% for GI and 19.2% for GU for {sup 125}I, respectively. Four-year actuarial estimates of freedom from biochemical failure were 99.5% for IMRT and 93.5% for {sup 125}I (p = 0.09). Conclusions: The IMRT and {sup 125}I produce similar outcomes, although IMRT appears to have less acute and late toxicity.

  8. Inhibition of the alternative complement pathway by antisense oligonucleotides targeting complement factor B improves lupus nephritis in mice.

    PubMed

    Grossman, Tamar R; Hettrick, Lisa A; Johnson, Robert B; Hung, Gene; Peralta, Raechel; Watt, Andrew; Henry, Scott P; Adamson, Peter; Monia, Brett P; McCaleb, Michael L

    2016-06-01

    Systemic lupus erythematosus is an autoimmune disease that manifests in widespread complement activation and deposition of complement fragments in the kidney. The complement pathway is believed to play a significant role in the pathogenesis and in the development of lupus nephritis. Complement factor B is an important activator of the alternative complement pathway and increasing evidence supports reducing factor B as a potential novel therapy to lupus nephritis. Here we investigated whether pharmacological reduction of factor B expression using antisense oligonucleotides could be an effective approach for the treatment of lupus nephritis. We identified potent and well tolerated factor B antisense oligonucleotides that resulted in significant reductions in hepatic and plasma factor B levels when administered to normal mice. To test the effects of factor B antisense oligonucleotides on lupus nephritis, we used two different mouse models, NZB/W F1 and MRL/lpr mice, that exhibit lupus nephritis like renal pathology. Antisense oligonucleotides mediated reductions in circulating factor B levels were associated with significant improvements in renal pathology, reduced glomerular C3 deposition and proteinuria, and improved survival. These data support the strategy of using factor B antisense oligonucleotides for treatment of lupus nephritis in humans.

  9. Evaluation of genotoxicity of the acute gamma radiation on earthworm Eisenia fetida using single cell gel electrophoresis technique (Comet assay).

    PubMed

    Sowmithra, K; Shetty, N J; Jha, S K; Chaubey, R C

    2015-12-01

    Earthworms (Eisenia fetida) most suitable biological indicators of radioactive pollution. Radiation-induced lesions in DNA can be considered to be molecular markers for early effects of ionizing radiation. Gamma radiation produces a wide spectrum of DNA. Some of these lesions, i.e., DNA strand breaks and alkali labile sites can be detected by the single-cell gel electrophoresis (SCGE) or comet assay by measuring the migration of DNA from immobilized nuclear DNA. E. fetida were exposed to different doses of gamma radiation, i.e., 1, 5, 10, 20, 30, 40 and 50Gy, and comet assay was performed for all the doses along with control at 1, 3 and 5h post irradiation to evaluate the genotoxicity of gamma radiation in this organism. The DNA damage was measured as percentage of comet tail DNA. A significant increase in DNA damage was observed in samples exposed to 5Gy and above, and the increase in DNA damage was dose dependent i.e., DNA damage was increased with increased doses of radiation. The highest DNA damage was noticed at 1h post irradiation and gradually decreased with time, i.e., at 3 and 5h post irradiation. The present study reveals that gamma radiation induces DNA damage in E. fetida and the comet assay is a sensitive and rapid method for its detection to detect genotoxicity of gamma radiation.

  10. Acute Skin Toxicity Following Stereotactic Body Radiation Therapy for Stage I Non-Small-Cell Lung Cancer: Who's at Risk?

    SciTech Connect

    Hoppe, Bradford S.; Laser, Benjamin; Kowalski, Alex V.; Fontenla, Sandra C.; Pena-Greenberg, Elizabeth; Yorke, Ellen D.; Lovelock, D. Michael; Hunt, Margie A.; Rosenzweig, Kenneth E.

    2008-12-01

    Purpose: We examined the rate of acute skin toxicity within a prospectively managed database of patients treated for early-stage non-small-cell lung cancer (NSCLC) and investigated factors that might predict skin toxicity. Methods: From May 2006 through January 2008, 50 patients with Stage I NSCLC were treated at Memorial Sloan-Kettering Cancer Center with 60 Gy in three fractions or 44-48 Gy in four fractions. Patients were treated with multiple coplanar beams (3-7, median 4) with a 6 MV linac using intensity-modulated radiotherapy (IMRT) and dynamic multileaf collimation. Toxicity grading was performed and based on the National Cancer Institute Common Terminology Criteria for Adverse Effects. Factors associated with Grade 2 or higher acute skin reactions were calculated by Fisher's exact test. Results: After a minimum 3 months of follow-up, 19 patients (38%) developed Grade 1, 4 patients (8%) Grade 2, 2 patients (4%) Grade 3, and 1 patient Grade 4 acute skin toxicity. Factors associated with Grade 2 or higher acute skin toxicity included using only 3 beams (p = 0.0007), distance from the tumor to the posterior chest wall skin of less than 5 cm (p = 0.006), and a maximum skin dose of 50% or higher of the prescribed dose (p = 0.02). Conclusions: SBRT can be associated with significant skin toxicity. One must consider the skin dose when evaluating the treatment plan and consider the bolus effect of immobilization devices.

  11. Lipoproteins accumulate in immune deposits and are modified by lipid peroxidation in passive Heymann nephritis.

    PubMed Central

    Exner, M.; Susani, M.; Witztum, J. L.; Hovorka, A.; Curtiss, L. K.; Spitzauer, S.; Kerjaschki, D.

    1996-01-01

    Proteinuria in passive Heymann nephritis is primarily caused by reactive oxygen species that are produced by glomerular cells. Reactive oxygen species apparently exert their damaging effects on the glomerular filter by lipid peroxidation and subsequent adduct formation on matrix proteins of glomerular basement membranes. This raised the question as to the source of polyunsaturated fatty acids required as substrates for lipid peroxidation. Here we have localized by immunocytochemistry rat apolipoprotein E and apolipoprotein B within subepithelial immune deposits. Moreover, apolipoprotein B extracted from isolated glomeruli of proteinuric passive Heymann nephritis rats shows degradation and lipid peroxidation adduct formation, similar to apoproteins of oxidized lipoproteins in atherosclerotic lesions. These data provide evidence that lipoproteins accumulate within immune deposits and suggest that their lipids generate lipid-peroxidation-derived reactive compounds. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:8863678

  12. Systemic karyomegaly associated with chronic interstitial nephritis. A new disease entity?

    PubMed

    Mihatsch, M J; Gudat, F; Zollinger, H U; Heierli, C; Thölen, H; Reutter, F W

    1979-08-01

    In 3 patients, two 26 and one 29 years of age, a nephropathy was accidentally discovered which progressed to end stage renal failure within 4 to 6 years. Renal biopsy revealed an unusually marked karyomegaly particularly of the tubular epithelium. These cytopathological changes were associated with chronic interstitial nephritis. Biopsies of other organs, i.e. liver, colon, bronchus and lungs indicated in 2 patients a systemic distribution of the karyomegaly, particularly in mesenchymal cells. Neither the chronic interstitial nephritis nor the karyomegaly could be ascribed to a recognized etiology. This suggests, therefore, that there is a relationship between these changes. The karyomegaly could be the result of the action of some antimitotic agent such as chemical toxins or virus infections.

  13. [Systemic karyomegaly with chronic interstitial nephritis. Discussion of the disease picture based on an autopsy case].

    PubMed

    Moch, H; Spöndlin, M; Schmassmann, A; Mihatsch, M J

    1994-02-01

    Systemic karyomegaly associated with interstitial nephritis was first described in 1978 by Mihatsch. Seven cases have been reported to date. We give an account of an autopsy case of systemic karyomegaly in a 30-year-old Italian man. Bizarre enlargement of nuclei was found in renal tubular epithelial cells, Schwann cells and in smooth muscle cells of vessels and bowel and, less obviously, in endothelial and adventitial cells of vessels, in alveolar epithelial cells and in astrocytes of the brain. These findings were associated with chronic interstitial nephritis, nonspecific hepatopathy, adenocarcinoma of the rectum and multiple sclerosis. The clinical course was marked by chronic renal failure, chronic haemodialysis and renal transplantation. The patient died 8 years after diagnosis in septic-toxic shock. The aetiology and pathogenesis of the disease are discussed.

  14. Live cell detection of chromosome 2 deletion and Sfpi1/PU1 loss in radiation-induced mouse acute myeloid leukaemia☆

    PubMed Central

    Olme, C.-H.; Finnon, R.; Brown, N.; Kabacik, S.; Bouffler, S.D.; Badie, C.

    2013-01-01

    The CBA/H mouse model of radiation-induced acute myeloid leukaemia (rAML) has been studied for decades to bring to light the molecular mechanisms associated with multistage carcinogenesis. A specific interstitial deletion of chromosome 2 found in a high proportion of rAML is recognised as the initiating event. The deletion leads to the loss of Sfpi, a gene essential for haematopoietic development. Its product, the transcription factor PU.1 acts as a tumour suppressor in this model. Although the deletion can be detected early following ionising radiation exposure by cytogenetic techniques, precise characterisation of the haematopoietic cells carrying the deletion and the study of their fate in vivo cannot be achieved. Here, using a genetically engineered C57BL/6 mouse model expressing the GFP fluorescent molecule under the control of the Sfpi1 promoter, which we have bred onto the rAML-susceptible CBA/H strain, we demonstrate that GFP expression did not interfere with X-ray induced leukaemia incidence and that GFP fluorescence in live leukaemic cells is a surrogate marker of radiation-induced chromosome 2 deletions with or without point mutations on the remaining allele of the Sfpi1 gene. This study presents the first experimental evidence for the detection of this leukaemia initiating event in live leukemic cells. PMID:23806234

  15. Inhibition of the TWEAK/Fn14 pathway attenuates renal disease in nephrotoxic serum nephritis.

    PubMed

    Xia, Yumin; Campbell, Sean R; Broder, Anna; Herlitz, Leal; Abadi, Maria; Wu, Ping; Michaelson, Jennifer S; Burkly, Linda C; Putterman, Chaim

    2012-11-01

    Previously it was shown that the TNF superfamily member TWEAK (TNFSF12) acts through its receptor, Fn14, to promote proinflammatory responses in kidney cells, including the production of MCP-1, RANTES, IP-10 and KC. In addition, the TWEAK/Fn14 pathway promotes mesangial cell proliferation, vascular cell activation, and renal cell death. To study the relevance of the TWEAK/Fn14 pathway in the pathogenesis of antibody-induced nephritis using the mouse model of nephrotoxic serum nephritis (NTN), we induced NTN by passive transfer of rabbit anti-glomerular antibodies into Fn14 knockout (KO) and wild type (WT) mice. Severe proteinuria as well as renal histopathology were induced in WT but not in Fn14 KO mice. Similarly, a pharmacologic approach of anti-TWEAK mAb administration into WT mice in the NTN model significantly ameliorated proteinuria and improved kidney histology. Anti-TWEAK treatment did not affect the generation of mouse anti-rabbit antibodies; however, within the kidney there was a significant decrease in glomerular immunoglobulin deposition, as well as macrophage infiltrates and tubulointerstitial fibrosis. The mechanism of action is most likely due to reductions in downstream targets of TWEAK/Fn14 signaling, including reduced renal expression of MCP-1, VCAM-1, IP-10, RANTES as well as Fn14 itself, and other molecular pathways associated with fibrosis in anti-TWEAK treated mice. Thus, TWEAK/Fn14 interactions are instrumental in the pathogenesis of nephritis in the NTN model, apparently mediating a cascade of pathologic events locally in the kidney rather than by impacting the systemic immune response. Disrupting TWEAK/Fn14 interactions may be an innovative kidney-protective approach for the treatment of lupus nephritis and other antibody-induced renal diseases.

  16. Treatment of lupus nephritis with total lymphoid irradiation. Observations during a 12-79-month followup

    SciTech Connect

    Strober, S.; Farinas, M.C.; Field, E.H.; Solovera, J.J.; Kiberd, B.A.; Myers, B.D.; Hoppe, R.T.

    1988-07-01

    Seventeen patients with intractable lupus nephritis and nephrotic syndrome were treated with total lymphoid irradiation. Statistically significant improvement in mean renal disease and serologic activity parameters occurred within 3 months and persisted for at least 3 years. Although there was a marked reduction of T helper cell numbers and function after total lymphoid irradiation, recovery of these parameters was not associated with a return of disease activity. Risks of sterility, severe infections, and hematologic malignancy appeared to be lower than with alkylating agents.

  17. Nuclear medicine in acute and chronic renal failure

    SciTech Connect

    Sherman, R.A.; Byun, K.J.

    1982-07-01

    The diagnostic value of renal scintiscans in patients with acute or chronic renal failure has not been emphasized other than for the estimation of renal size. /sup 131/I OIH, /sup 67/gallium, /sup 99m/TcDTPA, glucoheptonate and DMSA all may be valuable in a variety of specific settings. Acute renal failure due to acute tubular necrosis, hepatorenal syndrome, acute interstitial nephritis, cortical necrosis, renal artery embolism, or acute pyelonephritis may be recognized. Data useful in the diagnosis and management of the patient with obstructive or reflux nephropathy may be obtained. Radionuclide studies in patients with chronic renal failure may help make apparent such causes as renal artery stenosis, chronic pyelonephritis or lymphomatous kidney infiltration. Future correlation of scanning results with renal pathology promises to further expand nuclear medicine's utility in the noninvasive diagnosis of renal disease.

  18. Acute and chronic intakes of fallout radionuclides by Marshallese from nuclear weapons testing at Bikini and Enewetak and related internal radiation doses.

    PubMed

    Simon, Steven L; Bouville, André; Melo, Dunstana; Beck, Harold L; Weinstock, Robert M

    2010-08-01

    Annual internal radiation doses resulting from both acute and chronic intakes of all important dose-contributing radionuclides occurring in fallout from nuclear weapons testing at Bikini and Enewetak from 1946 through 1958 have been estimated for the residents living on all atolls and separate reef islands of the Marshall Islands. Internal radiation absorbed doses to the tissues most at risk to cancer induction (red bone marrow, thyroid, stomach, and colon) have been estimated for representative persons of all population communities for all birth years from 1929 through 1968, and for all years of exposure from 1948 through 1970. The acute intake estimates rely on a model using, as its basis, historical urine bioassay data, for members of the Rongelap Island and Ailinginae communities as well as for Rongerik residents. The model also utilizes fallout times of arrival and radionuclide deposition densities estimated for all tests and all atolls. Acute intakes of 63 radionuclides were estimated for the populations of the 20 inhabited atolls and for the communities that were relocated during the testing years for reasons of safety and decontamination. The model used for chronic intake estimates is based on reported whole-body, urine, and blood counting data for residents of Utrik and Rongelap. Dose conversion coefficients relating intake to organ absorbed dose were developed using internationally accepted models but specifically tailored for intakes of particulate fallout by consideration of literature-based evidence to choose the most appropriate alimentary tract absorption fraction (f1) values. Dose estimates were much higher for the thyroid gland than for red marrow, stomach wall, or colon. The highest thyroid doses to adults were about 7,600 mGy for the people exposed on Rongelap; thyroid doses to adults were much lower, by a factor of 100 or more, for the people exposed on the populated atolls of Kwajalein and Majuro. The estimates of radionuclide intake and

  19. Normal Tissue Complication Probability Analysis of Acute Gastrointestinal Toxicity in Cervical Cancer Patients Undergoing Intensity Modulated Radiation Therapy and Concurrent Cisplatin

    SciTech Connect

    Simpson, Daniel R.; Song, William Y.; Moiseenko, Vitali; Rose, Brent S.; Yashar, Catheryn M.; Mundt, Arno J.; Mell, Loren K.

    2012-05-01

    Purpose: To test the hypothesis that increased bowel radiation dose is associated with acute gastrointestinal (GI) toxicity in cervical cancer patients undergoing concurrent chemotherapy and intensity-modulated radiation therapy (IMRT), using a previously derived normal tissue complication probability (NTCP) model. Methods: Fifty patients with Stage I-III cervical cancer undergoing IMRT and concurrent weekly cisplatin were analyzed. Acute GI toxicity was graded using the Radiation Therapy Oncology Group scale, excluding upper GI events. A logistic model was used to test correlations between acute GI toxicity and bowel dosimetric parameters. The primary objective was to test the association between Grade {>=}2 GI toxicity and the volume of bowel receiving {>=}45 Gy (V{sub 45}) using the logistic model. Results: Twenty-three patients (46%) had Grade {>=}2 GI toxicity. The mean (SD) V{sub 45} was 143 mL (99). The mean V{sub 45} values for patients with and without Grade {>=}2 GI toxicity were 176 vs. 115 mL, respectively. Twenty patients (40%) had V{sub 45} >150 mL. The proportion of patients with Grade {>=}2 GI toxicity with and without V{sub 45} >150 mL was 65% vs. 33% (p = 0.03). Logistic model parameter estimates V50 and {gamma} were 161 mL (95% confidence interval [CI] 60-399) and 0.31 (95% CI 0.04-0.63), respectively. On multivariable logistic regression, increased V{sub 45} was associated with an increased odds of Grade {>=}2 GI toxicity (odds ratio 2.19 per 100 mL, 95% CI 1.04-4.63, p = 0.04). Conclusions: Our results support the hypothesis that increasing bowel V{sub 45} is correlated with increased GI toxicity in cervical cancer patients undergoing IMRT and concurrent cisplatin. Reducing bowel V{sub 45} could reduce the risk of Grade {>=}2 GI toxicity by approximately 50% per 100 mL of bowel spared.

  20. ACUTE AND CHRONIC INTAKES OF FALLOUT RADIONUCLIDES BY MARSHALLESE FROM NUCLEAR WEAPONS TESTING AT BIKINI AND ENEWETAK AND RELATED INTERNAL RADIATION DOSES

    PubMed Central

    Simon, Steven L.; Bouville, André; Melo, Dunstana; Beck, Harold L.; Weinstock, Robert M.

    2014-01-01

    Annual internal radiation doses resulting from both acute and chronic intakes of all important dose-contributing radionuclides occurring in fallout from nuclear weapons testing at Bikini and Enewetak from 1946 through 1958 have been estimated for the residents living on all atolls and separate reef islands of the Marshall Islands. Internal radiation absorbed doses to the tissues most at risk to cancer induction (red bone marrow, thyroid, stomach, and colon) have been estimated for representative persons of all population communities for all birth years from 1929 through 1968, and for all years of exposure from 1948 through 1970. The acute intake estimates rely on a model using, as its basis, historical urine bioassay data, for members of the Rongelap Island and Ailinginae communities as well as for Rongerik residents. The model also utilizes fallout times of arrival and radionuclide deposition densities estimated for all tests and all atolls. Acute intakes of 63 radionuclides were estimated for the populations of the 20 inhabited atolls and for the communities that were relocated during the testing years for reasons of safety and decontamination. The model used for chronic intake estimates is based on reported whole-body, urine, and blood counting data for residents of Utrik and Rongelap. Dose conversion coefficients relating intake to organ absorbed dose were developed using internationally accepted models but specifically tailored for intakes of particulate fallout by consideration of literature-based evidence to choose the most appropriate alimentary tract absorption fraction (f1) values. Dose estimates were much higher for the thyroid gland than for red marrow, stomach wall, or colon. The highest thyroid doses to adults were about 7,600 mGy for the people exposed on Rongelap; thyroid doses to adults were much lower, by a factor of 100 or more, for the people exposed on the populated atolls of Kwajalein and Majuro. The estimates of radionuclide intake and

  1. Acute and chronic intakes of fallout radionuclides by Marshallese from nuclear weapons testing at Bikini and Enewetak and related internal radiation doses.

