Group B rotavirus associated with an outbreak of neonatal lamb diarrhea

A 66-year-old woman was admitted because of postmenopausal vaginal bleeding. Diagnostic workup revealed a poorly differentiated endometrial adenocarcinoma. A total abdominal hysterectomy and bilateral salpingo-oophorectomy was carried out (FIGO stage Ia, G3). One and a half years later she developed a solitary humeral metastasis which was treated by local radiotherapy and progesterone acetate. Because osseous metastases in endometrial adenocarcinoma are rare, the literature is reviewed. In analogy to the treatment of pulmonary metastases the option of disarticulation of the patient's arm is discussed.     

The comparative amino acid sequences, substrate specificities and gene or cDNA nucleotide sequences of some prokaryote and eukaryote amidinotransferases: implications for evolution

The amino acid sequences of the amidinotransferases and the nucleotide sequences of their genes or cDNA from four Streptomyces species (seven genes) and from the kidneys of rat, pig, human and human pancreas were compared. The overall amino acid and nucleotide sequences of the prokaryotes and eukaryotes were very similar and further, three regions were identified that were highly identical. Evidence is presented that there is virtually zero chance that the overall and high identity regions of the amino acid sequence similarities and the overall nucleotide sequence similarities between Streptomyces and mammals represent random match. Both rat and lamprey amidinotransferases were able to use inosamine phosphate, the amidine group acceptor of Streptomyces. We have concluded that the structure and function of the amidinotransferases and their genes has been highly conserved through evolution from prokaryotes to eukaryotes. The evolution has occurred with: (1) a high degree of retention of nucleotide and amino acid sequences; (2) a high degree of retention of the primitive Streptomyces guanine + cytosine (G + C) third codon position composition in certain high identity regions of the eukaryote cDNA; (3) a decrease in the specificities for the amidine group acceptors; and (4) most of the mutations silent in the regions suggested to code for active sites in the enzymes.     

The xenoestrogen bisphenol A induces growth, differentiation, and c-fos gene expression in the female reproductive tract

The xenoestrogen bisphenol A (BPA) has been shown to mimic estrogen both in vivo and in vitro. BPA stimulates PRL secretion and the expression of a PRL regulating factor from the posterior pituitary in the estrogen-sensitive Fischer 344 rat (F344), but not in Sprague-Dawley (SD) rats. The goal of the present studies was to examine the in vivo actions of BPA on the reproductive tract. The specific objectives were 1) to characterize the short term effects of BPA on cell proliferation and c-fos expression in the uterus and vagina, and 2) to compare the effects of prolonged exposure to low doses of BPA on the reproductive tract of F344 and SD rats. Treatment with single high doses of BPA induced cell proliferation in the uterus and vagina of ovariectomized F344 rats, as determined by bromodeoxyuridine immunostaining. This proliferation was dose dependent (from 37.5-150 mg/kg) and followed a time course similar to that of estradiol (E2). Quantitative RT-PCR revealed that both BPA and E2 increased c-fos messenger RNA levels in the uterus 14- to 16-fold within 2 h, which returned to basal levels after 6 h. In the vagina, BPA-induced c-fos expression remained elevated for up to 6 h, compared with the transient increase caused by E2. Treatment of F344 rats for 3 days with continuous release capsules that supplied a much lower dose of BPA (approximately 0.3 mg/kg x day) resulted in hypertrophy, hyperplasia, and mucus secretion in the uterus and hyperplasia and cornification of the vaginal epithelium. The reproductive tract of SD rats did not respond to this treatment paradigm with BPA. These studies demonstrate that 1) the molecular and morphological alterations induced by BPA in the uterus and vagina are nearly identical to those induced by estradiol; 2) the vagina appears to be especially sensitive to the estrogenic actions of BPA; 3) the reproductive tract of the inbred F344 rat appears more sensitive to BPA than that of the outbred SD rat; and 4) continuous exposure to microgram levels of BPA is sufficient for exerting estrogenic actions.     

