Acetohydroxy acid synthase and threonine deaminase activities, and the biosynthesis of isoleucine-leucine-valine in Streptococcus bovis

Acetohydroxy acid synthase (AHAS) and threonine deaminase (TD) activities were found in Streptococcus bovis and shown to be involved in the biosynthesis of the branched chain amino acids isoleucine, leucine and valine. Apparent lack of repression of AHAS synthesis by the end-products and reduced sensitivity of S. bovis growth to analogues of the branched chain amino acids suggested that secretion of isoleucine, leucine and valine in the growth medium may be a consequence of the regulatory features of AHAS. A glycyl-leucine-resistant mutant with reduced TD activity secreted a reduced amount of isoleucine and an increased amount of valine, which might be a result of the reduced rate of synthesis of the isoleucine precursor alpha-ketobutyrate and of a consequent preferential carbon flow through the valine branch of the pathway.     

Epidemiology of hepatitis C and G in sporadic and familial porphyria cutanea tarda

From 1995 to 1997, we prospectively evaluated the prevalence of hepatitis C virus (HCV) RNA in 124 patients with porphyria cutanea tarda (PCT) from Northern France (83 sporadic and 41 familial PCT). Serum samples were analyzed for ferritin, transaminases, HCV antibodies, and HCV RNA. In addition, genotyping of HCV and searches for HCV infection risk factors (blood transfusion, iv drug abuse, and surgical intervention) were performed. Twenty-six of 124 patients (21%; 95% CI: 13.9-28) were positive for serum HCV antibodies. All of them were also positive for HCV RNA. The prevalence of HCV infection was higher in the sporadic PCT group (26.5%, 22 out of 83) than in the familial PCT group (9.7%, 4 out of 41). Risk factors for hepatitis C infection were found to be significantly increased in the HCV-positive group when compared with the HCV-negative PCT group. In all HCV-positive patients with a risk factor, the suspected date of exposure to the virus always preceded the clinical onset of PCT. The HCV genotype pattern in PCT patients was similar to that observed in nonporphyric HCV patients in western European countries. Serum ferritin level was increased in both HCV-positive and HCV-negative porphyric patients. Transaminase levels were significantly higher in HCV-infected PCT patients. Sixty-seven out of 124 patients were retrospectively studied for hepatitis G virus (HGV) infection. Six of these 67 patients (8.9%; 95% CI: 2.1-15.8) were positive for HGV RNA. None of the six HGV-infected patients were positive for HCV RNA. The HGV-infected patients did not differ statistically from those without HGV infection with regard to age, ferritin, transaminase levels, and PCT treatment. These results support the view that sporadic cases of HGV infection may occur frequently. This study of a large cohort of HCV and PCT patients further documents an increasing gradient in HCV prevalence from northern to southern Europe, and shows that HCV infection acts as a triggering factor of PCT. Finally, the HGV prevalence found in the PCT patients was comparable with that found in French blood donors, suggesting that HGV is not a PCT triggering factor.     

Interleukin 8 (IL-8) induces the expression of kinin B1 receptor in human lung fibroblasts

Near-haploidy is a rare cytogenetic finding in childhood acute lymphoblastic leukaemia (ALL) and is associated with a poor prognosis. A second hyperdiploid line, occurring presumably by endoreduplication of the near-haploid stemline, is often observed. We present a case of common ALL in relapse characterized morphologically by a dual population of small and large lymphoblasts. Cytogenetic analysis supplemented with fluorescence in-situ hybridization (FISH) studies localized near-haploidy and hyperdiploidy to the small and large blast population respectively. DNA ploidy determination confirmed two abnormal clones with near-haploidy as the predominant one. A novel t(9;12)(q11;q13) was present in the near-haploid clone and was duplicated in the hyperdiploid clone. This finding identified cells bearing near-haploidy to be the clonogenic population following malignant transformation and confirmed endoreduplication as the mechanism for the presence of associated hyperdiploidy.     

High levels of interleukin-12 in the aqueous humor and vitreous of patients with uveitis

OBJECTIVE: This study aimed to investigate the role of interleukin-12 (IL-12) and interleukin-10 (IL-10) in initiation and maintenance of intraocular inflammation. DESIGN: Case series. PARTICIPANTS: Aqueous humor and vitreous levels of IL-12 and IL-10 were measured in 22 patients with uveitis undergoing cataract surgery, paracentesis of the anterior chamber, and/or vitrectomy for diagnostic reasons, and in 4 patients with cataract only. INTERVENTION: Aqueous humor and vitreous levels of IL-12 and IL-10 were measured with specific enzyme-linked immunosorbent assays. MAIN OUTCOME MEASURES: Disease activity was correlated to IL-12 levels in the aqueous humor and the vitreous of patients with uveitis. RESULTS: Cytokine levels found in the anterior chamber and the vitreous are presented in picogram/milliliter (medium; range). The highest IL-12 levels were found in patients with active uveitis (108.5 pg/ml; 72-293 pg/ml). Interleukin-12 in patients with moderate uveitis or with their disease in remission was lower (32 pg/ml; 15-94 pg/ml) than in patients with active disease (P > 0.001) but higher than in the control group (10.5 pg/ml; 9-14 pg/ml). Interleukin-10 was detectable in only 3 of 22 patients with uveitis (12 pg/ml; 9-23 pg/ml). CONCLUSION: The authors found statistically significant differences of IL-12 levels in the various patient groups (active vs. inactive vs. control). These results support the idea that these uveitis cases represent type 1 (Th1)-T lymphocyte-mediated diseases in which IL-12 plays a pivotal role in the initiation and maintenance of the intraocular inflammation. The high levels of IL-12 in the vitreous and/or aqueous humor of the patients with uveitis suggest that susceptibility or resistance to ocular autoimmunity may be connected to a genetic predisposition to an elevated Th1 response.     