    PubMed

    Simon, Steven L; Bouville, André; Melo, Dunstana; Beck, Harold L; Weinstock, Robert M

    2010-08-01

    Annual internal radiation doses resulting from both acute and chronic intakes of all important dose-contributing radionuclides occurring in fallout from nuclear weapons testing at Bikini and Enewetak from 1946 through 1958 have been estimated for the residents living on all atolls and separate reef islands of the Marshall Islands. Internal radiation absorbed doses to the tissues most at risk to cancer induction (red bone marrow, thyroid, stomach, and colon) have been estimated for representative persons of all population communities for all birth years from 1929 through 1968, and for all years of exposure from 1948 through 1970. The acute intake estimates rely on a model using, as its basis, historical urine bioassay data, for members of the Rongelap Island and Ailinginae communities as well as for Rongerik residents. The model also utilizes fallout times of arrival and radionuclide deposition densities estimated for all tests and all atolls. Acute intakes of 63 radionuclides were estimated for the populations of the 20 inhabited atolls and for the communities that were relocated during the testing years for reasons of safety and decontamination. The model used for chronic intake estimates is based on reported whole-body, urine, and blood counting data for residents of Utrik and Rongelap. Dose conversion coefficients relating intake to organ absorbed dose were developed using internationally accepted models but specifically tailored for intakes of particulate fallout by consideration of literature-based evidence to choose the most appropriate alimentary tract absorption fraction (f1) values. Dose estimates were much higher for the thyroid gland than for red marrow, stomach wall, or colon. The highest thyroid doses to adults were about 7,600 mGy for the people exposed on Rongelap; thyroid doses to adults were much lower, by a factor of 100 or more, for the people exposed on the populated atolls of Kwajalein and Majuro. The estimates of radionuclide intake and

  2. Serum Thiols as a Biomarker of Disease Activity in Lupus Nephritis

    PubMed Central

    Lalwani, Pritesh; de Souza, Giselle Katiane Bonfim Bacelar; de Lima, Domingos Savio Nunes; Passos, Luiz Fernando Souza; Boechat, Antonio Luiz; Lima, Emerson Silva

    2015-01-01

    Lupus Nephritis (LN) develops in more than half of the Systemic Lupus Erythematous (SLE) patients. However, lack of reliable, specific biomarkers for LN hampers clinical management of patients and impedes development of new therapeutics. The goal of this study was to investigate whether oxidative stress biomarkers in patients with SLE is predictive of renal pathology. Serum biochemical and oxidative stress markers were measured in patients with inactive lupus, active lupus with and without nephritis and compared to healthy control group. To assess the predictive performance of biomarkers, Receiver Operating Characteristic (ROC) curves were constructed and cut-offs were used to identify SLE patients with nephritis. We observed an increased oxidative stress response in all SLE patients compared to healthy controls. Among the several biomarkers tested, serum thiols had a significant inverse association with SLE Disease Activity Index (SLEDAI). Interestingly, thiols were able too aptly differentiate between SLE patients with and without renal pathology, and serum thiol levels were not affected by immunosuppressive drug therapy. The decreased thiols in SLE correlated significantly with serum creatinine and serum C3 levels. Further retrospective evaluation using serum creatinine or C3 levels in combination with thiol’s cutoff values from ROC analysis, we could positively predict chronicity of renal pathology in SLE patients. In summary, serum thiols emerge as an inexpensive and reliable indicator of LN, which may not only help in early identification of renal pathology but also aid in the therapeutic management of the disease, in developing countries with resource poor settings. PMID:25799079

  3. Evidence suggesting a role for hydroxyl radical in passive Heymann nephritis in rats

    SciTech Connect

    Shah, S.V. )

    1988-03-01

    The authors examined the effect of scavengers of reactive oxygen metabolites on proteinuria in the passive Heymann nephritis model of membranous nephropathy. Passive Heymann nephritis was induced by a single intravenous injection of anti-Fx1A IgG in a dose of 10 mg/100 g body weight. Superoxide dismutase, a scavenger of superoxide or catalase which destroys hydrogen peroxide, did not affect the proteinuria. In contrasts, dimethylthiourea (DMTU), a scavenger of hydroxyl radical, markedly reduced the proteinuria. Experiments with {sup 125}I-labeled anti-Fx1A antibody demonstrated that DMTU did not affect the amount of antibody deposited in the kidney. Semiquantitative estimation of IgG and complement deposition in the kidneys showed no differences between the DMTU-treated and control rats. A second hydroxyl radical scavenger, sodium benzoate also resulted in marked reduction in proteinuria. Because of the participation of iron in biological systems to generate hydroxyl radical, they also examined the effect of deferoxamine (DFO) an iron chelator, on the anti-Fx1A-induced proteinuria. There was a significant reduction in proteinuria in rats treated concurrently with DFO. These results suggest a potential role of the hydroxyl radical in passive Heymann nephritis.

  4. Tubular up-regulation of clusterin mRNA in murine lupus-like nephritis.

    PubMed Central

    Moll, S.; Menoud, P. A.; French, L.; Sappino, A. P.; Pastore, Y.; Schifferli, J. A.; Izui, S.

    1998-01-01

    Clusterin, a widely distributed glycoprotein, is detected in most tissues and in numerous physiological fluids. In the kidney, this protein is constitutively expressed in tubular epithelial cells, and its expression is enhanced following tubular injuries. In addition, clusterin has been detected in glomerular immune deposits of glomerulonephritis. The present study was designed to define the sites of clusterin mRNA accumulation in murine lupus-like nephritis in comparison with murine tubulopathies. In lupus-like nephritis, a significant increase of clusterin mRNA abundance was demonstrated. This up-regulation was localized exclusively in tubular epithelial cells exhibiting tubulointerstitial alterations, whereas no clusterin mRNA was detectable in diseased glomeruli, excluding an active synthesis of clusterin by glomerular cells. A similar tubular increase of clusterin mRNA abundance was observed in myeloma-like cast nephropathy induced by IgG3 monoclonal cryoglobulins and even in the absence of any detectable histological alterations in a model of septic shock induced by the injection of bacterial lipopolysaccharides. Our results suggest that tubular epithelial cells are the only sites of clusterin mRNA accumulation during the course of lupus-like nephritis and that the tubular up-regulation of clusterin gene expression may reflect the cellular response to various types of tubular injuries. Images Figure 1 Figure 3 Figure 4 Figure 5 Figure 7 PMID:9546356

  5. Renal Interstitial Arteriosclerotic Lesions in Lupus Nephritis Patients: A Cohort Study from China

    PubMed Central

    Qin, Dan-dan; Wu, Li-hua; Song, Yan; Yu, Feng; Wang, Su-xia; Liu, Gang; Zhao, Ming-hui

    2015-01-01

    Objective The aim of this study was to evaluate renal arteriosclerotic lesions in patients with lupus nephritis and investigate their associations with clinical and pathological characteristics, especially cardio-vascular features. Design A retrospective cohort study. Participants Seventy-nine patients with renal biopsy-proven lupus nephritis, diagnosed between January 2000 and June 2008 from Peking University First Hospital. Results In clinico-pathological data, patients with arteriosclerosis had higher ratio of hypertension and more severe renal injury indices compared with patients with no renal vascular lesions. More importantly, patients with renal arteriosclerosis had worse cardiac structure and function under transthoracic echocardiographic examination. Patients with renal arteriosclerosis tend to have higher ratios of combined endpoints compared with those of no renal vascular lesions, although the difference didn’t reach statistical meanings (P = 0.104). Conclusion Renal arteriosclerotic lesion was common and associated with vascular immune complex deposits in lupus nephritis. It might have a certain degree of association with poor outcomes and cardiovascular events, which needs further explorations. PMID:26544865

  6. Karyomegalic interstitial nephritis: further support for a distinct entity and evidence for a genetic defect.

    PubMed

    Spoendlin, M; Moch, H; Brunner, F; Brunner, W; Burger, H R; Kiss, D; Wegmann, W; Dalquen, P; Oberholzer, M; Thiel, G

    1995-02-01

    Karyomegalic interstitial nephritis was first described in 1979 by Mihatsch, who was reporting three such cases. We report here four additional cases as well as two family investigations. Our findings support the association of karyomegaly and interstitial nephritis as a distinct entity. Typical clinical features are asymptomatic progressive renal failure in the third decade of life and recurrent infections, mostly of the upper respiratory tract. Histologic alterations consist of markedly enlarged and hyperchromic nuclei in many tubular epithelial cells throughout the nephron accompanied by interstitial fibrosis in the surrounding atrophic tubules. Karyomegaly is not limited to the kidneys. In one case, autopsy revealed karyomegaly in epithelial and mesenchymal cells of many other organs. However, no association of karyomegaly with further histologic damage is evident except in the kidneys. Because of the familial clustering, karyomegalic interstitial nephritis seems to be an inherited disease. Examination of the nuclear proliferation-associated structures proliferating cell nuclear antigen/cyclin, Ki 67, and p53 suggests an inhibition of mitosis in karyomegalic cells. The finding of the same HLA haplotype, A9/B35, in four of six HLA-typed cases suggests the possibility of a genetic defect on chromosome 6, which is inherited and linked to the HLA locus.

  7. Tubulointerstitial nephritis is a dominant feature of hereditary apolipoprotein A-I amyloidosis.

    PubMed

    Gregorini, Gina; Izzi, Claudia; Ravani, Pietro; Obici, Laura; Dallera, Nadia; Del Barba, Andrea; Negrinelli, Alessandro; Tardanico, Regina; Nardi, Matilde; Biasi, Luciano; Scalvini, Tiziano; Merlini, Giampaolo; Scolari, Francesco

    2015-06-01

    Apolipoprotein A-I is the main protein of high-density lipoprotein particles, and is encoded by the APOA1 gene. Several APOA1 mutations have been found, either affecting the lecithin:cholesterol acyltransferase activity, determining familial HDL deficiency, or resulting in amyloid formation with prevalent deposits in the kidney and liver. Evaluation of familial tubulointerstitial nephritis in patients with the Leu75Pro APOA-I amyloidosis mutation resulted in the identification of 253 carriers belonging to 50 families from Brescia, Italy. A total of 219 mutation carriers underwent clinical, laboratory, and instrumental tests. Of these, 62% had renal, hepatic, and testicular disease; 38% were asymptomatic. The disease showed an age-dependent penetrance. Tubulointerstitial nephritis was diagnosed in 49% of the carriers, 13% of whom progressed to kidney failure requiring dialysis. Hepatic involvement with elevation of cholestasis indices was diagnosed in 30% of the carriers, 38% of whom developed portal hypertension. Impaired spermatogenesis and hypogonadism was found in 68% of male carriers. The cholesterol levels were lower than normal in 80% of the mutation carriers. Thus, tubulointerstitial nephritis was highly prevalent in this large series of patients with Leu75Pro apoA-I amyloidosis. Persistent elevation of alkaline phosphatase, reduced HDL cholesterol plasma levels, and hypogonadism in men are key diagnostic features of this form of amyloidosis.

  8. Tubular up-regulation of clusterin mRNA in murine lupus-like nephritis.

    PubMed

    Moll, S; Menoud, P A; French, L; Sappino, A P; Pastore, Y; Schifferli, J A; Izui, S

    1998-04-01

    Clusterin, a widely distributed glycoprotein, is detected in most tissues and in numerous physiological fluids. In the kidney, this protein is constitutively expressed in tubular epithelial cells, and its expression is enhanced following tubular injuries. In addition, clusterin has been detected in glomerular immune deposits of glomerulonephritis. The present study was designed to define the sites of clusterin mRNA accumulation in murine lupus-like nephritis in comparison with murine tubulopathies. In lupus-like nephritis, a significant increase of clusterin mRNA abundance was demonstrated. This up-regulation was localized exclusively in tubular epithelial cells exhibiting tubulointerstitial alterations, whereas no clusterin mRNA was detectable in diseased glomeruli, excluding an active synthesis of clusterin by glomerular cells. A similar tubular increase of clusterin mRNA abundance was observed in myeloma-like cast nephropathy induced by IgG3 monoclonal cryoglobulins and even in the absence of any detectable histological alterations in a model of septic shock induced by the injection of bacterial lipopolysaccharides. Our results suggest that tubular epithelial cells are the only sites of clusterin mRNA accumulation during the course of lupus-like nephritis and that the tubular up-regulation of clusterin gene expression may reflect the cellular response to various types of tubular injuries.

  9. IgG4 deposits in pure and combined membranous lupus nephritis.

    PubMed

    Herrera van Oostdam, David; Martínez Martínez, Marco U; Oros-Ovalle, Cuauhtémoc; Martínez-Gala, David; Jaimes Piñón, Gerardo T; Abud Mendoza, Carlos

    2016-06-01

    The aim of this study is to determine the frequency and prognosis of IgG4 deposits in renal biopsy of patients with membranous lupus nephritis (MLN). This is a retrospective cohort study in which we included patients with class V alone or combined (III/V or IV/V) of lupus nephritis according to the 2004 ISN/RPS. All the patients included must have availability of renal tissue for immunohistochemistry analyses. We excluded other classes of lupus nephritis. The renal tissue was examined by a nephro-pathologist. We included 65 patients with MLN; of these, 24 (37 %) were class V, and the other had proliferative concomitant with membranous patterns. Seven renal specimens had IgG4 deposits (10 %). Patients with IgG4 deposits had higher levels of eosinophils in serum. All of the patients with IgG4 had renal involvement as first manifestations of systemic lupus erythematosus. The rate of renal failure was 42 and 43 % in IgG4 positive and negative, respectively, 28 % of IgG4 required renal replacement therapy. From a histological view, 42 % of IgG4 had evidence of arteriolar vasculitis in renal biopsies. Lupus patients with IgG4 deposits were more likely to have renal involvement as a first manifestation of systemic lupus erythematosus, and they course with a worse prognosis since they required more dialysis. Also, they have more probability of vascular inflammation on the renal biopsy.

  10. Complete Remission of Acute Myeloid Leukemia following Cisplatin Based Concurrent Therapy with Radiation for Squamous Cell Laryngeal Cancer

    PubMed Central

    Gill, Harpaul S.; Higgins, Kristin A.; Saba, Nabil F.; Kota, Vamsi K.

    2016-01-01

    Acute myeloid leukemia (AML) is a myeloid disorder with several established treatment regimens depending on patient and leukemic factors. Cisplatin is known to have strong leukemogenic potential and is rarely used even as salvage therapy in relapsed or refractory AML. We present a patient simultaneously diagnosed with AML and squamous cell carcinoma of the larynx, who was found to be in complete remission from AML following treatment with cisplatin based chemoradiotherapy for his laryngeal cancer. PMID:27127664

  11. Neurobehavioural Changes and Brain Oxidative Stress Induced by Acute Exposure to GSM900 Mobile Phone Radiations in Zebrafish (Danio rerio).

    PubMed

    Nirwane, Abhijit; Sridhar, Vinay; Majumdar, Anuradha

    2016-04-01

    The impact of mobile phone (MP) radiation on the brain is of specific interest to the scientific community and warrants investigations, as MP is held close to the head. Studies on humans and rodents revealed hazards MP radiation associated such as brain tumors, impairment in cognition, hearing etc. Melatonin (MT) is an important modulator of CNS functioning and is a neural antioxidant hormone. Zebrafish has emerged as a popular model organism for CNS studies. Herein, we evaluated the impact of GSM900MP (GSM900MP) radiation exposure daily for 1 hr for 14 days with the SAR of 1.34W/Kg on neurobehavioral and oxidative stress parameters in zebrafish. Our study revealed that, GSM900MP radiation exposure, significantly decreased time spent near social stimulus zone and increased total distance travelled, in social interaction test. In the novel tank dive test, the GSM900MP radiation exposure elicited anxiety as revealed by significantly increased time spent in bottom half; freezing bouts and duration and decreased distance travelled, average velocity, and number of entries to upper half of the tank. Exposed zebrafish spent less time in the novel arm of the Y-Maze, corroborating significant impairment in learning as compared to the control group. Exposure decreased superoxide dismutase (SOD), catalase (CAT) activities whereas, increased levels of reduced glutathione (GSH) and lipid peroxidation (LPO) was encountered showing compromised antioxidant defense. Treatment with MT significantly reversed the above neurobehavioral and oxidative derangements induced by GSM900MP radiation exposure. This study traced GSM900MP radiation exposure induced neurobehavioral aberrations and alterations in brain oxidative status. Furthermore, MT proved to be a promising therapeutic candidate in ameliorating such outcomes in zebrafish.

  12. Neurobehavioural Changes and Brain Oxidative Stress Induced by Acute Exposure to GSM900 Mobile Phone Radiations in Zebrafish (Danio rerio).

    PubMed

    Nirwane, Abhijit; Sridhar, Vinay; Majumdar, Anuradha

    2016-04-01

    The impact of mobile phone (MP) radiation on the brain is of specific interest to the scientific community and warrants investigations, as MP is held close to the head. Studies on humans and rodents revealed hazards MP radiation associated such as brain tumors, impairment in cognition, hearing etc. Melatonin (MT) is an important modulator of CNS functioning and is a neural antioxidant hormone. Zebrafish has emerged as a popular model organism for CNS studies. Herein, we evaluated the impact of GSM900MP (GSM900MP) radiation exposure daily for 1 hr for 14 days with the SAR of 1.34W/Kg on neurobehavioral and oxidative stress parameters in zebrafish. Our study revealed that, GSM900MP radiation exposure, significantly decreased time spent near social stimulus zone and increased total distance travelled, in social interaction test. In the novel tank dive test, the GSM900MP radiation exposure elicited anxiety as revealed by significantly increased time spent in bottom half; freezing bouts and duration and decreased distance travelled, average velocity, and number of entries to upper half of the tank. Exposed zebrafish spent less time in the novel arm of the Y-Maze, corroborating significant impairment in learning as compared to the control group. Exposure decreased superoxide dismutase (SOD), catalase (CAT) activities whereas, increased levels of reduced glutathione (GSH) and lipid peroxidation (LPO) was encountered showing compromised antioxidant defense. Treatment with MT significantly reversed the above neurobehavioral and oxidative derangements induced by GSM900MP radiation exposure. This study traced GSM900MP radiation exposure induced neurobehavioral aberrations and alterations in brain oxidative status. Furthermore, MT proved to be a promising therapeutic candidate in ameliorating such outcomes in zebrafish. PMID:27123163

  13. Neurobehavioural Changes and Brain Oxidative Stress Induced by Acute Exposure to GSM900 Mobile Phone Radiations in Zebrafish (Danio rerio)

    PubMed Central

    Nirwane, Abhijit; Sridhar, Vinay; Majumdar, Anuradha

    2016-01-01

    The impact of mobile phone (MP) radiation on the brain is of specific interest to the scientific community and warrants investigations, as MP is held close to the head. Studies on humans and rodents revealed hazards MP radiation associated such as brain tumors, impairment in cognition, hearing etc. Melatonin (MT) is an important modulator of CNS functioning and is a neural antioxidant hormone. Zebrafish has emerged as a popular model organism for CNS studies. Herein, we evaluated the impact of GSM900MP (GSM900MP) radiation exposure daily for 1 hr for 14 days with the SAR of 1.34W/Kg on neurobehavioral and oxidative stress parameters in zebrafish. Our study revealed that, GSM900MP radiation exposure, significantly decreased time spent near social stimulus zone and increased total distance travelled, in social interaction test. In the novel tank dive test, the GSM900MP radiation exposure elicited anxiety as revealed by significantly increased time spent in bottom half; freezing bouts and duration and decreased distance travelled, average velocity, and number of entries to upper half of the tank. Exposed zebrafish spent less time in the novel arm of the Y-Maze, corroborating significant impairment in learning as compared to the control group. Exposure decreased superoxide dismutase (SOD), catalase (CAT) activities whereas, increased levels of reduced glutathione (GSH) and lipid peroxidation (LPO) was encountered showing compromised antioxidant defense. Treatment with MT significantly reversed the above neurobehavioral and oxidative derangements induced by GSM900MP radiation exposure. This study traced GSM900MP radiation exposure induced neurobehavioral aberrations and alterations in brain oxidative status. Furthermore, MT proved to be a promising therapeutic candidate in ameliorating such outcomes in zebrafish. PMID:27123163

  14. [Lipid profile in patients with systemic lupus erythematosus, with special focus on lipoprotein(a) in lupus nephritis].