Pulmonary carcinogenicity of relatively low doses of beta-particle radiation from inhaled 144CeO2 in rats

This study was conducted to examine the carcinogenic effects of inhaled beta-particle-emitting radionuclides, particularly in lower dose regions in which there were substantial uncertainties associated with available information. A total of 2751 F344/N rats (1358 males and 1393 females) approximately 12 weeks of age at exposure were used. Of these, 1059 rats were exposed to aerosols of 144CeO2 to achieve mean desired initial lung burdens (ILBs) of 18 kBq (low level), 247 rats to achieve mean ILBs of 60 kBq (medium level) and 381 rats to achieve mean ILBs of 180 kBq (high level). Control rats (total of 1064) were exposed to aerosols of stable CeO2. Based on the 95% confidence intervals of the median survival times and the cumulative survival curves, there were no significant differences in the survival of groups of female and male exposed rats relative to controls. The mean lifetime beta-particle doses to the lungs of the rats in the four groups were: low level, 3.6 +/- 1.3 (+/-SD) Gy; medium level, 12 +/- 4.5 Gy; and high level, 37 +/- 5.9 Gy. The crude incidence of lung neoplasms increased linearly with increasing doses to the lungs (controls, 0.57%; low level, 2.0%; medium level, 6.1%; and high level, 19%). The estimated linear risk coefficients for lung neoplasms per unit of dose to the lung were not significantly different for the three dose levels studied. The risk coefficient at the lower level was 39 +/- 14 (+/-SE) excess lung neoplasms per 10(4) rat Gy; at the medium level the risk was 47 +/- 12; and at the higher level the risk was 50 +/- 9.0. The relationship of beta-particle dose to the lung and the crude incidence of lung neoplasms was described adequately by a linear function. We concluded that the risk of lung neoplasms in rats per unit of radiation dose did not increase with decreasing mean beta-particle dose to the lung over the range of 3.6 to 37 Gy. The weighted average of these three values was 47 +/- 6.4 (+/-SE) excess lung neoplasms per 10(4) rat Gy. To extend the risk coefficients for lung neoplasms to lower doses by experimentation will require much larger numbers of rats than used in this study.     

Mitogenic effect of erythropoietin on cultured aortic myocytes

The administration of recombinant erythropoietin (rHuEpo) to anemic chronic renal failure patients may be associated with an increase in blood pressure, possibly by direct effects on peripheral blood vessels. In the present study, experiments were designed to explore the hypothesis that rHuEpo could enhance vascular resistance through mitogenic effect on vascular smooth muscle cells (VSMCs), and that preexisting hypertension might be a predisposing condition. Cultured VSMCs from the thoracic aortae of spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats were studied for DNA synthesis, phospholipase C activity, and cell growth related proto-oncogene expression in the presence of rHuEpo. In cells from both strains, rHuEpo dose-dependently increased DNA synthesis and stimulated phospholipase C activity, as indicated by 3H-thymidine incorporation and 3H-inositol phosphate formation, respectively (EC50 approximately 4 U/ml). Exposure of VSMCs to rHuEpo for various times gradually increased the levels of c-myc and junB and transiently induced c-fos expression, as determined by Northern analysis. rHuEpo-induced DNA synthesis was markedly enhanced in VSMCs from SHR compared to those from WKY. In contrast, rHuEpo-induced phospholipase C activity and proto-oncogene expression did not differ between the two strains. Taken together, these results suggest that rHuEpo may function as a vascular smooth muscle cell growth promoting factor through activation of the phospholipase C cascade and modulation of proto-oncogene expression. It could thereby contribute to vascular hypertrophy and arterial hypertension.     

Cellular depletion of p56lck during thymocyte apoptosis

The src-related protein tyrosine kinase p56lck is thought to be important in regulating maturation and functional responsiveness of T cells and thymocytes. In the present studies we report that expression of p56lck is suppressed during apoptosis. Using primary cultures of rat thymocytes, we found that agents that are effective in inducing apoptosis, including okadaic acid, dexamethasone, and antibodies to the CD3 receptor, also deplete cells of p56lck. This process is rapid, occurring within 24 h, and is not due to cytotoxicity. Inhibition of DNA fragmentation in apoptotic cells with the endonuclease inhibitor ZnCl2 failed to prevent depletion of p56lck, suggesting that it was not a consequence of the DNA degradation process. Using the thymic lymphoma cell line LSTRA, apoptosis was also associated with cellular depletion of p56lck. In contrast to thymocytes, this process required 48-72 h possibly because these cells overexpress p56lck. Although at this time we are uncertain as to the precise role of p56lck in the process of apoptosis, our results indicate that changes in the expression of this protein in thymocytes is an important marker of programmed cell death.     

