Influence of N-methyl-N-nitrosourea, testosterone, and N-(4-hydroxyphenyl)-all-trans-retinamide on prostate cancer induction in Wistar-Unilever rats

The influence of chemical carcinogen, hormonal stimulation, and chronic dietary administration of the synthetic retinoid, N-(4-hydroxyphenyl)-all-trans-retinamide (4-HPR), on the induction of prostate cancer in male Wistar-Unilever rats was determined. Three different tumor induction regimens were used: (a) a single i.v. dose of 50 mg of N-methyl-N-nitrosourea (MNU) per kg body weight, followed by chronic androgen stimulation via s.c. implantation of two silastic capsules containing 40 mg testosterone each; (b) a single i.v. dose of 50 mg of MNU per kg body weight (no testosterone treatment); and (c) chronic androgen stimulation with implanted testosterone capsules (no MNU treatment). In a fourth series of animals, the incidence of spontaneous prostate tumors was determined in groups of rats receiving neither carcinogen nor hormone stimulation. Within each series, parallel groups of animals were fed a control (vehicle-supplemented) diet or control diet supplemented with 4-HPR beginning 1 day after carcinogen administration; retinoid administration was continuous until termination of the study at 450 days. The incidence of accessory sex gland cancer in rats treated sequentially with MNU + testosterone was >60%, in comparison with cancer incidences of <20% in rats receiving MNU only and <5% in rats treated with testosterone only. No spontaneous accessory sex gland tumors were observed in rats receiving no carcinogen and no testosterone. Tumor induction in the accessory sex glands by MNU + testosterone was relatively specific for the prostate: the incidence of carcinoma of the dorsolateral/anterior prostate was more than 5-fold greater than the incidence of cancer present only in the seminal vesicle. 4-HPR conferred no protection against cancer induction in the prostate by any regimen of MNU and/or testosterone. These results demonstrate the importance of both carcinogen exposure and hormone stimulation on the induction of neoplasia in the prostate of Wistar-Unilever rats.     

Transabdominal ultrasound study of stomach and duodenum: standardization and potentialities

The paper presents an original procedure for transabdominal ultrasound examination of the stomach and duodenum, which yields an objective piece of information on the status of all wall layers of the above organs. The procedure is rather easy-to-use, noninvasive, and well tolerable. Its efficiency is confirmed by the date of examination of 46 patients.     

Medical Information Bus usage for automated IV pump data acquisition: evaluation of usage patterns

SUMMARY: lymph node involvement in renal cell carcinoma is factor of very poor prognosis. In a series of 55 node-positive patients, 33 (60%) had simultaneous renal vein or vena cava invasion and 32 (58.2%) had metastases. Gross lymph node involvement was found in 39 patients (70.9%). Patients without venous invasion or metastasis may have a prolonged survival. In this group, those with microscopic nodal involvement can be cured, as the 10 and 15-year the actuarial survival rate is 54.5% Formal lymphadenectomy might have played a role in these results. Surgery can be performed when vein invasion is present without metastasis, but the prognosis is generally poor. Survival does not seem to be influenced by surgery when metastasis is present, regardless of the vein status.     

The transition from the dose-area product to the effective dose in x-ray studies

The effective dose obtained by a patient on X-ray diagnostic studies may be determined by the Russian and foreign devices that measure the product of the absorbed dose by the radiation area while using the transition factors presented. They are calculated by the published data on the surface and effective doses per exposure unit, which are obtained on the phantoms by thermoluminescence dosimetry by taking into account the area of radiation, anode voltage, and projection, which characterize the standard conditions for performing basic X-ray diagnostic studies of adults and children (5 age groups). In the anode voltage range 40-120 kV, the factors are 10(-4) to 2.10.cm2) with errors of about +/- 32%.     

Novel function of the regulatory subunit of protein kinase A: regulation of cytochrome c oxidase activity and cytochrome c release

There have been speculations that the regulatory (R) subunit of the cAMP-dependent protein kinase (PKA) may have other functions. A recent study has shown that the catalytic (C) subunit of PKA may be regulated in a cAMP- and R subunit-independent manner. However, evidence linking a function to the R subunit apart from inhibiting the C subunit has been elusive. In this report, interaction cloning experiments showed that the RIalpha subunit association with the cytochrome c oxidase subunit Vb (CoxVb) is cAMP-sensitive. Interaction was detected with a GST-RIalpha fusion protein as well as by coimmunoprecipitation. Transient treatment with cAMP-elevating agents inhibited cytochrome c oxidase in Chinese hamster ovary (CHO) cells with a concomitant decrease in cytochrome c levels in the mitochondria and an increase in its release into the cytosol. Furthermore, mutant cells harboring a defective RIalpha show increased cytochrome c oxidase activity and also constitutively lower levels of cytochrome c in comparison to either the wild-type cells or the C subunit mutant. These results suggest a novel mechanism of cAMP signaling through the interaction of RIalpha with CoxVb thereby regulating cytochrome c oxidase activity as well as the cytochrome c levels.     