    PubMed

    Kiss, Emese; Fazekas, Brigitta; Tarr, Tünde; Muszbek, László; Zeher, Margit; Szegedi, Gyula

    2004-02-01

    Systemic lupus erythematosus (SLE) is a multifactorial polysystemic autoimmune disorder. Although life expectance in SLE has been improved by adequate immune suppressive therapy, the importance of chronic renal failure has not been reduced. Among late complications of the disease accelerated atherosclerosis attempts increasing attention. Dyslipoproteinemia and increased concentration of lipoproteins are important risk factors of atherosclerotic cardiovascular complication in SLE. Serum lipid parameters of 50 patients with lupus were examined in the present work. Thirty patients had histologically proven lupus nephritis (LN+), while the other group did not have renal involvement (LN-). Serum triglyceride, total cholesterol, LDL-C and apolipoprotein B (apoB) concentrations were significantly higher in the lupus nephritis (LN+) group. On the other hand, HDL-C and apoAI levels were also elevated in patients with LN. As a consequence of that, LDL-C/HDL-C and the apoB/apoAI ratios did not differ between patients with or without kidney involvement. This concluded the authors to measure the concentration of lipoprotein (a) in SLE patients, as Lp(a) is known to be an independent risk factor of atherosclerosis. Results indicated a significantly increased Lp(a) concentration in patients with lupus nephritis as compared to the LN- group. All but 2 patients without kidney involvement had lower than 100 mg/L Lp(a) concentration, while 27% of patients with lupus nephritis has an Lp(a) level between 100-300 mg/L. Further more, Lp(a) concentration was higher than 300 mg/L in 13% of the LN+ group. In a good correlation of these observations patients with nephritis suffered more frequently from deep venous thrombosis and ischaemic heart disease. The frequencies of hypertension and non-insulin dependent diabetes mellitus were slightly elevated in patients with nephritis. Present results suggest the importance of elevated lipoprotein (a) concentration in patients with lupus nephritis

  15. Higher Serum Angiotensinogen Is an Indicator of IgA Vasculitis with Nephritis Revealed by Comparative Proteomes Analysis

    PubMed Central

    Luan, Jiangwei; Zhao, Peiwei; Yue, Xin; Yu, Chunhua; Laing, Xiaohui; Zhao, YuLan

    2015-01-01

    IgA vasculitis (IgAV), previously named as Henoch–Schönlein purpura, is the most common systematic vasculitis with unknown etiology. Lack of appropriate study system and/or animal model limits the understanding of its molecular pathogenesis and hinders the identification of targets for rational therapy, especially for its long-term complication, IgAV nephritis (IgAVN). In this study, we applied comparative analysis of serum proteomes to obtain an insight about disease pathogenesis. This study has utilized high sensitivity nanoscale ultra performance liquid chromatography-mass spectrometry (nanoLC-MS/MS) to investigate the alterations in serum proteomic profiles in patients with IgAV (n=6), IgAVN (n=6) and healthy subjects (n=7). The differentially expressed proteins were subjected to functional pathway analysis by PANTHER and DAVID software. We identified 107 differentially expressed proteins among three different groups, and functional analysis suggested that, in addition to earlier reported pathways, such as acute phase response, immune response, complement and blood coagulation pathways, hemostasis and Wnt signaling pathway were probably involved in pathogenesis of IgAV. A few differentially abundant proteins identified, such as C4a, serum amyloid A, angiotensinogen, and kininogen 1, were further validated by ELISA. More importantly, we found that angiotensinogen concentration is correlated with IgAVN and could be used as a potential marker for the progression of IgAV. This is the first report of analyzing the proteomic alterations in IgAV patients and the differentially proteins identified in this study may enhance understanding of the pathology of IgAV and a few of them may be used to monitor disease progression. PMID:26098644

  16. Low Dose Radiation Response Curves, Networks and Pathways in Human Lymphoblastoid Cells Exposed from 1 to 10 cGy of Acute Gamma Radiation

    SciTech Connect

    Wyrobek, A. J.; Manohar, C. F.; Nelson, D. O.; Furtado, M. R.; Bhattacharya, M. S.; Marchetti, F.; Coleman, M.A.

    2011-04-18

    We investigated the low dose dependency of the transcriptional response of human cells to characterize the shape and biological functions associated with the dose response curve and to identify common and conserved functions of low dose expressed genes across cells and tissues. Human lymphoblastoid (HL) cells from two unrelated individuals were exposed to graded doses of radiation spanning the range of 1-10 cGy were analyzed by transcriptome profiling, qPCR and bioinformatics, in comparison to sham irradiated samples. A set of {approx}80 genes showed consistent responses in both cell lines; these genes were associated with homeostasis mechanisms (e.g., membrane signaling, molecule transport), subcellular locations (e.g., Golgi, and endoplasmic reticulum), and involved diverse signal transduction pathways. The majority of radiation-modulated genes had plateau-like responses across 1-10 cGy, some with suggestive evidence that transcription was modulated at doses below 1 cGy. MYC, FOS and TP53 were the major network nodes of the low-dose response in HL cells. Comparison our low dose expression findings in HL cells with those of prior studies in mouse brain after whole body exposure, in human keratinocyte cultures, and in endothelial cells cultures, indicates that certain components of the low dose radiation response are broadly conserved across cell types and tissues, independent of proliferation status.

  17. Anthocyanin-rich blueberry diets enhance protection of critical brain regions exposed to acute levels of 56Fe cosmic radiation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The protective effects of anthocyanin-rich blueberries on brain health are well documented and are particularly important under conditions of high oxidative stress which can lead to “accelerated aging”. One such scenario is exposure to space radiation, which consists of high-energy and -charge parti...

  18. Assessment of detached podocytes in the Bowman's space as a marker of disease activity in lupus nephritis.

    PubMed

    Moustafa, F E; Soliman, N A; Bakr, A M A; El Shwaf, I M

    2014-02-01

    Podocyte damage is an important pathogenic component of glomerular disease progression. This study is a trial to clarify the value of counting and scoring the number of shed Bowman's space podocytes as an activity parameter of lupus nephritis, a trial that has not been conducted before. This study was performed on 42 female patients with the clinical diagnosis of lupus nephritis. Beside the routine stains tissue sections were stained by colloidal iron and anti podocalyxin for sialomucin. Podocytes in the Bowman's space were counted and scored. Thorough statistical work was carried out to correlate the podocyte scores with the morphological lesions of lupus nephritis. This study revealed significant association and correlation of shed Bowman's space podocytes with histopathological parameters of activity in different classes of lupus nephritis. We concluded that counting and scoring shed Bowman's space podocytes is statistically significant as a marker of disease activity in lupus nephritis. It can be one of the parameters of activity index but not of chronicity index.

  19. Radiation Proctopathy

    PubMed Central

    Grodsky, Marc B.; Sidani, Shafik M.

    2015-01-01

    Radiation therapy is a widely utilized treatment modality for pelvic malignancies, including prostate cancer, rectal cancer, and cervical cancer. Given its fixed position in the pelvis, the rectum is at a high risk for injury secondary to ionizing radiation. Despite advances made in radiation science, up to 75% of the patients will suffer from acute radiation proctitis and up to 20% may experience chronic symptoms. Symptoms can be variable and include diarrhea, bleeding, incontinence, and fistulization. A multitude of treatment options exist. This article summarizes the latest knowledge relating to radiation proctopathy focusing on the vast array of treatment options. PMID:26034407

  20. Radiation proctopathy.

    PubMed

    Grodsky, Marc B; Sidani, Shafik M

    2015-06-01

    Radiation therapy is a widely utilized treatment modality for pelvic malignancies, including prostate cancer, rectal cancer, and cervical cancer. Given its fixed position in the pelvis, the rectum is at a high risk for injury secondary to ionizing radiation. Despite advances made in radiation science, up to 75% of the patients will suffer from acute radiation proctitis and up to 20% may experience chronic symptoms. Symptoms can be variable and include diarrhea, bleeding, incontinence, and fistulization. A multitude of treatment options exist. This article summarizes the latest knowledge relating to radiation proctopathy focusing on the vast array of treatment options. PMID:26034407

  1. Acute exposure to 930 MHz CW electromagnetic radiation in vitro affects reactive oxygen species level in rat lymphocytes treated by iron ions.

    PubMed

    Zmyślony, Marek; Politanski, Piotr; Rajkowska, Elzbieta; Szymczak, Wieslaw; Jajte, Jolanta

    2004-07-01

    The aim of this study was to test the hypothesis that the 930 MHz continuous wave (CW) electromagnetic field, which is the carrier of signals emitted by cellular phones, affects the reactive oxygen species (ROS) level in living cells. Rat lymphocytes were used in the experiments. A portion of the lymphocytes was treated with iron ions to induce oxidative processes. Exposures to electromagnetic radiation (power density 5 W/m2, theoretical calculated SAR = 1.5 W/kg) were performed within a GTEM cell. Intracellular ROS were measured by the fluorescent probe dichlorofluorescin diacetate (DCF-DA). The results show that acute (5 and 15 min) exposure does not affect the number of produced ROS. If, however, FeCl2 with final concentration 10 microg/ml was added to the lymphocyte suspensions to stimulate ROS production, after both durations of exposure, the magnitude of fluorescence (ROS level during the experiment) was significantly greater in the exposed lymphocytes. The character of the changes in the number of free radicals observed in our experiments was qualitatively compatible with the theoretical prediction from the model of electromagnetic radiation effect on radical pairs. PMID:15197754

  2. Prediction of Acute Radiation Mucositis using an Oral Mucosal Dose Surface Model in Carbon Ion Radiotherapy for Head and Neck Tumors

    PubMed Central

    Musha, Atsushi; Shimada, Hirofumi; Shirai, Katsuyuki; Saitoh, Jun-ichi; Yokoo, Satoshi; Chikamatsu, Kazuaki; Ohno, Tatsuya; Nakano, Takashi

    2015-01-01

    Purpose To evaluate the dose-response relationship for development of acute radiation mucositis (ARM) using an oral mucosal dose surface model (OMDS-model) in carbon ion radiotherapy (C-ion RT) for head and neck tumors. Methods Thirty-nine patients receiving C-ion RT for head and neck cancer were evaluated for ARM (once per week for 6 weeks) according to the Common Terminology Criteria for Adverse Events (CTCAE), version 4.0, and the Radiation Therapy Oncology Group (RTOG) scoring systems. The irradiation schedule typically used was 64 Gy [relative biological effectiveness (RBE)] in 16 fractions for 4 weeks. Maximum point doses in the palate and tongue were compared with ARM in each patient. Results The location of the ARM coincided with the high-dose area in the OMDS-model. There was a clear dose-response relationship between maximum point dose and ARM grade assessed using the RTOG criteria but not the CTCAE. The threshold doses for grade 2–3 ARM in the palate and tongue were 43.0 Gy(RBE) and 54.3 Gy(RBE), respectively. Conclusions The OMDS-model was useful for predicting the location and severity of ARM. Maximum point doses in the model correlated well with grade 2–3 ARM. PMID:26512725

  3. Acute exposure to 930 MHz CW electromagnetic radiation in vitro affects reactive oxygen species level in rat lymphocytes treated by iron ions.

    PubMed

    Zmyślony, Marek; Politanski, Piotr; Rajkowska, Elzbieta; Szymczak, Wieslaw; Jajte, Jolanta

    2004-07-01

    The aim of this study was to test the hypothesis that the 930 MHz continuous wave (CW) electromagnetic field, which is the carrier of signals emitted by cellular phones, affects the reactive oxygen species (ROS) level in living cells. Rat lymphocytes were used in the experiments. A portion of the lymphocytes was treated with iron ions to induce oxidative processes. Exposures to electromagnetic radiation (power density 5 W/m2, theoretical calculated SAR = 1.5 W/kg) were performed within a GTEM cell. Intracellular ROS were measured by the fluorescent probe dichlorofluorescin diacetate (DCF-DA). The results show that acute (5 and 15 min) exposure does not affect the number of produced ROS. If, however, FeCl2 with final concentration 10 microg/ml was added to the lymphocyte suspensions to stimulate ROS production, after both durations of exposure, the magnitude of fluorescence (ROS level during the experiment) was significantly greater in the exposed lymphocytes. The character of the changes in the number of free radicals observed in our experiments was qualitatively compatible with the theoretical prediction from the model of electromagnetic radiation effect on radical pairs.

  4. DNA Double-Strand Break Analysis by {gamma}-H2AX Foci: A Useful Method for Determining the Overreactors to Radiation-Induced Acute Reactions Among Head-and-Neck Cancer Patients

    SciTech Connect

    Goutham, Hassan Venkatesh; Mumbrekar, Kamalesh Dattaram; Vadhiraja, Bejadi Manjunath; Fernandes, Donald Jerard; Sharan, Krishna; Kanive Parashiva, Guruprasad; Kapaettu, Satyamoorthy; Bola Sadashiva, Satish Rao

    2012-12-01

    Purpose: Interindividual variability in normal tissue toxicity during radiation therapy is a limiting factor for successful treatment. Predicting the risk of developing acute reactions before initiation of radiation therapy may have the benefit of opting for altered radiation therapy regimens to achieve minimal adverse effects with improved tumor cure. Methods and Materials: DNA double-strand break (DSB) induction and its repair kinetics in lymphocytes of head-and-neck cancer patients undergoing chemoradiation therapy was analyzed by counting {gamma}-H2AX foci, neutral comet assay, and a modified version of neutral filter elution assay. Acute normal tissue reactions were assessed by Radiation Therapy Oncology Group criteria. Results: The correlation between residual DSBs and the severity of acute reactions demonstrated that residual {gamma}-H2AX foci in head-and-neck cancer patients increased with the severity of oral mucositis and skin reaction. Conclusions: Our results suggest that {gamma}-H2AX analysis may have predictive implications for identifying the overreactors to mucositis and skin reactions among head-and-neck cancer patients prior to initiation of radiation therapy.

  5. Somatic mutational transients: models of response to acute and distributed doses of radiation applied to growing plants.

    PubMed

    Sand, S A

    1972-08-01

    After limited exposures of whole plants to gamma radiation, the induced-mutation frequency, measured in somatic tissue of successively blooming flowers, is a transient function of time. Quantitative interpretation of the data is aided by construction of a cell-generation model. Seven theoretical models are designed to represent interaction between the cell-generation model and seven different modes of application of the radiation treatment. The models provide a structure for integration of the mutational contributions from different floral primordia. These different contributions are distributed over the array of mature flowers by the quantitative relationships of each model. A mathematical expression for the average response of a model can be equated to the average observed response and solved for the implied mutation rate per cell per roentgen.

  6. The Toll-Like Receptor 5 Agonist Entolimod Mitigates Lethal Acute Radiation Syndrome in Non-Human Primates

    PubMed Central

    Krivokrysenko, Vadim I.; Toshkov, Ilia A.; Gleiberman, Anatoli S.; Krasnov, Peter; Shyshynova, Inna; Bespalov, Ivan; Maitra, Ratan K.; Narizhneva, Natalya V.; Singh, Vijay K.; Whitnall, Mark H.; Purmal, Andrei A.; Shakhov, Alexander N.; Gudkov, Andrei V.; Feinstein, Elena

    2015-01-01

    There are currently no approved medical radiation countermeasures (MRC) to reduce the lethality of high-dose total body ionizing irradiation expected in nuclear emergencies. An ideal MRC would be effective even when administered well after radiation exposure and would counteract the effects of irradiation on the hematopoietic system and gastrointestinal tract that contribute to its lethality. Entolimod is a Toll-like receptor 5 agonist with demonstrated radioprotective/mitigative activity in rodents and radioprotective activity in non-human primates. Here, we report data from several exploratory studies conducted in lethally irradiated non-human primates (rhesus macaques) treated with a single intramuscular injection of entolimod (in the absence of intensive individualized supportive care) administered in a mitigative regimen, 1–48 hours after irradiation. Following exposure to LD50-70/40 of radiation, injection of efficacious doses of entolimod administered as late as 25 hours thereafter reduced the risk of mortality 2-3-fold, providing a statistically significant (P<0.01) absolute survival advantage of 40–60% compared to vehicle treatment. Similar magnitude of survival improvement was also achieved with drug delivered 48 hours after irradiation. Improved survival was accompanied by predominantly significant (P<0.05) effects of entolimod administration on accelerated morphological recovery of hematopoietic and immune system organs, decreased severity and duration of thrombocytopenia, anemia and neutropenia, and increased clonogenic potential of the bone marrow compared to control irradiated animals. Entolimod treatment also led to reduced apoptosis and accelerated crypt regeneration in the gastrointestinal tract. Together, these data indicate that entolimod is a highly promising potential life-saving treatment for victims of radiation disasters. PMID:26367124

  7. The Toll-Like Receptor 5 Agonist Entolimod Mitigates Lethal Acute Radiation Syndrome in Non-Human Primates.

    PubMed

    Krivokrysenko, Vadim I; Toshkov, Ilia A; Gleiberman, Anatoli S; Krasnov, Peter; Shyshynova, Inna; Bespalov, Ivan; Maitra, Ratan K; Narizhneva, Natalya V; Singh, Vijay K; Whitnall, Mark H; Purmal, Andrei A; Shakhov, Alexander N; Gudkov, Andrei V; Feinstein, Elena

    2015-01-01

    There are currently no approved medical radiation countermeasures (MRC) to reduce the lethality of high-dose total body ionizing irradiation expected in nuclear emergencies. An ideal MRC would be effective even when administered well after radiation exposure and would counteract the effects of irradiation on the hematopoietic system and gastrointestinal tract that contribute to its lethality. Entolimod is a Toll-like receptor 5 agonist with demonstrated radioprotective/mitigative activity in rodents and radioprotective activity in non-human primates. Here, we report data from several exploratory studies conducted in lethally irradiated non-human primates (rhesus macaques) treated with a single intramuscular injection of entolimod (in the absence of intensive individualized supportive care) administered in a mitigative regimen, 1-48 hours after irradiation. Following exposure to LD50-70/40 of radiation, injection of efficacious doses of entolimod administered as late as 25 hours thereafter reduced the risk of mortality 2-3-fold, providing a statistically significant (P<0.01) absolute survival advantage of 40-60% compared to vehicle treatment. Similar magnitude of survival improvement was also achieved with drug delivered 48 hours after irradiation. Improved survival was accompanied by predominantly significant (P<0.05) effects of entolimod administration on accelerated morphological recovery of hematopoietic and immune system organs, decreased severity and duration of thrombocytopenia, anemia and neutropenia, and increased clonogenic potential of the bone marrow compared to control irradiated animals. Entolimod treatment also led to reduced apoptosis and accelerated crypt regeneration in the gastrointestinal tract. Together, these data indicate that entolimod is a highly promising potential life-saving treatment for victims of radiation disasters. PMID:26367124

  8. The protective effect of amifostine on radiation-induced acute pulmonary toxicity: Detection by {sup 99m}Tc-DTPA transalveolar clearances

    SciTech Connect

    Uzal, Cem . E-mail: cemuzal@yahoo.com; Durmus-Altun, Gulay; Caloglu, Murat; Erguelen, Alev; Altaner, Semsi; Yigitbasi, N. Omer

    2004-10-01

    Purpose: The purpose of this study was to determine by using {sup 99m}Tc-diethylenetriaminepentaacetic acid (DTPA) lung scintigraphy whether amifostine given before irradiation protects alveolocapillary integrity in a rabbit model. Methods and materials: Twenty white New Zealand rabbits were randomly divided into 4 groups: (1) control (CONT), (2) amifostine alone (AMF), (3) radiation (RAD), and (4) radiation plus amifostine (RAD+AMF). The AMF and RAD+AMF groups received amifostine. The RAD and RAD+AMF groups were irradiated to the right hemithorax with a single dose of 20 Gy using a {sup 60}Co treatment unit. Amifostine (200 mg/kg) was given i.p. 30 min before irradiation. The {sup 99m}Tc-DTPA radioaerosol study was performed 14 day after irradiation. Results: The mean clearance rate of {sup 99m}Tc-DTPA in control subjects was 140 {+-} 21 min. The highest t{sub 1}/2 value was noted in the RAD group (603 {+-} 105 min, p = 0.001). There were no significant differences between the {sup 99m}Tc-DTPA lung clearance rates of the CONT, RAD+AMF (238 {+-} 24 min), and AMF groups (227 {+-} 54 min). The mean penetration index values of CONT, RAD, AMF, and RAD+AMF are 63% {+-} 1.6%, 63% {+-} 2.5%, 60% {+-} 2.9%, and 63% {+-} 2%, respectively. Conclusions: We concluded that amifostine treatment before the lung irradiation protects the lung alveolocapillary integrity. This study confirms the protective effect of amifostine in an acute phase of radiation lung injury.

