Immunolocalization of GLUTX1 in the testis and to specific brain areas and vasopressin-containing neurons.

GLUTX1 or GLUT8 is a newly characterized glucose transporter isoform that is expressed at high levels in the testis and brain and at lower levels in several other tissues. Its expression was mapped in the testis and brain by using specific antibodies. In the testis, immunoreactivity was expressed in differentiating spermatocytes of type 1 stage but undetectable in mature spermatozoa. In the brain, GLUTX1 distribution was selective and localized to a variety of structures, mainly archi- and paleocortex. It was found in hippocampal and dentate gyrus neurons as well as amygdala and primary olfactory cortex. In these neurons, its location was close to the plasma membrane of cell bodies and sometimes in proximal dendrites. High GLUTX1 levels were detected in the hypothalamus, supraoptic nucleus, median eminence, and the posterior pituitary. Neurons of these areas synthesize and secrete vasopressin and oxytocin. As shown by double immunofluorescence microscopy and immunogold labeling, GLUTX1 was expressed only in vasopressin neurons. By immunogold labeling of ultrathin cryosections microscopy, GLUTX1 was identified in dense core vesicles of synaptic nerve endings of the supraoptic nucleus and secretory granules of the vasopressin positive neurons. This localization suggests an involvement of GLUTX1 both in specific neuron function and endocrine mechanisms.

Iowa Surveillance of Notifiable and Other Diseases Annual Report, 2012

Promoting and protecting the health of Iowans is the mission of the Iowa Department of Public Health (IDPH). Surveillance of notifiable health conditions is essential in establishing what, how, and when events impact the public’s health. Multiple divisions and bureaus are dedicated to accomplishing the goals of surveillance. In 2012, in addition to 850 cases reported with no lab results, there were more than 79,000 laboratory results of infectious diseases and conditions submitted to IDPH disease surveillance programs. IDPH also investigates non-infectious conditions related to lead, occupational, and environmental hazards like carbon monoxide. Approximately 100,000 blood lead test results were reported to IDPH in 2012.

Microbial influences on epithelial integrity and immune function as a basis for inflammatory diseases.

Certain autoimmune diseases as well as asthma have increased in recent decades, particularly in developed countries. The hygiene hypothesis has been the prevailing model to account for this increase; however, epidemiology studies also support the contribution of diet and obesity to inflammatory diseases. Diet affects the composition of the gut microbiota, and recent studies have identified various molecules and mechanisms that connect diet, the gut microbiota, and immune responses. Herein, we discuss the effects of microbial metabolites, such as short chain fatty acids, on epithelial integrity as well as immune cell function. We propose that dysbiosis contributes to compromised epithelial integrity and disrupted immune tolerance. In addition, dietary molecules affect the function of immune cells directly, particularly through lipid G-protein coupled receptors such as GPR43.

Maladies inflammatoires cryptogéniques de l'intestin de novo après transplantation hépatique: rapport de quatre nouveaux cas et revue de la littérature [De novo inflammatory bowel diseases after liver transplantation: description of four new cases and a review of the literature]

Inflammatory bowel diseases are a result of an aberrant mucosal immune response to gut microflora. Several groups have reported newly diagnosed inflammatory bowel diseases following solid organ transplantation and subsequent immunosuppressive therapy. We describe four cases of newly diagnosed inflammatory bowel diseases following liver transplantation in a pool of 120 transplanted patients. These patients had no prior history of inflammatory bowel diseases or primary sclerosing cholangitis and were immunosuppressed. Two patients were transplanted for a hepatitis C related cirrhosis, one for alcoholic cirrhosis and one patient for autoimmune cirrhosis. Three patients were diagnosed with ulcerative colitis and one with Crohn's disease. These four patients were on a cyclosporin monotherapy when their inflammatory bowel diseases were diagnosed. These data suggest that cyclosporin monotherapy following solid organ transplantation does not prevent development of inflammatory bowel diseases.

R6le de l'urotlogue dans le dépistage des maladies osseuses [Role of the urologist in the screening of bone diseases].