Healon GV versus Healon in demanding cataract surgery

Spontaneous nasal tumors are rare in mice, and only one adenocarcinoma and two more primary neoplasms of the nose have been observed in our files of long-term feeding studies, which are composed of 3,419 male and 3,521 female CD-1 (Crl:CD-1 (ICR)BR) mice. This adenocarcinoma was a 1-cm-diameter mass observed grossly in the right nasal cavity of a 454-day-old, male CD-1 mouse from a treated group in a bioassay study conducted with 340 males and 340 females. The neoplastic epithelial cells affected the normal nasal architecture on the right side of the nose. Roughly, tumor neoplastic cells of the outer, lateral portion occurred as cuboidal to low columnar cells with basilarily located nuclei and eosinophilic cytoplasm. These cells were arranged in cylindrical profiles and frequently entrapped acini of the glands of the maxillary sinus. Neoplastic epithelial cells of the inner, medial portion appeared as serous acinar or ductular structures circumscribed by multiple lagers of myoepithelial-like cells. Staining failed to demonstrate mucous secretion. The site of origin of this neoplasm appeared to be the serous glands of the maxillary sinus. The adenocarcinoma was believed to be spontaneous.     

Acamprosate and alcohol: I. Effects on alcohol intake following alcohol deprivation in the rat

Acamprosate (calcium-acetyl homotaurinate) is a new compound in the treatment of alcoholism. Its efficacy has been proven in several clinical trials and registration is now pending in most European countries. The basic mechanisms by which acamprosate elicits its anti-craving action, thereby leading to reduced relapse rates, is not known at the moment. In the present study we describe a rat model of long-term alcohol-drinking which mimics relapse behavior in human alcoholics. The effect of acamprosate was studied in this model. Wistar rats had a free choice between water and alcohol solutions of different concentrations (5, 10, 20% v/v). After two months of continuous alcohol access, rats were deprived of alcohol for three days. Following this deprivation phase, all alcohol solutions were presented again. This procedure was repeated monthly for the following six months. The rats consumed 3.5 +/- 0.3 g/kg alcohol a day. After alcohol deprivation, alcohol intake rose to 5.2 +/- 0.3 g/kg per day resulting in blood alcohol levels of 30 +/- 6 mg/dl. Interestingly, the addition of quinine to the alcohol solutions or the additional presentation of a 5% sucrose solution did not affect the alcohol-deprivation effect after eight months of this intermittent alcohol exposure. However, when acamprosate (50-200 mg/kg i.p.) was administered twice daily, alcohol-drinking following an alcohol-deprivation phase was decreased dose dependently. Given at the highest dose alcohol intake even dropped significantly below baseline drinking. Together, these results show that acamprosate effectively diminishes the alcohol-deprivation effect. Furthermore, the described model seems to be a suitable animal model to screen compounds for their anti-relapse properties and subsequently for their anti-craving action.     

Prenatal cocaine delays astroglial maturation: immunodensitometry shows increased markers of immaturity (vimentin and GAP-43) and decreased proliferation and production of the growth factor S-100

Exposure to cocaine during fetal development has been demonstrated to produce a variety of brain and behavioral changes. Cocaine is a potent releaser of a variety of neurotransmitters, such as serotonin, which act as developmental signals. Since serotonin plays an important role in astroglial maturation, migration, and growth factor production (e.g. S-100 beta), we proposed that these properties of astroglial cells will be altered in a brain prenatally exposed to cocaine. To observe cocaine's effects on astroglial development, we performed immunocytochemical analyses of a variety of developmental protein makers including BrdU, Gap-43, vimentin, and S100 beta. Our results demonstrate that prenatal cocaine administration produces decreased cell proliferation as measured by BrdU staining, retarded neurite outgrowth as ascertained by increased Gap-43 immunoreactivity, increased density of vimentin-positive radial glial cells, and diminished tissue S100 beta immunoreactivity. Overall, these results suggest that cocaine delays astroglial development. This delay would have profound effects on neuronal development and outgrowth and, thus, development of the entire brain.     

Transconductance and mobility of Si:B delta MOSFETs

Delta-doped MOSFETs have been fabricated in MBE-grown silicon using for the first time boron as the dopant within the delta layer. Current-voltage characteristics have been measured, and secondary ion mass spectrometry (SIMS) is used to confirm the location of the delta layer and the extent of layer broadening by diffusion during processing. Precise threshold voltages of the devices are difficult to determine since the devices (which all operate in depletion mode) take several volts to switch off. Transconductances of the devices have been measured, and it is shown how analysis of these results can yield estimates of the carrier mobility for transport along the delta layers despite the uncertainty in the threshold voltage. A clear transition is observed in the results which is attributed to the formation of a parasitic surface-channel field-effect transistor, providing conclusive evidence that the devices are conducting along a delta channel for part of the measured range of applied gate biases