  9. Analysis of cellular response by exposure to acute or chronic radiation in human lymphoblastoid TK-6 cells

    NASA Astrophysics Data System (ADS)

    Ohnishi, T.; Yasumoto, J.; Takahashi, A.; Ohnishi, K.

    To clarify the biological effects of low-dose rate radiation on human health for long-term stay in space, we analyzed the induction of apoptosis and apoptosis-related gene expression after irradiation with different dose-rate in human lymphoblastoid TK-6 cells harboring wild-type p53 gene. We irradiated TK-6 cells by X-ray at 1.5 Gy (1 Gy/min) and then sampled at 25 hr after culturing. We also irradiated by gamma-ray at 1.5 Gy (1 mGy/min) and then sampled immediately or 25 hr after irradiation. For DNA ladder analysis, we extracted DNA from these samples and electrophoresed with 2% agarose gel. In addition, we extracted mRNA from these samples for DNA-array analysis. mRNA from non-irradiated cells was used as a control. After labeling the cDNA against mRNA with [α -33P]-dCTP and hybridizing onto DNA array (Human Apoptosis Expression Array, R&D Systems), we scanned the profiles of the spots by a phosphorimager (BAS5000, FUJI FILM) and calculated using a NIH Image program. The data of each DNA-array were normalized with eight kinds of house keeping genes. We analyzed the expression level of apoptosis-related genes such as p53-related, Bcl-2 family, Caspase family and Fas-related genes. DNA ladders were obviously detected in the cells exposed to a high dose-rate radiation. We detected the induction of the gene expression of apoptosis-promotive genes. In contrast, almost no apoptosis was observed in the cells exposed to the chronic radiation at a low dose-rate. In addition, we detected the induction of the gene expression of apoptosis-suppressive genes as compared with apoptosis promotive-genes immediately after chronic irradiation. These results lead the importance of biological meaning of exposure to radiation at low dose-rate from an aspect of carcinogenesis. Finally, the effects of chronic irradiation become a highly important issue in space radiation biology for human health.

  10. microRNA Alterations Driving Acute and Late Stages of Radiation-Induced Fibrosis in a Murine Skin Model

    SciTech Connect

    Simone, Brittany A.; Ly, David; Savage, Jason E.; Hewitt, Stephen M.; Dan, Tu D.; Ylaya, Kris; Shankavaram, Uma; Lim, Meng; Jin, Lianjin; Camphausen, Kevin; Mitchell, James B.; Simone, Nicole L.

    2014-09-01

    Purpose: Although ionizing radiation is critical in treating cancer, radiation-induced fibrosis (RIF) can have a devastating impact on patients' quality of life. The molecular changes leading to radiation-induced fibrosis must be elucidated so that novel treatments can be designed. Methods and Materials: To determine whether microRNAs (miRs) could be responsible for RIF, the fibrotic process was induced in the right hind legs of 9-week old CH3 mice by a single-fraction dose of irradiation to 35 Gy, and the left leg served as an unirradiated control. Fibrosis was quantified by measurements of leg length compared with control leg length. By 120 days after irradiation, the irradiated legs were 20% (P=.013) shorter on average than were the control legs. Results: Tissue analysis was done on muscle, skin, and subcutaneous tissue from irradiated and control legs. Fibrosis was noted on both gross and histologic examination by use of a pentachrome stain. Microarrays were performed at various times after irradiation, including 7 days, 14 days, 50 days, 90 days, and 120 days after irradiation. miR-15a, miR-21, miR-30a, and miR-34a were the miRs with the most significant alteration by array with miR-34a, proving most significant on confirmation by reverse transcriptase polymerase chain reaction, c-Met, a known effector of fibrosis and downstream molecule of miR-34a, was evaluated by use of 2 cell lines: HCT116 and 1522. The cell lines were exposed to various stressors to induce miR changes, specifically ionizing radiation. Additionally, in vitro transfections with pre-miRs and anti-miRs confirmed the relationship of miR-34a and c-Met. Conclusions: Our data demonstrate an inverse relationship with miR-34a and c-Met; the upregulation of miR-34a in RIF causes inhibition of c-Met production. miRs may play a role in RIF; in particular, miR-34a should be investigated as a potential target to prevent or treat this devastating side effect of irradiation.

  11. Reactivity in ELISA with DNA-loaded nucleosomes in patients with proliferative lupus nephritis.

    PubMed

    Dieker, Jürgen; Schlumberger, Wolfgang; McHugh, Neil; Hamann, Philip; van der Vlag, Johan; Berden, Jo H

    2015-11-01

    Autoantibodies against nucleosomes are considered a hallmark of systemic lupus erythematosus (SLE). We compared in patients with proliferative lupus nephritis the diagnostic usefulness of a dsDNA-loaded nucleosome ELISA (anti-dsDNA-NcX) with ELISAs in which dsDNA or nucleosomes alone were coated. First, we analysed whether DNA loading on nucleosomes led to masking of epitopes by using defined monoclonal anti-DNA, anti-histone and nucleosome-specific autoantibodies to evaluate the accessibility of nucleosomal epitopes in the anti-dsDNA-NcX ELISA. Second, autoantibody levels were measured in these 3 ELISAs in 100 patients with proliferative lupus nephritis (LN) before immunosuppressive treatment and in 128 non-SLE disease controls. In patients with LN inter-assay comparisons and associations with clinical and serological parameters were analysed. The panel of monoclonal antibodies revealed that all epitopes were equally accessible in the anti-dsDNA-NcX ELISA as in the two other ELISAs. Patients with proliferative lupus nephritis were positive with dsDNA-loaded nucleosomes in 86%, with DNA in 66% and with nucleosomes in 85%. In the non-lupus disease control group these frequencies were 1.6% (2 out of 128) for both the anti-dsDNA-NcX and the anti-dsDNA ELISA and 0% in the anti-nucleosome ELISA. The levels in the anti-dsDNA-NcX ELISA were high in a group of patients with LN that showed absent reactivity in the anti-DNA or low levels in the anti-nucleosome ELISA. Anti-dsDNA-NcX positivity was associated with higher SLEDAI scores within this group. Within nucleosome-based ELISAs, we propose the anti-dsDNA-NcX ELISA as the preferred test system. PMID:26597199

  12. Reactivity in ELISA with DNA-loaded nucleosomes in patients with proliferative lupus nephritis.

    PubMed

    Dieker, Jürgen; Schlumberger, Wolfgang; McHugh, Neil; Hamann, Philip; van der Vlag, Johan; Berden, Jo H

    2015-11-01

    Autoantibodies against nucleosomes are considered a hallmark of systemic lupus erythematosus (SLE). We compared in patients with proliferative lupus nephritis the diagnostic usefulness of a dsDNA-loaded nucleosome ELISA (anti-dsDNA-NcX) with ELISAs in which dsDNA or nucleosomes alone were coated. First, we analysed whether DNA loading on nucleosomes led to masking of epitopes by using defined monoclonal anti-DNA, anti-histone and nucleosome-specific autoantibodies to evaluate the accessibility of nucleosomal epitopes in the anti-dsDNA-NcX ELISA. Second, autoantibody levels were measured in these 3 ELISAs in 100 patients with proliferative lupus nephritis (LN) before immunosuppressive treatment and in 128 non-SLE disease controls. In patients with LN inter-assay comparisons and associations with clinical and serological parameters were analysed. The panel of monoclonal antibodies revealed that all epitopes were equally accessible in the anti-dsDNA-NcX ELISA as in the two other ELISAs. Patients with proliferative lupus nephritis were positive with dsDNA-loaded nucleosomes in 86%, with DNA in 66% and with nucleosomes in 85%. In the non-lupus disease control group these frequencies were 1.6% (2 out of 128) for both the anti-dsDNA-NcX and the anti-dsDNA ELISA and 0% in the anti-nucleosome ELISA. The levels in the anti-dsDNA-NcX ELISA were high in a group of patients with LN that showed absent reactivity in the anti-DNA or low levels in the anti-nucleosome ELISA. Anti-dsDNA-NcX positivity was associated with higher SLEDAI scores within this group. Within nucleosome-based ELISAs, we propose the anti-dsDNA-NcX ELISA as the preferred test system.

  13. The prevalence of leptospirosis and its association with multifocal interstitial nephritis in swine at slaughter.

    PubMed Central

    Baker, T F; McEwen, S A; Prescott, J F; Meek, A H

    1989-01-01

    An abattoir survey was undertaken to determine the prevalence of leptospirosis and its association with lesions of multifocal interstitial nephritis (so-called "white spotted kidneys") in swine at slaughter. Both cross-sectional and case-control study designs were used. Of 197 kidneys from hogs randomly selected at slaughter, 11 (5.6%) had generalized grey-white foci typical of multifocal interstitial nephritis (MFIN). Antibody titers greater than or equal to 1:80 against Leptospira pomona were detected in nine (4.6%) hogs and against L. bratislava in 63 (32%) of these hogs. Leptospira pomona (kennewicki) was detected by immunofluorescence in 5/197 (2.5%) of randomly selected hogs. Leptospires identified as genotype kennewicki were isolated from six (9.8%) of 61 kidneys cultured. Leptospira bratislava was not detected by immunofluorescence or culture. There was a highly significant (p = 0.00) and strong association (odds ratio (OR) = 195) between high L. pomona titer (greater than or equal to 1:80) and the presence of leptospires in the kidneys, as detected by culture. There was also a significant (p = 0.046) and strong (OR = 8.10) association between multifocal interstitial nephritis and the presence of renal leptospires as detected by culture. The association between leptospiral titer and MFIN lesions in the prevalence survey group of animals was statistically significant (p = 0.031), but this association was not significant in the case-control study group (p = 0.071) The failure to identify L. bratislava despite serological evidence of infection suggests that some of these seropositive animals may have been transiently infected at an early age, that serological findings were falsely positive, or that immunofluorescence and isolation attempts failed to detect L. bratislava if they were indeed present in the kidneys.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2766150

  14. Multi-antibody composition in lupus nephritis: isotype and antigen specificity make the difference.

    PubMed

    Bonanni, Alice; Vaglio, Augusto; Bruschi, Maurizio; Sinico, Renato Alberto; Cavagna, Lorenzo; Moroni, Gabriella; Franceschini, Franco; Allegri, Landino; Pratesi, Federico; Migliorini, Paola; Candiano, Giovanni; Pesce, Giampaola; Ravelli, Angelo; Puppo, Francesco; Martini, Alberto; Tincani, Angela; Ghiggeri, Gian Marco

    2015-08-01

    Research on autoimmune processes involved in glomerulonephritis has been for years based on experimental models. Recent progress in proteomics has radically modified perspectives: laser microdissection and proteomics were crucial for an in vivo analysis of autoantibodies eluted from human biopsies. Lupus nephritis has been the subject of recent independent researches. Main topics have been the definition of renal autoimmune components in human lupus biopsies; methods were laser capture of glomeruli and/or of single cells (CD38+ or Ki-67+) from tubulointerstitial areas as starting step followed by elution and characterization of renal antibodies by proteomics. The innovative approach highlighted different panels of autoantibodies deposited in glomeruli and in tubulo-interstitial areas that actually represented the unique autoimmune components in these patients. IgG2 was the major isotype; new podocyte proteins (αenolase, annexin AI) and already known implanted molecules (DNA, histone 3, C1q) were their target antigens in glomeruli. Vimentin was the antigen in tubulo-interstitial areas. Matching renal autoantibodies with serum allowed the definition of a typical autoantibody serum map that included the same anti-αenolase, anti-annexin AI, anti-DNA, and anti-histone 3 IgG2 already detected in renal tissue. Serum levels of specific autoantibodies were tenfold increased in patients with lupus nephritis allowing a clear differentiation from both rheumatoid arthritis and other glomerulonephritis. In all cases, targeted antigens were characterized as components of lupus NETosis. Matching renal/serum autoantibody composition in vivo furnishes new insights on human lupus nephritis and allows to refine composition of circulating antibodies in patients with lupus. A thoughtful passage from bench to bedside of new knowledge would expand our clinical and therapeutic opportunities.

  15. Unmet medical needs in lupus nephritis: solutions through evidence-based, personalized medicine

    PubMed Central

    Anders, Hans-Joachim; Weidenbusch, Marc; Rovin, Brad

    2015-01-01

    Lupus nephritis (LN) remains a kidney disease with significant unmet medical needs despite extensive clinical and translational research over the past decade. These include the need to (i) predict the individual risk for LN in a patient with systemic lupus erythematosus, (ii) identify the best therapeutic option for an individual patient, (iii) distinguish chronic kidney damage from active immunologic kidney injury, (iv) develop efficient treatments with acceptable or no side effects and improve the design of randomized clinical trials so that effective drugs demonstrate efficacy. This review discusses the underlying reasons for these unmet medical needs and options of how to overcome them in the future. PMID:26413272

  16. Mycophenolate mofetil as maintenance therapy for proliferative lupus nephritis: a long-term observational prospective study

    PubMed Central

    2010-01-01

    Introduction While the role of mycophenolate mofetil (MMF) in the management of lupus nephritis has been increasingly recognized, limited information is available regarding its efficacy and safety as a long-term maintenance treatment. The aim of the present study was to evaluate the efficacy and safety profile of MMF as maintenance therapy for proliferative lupus nephritis. Methods Thirty-three consecutive patients with proliferative lupus nephritis received induction therapy with five to seven monthly intravenous (iv) pulses of cyclophosphamide (CYC) plus iv steroids followed by oral MMF 2 g/day as maintenance therapy for a median time of 29 months (range 9 to 71 months). Primary end points were the achievement of renal remission, complete renal remission, disease remission - renal and extrarenal -, the occurrence of renal relapse, chronic renal failure and death. Secondary end points were the extrarenal disease activity and drug adverse events. The clinical and laboratory parameters were compared during follow-up by means of nonparametric statistical tests. Time to event analysis was performed according to the Kaplan-Meier method. Results A significant improvement of all renal parameters was observed at the end of the induction treatment and at the latest follow-up compared to baseline. The rate of patients achieving renal remission until the end of follow-up was 73%, whereas that of complete renal remission was 58%. The median survival times in the Kaplan-Meier analyses were 7 and 16 months, respectively. Remission was maintained in all but four (12%) patients who relapsed within 19 to 39 months after initial response. At the end of follow-up, 51% of the patients had reached disease remission. The median survival time of disease remission was 18 months. Extrarenal manifestations were well controlled in most of the patients. In one patient receiving MMF, extrarenal activity led to treatment discontinuation. Non life-threatening drug adverse events developed in 18

  17. [Effects of an antiinflammatory drug (diclofenac) in primary chronic glomerulo-nephritis (author's transl)].

    PubMed

    Lagrue, G; Hirbec, G

    Chronic Glomerulo-Nephritis (GN) are among nephrologic diseases, frequent and severe. In most of them immunological process are involved. Non steroïdal antiinflammatory drugs are able to reduce proteinuria, mainly in Membrano-Proliferative GN and IgA Mesengial GN. A protracted administration is necessary for proteinuria reappeared when treatment is interrupted. With long term administration renal prognosis is improved and severe renal insufficiency delayed. Among active antiinflammatory drugs (indometacine, ketoprofen, diclofenac, flurbiprofen, etc.) diclofenac is one of the best tolerated.

  18. Mycotic encephalitis and nephritis in a dog due to infection with Cladosporium cladosporioides.

    PubMed

    Poutahidis, T; Angelopoulou, K; Karamanavi, E; Polizopoulou, Z S; Doulberis, M; Latsari, M; Kaldrymidou, E

    2009-01-01

    The dematiaceous fungus Cladosporium cladosporioides is a widely distributed saprophyte that is reported to occasionally infect the lung, skin, eye and brain of humans. This report describes a German shepherd dog with granulomatous encephalitis and nephritis due to C. cladosporioides infection. Although the fungal organisms appeared non-pigmented in haematoxylin and eosin stained sections, they were readily identified with histochemical stains. Semi-nested polymerase chain reaction using universal fungal primers amplified fungal DNA from fixed tissue that had identity to that of C. cladosporioides on sequencing.

  19. Modeling the Risk of Radiation-Induced Acute Esophagitis for Combined Washington University and RTOG Trial 93-11 Lung Cancer Patients

    SciTech Connect

    Huang, Ellen X.; Bradley, Jeffrey D.; El Naqa, Issam; Hope, Andrew J.; Lindsay, Patricia E.; Bosch, Walter R.; Matthews, John W.; Sause, William T.; Graham, Mary V.; Deasy, Joseph O.

    2012-04-01

    Purpose: To construct a maximally predictive model of the risk of severe acute esophagitis (AE) for patients who receive definitive radiation therapy (RT) for non-small-cell lung cancer. Methods and Materials: The dataset includes Washington University and RTOG 93-11 clinical trial data (events/patients: 120/374, WUSTL = 101/237, RTOG9311 = 19/137). Statistical model building was performed based on dosimetric and clinical parameters (patient age, sex, weight loss, pretreatment chemotherapy, concurrent chemotherapy, fraction size). A wide range of dose-volume parameters were extracted from dearchived treatment plans, including Dx, Vx, MOHx (mean of hottest x% volume), MOCx (mean of coldest x% volume), and gEUD (generalized equivalent uniform dose) values. Results: The most significant single parameters for predicting acute esophagitis (RTOG Grade 2 or greater) were MOH85, mean esophagus dose (MED), and V30. A superior-inferior weighted dose-center position was derived but not found to be significant. Fraction size was found to be significant on univariate logistic analysis (Spearman R = 0.421, p < 0.00001) but not multivariate logistic modeling. Cross-validation model building was used to determine that an optimal model size needed only two parameters (MOH85 and concurrent chemotherapy, robustly selected on bootstrap model-rebuilding). Mean esophagus dose (MED) is preferred instead of MOH85, as it gives nearly the same statistical performance and is easier to compute. AE risk is given as a logistic function of (0.0688 Asterisk-Operator MED+1.50 Asterisk-Operator ConChemo-3.13), where MED is in Gy and ConChemo is either 1 (yes) if concurrent chemotherapy was given, or 0 (no). This model correlates to the observed risk of AE with a Spearman coefficient of 0.629 (p < 0.000001). Conclusions: Multivariate statistical model building with cross-validation suggests that a two-variable logistic model based on mean dose and the use of concurrent chemotherapy robustly predicts

  20. Normal Tissue Complication Probability Modeling of Acute Hematologic Toxicity in Patients Treated With Intensity-Modulated Radiation Therapy for Squamous Cell Carcinoma of the Anal Canal

    SciTech Connect

    Bazan, Jose G.; Luxton, Gary; Mok, Edward C.; Koong, Albert C.; Chang, Daniel T.

    2012-11-01

    Purpose: To identify dosimetric parameters that correlate with acute hematologic toxicity (HT) in patients with squamous cell carcinoma of the anal canal treated with definitive chemoradiotherapy (CRT). Methods and Materials: We analyzed 33 patients receiving CRT. Pelvic bone (PBM) was contoured for each patient and divided into subsites: ilium, lower pelvis (LP), and lumbosacral spine (LSS). The volume of each region receiving at least 5, 10, 15, 20, 30, and 40 Gy was calculated. Endpoints included grade {>=}3 HT (HT3+) and hematologic event (HE), defined as any grade {>=}2 HT with a modification in chemotherapy dose. Normal tissue complication probability (NTCP) was evaluated with the Lyman-Kutcher-Burman (LKB) model. Logistic regression was used to test associations between HT and dosimetric/clinical parameters. Results: Nine patients experienced HT3+ and 15 patients experienced HE. Constrained optimization of the LKB model for HT3+ yielded the parameters m = 0.175, n = 1, and TD{sub 50} = 32 Gy. With this model, mean PBM doses of 25 Gy, 27.5 Gy, and 31 Gy result in a 10%, 20%, and 40% risk of HT3+, respectively. Compared with patients with mean PBM dose of <30 Gy, patients with mean PBM dose {>=}30 Gy had a 14-fold increase in the odds of developing HT3+ (p = 0.005). Several low-dose radiation parameters (i.e., PBM-V10) were associated with the development of HT3+ and HE. No association was found with the ilium, LP, or clinical factors. Conclusions: LKB modeling confirms the expectation that PBM acts like a parallel organ, implying that the mean dose to the organ is a useful predictor for toxicity. Low-dose radiation to the PBM was also associated with clinically significant HT. Keeping the mean PBM dose <22.5 Gy and <25 Gy is associated with a 5% and 10% risk of HT, respectively.