Molecular dynamics of oligopeptides. 1. The use of long trajectory and high temperature data for determination of statistical weight of conformational substates

The purpose of this study was to assess the accuracy of chest x-ray (CXR) interpretation in the diagnosis of pneumocystis carinii pneumonia (PCP), bacterial pneumonia (BP), and pulmonary tuberculosis (TB) in human immunodeficiency virus (HIV)-positive patients and to identify the frequency with which these infections mimic one another radiographically. The admitting CXRs of 153 HIV-positive patients with laboratory proven BP (n = 71), PCP (n = 73), and TB (n = 9) and those of 10 HIV-positive patients with no active disease were reviewed retrospectively and independently by three radiologists who were blinded to clinical and laboratory data. Median percent accuracies were as follows: TB, 84%; PCP, 75%; BP, 64%; and no active disease, 100%. Fifteen of 153 cases (9.8%) were shown to mimic other infections radiographically. A confident and accurate diagnosis can be made radiographically in the majority of cases of PCP, BP, and TB in HIV-positive patients at the time of hospitalization. In approximately 10% of cases, these infections may mimic one another radiographically.     

Chronic viral hepatitis enhances the risk of infection but not acute rejection in renal transplant recipients

To assess the impact of chronic viral hepatitis on host immune response, we analyzed the incidence of acute rejection and the frequency of infections in 86 patients infected with hepatitis B and C viruses and had developed clinical evidence of chronic liver disease and 1283 control patients who were transplanted at our center during the same period, but had no evidence of chronic viral hepatitis. To compare the mean number of rejections and the mean number of infections between the two groups, we used multivariate linear regression analysis, which allowed us to adjust simultaneously for the effects of 10 other risk variables with potential impact on graft rejection and posttransplant infection. During a mean follow up of 5.3+/-5.2 years, 62% of hepatitis patients and 54% of control patients had experienced an acute rejection (P=NS). The mean rejections/patient in the hepatitis group was 1.3+/-0.14 versus 1.03+/-0.03 in control (P=NS). In the linear regression analysis, the number of acute rejections in the hepatitis group was 0.16 higher than in control (P=NS). With reference to infection, 84% of hepatitis patients experienced an infectious complication in the posttransplant period, compared with 75% in the control (P=0.05). The mean number of infections/patient was 5.7+/-0.73 in the hepatitis group compared with 3.9+/-0.14 in the control group (P=0.002). The linear regression model had shown that the hepatitis group had a relative increase of 1.18 infections/pt, compared with control. Of the different sites of infection, the hepatitis group had a significant increase in bloodstream (0.48+/-0.08 vs. 0.25+/-0.02) P=0.003; pulmonary (0.60+/-0.09 vs. 0.38+/-0.03) P=0.03; and CNS infections (0.08+/-0.03 vs. 0.02+/-0.004) P=0.05 compared with control. Among the different microorganisms causing infection, the hepatitis patients had a significant increase in gram negative bacterial infections compared with the control group (74% vs. 61%) P=0.04. Our data suggest that chronic viral hepatitis is associated with a significant increase in overall infections, and that of potentially fatal infections involving CNS, lungs and bloodstream. Since there is no significant increase in the rate of graft rejection, one could consider a cautious reduction in the doses of maintenance immunosuppressive agents in renal transplant patients with chronic viral hepatitis. The reduced immunosuppression may in turn lower the death rate from sepsis and progressive hepatic failure.     

Mutational analysis of the virus and monoclonal antibody binding sites in MHVR, the cellular receptor of the murine coronavirus mouse hepatitis virus strain A59

The primary cellular receptor for mouse hepatitis virus (MHV), a murine coronavirus, is MHVR (also referred to as Bgp1a or C-CAM), a transmembrane glycoprotein with four immunoglobulin-like domains in the murine biliary glycoprotein (Bgp) subfamily of the carcinoembryonic antigen (CEA) family. Other murine glycoproteins in the Bgp subfamily, including Bgp1b and Bgp2, also can serve as MHV receptors when transfected into MHV-resistant cells. Previous studies have shown that the 108-amino-acid N-terminal domain of MHVR is essential for virus receptor activity and is the binding site for monoclonal antibody (MAb) CC1, an antireceptor MAb that blocks MHV infection in vivo and in vitro. To further elucidate the regions of MHVR required for virus receptor activity and MAb CC1 binding, we constructed chimeras between MHVR and other members of the CEA family and tested them for MHV strain A59 (MHV-A59) receptor activity and MAb CC1 binding activity. In addition, we used site-directed mutagenesis to introduce selected amino acid changes into the N-terminal domains of MHVR and these chimeras and tested the abilities of these mutant glycoproteins to bind MAb CC1 and to function as MHV receptors. Several recombinant glycoproteins exhibited virus receptor activity but did not bind MAb CC1, indicating that the virus and MAb binding sites on the N-terminal domain of MHVR are not identical. Analysis of the recombinant glycoproteins showed that a short region of MHVR, between amino acids 34 and 52, is critical for MHV-A59 receptor activity. Additional regions of the N-terminal variable domain and the constant domains, however, greatly affected receptor activity. Thus, the molecular context in which the amino acids critical for MHV-A59 receptor activity are found profoundly influences the virus receptor activity of the glycoprotein.