During their lifetime, 20% of men will suffer from a fracture secondary to osteoporosis, and morbidity and mortality of a hip fracture in men are more severe than in women. Despite these facts, there are only few studies on osteoporosis in men. Hyopgonadism is a known risk factor for bone mineral density decrease. Hypogonadism can be found in patients diagnosed with prostate cancer who are receiving androgen deprivation therapy, but can also be discovered in patients with male infertility or erectile dysfunction. Urologists have central role in men's health aftercare, and therefore have key role in the screening and in the multidisciplinary treatment of osteoporosis and osteopenia.

A next step in adeno-associated virus-mediated gene therapy for neurological diseases: regulation and targeting.

Recombinant adeno-associated virus (rAAV) vectors mediating long term transgene expression are excellent gene therapy tools for chronic neurological diseases. While rAAV2 was the first serotype tested in the clinics, more efficient vectors derived from the rh10 serotype are currently being evaluated and other serotypes are likely to be tested in the near future. In addition, aside from the currently used stereotaxy-guided intraparenchymal delivery, new techniques for global brain transduction (by intravenous or intra-cerebrospinal injections) are very promising. Various strategies for therapeutic gene delivery to the central nervous system have been explored in human clinical trials in the past decade. Canavan disease, a genetic disease caused by an enzymatic deficiency, was the first to be approved. Three gene transfer paradigms for Parkinson's disease have been explored: converting L-dopa into dopamine through AADC gene delivery in the putamen; synthesizing GABA through GAD gene delivery in the overactive subthalamic nucleus and providing neurotrophic support through neurturin gene delivery in the nigro-striatal pathway. These pioneer clinical trials demonstrated the safety and tolerability of rAAV delivery in the human brain at moderate doses. Therapeutic effects however, were modest, emphasizing the need for higher doses of the therapeutic transgene product which could be achieved using more efficient vectors or expression cassettes. This will require re-addressing pharmacological aspects, with attention to which cases require either localized and cell-type specific expression or efficient brain-wide transgene expression, and when it is necessary to modulate or terminate the administration of transgene product. The ongoing development of targeted and regulated rAAV vectors is described.

Unusual association of diseases/symptoms: Encephalitis with herpes simplex-2 in the cerebrospinal fluid and anti-RI (ANNA-2) antibodies: an infectious or a paraneoplastic syndrome?

We report on a 70-year-old woman with partial complex status epilepticus who was initially diagnosed with herpes simplex-2 (HSV-2) encephalitis, based on brain magnetic resonance imaging (MRI) findings, cerebrospinal fluid (CSF) lymphocytic pleocytosis and HSV-2 DNA detection by polymerase chain reaction (PCR) in the CSF, but without improvement on intravenous acyclovir. Anti-Ri antibodies were positive and computed tomography (CT) investigations revealed a small cell carcinoma at biopsy suggesting paraneoplastic encephalitis. The outcome was unfavourable and the autopsy showed typical features of paraneoplastic encephalitis but no evidence of viral inclusions. This case report is interesting because: (1) it is the first report of an autopsy proven paraneoplastic widespread encephalitis with anti-Ri antibodies; (2) despite a positive HSV-2 PCR in the CSF, there was no sign of herpetic infections of the nervous system; and (3) it illustrates the fact that if paraneoplastic antibodies are usually good markers of the underlying tumour, they are not always predictive of neurological deficits.

Analysis of naturally acquired CD4+T-cell responses to MAGE-A3 and MAGE-A4 cancer/testis antigens in patients with resected head and neck squamous cell carcinoma