  1. Randomized trial of radiation-free central nervous system prophylaxis comparing intrathecal triple therapy with liposomal cytarabine in acute lymphoblastic leukemia

    PubMed Central

    Bassan, Renato; Masciulli, Arianna; Intermesoli, Tamara; Audisio, Ernesta; Rossi, Giuseppe; Pogliani, Enrico Maria; Cassibba, Vincenzo; Mattei, Daniele; Romani, Claudio; Cortelezzi, Agostino; Corti, Consuelo; Scattolin, Anna Maria; Spinelli, Orietta; Tosi, Manuela; Parolini, Margherita; Marmont, Filippo; Borlenghi, Erika; Fumagalli, Monica; Cortelazzo, Sergio; Gallamini, Andrea; Marfisi, Rosa Maria; Oldani, Elena; Rambaldi, Alessandro

    2015-01-01

    Developing optimal radiation-free central nervous system prophylaxis is a desirable goal in acute lymphoblastic leukemia, to avoid the long-term toxicity associated with cranial irradiation. In a randomized, phase II trial enrolling 145 adult patients, we compared intrathecal liposomal cytarabine (50 mg: 6/8 injections in B-/T-cell subsets, respectively) with intrathecal triple therapy (methotrexate/cytarabine/prednisone: 12 injections). Systemic therapy included methotrexate plus cytarabine or L-asparaginase courses, with methotrexate augmented to 2.5 and 5 g/m2 in Philadelphia-negative B- and T-cell disease, respectively. The primary study objective was the comparative assessment of the risk/benefit ratio, combining the analysis of feasibility, toxicity and efficacy. In the liposomal cytarabine arm 17/71 patients (24%) developed grade 3–4 neurotoxicity compared to 2/74 (3%) in the triple therapy arm (P=0.0002), the median number of episodes of neurotoxicity of any grade was one per patient compared to zero, respectively (P=0.0001), and even though no permanent disabilities or deaths were registered, four patients (6%) discontinued intrathecal prophylaxis on account of these toxic side effects (P=0.06). Neurotoxicity worsened with liposomal cytarabine every 14 days (T-cell disease), and was improved by the adjunct of intrathecal dexamethasone. Two patients in the liposomal cytarabine arm suffered from a meningeal relapse (none with T-cell disease, only one after high-dose chemotherapy) compared to four in the triple therapy arm (1 with T-cell disease). While intrathecal liposomal cytarabine could contribute to improved, radiation-free central nervous system prophylaxis, the toxicity reported in this trial does not support its use at 50 mg and prompts the investigation of a lower dosage. (clinicaltrials.gov identifier: NCT-00795756). PMID:25749825

  2. Acute lead poisoning in two users of illicit methamphetamine

    SciTech Connect

    Allcott, J.V. III; Barnhart, R.A.; Mooney, L.A.

    1987-07-31

    Acute lead poisoning can present a difficult diagnostic dilemma, with symptoms that mimic those of hepatitis, nephritis, and encephalopathy. The authors report two cases in intravenous methamphetamine users who presented with abnormal liver function values, low hematocrit values, basophilic stippling of red blood cells, and elevated blood lead levels. Both patients excreted large amounts of lead in their urine after treatment with edetic acid, followed by resolution of their symptoms. Lead contamination was proved in one drug sample. Basophilic stippling of the red blood cells was the one key laboratory result that led to the definitive diagnosis in both cases.

  3. Atypical Hemolytic Uremic Syndrome Secondary to Lupus Nephritis, Responsive to Eculizumab

    PubMed Central

    Raufi, Alexander G.; Scott, Shruti; Darwish, Omar; Harley, Kevin; Kahlon, Kanwarpal; Desai, Sheetal; Lu, Yuxin; Tran, Minh-Ha

    2016-01-01

    Among the spectrum of disease manifestations associated with systemic lupus erythematosus, lupus nephritis is particularly concerning due to the potential for renal failure. This autoimmune attack may not, however, be limited to the kidney and is increasingly being recognized as a trigger for atypical Hemolytic Uremic Syndrome (aHUS). Atypical HUS falls under the spectrum of the thrombotic microangiopathies (TMAs) – a group of disorders characterized by microangiopathic hemolytic anemia, thrombocytopenia, and end organ damage. Although plasma exchange is considered first-line therapy for thrombotic thrombocytopenic purpura – a TMA classically associated with autoimmune depletion of ADAMTS-13 – aHUS demonstrates less reliable responsiveness to this modality. Instead, use of the late complement inhibitor Eculizumab has emerged as an effective modality for the management of such patients. Diagnosis of aHUS, however, is largely clinically based, relying heavily upon a multidisciplinary approach. Herein we present the case of a patient with atypical HUS successfully treated with Eculizumab in the setting of Class IV-G (A) lupus nephritis and hypocomplementemia. PMID:27781079

  4. IgA myeloma presenting as Henoch-Schönlein purpura with nephritis.

    PubMed

    Zickerman, A M; Allen, A C; Talwar, V; Olczak, S A; Brownlee, A; Holland, M; Furness, P N; Brunskill, N J; Feehally, J

    2000-09-01

    IgA nephropathy (IgAN) and Henoch-Schönlein purpura (HSP) are both characterized by IgA-mediated tissue injury, including mesangial proliferative glomerulonephritis. Abnormalities of IgA1 glycosylation are described in IgA nephropathy and HSP nephritis. IgA-antineutrophil cytoplasmic antibodies (ANCA) have been inconsistently described in the serum of patients with HSP. In IgA myeloma, the paraprotein-mediated renal lesion is typically cast nephropathy; IgAN or HSP have only rarely been reported in myeloma even when an IgA paraprotein is circulating in large concentrations. We report the case of a 50-year-old man with IgA myeloma who presented with HSP including nephritis and rapidly progressive renal failure. His IgA1 had altered O-glycosylation in the pattern seen in IgAN and also contained an IgA-ANCA. This case adds further weight to the evidence that IgA1 O-glycosylation abnormalities predispose to mesangial IgA deposition and also that IgA-ANCA may have a pathogenic role in the development of HSP. PMID:10977812

  5. Immunoadsorption: A New Strategy to Induce Remission in Membranous Lupus Nephritis

    PubMed Central

    Ulinski, Tim; Davourie-Salandre, Aurélie; Brocheriou, Isabelle; Aoun, Bilal

    2014-01-01

    We report the case of an 11-year-old previously healthy girl who presented for microscopic hematuria and nephrotic proteinuria with normal renal function, which persisted after 6 months of steroids, angiotensin-converting enzyme inhibitors (ACEi)/angiotensin receptor blockers, hydroxychloroquine, mycophenolic acid and a low-salt diet. A serum investigation suggested lupus nephritis and a renal biopsy, performed 2 weeks after the first proteinuria detection, revealed membranous lupus nephritis. We decided to perform ten sessions of daily immunoadsorption. Proteinuria decreased significantly over these ten sessions from 8 to 0.12 g/l. After the tenth immunoadsorption session, the patient received the first rituximab (RTX) infusion leading to complete B-cell depletion. The patient was maintained on ACEi associated with mycophenolic acid and hydroxychloroquine. Three RTX reinjections were performed when CD19-positive cells reappeared in peripheral blood. Despite complete B-cell recovery and positive anti-dsDNA-Ab, the patient remained in complete remission 18 months after the initial diagnosis with negative proteinuria and a normal renal function. PMID:24803916

  6. Clinicopathologic correlations of renal microthrombosis and inflammatory markers in proliferative lupus nephritis

    PubMed Central

    2012-01-01

    Introduction Microthrombosis is often observed in lupus nephritis (LN) lesions, but its clinical significance is unknown. We evaluated the clinicopathologic correlations of renal microthrombosis and inflammatory markers in LN. Methods Kidney biopsies from 58 patients with systemic lupus erythematosus (SLE) proliferative nephritis were analyzed with immunohistochemistry (IHC) for intravascular platelet aggregates (CD61), macrophagic infiltration (CD68), and activated complement deposition (C4d). Clinical data at the time of kidney biopsy and follow-up were analyzed with regard to pathologic IHC data. Results Microthrombosis was present in 52% of the tissues. It was significantly more prevalent in patients with antiphospholipid antibodies (aPLs) (62% versus 42%). The presence of microthrombosis significantly correlated with higher macrophagic infiltration. Macrophagic infiltration but not microthrombosis was significantly correlated with C4d deposition. Only macrophagic infiltration showed a correlation with SLE and renal activity (proteinuria and active sediment), whereas neither the presence of CD61+ microthrombi nor the extent of C4d deposition correlated with LN severity or outcome. Conclusions Microthrombosis is associated with higher macrophagic infiltration in LN but does not seem to increase independently the severity of renal damage. Macrophagic infiltration was the best marker of SLE and renal activity in this LN series. PMID:22640796

  7. A controlled trial of pulse cyclophosphamide versus pulse methylprednisolone in severe lupus nephritis.

    PubMed

    Sesso, R; Monteiro, M; Sato, E; Kirsztajn, G; Silva, L; Ajzen, H

    1994-04-01

    We carried out a prospective randomized trial comparing pulse cyclophosphamide and pulse methylprednisolone in 29 patients with severe lupus nephritis in activity. Patients were assigned to one of two regimens: monthly pulse cyclophosphamide (0.5-1.0 g/m2 body surface area) for 4 months, followed by bimonthly doses for 4 months and quarterly doses for 6 months (14 patients) or pulse methylprednisolone (10-20 mg/kg weight) initially for 3 consecutive days and thereafter in the same intervals as the alternative regimen (15 patients). The mean follow-up was 15 months. Two patients in the cyclophosphamide group and three in the methylprednisolone group died. Renal failure (doubling of serum creatinine) developed in four patients in the cyclophosphamide group compared with five patients in the methylprednisolone group. Cumulative probability of not doubling serum creatinine was similar for cyclophosphamide and methylprednisolone groups (0.66 vs 0.69, respectively, P > 0.20, after 18 months). Cumulative probability of survival without renal failure was also not significantly different (0.61 and 0.63, respectively, P > 0.20, after 18 months). These results suggest that pulse cyclophosphamide is as effective as pulse methylprednisolone in preserving renal function in patients with severe lupus nephritis. PMID:7920609

  8. Identification of a pathogenic epitope involved in initiation of Heymann nephritis.

    PubMed Central

    Kerjaschki, D; Ullrich, R; Diem, K; Pietromonaco, S; Orlando, R A; Farquhar, M G

    1992-01-01

    Heymann nephritis is an experimental autoimmune disease model for human membranous nephropathy. We have recently identified a pathogenic epitope, clone 14 (C14), responsible for formation and deposition of glomerular immune complexes that is contained within the small subunit of the Heymann nephritis antigenic complex (HNAC). HNAC is a heterodimer composed of a large subunit designated gp330 and a smaller (44 kDa) subunit, which is immunologically identical to the receptor-associated protein. In this study, we prepared antibodies to fusion proteins with C-terminal deletions in the C14 sequence and assessed their ability to promote formation of immune deposits (IDs). When IgG specific for the shortest truncated fusion protein (C14/delta 3; 86 amino acids) was injected into rats, small IDs developed. In contrast, when IgG raised against the full-length C14 sequence was depleted of its reactivity toward the C14/delta 3 fusion protein (C14/delta 3-fp), no IDs could be detected. These data indicate that at least one pathogenic epitope is contained within the N-terminal 86 amino acids of C14. Since the IDs induced with the C14/delta 3-fp-specific IgG are smaller than those induced with the poly-epitope-specific anti-gp330 antibodies, it is likely that other epitopes in addition to those expressed by the C14/delta 3-fp are required for formation and growth of immune complexes. Images PMID:1280820

  9. Insulin-Like Growth Factor Binding Protein-4 as a Marker of Chronic Lupus Nephritis

    PubMed Central

    Han, Jie; Ye, Yujin; Singh, Sandeep; Zhou, Jinchun; Li, Yajuan; Ding, Huihua; Li, Quan-zhen; Zhou, Xin; Putterman, Chaim; Saxena, Ramesh; Mohan, Chandra

    2016-01-01

    Kidney biopsy remains the mainstay of Lupus Nephritis (LN) diagnosis and prognostication. The objective of this study is to identify non-invasive biomarkers that closely parallel renal pathology in LN. Previous reports have demonstrated that serum Insulin-like growth factor binding protein 4 (IGFBP-4) was increased in diabetic nephropathy in both animal models and patients. We proceeded to assess if IGFBP4 could be associated with LN. We performed ELISA using the serum of 86 patients with LN. Normal healthy adults (N = 23) and patients with other glomerular diseases (N = 20) served as controls. Compared to the healthy controls or other glomerular disease controls, serum IGFBP-4 levels were significantly higher in the patients with LN. Serum IGFBP-4 did not correlate well with systemic lupus erythematosus disease activity index (SLEDAI), renal SLEDAI or proteinuria, but it did correlate with estimated glomerular filtration rate (R = 0.609, P < 0.0001). Interestingly, in 18 patients with proliferative LN whose blood samples were obtained at the time of renal biopsy, serum IGFBP-4 levels correlated strongly with the chronicity index of renal pathology (R = 0.713, P < 0.001). IGFBP-4 emerges a potential marker of lupus nephritis, reflective of renal pathology chronicity changes. PMID:27019456

  10. [Case report: tenesmus in a cow with a liver abscess and nephritis].

    PubMed

    Braun, U; Jehle, W; Thio, T; Pospischil, A

    2004-01-01

    A two-year-old Swiss Braunvieh cow was referred to our clinic because of tenesmus and weight loss. Clinical examination revealed a moderately abnormal general behaviour and condition, thin body condition and a rectal temperature of 40.1 degrees C. Tenesmus was evident, and rumen and intestinal motility were markedly reduced. All tests for a reticular foreign body were positive. On rectal examination, a round, smooth, firm, non-painful mass with a diameter of approximately 15 cm was palpated far cranially on the right side. Abnormal haematological and biochemical findings included marked anaemia, neutrophilic leucocytosis, markedly elevated concentration of fibrinogen and mildly elevated gamma-glutamyl-transferase activity. The clotting time of the glutaraldehyde test was one minute. Ultrasonographic examination revealed abscesses involving the liver and extending caudally into the right flank region. The liver parenchyma had diffuse changes. Because of a grave prognosis, the cow was euthanized. Postmortem findings substantiated ultrasonographic results; there were abscesses, caused by Fasciola hepatica infestation, originating in the liver and extending into the right flank. As well, there was severe, bilateral, multifocal, suppurative nephritis due to thromboembolism. Based on all the findings, a diagnosis of liver abscess caused by fascioliasis and bilateral suppurative nephritis was made.

  11. NMR based serum metabolomics reveals a distinctive signature in patients with Lupus Nephritis

    PubMed Central

    Guleria, Anupam; Pratap, Avadhesh; Dubey, Durgesh; Rawat, Atul; Chaurasia, Smriti; Sukesh, Edavalath; Phatak, Sanat; Ajmani, Sajal; Kumar, Umesh; Khetrapal, Chunni Lal; Bacon, Paul; Misra, Ramnath; Kumar, Dinesh

    2016-01-01

    Management of patient with Lupus Nephritis (LN) continues to remain a challenge for the treating physicians because of considerable morbidity and even mortality. The search of biomarkers in serum and urine is a focus of researchers to unravel new targets for therapy. In the present study, the utility of NMR-based serum metabolomics has been evaluated for the first time in discriminating LN patients from non-nephritis lupus patients (SLE) and further to get new insights into the underlying disease processes for better clinical management. Metabolic profiling of sera obtained from 22 SLE patients, 40 LN patients and 30 healthy controls (HC) were performed using high resolution 1D 1H-CPMG and diffusion edited NMR spectra to identify the potential molecular biomarkers. Using multivariate analysis, we could distinguish SLE and LN patients from HC and LN from SLE patients. Compared to SLE patients, the LN patients had increased serum levels of lipid metabolites (including LDL/VLDL lipoproteins), creatinine and decreased levels of acetate. Our results revealed that metabolic markers especially lipids and acetate derived from NMR spectroscopy has high sensitivity and specificity to distinguish LN among SLE patients and has the potential to be a useful adjunctive tool in diagnosis and clinical management of LN. PMID:27739464

  12. Effects of radiation on testicular function in long-term survivors of childhood acute lymphoblastic leukemia: A report from the Children Cancer Study Group

    SciTech Connect

    Sklar, C.A.; Robison, L.L.; Nesbit, M.E.; Sather, H.N.; Meadows, A.T.; Ortega, J.A.; Kim, T.H.; Hammond, G.D. )

    1990-12-01

    Testicular function was evaluated in 60 long-term survivors of childhood acute lymphoblastic leukemia (ALL). All the patients were treated on two consecutive Children Cancer Study Group protocols and received identical chemotherapy and either 18 or 24 Gy radiation therapy (RT) to one of the following fields: craniospinal plus 12 Gy abdominal RT including the gonads (group 1); craniospinal (group 2); or cranial (group 3). The median age at the time of their last evaluation was 14.5 years (range, 10.5 to 25.7), which took place a median of 5.0 years (range, 1 to 10.3) after discontinuing therapy. The incidence of primary germ cell dysfunction as judged by raised levels of follicle-stimulating hormone (FSH) and/or reduced testicular volume was significantly associated with field of RT; 55% of group 1, 17% of group 2, and 0% of group 3 were abnormal (P = .002). Leydig cell function, as assessed by plasma concentrations of luteinizing hormone (LH) and testosterone, and pubertal development, was unaffected in the majority of subjects regardless of RT field. These data indicate that in boys undergoing therapy for ALL, germ cell dysfunction is common following testicular irradiation and can occur following exposure to scattered irradiation from craniospinal RT. In contrast, Leydig cell function appears resistant to direct irradiation with doses as high as 12 Gy.

  13. Comparison of central nervous system prophylaxis with cranial radiation and intrathecal methotrexate versus intrathecal methotrexate alone in acute lymphoblastic leukemia

    SciTech Connect

    Muriel, F.S.; Svarch, E.; Pavlovsky, S.; Eppinger-Helft, M.; Braier, J.; Vergara, B.; Garay, G.; Kvicala, R.; Divito, J.M.; Failace, R.

    1983-08-01

    In acute lymphoblastic leukemia, central nervous system prophylaxis with irradiation plus intrathecal methotrexate (i.t. MTX) reduces the incidence of CNS relapse to 7%-15%. However, increased evidence of CNS delayed toxicity was recognized mainly in children as CT scan abnormalities and neuropsychologic alterations. Two questions were analyzed: (1) Will further doses of i.t. methotraxate and dexamethasone (i.t. MTX-DMT) decrease the incidence of CNS relapse. (2) Is i.t. MTX-DMT given during induction and maintenance as effective as cranium irradiation plus i.t. MTX-DMT. Incidence of primary CNS relapse in i.t. MTX-DMT-treated patients with a WBC count < 50,000 and in the untreated group was 11%. In patients with a WBC count > 50,000, it was 16% in the treated group and 19% in the control group. These patients were compared with patients which had received 3 doses of i.t. MTX-DMT alone during induction, 3 doses weekly during the first month of remission, and quarterly thereafter. The incidence of leukemia at 60 mo in patients with a WBC count < 50,000 was 20% in the irradiated group and 32% in the group with i.t. MTX-DMT alone. The relapse-free survival at 60 mo was 26% and 41%, respectively, (p < 0.0005). The incidence in patients with a WBC count > 50,000 at 48 mo was 28% and 42% in the irradiated and nonirradiated group respectively. Complete remission remained at 15% and 16% respectively of patients disease-free at 48 mo. We conclude that (A) after cranial irradiation plus i.t. MTX-DMT X 5, the use of additional doses of i.t. MTX-DMT is not of further benefit in preventing CNS relapse; (B) use of i.t. MTX-DMT alone compares with cranial irradiation plus i.t. MTX-DMT in incidence of CNS relapse; and (C) relapse-free survival and survival in patients with a WBC count < 50.000 were significantly longer in those without cranial irradiation.