Chronic interleukin-6 alters NMDA receptor-mediated membrane responses and enhances neurotoxicity in developing CNS neurons

Recent studies show that the cytokine interleukin-6 (IL-6) is expressed at elevated levels in the CNS in several disease states and contributes to the neuropathological process. The mechanisms through which IL-6 exerts its CNS effects are primarily unknown. We have investigated the pathophysiological effects of IL-6 on developing CNS neurons using a culture model system and a chronic treatment paradigm. Here, we show, using current- and voltage-clamp recordings, that chronic IL-6 treatment of developing cerebellar granule neurons increases the membrane and current response to NMDA and that these effects are the primary mechanism through which IL-6 produces an enhanced calcium signal to NMDA. We also show that calcium influx through voltage-sensitive calcium channels contributes to the enhanced calcium signal to NMDA in the IL-6-treated neurons in a developmentally regulated manner and that the membrane depolarization to NMDA is more sensitive to the NMDA receptor antagonist ifenprodil in the IL-6-treated neurons compared with control neurons at a late developmental stage, consistent with a larger proportion of NMDA receptors containing the NMDAR2B subunit in the IL-6-treated neurons. Additional studies show that IL-6 treatment reduces the number of granule neurons in culture and enhances neurotoxicity involving NMDA receptors. These results support a pathological role for IL-6 in the CNS and indicate that NMDA receptor-mediated functions are likely to play a critical role in neuropathological changes observed in CNS diseases associated with elevated CNS levels of IL-6.     

Smokeless tobacco use in an outpatient veteran population

Smokeless tobacco use is a significant health risk for carcinoma of the oropharynx, and has a high prevalence in the southern United States. To evaluate the potential demand for a smokeless tobacco cessation program, we surveyed patients attending the General Medicine Clinic of a Veterans Affairs Medical Center. The prevalence of smokeless tobacco use was 5.8%, which did not justify creation of a clinic-based cessation program. Since we observed adults using smokeless tobacco as a means to reduce or stop their smoking, smoking cessation programs should include counseling against smokeless tobacco use.     

Trabeculectomy function after cataract extraction

OBJECTIVE: To examine the effect of cataract extraction (CE) after trabeculectomy on intraocular pressure (IOP) control. DESIGN: Retrospective noncomparative case series. PARTICIPANTS: A total of 115 consecutive patients who underwent extracapsular CE (N = 58) or phacoemulsification (N = 57) with intraocular lens (IOL) placement after trabeculectomy were studied. INTERVENTION: Cataract extraction with IOL after trabeculectomy was performed. MAIN OUTCOME MEASURES: Preoperative, intraoperative, and postoperative factors were evaluated for association with loss of IOP control requiring additional medications, bleb needling, or further glaucoma surgery, using Kaplan-Meier survival analysis and Cox multivariate proportional hazards survival regression. RESULTS: After mean postoperative follow-up of 21.1 +/- 14.3 months, additional glaucoma medication or needling of the filtering bleb to maintain IOP control was required in 35 eyes (30.4%) and was significantly associated with intraoperative iris manipulation and early postoperative peak IOP greater than 25 mmHg. Additional glaucoma surgery was eventually required in 11 eyes (9.6%) and was significantly associated with age of 50 years or younger, preoperative IOP greater than 10 mmHg, and early postoperative peak IOP greater than 25 mmHg. The cumulative proportion of patients who did not require reoperation for glaucoma was 93% and 90% at 1 and 2 years, respectively. The mean IOP at last visit had increased 1.6 mmHg above the pre-CE level and did not vary significantly after the first postoperative month. The median interval from CE to the addition of glaucoma medication or bleb needling was 1.6 months (within 3 months in 20 of 33 eyes) and that from nonsurgical intervention to further glaucoma surgery was 3.6 months (before the 7th postoperative month in 6 of 11 eyes). Of 19 eyes with hypotony (IOP < or = 6 mmHg) before CE, 11 eyes remained hypotonous after CE despite an increase in the mean IOP from 4.6 to 7.5 mmHg. CONCLUSIONS: When CE is performed after trabeculectomy, age of 50 years or younger, preoperative IOP greater than 10 mmHg, intraoperative iris manipulation, and early postoperative IOP greater than 25 mmHg are associated with worsened postoperative IOP control. Most bleb failures occur soon after CE. Resolution of pre-existing hypotony after CE is unpredictable.