Despite advances in the medical and surgical treatment of Head and Neck (HN) squamous cell carcinoma (HNSCC), long term survival has remained unchanged in the last 20 years. The obvious limitations of traditional therapeutic options strongly urge the development of novel therapeutic approaches. The molecular cloning of tumor antigens recognized by T lymphocytes in recent years has provided targets for specific immunotherapy. In this regard, frequent expression of Cancer Testis Antigens (CTA) has been repeatedly observed among HN tumors. We analyzed CTA expression in 46 HNSCC patients and found that MAGE-A3 and/or -A4 CTA were positive in over 70% of samples, regardless of the anatomical site of primary tumors in the upper aerodigestive tract. Still, immune responses against these CTA in HNSCC patients have not yet been investigated in detail. In this study we assessed the responsiveness of HNSCC patient's lymphocytes against overlapping peptides spanning the entire MAGE-A3 and -A4 proteins. After depletion of CD4+CD25+ regulatory T cells, and following three rounds of in vitro stimulation with pools of overlapping peptides, peripheral blood mononuclear cells (PBMCs) of HNSCC patients were screened by IFN-g and TNF-a intracellular cytokine staining for reactivity against MAGE-A3 or -A4 derived peptides. Cytokine secreting CD4+ T cells, specific for several peptides, were detected in 7/7 patients. In contrast, only 2/5 PBMC from healthy donors showed weak T cell responses against 2 peptides. CD4+ T cells specific for one epitope MAGE-A3(281-295), previously described as an HLA-DR11 restricted epitope naturally processed and presented by dendritic cells and tumor cells, were detected in two patients. MAGE-A3(161-175) specific CD4+ T cells were found in one patient. Six MAGE-A3 and -A4 new epitopes are being characterized. Together, these data suggest that naturally acquired CD4+ T cell responses against CT antigens occur in vivo in HNSCC patients, providing a rational basis for the use of the identified peptides in vaccination protocols.

Sauerstoffsättigung der retinalen Gefässe bei hereditären Netzhauterkrankungen Retinal Vessel Oxygen Saturation in Patients Suffering from Inherited Diseases of the Retina.

Purpose: The aim of this study was to evaluate the oxygen saturation in patients with inherited diseases of the retina. Methods: Fundus oximetry images were taken using a retinal vessel analyser (IMEDOS Systems UG, Jena, Germany). Retinal vessel oximetry was performed in 53 eyes of 27 patients suffering from inherited retinal diseases and compared to 22 eyes of 11 healthy controls. The oxygen saturation in all four major retinal arterioles (A-SO2) and venules (V-SO2) were measured and their difference (A - V SO2) was calculated. The data were compared within groups and to controls. Results: Based on V-SO2 values, the rod-cone dystrophy group (66.46 %; SD, ± 5.09) could well be differentiated from controls 54.02 % (SD, ± 3.04), from cone-rod dystrophies 57.56 % (SD, ± 5.66), as well as from inherited maculopathies 58.42% (SD, ± 4.74). The mean A-SO2 in the rod-cone dystrophy group was increased to 98.96 % (SD, ± 6.06, p < 0.014), while in the cone-rod group and in the maculopathy group it was 92.75 % (SD, ± 3.75), respectively 94.44 % (SD ± 4.85), closer to the normal values (92.68 %; SD, ± 3.53, p > 0.05). The A - V SO2 difference, as an indirect indicator for retinal oxygen use, was reduced in the rod-cone patients, however only when the controls were taken into account (p = 0.01). Conclusion: This is to our knowledge the first study which proposes the retinal vessel oximetry to be a sensitive measure for differentiating rod-cone dystrophy patients not only from controls, but also from patients with other inherited retinal dystrophies.

Enzyme polymorphism and clinical variability of diseases: a study of diabetes mellitus.

We investigated possible relations among four common neonatal manifestations of diabetic pregnancy (macrosomia, hypoglycemia, hypocalcemia, jaundice) and four enzyme polymorphisms (PGM1, ADA, AK1, ACP1 in a sample of infants born of diabetic mothers. The pattern of associations observed between the two sets of variables is consistent with known differences in enzymatic activity within phenotypes of each system, suggesting that low enzymatic activity may have unfavorable effects on fetal development and on adaptability of the neonate to the extrauterine environment, Some of the polymorphic enzymes studied influence fetal growth in normal pregnancy as well. Analysis of relations between genetic polymorphisms and the clinical pattern of common diseases may provide a better understanding of the genetic basis of the clinical variability of diseases within and between human populations.