  14. Anti-DNA autoantibodies initiate experimental lupus nephritis by binding directly to the glomerular basement membrane in mice.

    PubMed

    Krishnan, Meera R; Wang, Congmiao; Marion, Tony N

    2012-07-01

    The strongest serological correlate for lupus nephritis is antibody to double-stranded DNA, although the mechanism by which anti-DNA antibodies initiate lupus nephritis is unresolved. Most recent reports indicate that anti-DNA must bind chromatin in the glomerular basement membrane or mesangial matrix to form glomerular deposits. Here we determined whether direct binding of anti-DNA antibody to glomerular basement membrane is critical to initiate glomerular binding of anti-DNA in experimental lupus nephritis. Mice were co-injected with IgG monoclonal antibodies or hybridomas with similar specificity for DNA and chromatin but different IgG subclass and different relative affinity for basement membrane. Only anti-DNA antibodies that bound basement membrane bound to glomeruli, activated complement, and induced proteinuria whether injected alone or co-injected with a non-basement-membrane-binding anti-DNA antibody. Basement membrane-binding anti-DNA antibodies co-localized with heparan sulfate proteoglycan in glomerular basement membrane and mesangial matrix but not with chromatin. Thus, direct binding of anti-DNA antibody to antigens in the glomerular basement membrane or mesangial matrix may be critical to initiate glomerular inflammation. This may accelerate and exacerbate glomerular immune complex formation in human and murine lupus nephritis.

  15. Genetic linkage of IgG autoantibody production in relation to lupus nephritis in New Zealand hybrid mice.

    PubMed

    Vyse, T J; Drake, C G; Rozzo, S J; Roper, E; Izui, S; Kotzin, B L

    1996-10-15

    F1 hybrids of New Zealand black (NZB) and New Zealand white (NZW) mice are a model of human systemic lupus erythematosus. These mice develop a severe immune com-plex-mediated nephritis, in which antinuclear autoantibodies are believed to play the major role. We used a genetic analysis of (NZB x NZW)F1 x NZW backcross mice to provide insight into whether different autoantibodies are subject to separate genetic influences and to determine which autoantibodies are most important in the development of lupus-like nephritis. The results showed one set of loci that coordinately regulated serum levels of IgG antibodies to double-stranded DNA, single-stranded DNA, total histones, and chromatin, which overlapped with loci that were linked to the production of autoantibodies to the viral glycoprotein, gp70. Loci linked with anti-gp70 compared with antinuclear antibodies demonstrated the strongest linkage with renal disease, suggesting that autoantibodies to gp70 are the major pathogenic antibodies in this model of lupus nephritis. Interestingly, a distal chromosome 4 locus, Nba1, was linked with nephritis but not with any of the autoantibodies measured, suggesting that it contributes to renal disease at a checkpoint distal to autoantibody production.

  16. HemaMax™, a recombinant human interleukin-12, is a potent mitigator of acute radiation injury in mice and non-human primates.

    PubMed

    Basile, Lena A; Ellefson, Dolph; Gluzman-Poltorak, Zoya; Junes-Gill, Katiana; Mar, Vernon; Mendonca, Sarita; Miller, Joseph D; Tom, Jamie; Trinh, Alice; Gallaher, Timothy K

    2012-01-01

    HemaMax, a recombinant human interleukin-12 (IL-12), is under development to address an unmet medical need for effective treatments against acute radiation syndrome due to radiological terrorism or accident when administered at least 24 hours after radiation exposure. This study investigated pharmacokinetics, pharmacodynamics, and efficacy of m-HemaMax (recombinant murine IL-12), and HemaMax to increase survival after total body irradiation (TBI) in mice and rhesus monkeys, respectively, with no supportive care. In mice, m-HemaMax at an optimal 20 ng/mouse dose significantly increased percent survival and survival time when administered 24 hours after TBI between 8-9 Gy (p<0.05 Pearson's chi-square test). This survival benefit was accompanied by increases in plasma interferon-γ (IFN-γ) and erythropoietin levels, recovery of femoral bone hematopoiesis characterized with the presence of IL-12 receptor β2 subunit-expressing myeloid progenitors, megakaryocytes, and osteoblasts. Mitigation of jejunal radiation damage was also examined. At allometrically equivalent doses, HemaMax showed similar pharmacokinetics in rhesus monkeys compared to m-HemaMax in mice, but more robustly increased plasma IFN-γ levels. HemaMax also increased plasma erythropoietin, IL-15, IL-18, and neopterin levels. At non-human primate doses pharmacologically equivalent to murine doses, HemaMax (100 ng/Kg and 250 ng/Kg) administered at 24 hours after TBI (6.7 Gy/LD(50/30)) significantly increased percent survival of HemaMax groups compared to vehicle (p<0.05 Pearson's chi-square test). This survival benefit was accompanied by a significantly higher leukocyte (neutrophils and lymphocytes), thrombocyte, and reticulocyte counts during nadir (days 12-14) and significantly less weight loss at day 12 compared to vehicle. These findings indicate successful interspecies dose conversion and provide proof of concept that HemaMax increases survival in irradiated rhesus monkeys by promoting hematopoiesis

  17. HemaMax™, a Recombinant Human Interleukin-12, Is a Potent Mitigator of Acute Radiation Injury in Mice and Non-Human Primates

    PubMed Central

    Basile, Lena A.; Ellefson, Dolph; Gluzman-Poltorak, Zoya; Junes-Gill, Katiana; Mar, Vernon; Mendonca, Sarita; Miller, Joseph D.; Tom, Jamie; Trinh, Alice; Gallaher, Timothy K.

    2012-01-01

    HemaMax, a recombinant human interleukin-12 (IL-12), is under development to address an unmet medical need for effective treatments against acute radiation syndrome due to radiological terrorism or accident when administered at least 24 hours after radiation exposure. This study investigated pharmacokinetics, pharmacodynamics, and efficacy of m-HemaMax (recombinant murine IL-12), and HemaMax to increase survival after total body irradiation (TBI) in mice and rhesus monkeys, respectively, with no supportive care. In mice, m-HemaMax at an optimal 20 ng/mouse dose significantly increased percent survival and survival time when administered 24 hours after TBI between 8–9 Gy (p<0.05 Pearson's chi-square test). This survival benefit was accompanied by increases in plasma interferon-γ (IFN-γ) and erythropoietin levels, recovery of femoral bone hematopoiesis characterized with the presence of IL-12 receptor β2 subunit–expressing myeloid progenitors, megakaryocytes, and osteoblasts. Mitigation of jejunal radiation damage was also examined. At allometrically equivalent doses, HemaMax showed similar pharmacokinetics in rhesus monkeys compared to m-HemaMax in mice, but more robustly increased plasma IFN-γ levels. HemaMax also increased plasma erythropoietin, IL-15, IL-18, and neopterin levels. At non-human primate doses pharmacologically equivalent to murine doses, HemaMax (100 ng/Kg and 250 ng/Kg) administered at 24 hours after TBI (6.7 Gy/LD50/30) significantly increased percent survival of HemaMax groups compared to vehicle (p<0.05 Pearson's chi-square test). This survival benefit was accompanied by a significantly higher leukocyte (neutrophils and lymphocytes), thrombocyte, and reticulocyte counts during nadir (days 12–14) and significantly less weight loss at day 12 compared to vehicle. These findings indicate successful interspecies dose conversion and provide proof of concept that HemaMax increases survival in irradiated rhesus monkeys by promoting

  18. Cystitis - acute

    MedlinePlus

    Uncomplicated urinary tract infection; UTI - acute; Acute bladder infection; Acute bacterial cystitis ... International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: A 2010 ...

  19. Radiation therapy of the para-aortic lymph nodes in carcinoma of the uterine cervix: The concurrent use of cimetidine to reduce acute and subacute side effects from radiation

    SciTech Connect

    Teshima, T.; Inoue, T.; Chatani, M.; Ikeda, H.; Nishiyama, K.; Inoue, T.; Matayoshi, Y.; Hishikawa, Y.; Tanaka, S.; Kamikonya, N. )

    1990-01-01

    A prospective study of the effects of radiation therapy (RT) on para-aortic lymph nodes in uterine cervical cancer was conducted. As part of the study, cimetidine (800 mg daily) was administered during RT to relieve and prevent adverse reactions of the gastrointestinal tract caused by RT. In half of the patients, cimetidine (400 mg daily) was continued after RT was finished. The RT field was 7 to 8 cm wide and covered the area from the 4th lumbar to 11th thoracic vertebrae. The total dose administered was 45 Gy in 25 fractions over a five-week period. From September 1986 through October 1987, 89 patients were entered in this study. During RT, only slight gastrointestinal symptoms, such as nausea, vomiting, appetite loss, fatigue, and epigastralgia, were observed. These symptoms increased when cimetidine was withdrawn, but not in the patients who continued to receive cimetidine. It is concluded that cimetidine during and after RT can reduce the acute and subacute side effects of RT.

  20. Comparative Transcriptional Profiling of 3 Murine Models of SLE Nephritis Reveals Both Unique and Shared Regulatory Networks

    PubMed Central

    Zhang, Weijia; Kretzler, Matthias; Davidson, Anne

    2013-01-01

    Objective To define shared and unique features of SLE nephritis in mouse models of proliferative and glomerulosclerotic renal disease. Methods Perfused kidneys from NZB/W F1, NZW/BXSB and NZM2410 mice were harvested before and after nephritis onset. Affymetrix based gene expression profiles of kidney RNA were analyzed using Genomatix Pathway Systems and Ingenuity Pathway Analysis software. Gene expression patterns were confirmed using real-time PCR. Results 955, 1168 and 755 genes were regulated in the kidneys of nephritic NZB/W F1, NZM2410 and NZW/BXSB mice respectively. 263 genes were regulated concordantly in all three strains reflecting immune cell infiltration, endothelial cell activation, complement activation, cytokine signaling, tissue remodeling and hypoxia. STAT3 was the top associated transcription factor, having a binding site in the gene promoter of 60/263 regulated genes. The two strains with proliferative nephritis shared a macrophage/DC infiltration and activation signature. NZB/W and NZM2410 mice shared a mitochondrial dysfunction signature. Dominant T cell and plasma cell signatures in NZB/W mice reflected lymphoid aggregates; this was the only strain with regulatory T cell infiltrates. NZW/BXSB mice manifested tubular regeneration and NZM2410 mice had the most metabolic stress and manifested loss of nephrin, indicating podocyte loss. Conclusions These findings identify shared inflammatory mechanisms of SLE nephritis that can be therapeutically targeted. Nevertheless, the heterogeneity of effector mechanisms suggests that individualized therapy might need to be based on biopsy findings. Some common mechanisms are shared with non-immune–mediated renal diseases, suggesting that strategies to prevent tissue hypoxia and remodeling may be useful in SLE nephritis. PMID:24167575

  1. Anti-dsDNA, anti-Sm antibodies, and the lupus anticoagulant: significant factors associated with lupus nephritis

    PubMed Central

    Alba, P; Bento, L; Cuadrado, M; Karim, Y; Tungekar, M; Abbs, I; Khamashta, M; D'Cruz, D; Hughes, G

    2003-01-01

    Background: Lupus nephritis (LN) is a common manifestation in patients with systemic lupus erythematosus (SLE). Autoantibodies and ethnicity have been associated with LN, but the results are controversial. Objective: To study the immunological and demographic factors associated with the development of LN. Patients and methods: A retrospective case-control study of 127 patients with biopsy-proven LN, and 206 randomly selected patients with SLE without nephritis as controls was designed. All patients had attended our lupus unit during the past 12 years. Standard methods were used for laboratory testing. Results: Patients with LN were significantly younger than the controls at the time of SLE diagnosis (mean (SD) 25.6 (8.8) years v 33.7 (12.5) years; p<0.0001). The proportion of patients of black ethnic origin was significantly higher in the group with nephritis (p=0.02). There were no differences in sex distribution or duration of follow up. A higher proportion of anti-dsDNA, anti-RNP, anti-Sm, and lupus anticoagulant (LA) was seen in the group with nephritis (p=0.002; p=0.005; p=0.0001; p=0.01, respectively). In univariate, but not in multivariate, analysis male sex and absence of anti-dsDNA were associated with earlier onset of renal disease (p=0.03; p=0.008). In multivariate analysis the only factors associated with nephritis were younger age at diagnosis of SLE, black race, presence of anti-dsDNA, anti-Sm, and LA. No demographic or immunological associations were seen with WHO histological classes. Conclusions: Young, black patients with anti-dsDNA, anti-Sm antibodies, and positive LA, appear to have a higher risk of renal involvement. These patients should be carefully monitored for the development of LN. PMID:12759294

  2. Comparison of renal response parameters for juvenile membranous plus proliferative lupus nephritis versus isolated proliferative lupus nephritis: a cross-sectional analysis of the CARRA Registry.

    PubMed

    Boneparth, A; Ilowite, N T

    2014-08-01

    Lupus nephritis (LN) affects many patients with juvenile systemic lupus erythematosus (SLE) and is a significant cause of disease morbidity. Membranous plus proliferative LN (M + PLN) may represent a more difficult to treat subtype of juvenile LN, compared to isolated proliferative LN (PLN). In this retrospective observational study, we utilized data from the Childhood Arthritis and Rheumatism Research Alliance (CARRA) registry to compare response rates for pediatric M + PLN versus PLN. Response was assessed at the most recent CARRA registry visit gathered ≥6 months after diagnostic kidney biopsy. Estimated glomerular filtration rate (GFR) less than 90 ml/min/1.73 m(2), indicating renal insufficiency, was found in 16.1% of patients with M + PLN and 6.1% of patients with PLN (P = 0.071). We found no significant difference in achievement of response in either hematuria or proteinuria between PLN and M + PLN groups or between subgroups determined by presence of class III vs. class IV proliferative disease. Exposure rates to mycophenolate, cyclophosphamide, and rituximab were similar between groups. Future studies will be necessary to correlate pediatric LN renal histology data with treatment response as well as other disease outcome measures.

  3. Impact of Chemotherapy on Normal Tissue Complication Probability Models of Acute Hematologic Toxicity in Patients Receiving Pelvic Intensity Modulated Radiation Therapy

    SciTech Connect

    Bazan, Jose G.; Luxton, Gary; Kozak, Margaret M.; Anderson, Eric M.; Hancock, Steven L.; Kapp, Daniel S.; Kidd, Elizabeth A.; Koong, Albert C.; Chang, Daniel T.

    2013-12-01

    Purpose: To determine how chemotherapy agents affect radiation dose parameters that correlate with acute hematologic toxicity (HT) in patients treated with pelvic intensity modulated radiation therapy (P-IMRT) and concurrent chemotherapy. Methods and Materials: We assessed HT in 141 patients who received P-IMRT for anal, gynecologic, rectal, or prostate cancers, 95 of whom received concurrent chemotherapy. Patients were separated into 4 groups: mitomycin (MMC) + 5-fluorouracil (5FU, 37 of 141), platinum ± 5FU (Cis, 32 of 141), 5FU (26 of 141), and P-IMRT alone (46 of 141). The pelvic bone was contoured as a surrogate for pelvic bone marrow (PBM) and divided into subsites: ilium, lower pelvis, and lumbosacral spine (LSS). The volumes of each region receiving 5-40 Gy were calculated. The endpoint for HT was grade ≥3 (HT3+) leukopenia, neutropenia or thrombocytopenia. Normal tissue complication probability was calculated using the Lyman-Kutcher-Burman model. Logistic regression was used to analyze association between HT3+ and dosimetric parameters. Results: Twenty-six patients experienced HT3+: 10 of 37 (27%) MMC, 14 of 32 (44%) Cis, 2 of 26 (8%) 5FU, and 0 of 46 P-IMRT. PBM dosimetric parameters were correlated with HT3+ in the MMC group but not in the Cis group. LSS dosimetric parameters were well correlated with HT3+ in both the MMC and Cis groups. Constrained optimization (0

  4. Prevention of acute radiation-induced proctosigmoiditis by balsalazide: A randomized, double-blind, placebo controlled trial in prostate cancer patients

    SciTech Connect

    Jahraus, Christopher D. . E-mail: cdjahraus@msn.com; Bettenhausen, Doug Phar; Malik, Uzma M.B.B.S.; Sellitti, Marguerite; St Clair, William H.

    2005-12-01

    Purpose: A common complication of pelvic radiotherapy (RT) is acute radiation-induced proctosigmoiditis (RIPS), for which a multitude of therapies have been tried. The 5-aminosalicylates (5-ASA), which are traditionally used to treat inflammatory bowel disease, have been tested; however, all but one prior randomized attempt to limit or prevent RIPS with 5-ASA-type agents have failed. We sought to evaluate balsalazide, a new 5-ASA drug, for its potential to prevent or limit RIPS in patients undergoing RT for carcinoma of the prostate, as a representative sample of pelvic RT patients. Balsalazide has a unique delivery system in that 99% of ingested drug is delivered to and activated in the colon, a higher yield than all other oral agents currently available in this class. Furthermore, it lacks the antigenic sulfa moiety present in sulfasalazine, the only other 5-ASA with demonstrated benefit in this setting. Thus, it was deemed an ideal candidate for preventing or limiting RIPS. Methods and Materials: Eligible patients included prostate cancer patients, American Joint Committee on Cancer Stage T1-3, M0 being treated with external beam radiotherapy in University of Kentucky Department of Radiation Medicine. Between January 1, 2003 and July 1, 2004, 27 eligible patients were enrolled in the study. Patients were administered 2250 mg of balsalazide or an identical-appearing placebo twice daily beginning 5 days before RT and continuing for 2 weeks after completion. Toxicities were graded weekly according to National Cancer Institute Common Toxicity Criteria v. 2.0 for each of the following: proctitis, diarrhea, dysuria, weight loss, fatigue, nausea, and vomiting. A symptom index was formulated for each toxicity consisting of the toxicity's numeric grade multiplied by the number of days it was experienced, and summed for each grade experienced throughout the course of RT. Results: With the exception of nausea or vomiting, seen in 3 patients on balsalazide and 2 on placebo

  5. The Value of Botox-A in Acute Radiation Proctitis: Results From a Phase I/II Study Using a Three-Dimensional Scoring System

    SciTech Connect

    Vuong, Te; Waschke, Kevin; Niazi, Tamim; Richard, Carole; Parent, Josee; Liberman, Sender; Mayrand, Serge; Loungnarath, Rasmy; Stein, Barry; Devic, Slobodan

    2011-08-01

    Purpose: Acute radiation proctitis (ARP) is a common side effect of pelvic radiotherapy, and its management is challenging in daily practice. The present phase I/II study evaluates the safety and efficacy of the botulinum toxin A (BTX-A) in ARP treatment for rectal cancer patients undergoing neoadjuvant high-dose-rate endorectal brachytherapy (HDREBT). Methods and Materials: Fifteen patients, treated with neoadjuvant HDREBT, 26-Gy in 4 fractions, received the study treatment that consisted of a single injection of BTX-A into the rectal wall. The injection was performed post-HDREBT and prior to the development of ARP. The control group, 20 such patients, did not receive the BTX-A injection. Both groups had access to standard treatment with hydrocortisone rectal aerosol foam (Cortifoam) and anti-inflammatory and narcotic medication. The ARP was clinically evaluated by self-administered daily questionnaires using visual analog scores to document frequency and urgency of bowel movements, rectal burning/tenesmus, and pain symptoms before and after HDREBT. Results: At the time of this analysis, there was no observed systemic toxicity. Patient compliance with the self-administered questionnaire was 100% from week 1 to 4, 70% during week 5, and 40% during week 6. The maximum tolerated dose was established at the 100-U dose level, and noticeable mean differences were observed in bowel frequency (p = 0.016), urgency (p = 0.007), and pain (p = 0.078). Conclusions: This study confirms the feasibility and efficacy of BTX-A intervention at 100-U dose level for study patients compared to control patients. A phase III study with this dose level is planned to validate these results.

  6. RTOG 0529: A Phase 2 Evaluation of Dose-Painted Intensity Modulated Radiation Therapy in Combination With 5-Fluorouracil and Mitomycin-C for the Reduction of Acute Morbidity in Carcinoma of the Anal Canal

    SciTech Connect

    Kachnic, Lisa A.; Winter, Kathryn; Myerson, Robert J.; Goodyear, Michael D.; Willins, John; Esthappan, Jacqueline; Haddock, Michael G.; Rotman, Marvin; Parikh, Parag J.; Safran, Howard; Willett, Christopher G.

    2013-05-01

    Purpose: A multi-institutional phase 2 trial assessed the utility of dose-painted intensity modulated radiation therapy (DP-IMRT) in reducing grade 2+ combined acute gastrointestinal and genitourinary adverse events (AEs) of 5-fluorouracil (5FU) and mitomycin-C (MMC) chemoradiation for anal cancer by at least 15% compared with the conventional radiation/5FU/MMC arm from RTOG 9811. Methods and Materials: T2-4N0-3M0 anal cancer patients received 5FU and MMC on days 1 and 29 of DP-IMRT, prescribed per stage: T2N0, 42 Gy elective nodal and 50.4 Gy anal tumor planning target volumes (PTVs) in 28 fractions; T3-4N0-3, 45 Gy elective nodal, 50.4 Gy ≤3 cm or 54 Gy >3 cm metastatic nodal and 54 Gy anal tumor PTVs in 30 fractions. The primary endpoint is described above. Planned secondary endpoints assessed all AEs and the investigator’s ability to perform DP-IMRT. Results: Of 63 accrued patients, 52 were evaluable. Tumor stage included 54% II, 25% IIIA, and 21% IIIB. In primary endpoint analysis, 77% experienced grade 2+ gastrointestinal/genitourinary acute AEs (9811 77%). There was, however, a significant reduction in acute grade 2+ hematologic, 73% (9811 85%, P=.032), grade 3+ gastrointestinal, 21% (9811 36%, P=.0082), and grade 3+ dermatologic AEs 23% (9811 49%, P<.0001) with DP-IMRT. On initial pretreatment review, 81% required DP-IMRT replanning, and final review revealed only 3 cases with normal tissue major deviations. Conclusions: Although the primary endpoint was not met, DP-IMRT was associated with significant sparing of acute grade 2+ hematologic and grade 3+ dermatologic and gastrointestinal toxicity. Although DP-IMRT proved feasible, the high pretreatment planning revision rate emphasizes the importance of real-time radiation quality assurance for IMRT trials.

  7. Clinical outcomes of kidney transplants on patients with end-stage renal disease secondary to lupus nephritis, polycystic kidney disease and diabetic nephropathy

    PubMed Central

    Nieto-Ríos, John Fredy; Builes-Rodriguez, Sheila Alexandra; Restrepo-Correa, Ricardo Cesar; Aristizabal-Alzate, Arbey; Ocampo-Kohn, Catalina; Serna-Campuzano, Angélica; Cardona-Díaz, Natalia; Giraldo-Ramirez, Nelson Darío; Zuluaga-Valencia, Gustavo Adolfo

    2016-01-01

    Background: Patients with lupus nephritis could progress to end-stage renal disease (10-22%); hence, kidney transplants should be considered as the treatment of choice for these patients. Objective: To evaluate the clinical outcomes after kidney transplants in patients with chronic kidney diseases secondary to lupus nephritis, polycystic kidney disease and diabetes nephropathy at Pablo Tobon Uribe Hospital. Methods: A descriptive and retrospective study performed at one kidney transplant center between 2005 and 2013. Results: A total of 136 patients, 27 with lupus nephritis (19.9%), 31 with polycystic kidney disease (22.8%) and 78 with diabetes nephropathy (57.4%), were included in the study. The graft survivals after one, three and five years were 96.3%, 82.5% and 82.5% for lupus nephritis; 90%, 86% and 76.5% for polycystic kidney disease and 91.7%, 80.3% and 67.9% for diabetes nephropathy, respectively, with no significant differences (p= 0.488); the rate of lupus nephritis recurrence was 0.94%/person-year. The etiology of lupus vs diabetes vs polycystic disease was not a risk factor for a decreased time of graft survival (Hazard ratio: 1.43; 95% CI: 0.52-3.93). Conclusion: Kidney transplant patients with end stage renal disease secondary to lupus nephritis has similar graft and patient survival success rates to patients with other kidney diseases. The complication rate and risk of recurrence for lupus nephritis are low. Kidney transplants should be considered as the treatment of choice for patients with end stage renal disease secondary to lupus nephritis. PMID:27226665

  8. Psychotic Symptoms in a Child with Long Standing SLE Nephritis: Neuropsychiatric Manifestation or Sequelae to Lupus?

    PubMed Central

    Mahapatra, Ananya; Sharma, Pawan; Sagar, Rajesh

    2016-01-01

    Systemic Lupus Erythematosus (SLE) is a prototypic autoimmune disease of unknown etiology, which affects multiple organ systems including the central nervous system (CNS). Though not common, childhood onset SLE is a known and established entity. Neuropsychiatric symptoms are common in childhood onset SLE. Of these, psychosis and behavioural symptoms are relatively rare, and there is no consensus on the proper treatment of such cases. We report a case of 13-year-old boy, diagnosed with lupus nephritis, and presented with psychosis and behavioural symptoms. The highlight of this case is that the psychiatric symptoms were present despite the primary illness being quiescent. Thus, the patient was treated with Olanzapine and lorazepam, while continuing immunosuppressive therapy as previously. Also, MRI brain revealed vasculitic changes in the right hemisphere, which might be one of the etiological factors playing role in the development of these neuropsychiatric symptoms. PMID:27274749

  9. Concurrent feline immune-complex nephritis. Tubular antigen-positive and renal amyloidosis.

    PubMed

    Saegusa, S; Shimizu, F; Nagase, M; Kasegawa, A

    1979-08-01

    We describe tubular antigen-positive immune-complex nephritis in a case of feline renal amyloidosis. Amyloid deposition was observed in mesangial area, and thickening of capillary walls was shown in the majority of the glomeruli. This case was also characterized with typical fluorescent granular depositions of cat IgG and C3 along the glomerular capillary walls as seen in human membranous glomerulonephritis. The fluorescent pattern of tubular antigen was identical with that of IgG and C3. Electron micrograph showed the thickening and irregularity of glomerular basement membranes, fusion of foot processes, and deposits of electron-dense or sometimes translucent materials, mostly in the intramembranous location. The causal sequence of the coincidental deposition of amyloid and immune complexes is discussed. PMID:157110

  10. [The dilemma with Lyme borreliosis in the dog with particular consideration of "Lyme nephritis"].

    PubMed

    Gerber, Bernhard; Eichenberger, S; Haug, K; Wittenbrink, M M

    2009-10-01

    Lyme borreliosis is the most commonly reported tick-transmitted infectious disease in the northern hemisphere in humans. Certain diseases are associated with Lyme borreliosis in the dog as well, but only intermittent lameness with articular swelling, lymphadenomegaly, fever, and anorexia were experimentally documented. Lyme borreliosis is considered an over diagnosed disease. The term "Lyme nephritis" was introduced for dogs with characteristic renal lesions and typical clinical signs, in which antibodies against Borrelia burgdorferi were found. Different studies have been aimed at showing a relation between renal disease and B. burgdorferi infection; however, this was not possible until now. Reasons for the uncertainty of the effects of B. burgdorferi in the dog are the high prevalence of circulating antibodies, the unspecific clinical picture and the inaccuracy of serologic tests.

  11. Immune Complex Tubulointerstitial Nephritis Due to Autoantibodies to the Proximal Tubule Brush Border.

    PubMed

    Rosales, Ivy A; Collins, A Bernard; do Carmo, Paula Alves S; Tolkoff-Rubin, Nina; Smith, R Neal; Colvin, Robert B

    2016-02-01

    Immune complex tubulointerstitial nephritis due to antibodies to brush border antigens of the proximal tubule has been demonstrated experimentally and rarely in humans. Our patient developed ESRD and early recurrence after transplantation. IgG and C3 deposits were conspicuous in the tubular basement membrane of proximal tubules, corresponding to deposits observed by electron microscopy. Rare subepithelial deposits were found in the glomeruli. The patient had no evidence of SLE and had normal complement levels. Serum samples from the patient reacted with the brush border of normal human kidney, in contrast with the negative results with 20 control serum samples. Preliminary characterization of the brush border target antigen excluded megalin, CD10, and maltase. We postulate that antibodies to brush border antigens cause direct epithelial injury, accumulate in the tubular basement membrane, and elicit an interstitial inflammatory response.

  12. γH2AX formation kinetics in PBMCs of rabbits exposed to acute and fractionated radiation and attenuation of focus frequency through preadministration of a combination of podophyllotoxin and rutin hydrate.

    PubMed

    Yashavarddhan, M H; Shukla, Sandeep K; Srivastava, Nitya N; Suar, Mrutyunjay; Dutta, Sangeeta; Kalita, Bhargab; Ranjan, Rajiv; Singh, Abhinav; Bajaj, Sania; Gupta, Manju L

    2016-07-01

    DNA damage can be assessed by the quantitation of γH2AX foci that form at DSB sites. This study examines the generation and persistence of γH2AX foci, variability in foci size after acute and fractionated radiation exposure, and the effect of pretreatment with a safe radioprotective formulation termed G-003M on foci generation and persistence. G-003M contains a combination of podophyllotoxin and rutin hydrate, and was administered intramuscularly to rabbits 1 hr prior to Co(60) gamma irradiation. Rabbits were assigned to one of the following treatment groups: untreated, G-003M alone, irradiated (single dose 8 Gy, fractionated 2 Gy/day for 4 days or single dose 2 Gy) or G-003M preadministration followed by radiation exposure. Foci continuously persisted for a week in peripheral blood mononuclear cells of rabbits exposed to a single 8 Gy dose. However, the number of foci gradually decreased after reaching a maximum at 1 h. In rabbits exposed to fractionated radiation, foci detected 1 hr after the final exposure were significantly larger (P < 0.001) than in rabbits exposed to a single 8 Gy dose, but disappeared completely after 24 h. In both groups, foci reappeared on days 11-15 in terminally ill animals. G-003M pretreatment significantly (P < 0.05) attenuated the formation of γH2AX foci in all irradiated rabbits. This study reveals that γH2AX focus assessment could be used to confirm radiation exposure, that focus size reflects the type of radiation exposure (acute or fractionated), that the re-appearance of foci is a strong indicator of imminent death in animals, and that G-003M provides protection against radiation. Environ. Mol. Mutagen. 57:455-468, 2016. © 2016 Wiley Periodicals, Inc. PMID:27338557

  13. Anti-Proliferative Actions of T-Type Calcium Channel Inhibition in Thy1 Nephritis

    PubMed Central

    Cove-Smith, Andrea; Mulgrew, Christopher J.; Rudyk, Olena; Dutt, Neelanjana; McLatchie, Linda M.; Shattock, Michael J.; Hendry, Bruce M.

    2014-01-01

    Aberrant proliferation of mesangial cells (MCs) is a key finding in progressive glomerular disease. TH1177 is a small molecule that has been shown to inhibit low-voltage activated T-type Ca2+ channels (TCCs). The current study investigates the effect of TH1177 on MC proliferation in vitro and in vivo. The effect of Ca2+ channel inhibition on primary rat MC proliferation in vitro was studied using the microculture tetrazolium assay and by measuring bromodeoxyuridine incorporation. In vivo, rats with Thy1 nephritis were treated with TH1177 or vehicle. Glomerular injury and average glomerular cell number were determined in a blinded fashion. Immunostaining for Ki-67 and phosphorylated ERK were also performed. The expression of TCC isoforms in healthy and diseased tissue was investigated using quantitative real-time PCR. TCC blockade caused a significant reduction in rat MC proliferation in vitro, whereas L-type inhibition had no effect. Treatment of Thy1 nephritis with TH1177 significantly reduced glomerular injury (P < 0.005) and caused a 49% reduction in glomerular cell number (P < 0.005) compared to the placebo. TH1177 also reduced Ki-67-positive and pERK-positive cells per glomerulus by 52% (P < 0.01 and P < 0.005, respectively). These results demonstrate that TH1177 inhibits MC proliferation in vitro and in vivo, supporting the hypothesis that TCC inhibition may be a useful strategy for studying and modifying MC proliferative responses to injury. PMID:23746655

  14. Comparison of Outcomes between Individuals with Pure and Mixed Lupus Nephritis: A Retrospective Study

    PubMed Central

    Ilori, Titilayo O.; Enofe, Nosayaba; Oommen, Anju; Cobb, Jason; Navarrete, Jose; Adedinsewo, Demilade A.; Oshikoya, Oluwatobiloba; Fevrier, Helene; Farris, Alton B.; Plantinga, Laura; Ojo, Akinlolu O.

    2016-01-01

    Introduction Lupus nephritis (LN) is a serious organ manifestation of systemic lupus erythematosus. Histologic overlap is relatively common in the six pathologic classes (I to VI) of LN. For example, mixed proliferative LN (MPLN) often includes features of classes III & V or classes IV & V combined. We performed a comparative evaluation of renal outcomes in patients with MPLN to patients with pure proliferative LN (PPLN) against pre-specified renal outcomes, and we also identified predictor of clinical outcomes among those with PPLN and MPLN. Hypothesis Individuals with MPLN will have worse short-term renal outcomes compared to those with PPLN. Methods We retrospectively reviewed 278 adult LN patients (≥18 years old) identified from an Emory University Hospital registry of native renal biopsies performed between January 2000 and December 2011. The final analytic sample consisted of individuals with a diagnosis of PPLN (n = 60) and MPLN (n = 96). We analyzed differences in clinical and laboratory characteristics at baseline. We also assessed associations between LN category and renal outcomes (complete remission and time to ESRD) with logistic and Cox proportional hazards models within two years of baseline. Results The study population was predominantly female (83.97%) and African American (71.8%) with a mean age of 33.4 years at baseline. Over a median follow up of 1.02 years, we did not find any statistically significant associations between MPLN and the development of ESRD or remission when compared to patients with PPLN (adjusted HR = 0.30, 95% CI = 0.07, 1.26). Conclusion There was no association between mixed or pure histopathologic features of LN at presentation and rate of complete or partial remission but higher baseline eGFR was associated with a lower probability of complete remission among patients with lupus nephritis. PMID:27304068

  15. Anti-proliferative actions of T-type calcium channel inhibition in Thy1 nephritis.

    PubMed

    Cove-Smith, Andrea; Mulgrew, Christopher J; Rudyk, Olena; Dutt, Neelanjana; McLatchie, Linda M; Shattock, Michael J; Hendry, Bruce M

    2013-08-01

    Aberrant proliferation of mesangial cells (MCs) is a key finding in progressive glomerular disease. TH1177 is a small molecule that has been shown to inhibit low-voltage activated T-type Ca(2+) channels (TCCs). The current study investigates the effect of TH1177 on MC proliferation in vitro and in vivo. The effect of Ca(2+) channel inhibition on primary rat MC proliferation in vitro was studied using the microculture tetrazolium assay and by measuring bromodeoxyuridine incorporation. In vivo, rats with Thy1 nephritis were treated with TH1177 or vehicle. Glomerular injury and average glomerular cell number were determined in a blinded fashion. Immunostaining for Ki-67 and phosphorylated ERK were also performed. The expression of TCC isoforms in healthy and diseased tissue was investigated using quantitative real-time PCR. TCC blockade caused a significant reduction in rat MC proliferation in vitro, whereas L-type inhibition had no effect. Treatment of Thy1 nephritis with TH1177 significantly reduced glomerular injury (P < 0.005) and caused a 49% reduction in glomerular cell number (P < 0.005) compared to the placebo. TH1177 also reduced Ki-67-positive and pERK-positive cells per glomerulus by 52% (P < 0.01 and P < 0.005, respectively). These results demonstrate that TH1177 inhibits MC proliferation in vitro and in vivo, supporting the hypothesis that TCC inhibition may be a useful strategy for studying and modifying MC proliferative responses to injury. PMID:23746655

  16. Satisfaction with control of systemic lupus erythematosus and lupus nephritis: physician and patient perspectives

    PubMed Central

    Mozaffarian, Neelufar; Lobosco, Steve; Lu, Peng; Roughley, Adam; Alperovich, Gabriela

    2016-01-01

    Purpose Patient satisfaction with disease control of systemic lupus erythematosus (SLE) is an important component of medical management. This analysis evaluated patient and physician satisfaction with disease control of SLE, factors associated with satisfaction/dissatisfaction, and the degree of physician–patient concordance of these parameters. Patients and methods Data were extracted from the US Adelphi Real World Lupus Disease Specific Programme®, a cross-sectional survey of 50 rheumatologists, 25 nephrologists, and their patients with non-nephritis SLE (NNSLE) or lupus nephritis (LN). Results Physicians reported moderate or severe disease activity in 25.0% of patients with NNSLE and in 50.5% of patients with LN, and were satisfied with disease control in 78.6% (132/168) and 73.8% (152/206) of patients, respectively. For patients, 75.8% (75/99) with NNSLE were satisfied with their current treatment, compared with 65.5% (74/113) with LN. Physician–patient agreement (70.7%) on the level of satisfaction was “slight” (kappa =0.1445) for NNSLE; patients were more frequently dissatisfied than physicians with regard to joint tenderness, fatigue, anxiety, pain on movement, malar rash, and photosensitivity. Physician–patient agreement (71.4%) on the level of satisfaction was “fair” (kappa =0.3695) for LN; patients expressed greater dissatisfaction than physicians for headache, photosensitivity, and anxiety, whereas physicians were more dissatisfied with regard to joint swelling, kidney function, and blood pressure control. In general, patients with NNSLE or LN who were dissatisfied (or whose physicians were dissatisfied) were more likely to have joint swelling, joint stiffness, malar rash, hair loss, depression, and fatigue, have moderate or severe disease, or to be currently experiencing disease flare. Conclusion These data highlight the patient and physician dissatisfaction with real-world disease control of SLE. PMID:27784995

  17. Remission of proteinuria indicates good prognosis in patients with diffuse proliferative lupus nephritis.

    PubMed

    Koo, H S; Kim, S; Chin, H J

    2016-01-01

    Proteinuria is a well-known risk factor for the progression of renal dysfunction in chronic kidney disease; however, its importance for estimating the prognosis of lupus nephritis requires verification. Korean adult patients with renal biopsy-diagnosed diffuse proliferative lupus nephritis who had undergone three or more consecutive urine protein to creatinine ratio or urine dipstick tests within six months after renal biopsy were enrolled. The cumulative risks, predictors, and outcomes of proteinuric remission and flare were evaluated. This study included 26 men and 167 women with a mean age at renal biopsy of 31.2 ± 9.8 years. Eighty-two (42.5%) patients experienced proteinuric remission during the follow-up period. During a mean follow-up of 157.9 ± 69.5 months, among patients who achieved proteinuric remission, one died, one developed end-stage renal disease (ESRD), and two had composite outcomes; among patients without remission, nine died, 24 developed ESRD, and 30 had composite outcomes. Patients who achieved proteinuric remission had a 0.089-fold risk (95% CI: 0.011-0.736) of mortality, 0.110-fold risk (95% CI: 0.013-0.904) of incident ESRD, and 0.210-fold risk (95% CI: 0.048-0.920) of a composite outcome compared to patients without remission. Among the 82 patients who achieved proteinuric remission, 59 (72.0%) experienced at least one proteinuria flare; however, relapse did not correlate with the incidence of outcomes. In conclusion, proteinuric remission is an independent predictive prognostic marker of good renal survival and mortality, regardless of the interval from biopsy to remission, recurrence of proteinuria after remission, renal function status at remission, or hematuria remission.

  18. Rho-kinase inhibition prevents proteinuria in immune-complex-mediated antipodocyte nephritis.

    PubMed

    Meyer-Schwesinger, Catherine; Dehde, Silke; Sachs, Marlies; Mathey, Sabrina; Arefi, Kazem; Gatzemeier, Stefan; Balabanov, Stefan; Becker, Jan U; Thaiss, Friedrich; Meyer, Tobias N

    2012-10-01

    Podocyte foot process retraction is a hallmark of proteinuric glomerulonephritis. Cytoskeletal rearrangement causes a redistribution of slit membrane proteins from the glomerular filtration barrier towards the cell body. However, the underlying signaling mechanisms are presently unknown. Recently, we have developed a new experimental model of immune-mediated podocyte injury in mice, the antipodocyte nephritis (APN). Podocytes were targeted with a polyclonal antipodocyte antibody causing massive proteinuria around day 10. Rho-kinases play a central role in the organization of the actin cytoskeleton of podocytes. We therefore investigated whether inhibition of Rho-kinases would prevent podocyte disruption. C57/BL6 mice received antipodocyte serum with or without daily treatment with the specific Rho-kinase inhibitor HA-1077 (5 mg/kg). Immunoblot analysis demonstrated activation of Rho-kinase in glomeruli of antipodocyte serum-treated mice, which was prevented by HA-1077. Increased Rho-kinase activity was localized to podocytes in APN mice by immunostainings against the phosphorylated forms of Rho-kinase substrates. Rho-kinase inhibition significantly reduced podocyte loss from the glomerular tuft. Periodic acid staining demonstrated less podocyte hypertrophy in Rho-kinase-inhibited APN mice, despite similar amounts of immune complex deposition. Electron microscopy revealed reduced foot process effacement compared with untreated APN mice. Internalization of the podocyte slit membrane proteins nephrin and synaptopodin was prevented by Rho-kinase inhibition. Functionally, Rho-kinase inhibition significantly reduced proteinuria without influencing blood pressure. In rats with passive Heymann nephritis and human kidney biopsies from patients with membranous nephropathy, Rho-kinase was activated in podocytes. Together, these data suggest that increased Rho-kinase activity in the podocyte may be a mechanism for in vivo podocyte foot process retraction.

  19. Autoantibodies against Modified Histone Peptides in SLE Patients Are Associated with Disease Activity and Lupus Nephritis

    PubMed Central

    Dieker, Jürgen; Berden, Jo H.; Bakker, Marinka; Briand, Jean-Paul; Muller, Sylviane; Voll, Reinhard; Sjöwall, Christopher; Herrmann, Martin; Hilbrands, Luuk B.; van der Vlag, Johan

    2016-01-01

    Persistent exposure of the immune system to death cell debris leads to autoantibodies against chromatin in patients with systemic lupus erythematosus (SLE). Deposition of anti-chromatin/chromatin complexes can instigate inflammation in multiple organs including the kidney. Previously we identified specific cell death-associated histone modifications as targets of autoantibodies in SLE. In this study we addressed, in a large cohort of SLE patients and controls, the question whether plasma reactivities with specific histone peptides associated with serology and clinical features. Plasma from SLE patients with and without lupus nephritis, disease controls, and healthy controls, were tested in ELISA with histone H4 peptide acetylated at lysines 8, 12 and 16 (H4pac), H2B peptide acetylated at lysine 12 (H2Bpac), H3 peptide trimethylated at lysine 27 (H3pme), and their unmodified equivalents. SLE patients displayed a higher reactivity with the modified equivalent of each peptide. Reactivity with H4pac showed both a high sensitivity (89%) and specificity (91%) for SLE, while H2Bpac exhibited a high specificity (96%) but lower sensitivity (69%). Reactivity with H3pme appeared not specific for SLE. Anti-H4pac and anti-H2Bpac reactivity demonstrated a high correlation with disease activity. Moreover, patients reacting with multiple modified histone peptides exhibited higher SLEDAI and lower C3 levels. SLE patients with renal involvement showed higher reactivity with H2B/H2Bpac and a more pronounced reactivity with the modified equivalent of H3pme and H2Bpac. In conclusion, reactivity with H4pac and H2Bpac is specific for SLE patients and correlates with disease activity, whereas reactivity with H2Bpac is in particular associated with lupus nephritis. PMID:27780265

  20. Glomerular Autoimmune Multicomponents of Human Lupus Nephritis In Vivo (2): Planted Antigens

    PubMed Central

    Bruschi, Maurizio; Galetti, Maricla; Sinico, Renato Alberto; Moroni, Gabriella; Bonanni, Alice; Radice, Antonella; Tincani, Angela; Pratesi, Federico; Migliorini, Paola; Murtas, Corrado; Franceschini, Franco; Trezzi, Barbara; Brunini, Francesca; Gatti, Rita; Tardanico, Regina; Barbano, Giancarlo; Piaggio, Giorgio; Messa, Piergiorgio; Ravani, Pietro; Scolari, Francesco; Candiano, Giovanni; Martini, Alberto; Allegri, Landino

    2015-01-01

    Glomerular planted antigens (histones, DNA, and C1q) are potential targets of autoimmunity in lupus nephritis (LN). However, the characterization of these antigens in human glomeruli in vivo remains inconsistent. We eluted glomerular autoantibodies recognizing planted antigens from laser-microdissected renal biopsy samples of 20 patients with LN. Prevalent antibody isotypes were defined, levels were determined, and glomerular colocalization was investigated. Renal and circulating antibodies were matched, and serum levels were compared in 104 patients with LN, 84 patients with SLE without LN, and 50 patients with rheumatoid arthritis (RA). Autoantibodies against podocyte antigens (anti–α-enolase/antiannexin AI) were also investigated. IgG2 autoantibodies against DNA, histones (H2A, H3, and H4), and C1q were detected in 50%, 55%, and 70% of biopsy samples, respectively. Anti-DNA IgG3 was the unique non-IgG2 anti-DNA deposit, and anti-C1q IgG4 was mainly detected in subepithelial membranous deposits. Anti-H3, anti-DNA, and anti-C1q IgG2 autoantibodies were also prevalent in LN serum, which also contained IgG3 against the antigen panel and anti-C1q IgG4. Serum and glomerular levels of autoantibodies were not strictly associated. High serum levels of all autoantibodies detected, including anti–α-enolase and antiannexin AI, identified LN versus SLE and RA. Anti-H3 and anti–α-enolase IgG2 levels had the most remarkable increase in LN serum and represented a discriminating feature of LN in principal component analysis. The highest levels of these two autoantibodies were also associated with proteinuria>3.5 g/24 hours and creatinine>1.2 mg/dl. Our findings suggest that timely autoantibody characterization might allow outcome prediction and targeted therapies for patients with nephritis. PMID:25398787

  1. Functional relevance of activated beta1 integrins in mercury-induced nephritis.

    PubMed

    Escudero, E; Martín, A; Nieto, M; Nieto, E; Navarro, E; Luque, A; Cabañas, C; Sánchez-Madrid, F; Mampaso, F

    2000-06-01

    Cell adhesion through different adhesion molecules is a crucial event in the inflammatory response. Integrins can only bind and mediate cellular adhesion after their activation by different specific stimuli. The state of beta1 integrin activation can be assessed by a group of monoclonal antibodies (HUTS) that selectively recognize beta1 integrins in their active form. A similar activated epitope in the rat was defined using the anti-human monoclonal antibody HUTS-21, which recognizes an activation-dependent epitope on the beta1 chain. It was found that the divalent cations Mn(2+) and Hg(2+) were able to induce in vitro the activation of beta1 integrins on rat lymphocytes. The Hg(2+) cation induces an autoimmune disease in the Brown Norway rat characterized by synthesis and glomerular deposits of anti-glomerular basement membrane antibodies, proteinuria, and interstitial nephritis. Using the mercury model of nephritis, it was found that the expression of HUTS-21 epitope is induced in vivo in rat lymphocytes, and its appearance is correlated with the other parameters at the onset of the disease. In addition, the administration of HUTS-21 monoclonal antibody to HgCl(2)-treated rats offered evidence of its protective effects (1) against infiltration of renal interstitium by leukocytes, and (2) in the reduction of anti-glomerular basement membrane synthesis and glomerular deposition. Nevertheless, urinary protein values remained unaffected. These results demonstrate a key role of beta1-activated integrins in both leukocyte cell-cell interactions and leukocyte infiltration pathway mechanism, and also indicate that leukocyte migration may have less importance in the development of this disease than previously thought.

  2. Phase 3 Trial of Domiciliary Humidification to Mitigate Acute Mucosal Toxicity During Radiation Therapy for Head-and-Neck Cancer: First Report of Trans Tasman Radiation Oncology Group (TROG) 07.03 RadioHUM Study

    SciTech Connect

    Macann, Andrew; Fua, Tsien; Milross, Chris G.; Porceddu, Sandro V.; Penniment, Michael; Wratten, Chris; Krawitz, Hedley; Poulsen, Michael; Tang, Colin I.; Morton, Randall P.; Hay, K. David; Thomson, Vicki; Bell, Melanie L.; King, Madeleine T.; Fraser-Browne, Carol L.; Hockey, Hans-Ulrich P.

    2014-03-01

    Purpose: To assess the impact of domicile-based humidification on symptom burden during radiation therapy (RT) for head-and-neck (H and N) cancer. Methods and Materials: From June 2007 through June 2011, 210 patients with H and N cancer receiving RT were randomized to either a control arm or to receive humidification using the Fisher and Paykel Healthcare MR880 humidifier. Humidification commenced on day 1 of RT and continued until Common Terminology Criteria for Adverse Events (CTCAE), version 3.0, clinical mucositis (CMuc) grade ≤1 occurred. Forty-three patients (42%) met a defined benchmark for humidification compliance and contributed to per protocol (PP) analysis. Acute toxicities, hospitalizations, and feeding tube events were recorded prospectively. The McMaster University Head and Neck Radiotherapy Questionnaire (HNRQ) was used for patient-reported outcomes. The primary endpoint was area under the curve (AUC) for CMuc grade ≥2. Results: There were no significant differences in AUC for CMuc ≥2 between the 2 arms. Humidification patients had significantly fewer days in hospital (P=.017). In compliant PP patients, the AUC for CTCAE functional mucositis score (FMuc) ≥2 was significantly reduced (P=.009), and the proportion who never required a feeding tube was significantly greater (P=.04). HNRQ PP analysis estimates also in the direction favoring humidification with less symptom severity, although differences at most time points did not reach significance. Conclusions: TROG 07.03 has provided efficacy signals consistent with a role for humidification in reducing symptom burden from mucositis, but the influence of humidification compliance on the results moderates recommendations regarding its practical utility.

  3. Lupus Nephritis

    MedlinePlus

    ... Griffin Rodgers, Director of the NIDDK Clinical Trials Current research studies and how you can volunteer Community Outreach and Health Fairs Science-based information and tips for planning an outreach effort or community event For Health Care Professionals Patient and provider resources ...

  4. Radiation port dermatophytosis

    SciTech Connect

    Rosen, T.; Dupuy, J.; Maor, M.; Altman, A.

    1988-12-01

    We report two cases in which dermatophytic infection developed almost entirely within a radiation field mimicking an acute radiation effect. Radiotherapists and dermatologists should be aware of this possibility and be able to differentiate it from radiation dermatitis. Topical antifungal agents are the recommended treatment after diagnosis is established.

  5. Acute Kidney Injury and Atypical Features during Pediatric Poststreptococcal Glomerulonephritis

    PubMed Central

    Ayoob, Rose M.

    2016-01-01

    The most common acute glomerulonephritis in children is poststreptococcal glomerulonephritis (PSGN) usually occurring between 3 and 12 years old. Hypertension and gross hematuria are common presenting symptoms. Most PSGN patients do not experience complications, but rapidly progressive glomerulonephritis and hypertensive encephalopathy have been reported. This paper reports 17 patients seen in 1 year for PSGN including 4 with atypical PSGN, at a pediatric tertiary care center. Seventeen children (11 males), mean age of 8 years, were analyzed. Ninety-four percent had elevated serum BUN levels and decreased GFR. Four of the hospitalized patients had complex presentations that included AKI along with positive ANA or ANCAs. Three patients required renal replacement therapy and two were thrombocytopenic. PSGN usually does not occur as a severe nephritis. Over the 12-month study period, 17 cases associated with low serum albumin in 53%, acute kidney injury in 94%, and thrombocytopenia in 18% were treated. The presentation of PSGN may be severe and in a small subset have associations similar to SLE nephritis findings including AKI, positive ANA, and hematological anomalies. PMID:27642522

  6. Acute Kidney Injury and Atypical Features during Pediatric Poststreptococcal Glomerulonephritis.

    PubMed

    Ayoob, Rose M; Schwaderer, Andrew L

    2016-01-01

    The most common acute glomerulonephritis in children is poststreptococcal glomerulonephritis (PSGN) usually occurring between 3 and 12 years old. Hypertension and gross hematuria are common presenting symptoms. Most PSGN patients do not experience complications, but rapidly progressive glomerulonephritis and hypertensive encephalopathy have been reported. This paper reports 17 patients seen in 1 year for PSGN including 4 with atypical PSGN, at a pediatric tertiary care center. Seventeen children (11 males), mean age of 8 years, were analyzed. Ninety-four percent had elevated serum BUN levels and decreased GFR. Four of the hospitalized patients had complex presentations that included AKI along with positive ANA or ANCAs. Three patients required renal replacement therapy and two were thrombocytopenic. PSGN usually does not occur as a severe nephritis. Over the 12-month study period, 17 cases associated with low serum albumin in 53%, acute kidney injury in 94%, and thrombocytopenia in 18% were treated. The presentation of PSGN may be severe and in a small subset have associations similar to SLE nephritis findings including AKI, positive ANA, and hematological anomalies. PMID:27642522

  7. Acute Kidney Injury and Atypical Features during Pediatric Poststreptococcal Glomerulonephritis

    PubMed Central

    Ayoob, Rose M.

    2016-01-01

    The most common acute glomerulonephritis in children is poststreptococcal glomerulonephritis (PSGN) usually occurring between 3 and 12 years old. Hypertension and gross hematuria are common presenting symptoms. Most PSGN patients do not experience complications, but rapidly progressive glomerulonephritis and hypertensive encephalopathy have been reported. This paper reports 17 patients seen in 1 year for PSGN including 4 with atypical PSGN, at a pediatric tertiary care center. Seventeen children (11 males), mean age of 8 years, were analyzed. Ninety-four percent had elevated serum BUN levels and decreased GFR. Four of the hospitalized patients had complex presentations that included AKI along with positive ANA or ANCAs. Three patients required renal replacement therapy and two were thrombocytopenic. PSGN usually does not occur as a severe nephritis. Over the 12-month study period, 17 cases associated with low serum albumin in 53%, acute kidney injury in 94%, and thrombocytopenia in 18% were treated. The presentation of PSGN may be severe and in a small subset have associations similar to SLE nephritis findings including AKI, positive ANA, and hematological anomalies.

  8. Acute Bronchitis

    MedlinePlus

    ... tightness. There are two main types of bronchitis: acute and chronic. Most cases of acute bronchitis get better within several days. But your ... that cause colds and the flu often cause acute bronchitis. These viruses spread through the air when ...

  9. Co-existing autosomal dominant polycystic kidney disease and nephrotic syndrome in a Nigerian patient with lupus nephritis.

    PubMed

    Akinbodewa, A A; Adejumo, O A; Ogunsemoyin, A O; Osasan, S A; Adefolalu, O A

    2016-01-01

    A little over 30 cases on co-existing nephrotic syndrome and autosomal dominant polycystic kidney disease (ADPKD) have been reported from different regions of the world since 1957. We present a case report on co-existence of nephrotic syndrome (secondary to lupus nephritis) with ADPKD in a 24-year-old woman from Nigeria. She was positive for anti-double stranded DNA. Renal histology showed International Society of Nephrology/Renal Pathology Society Class II lupus nephritis. The co-existence of nephrotic syndrome and ADPKD may have been overlooked in Africa in the past. There is a need to screen for nephrotic syndrome in patients with ADPKD among clinicians in the African setting. PMID:27044732

  10. Treatment with Anti-HMGB1 Monoclonal Antibody Does Not Affect Lupus Nephritis in MRL/lpr Mice

    PubMed Central

    Schaper, Fleur; van Timmeren, Mirjan M; Petersen, Arjen; Horst, Gerda; Bijl, Marc; Limburg, Pieter C; Westra, Johanna; Heeringa, Peter

    2016-01-01

    High mobility group box 1 (HMGB1) is a nuclear DNA binding protein that acts as an alarmin when secreted. HMGB1 is increased in systemic lupus erythematosus and might represent a potential therapeutic target. We investigated whether treatment with an anti-HMGB1 antibody affects the development of lupus nephritis in MRL/lpr mice. Seven-week-old MRL/lpr mice were injected intraperitoneally twice weekly for 10 wks with 50 μg monoclonal anti-HMGB1 (2G7, mouse IgG2b) (n = 12) or control antibody (n = 11). Control MRL/MPJ mice (n = 10) were left untreated. Every 2 wks, blood was drawn and urine was collected at wk 7, 11 and 17. Mice were sacrificed at 17 wks for complete disease evaluation. Plasma HMGB1 and anti-HMGB1 levels were increased in MRL/lpr mice compared with control MRL/MPJ mice. There were no differences in albuminuria, urine HMGB1 and plasma levels of complement C3, anti-dsDNA and proinflammatory cytokines between untreated and treated mice at any time point. Lupus nephritis of mice treated with anti-HMGB1 monoclonal antibody (mAb) was classified as class III (n = 3) and class IV (n = 9), while mice treated with control mAb were classified as class II (n = 4), class III (n = 2) and class IV (n = 5). IgG and C3 deposits in kidneys were similar in mice treated with anti-HMGB1 mAb or control mAb. In conclusion, treatment with monoclonal anti–HMGB-1 antibody 2G7 does not affect development of lupus nephritis, disease progression or proinflammatory cytokine levels in MRL/lpr mice. This result indicates that blocking of HMGB1 by this neutralizing antibody does not affect lupus nephritis in MRL/lpr mice. PMID:26837069

  11. Immune-Mediated Necrotizing Myopathy, Associated With Antibodies to Signal Recognition Particle, Together With Lupus Nephritis: Case Presentation and Management

    PubMed Central

    O’Grady, John; Harty, Len; Mayer, Nick; Critcher, Val; Ryan, John

    2015-01-01

    A male patient with limb weakness, myalgia and edema was subsequently found to have an immune-mediated necrotizing myopathy (IMNM) on biopsy. Targeted myopathic antibody analysis revealed antibodies to signal recognition particle (SRP). Anti-SRP-associated necrotizing myopathy was diagnosed. This case was complicated by the concurrent development of class III lupus nephritis. We discuss an interesting case progression and development as well as the management of these difficult to treat conditions. PMID:25883715

  12. Radiation enteritis.

    PubMed

    Harb, Ali H; Abou Fadel, Carla; Sharara, Ala I

    2014-01-01

    Radiation enteritis continues to be a major health concern in recipients of radiation therapy. The incidence of radiation enteritis is expected to continue to rise during the coming years paralleling the unprecedented use of radiotherapy in pelvic cancers. Radiation enteritis can present as either an acute or chronic syndrome. The acute form presents within hours to days of radiation exposure and typically resolves within few weeks. The chronic form may present as early as 2 months or as long as 30 years after exposure. Risk factors can be divided into patient and treatment-related factors. Chronic radiation enteritis is characterized by progressive obliterative endarteritis with exaggerated submucosal fibrosis and can manifest by stricturing, formation of fistulae, local abscesses, perforation, and bleeding. In the right clinical context, diagnosis can be confirmed by cross-sectional imaging, flexible or video capsule endoscopy. Present treatment strategies are directed primarily towards symptom relief and management of emerging complications. Recently, however, there has been a shift towards rational drug design based on improved understanding of the molecular basis of disease in an effort to limit the fibro