Coping in chest pain patients with and without psychiatric disorders

We first examined relations between psychiatric disorder and coronary heart disease (CHD) in 77 patients presenting with chest pain. The coping profiles of chest pain patients with and without psychiatric disorder and CHD were then compared. Psychiatric patients with no medical illness (n = 129) were also studied. On the basis of previous research we hypothesized specific coping differences across the groups. As expected, chest pain patients without psychiatric disorder scored significantly higher on a problem-focused coping scale than chest pain patients with psychiatric disorder, who in scored higher on this scale than psychiatric patients with no medical illness. The opposite pattern occurred for a measure of wishful thinking. Scores of chest pain patients with psychiatric disorder were higher on a measure of avoidance and lower on a measure of seeking of social supports than those without psychiatric disorder. Scores on a self-blame measure were not different across the groups. The results are discussed in the context of illness behavior and somatization.     

Molecular cloning and complete nucleotide sequence of carnation Italian ringspot tombusvirus genomic and defective interfering RNAs

Summary The complete sequences of genomic and defective interfering (DI) RNAs of carnation Italian ringspot tombusvirus (CIRV) were determined. The genome (4760 nt) has an organization identical to that reported for other tombusviruses except that the pre-readthrough domain of the viral replicase encoded by the 5-proximal open reading frame (ORF) is larger. In particular, the N-terminal region of this protein differs from the corresponding region of the other members of the genusTombusvirus andCarmovirus. Two DI RNAs were found in infected tissues whose sequences were completely derived from genomic RNA. The smaller molecule (474 nt) is contained completely within the larger molecule (656 nt), which suggests that it is derived from the larger one.The nucleotide sequence data reported in this paper will appear in the EMBL, GenBank and DDBJ Nucleotide Database under the accession number X85215.     

A radio (51Cr) micro-tube leukocyte adherence inhibition assay: specific tumor-associated immunity in 3 murine tumor systems.

A radio (51Cr) micro-tube leukocyte adherence inhibition assay is described. In this study, murine mononuclear cells were labeled with 51Cr, plated into tissue culture plates with different tumor extracts and counts/min (cpm) of the non-adherent cells were used as a parameter of adherence inhibition. This assay was used to measure anti-tumor immunity, in vitro, in 3 murine tumor systems: MCA-38 colon adenocarcinoma, L1210 lymphoma and P815 mastocytoma. Tumor immunity was detected using 3 doses (0.01-0.001 mg/ml) of tumor extract in the MCA-38 tumor model, and using 2 doses (0.1-0.05 mg/ml) of tumor extract in both the L1210 and P815 tumor models. It was observed that specific tumor-associated adherence inhibition could be measured in the MCA-38 tumor model between days 7 and 22 of tumor growth and in the L1210 and P815 tumor models between days 7 and 17 of tumor growth. The radio-LAI assay described is an easy, specific and reproducible way to measure tumor-associated adherence inhibition, in vitro.     

The stage-specific 90-kilodalton surface antigen of metacyclic trypomastigotes of Trypanosoma cruzi

The 90-kDa antigen, previously identified by the monoclonal antibody 1G7 to be a stage-specific surface protein of metacyclic trypomastigotes of Trypanosoma cruzi, has been further characterized in this study. Experiments of metabolic labeling with [35S]methionine, [2H]mannose and [3H]galactose revealed that the 90-kDa antigen is the main glycoprotein synthesized by metacyclic forms (G strain). Through pulse-chase experiments with [35S]methionine-labeled metacyclic trypomastigotes, it was found that the antigen is synthesized as a 75-kDa precursor polypeptide that is rapidly processed to the mature 90-kDa molecule. When metacyclic trypomastigotes were treated with tunicamycin, the production of 90-kDa antigen was greatly diminished, and the 75-kDa species, which was also expressed on the cell surface, accumulated. Concanavalin A bound strongly to the 90-kDa antigen, but failed to recognize the 75-kDa polypeptide. Treatment of neuraminidase had no effect on the 90-kDa antigen, whereas digestion by endoglycosidase H generated a polypeptide of 82 kDa. Altogether these data indicate that the 90-kDa antigen is a glycoprotein containing N-linked oligosaccharide side chains of the high-mannose type. The 90-kDa glycoprotein may be involved in the process of host cell invasion, since the internalization of metacyclic forms into Vero cells was partially inhibited by monoclonal antibody 1G7.     

Susceptibility of the mammary gland to carcinogenesis: I Differentiation of the mammary gland as determinant of tumor incidence and type of lesion.

The influence of age and mammary gland differentiation on the incidence of tumors induced by 7,12-dimethylbenz(a)anthracene (DMBA) was studied by correlating the development of the mammary glands of 20-180-day-old, virgin Sprague-Dawley rats with the number and type of tumors induced by DMBA administered at those various ages. The number of terminal end buds (TEBs), terminal ducts (TDs), and alveolar buds (ABs)/sq mm and their DNA-labeling indices (DNA-LI) were determined. Highest density of TEB occurred when the rats were 20 days old, decreasing thereafter. DNA-LI ranged between 25.2 and 29 in TEB of rats aged 30-55 days, which was coincident with the highest incidence of carcinomas. With aging, the number of TEBs and their DNA-LI decreased and the number of TDs and ABs increased, although with a low DNA-LI, which correlated with a lower incidence of carcinomas and higher incidence of benign lesions.     

The surgical anatomy of hearts with no direct communication between the right atrium and the ventricular mass--so-called tricuspid atresia

Seventy-six hearts were studied having no direct communication between the right atrium and the ventricular mass. The different cardiac chamber combinations producing so-called "tricuspid atresia" were considered. The nature of the atrioventricular valve atresia, the morphology of the ventricular mass, the size and position of the interventricular communication, the ventriculoarterial connection, and the presence of subarterial outflow tract obstruction were all analyzed. The majority of cases were of the "classical" type, i.e., absent right atrioventricular connection with the left atrium connected to the left ventricle. In another group there was absence of the right atrioventricular connection but the left atrium drained into the morphologically right ventricle, which was left-sided. In a third group both atrial chambers connected with the ventricular mass but some structure, an imperforate valve or muscular partition, completely blocked the flow pathway through the right side of the heart. All the hearts described are candidates for the Fontan procedure with either an atrioventricular or an atriopulmonary conduit. The surgical options would not be affected by the observed variability at the atrioventricular junction but would be dictated by the feasibility of incorporating the subpulmonary ventricle within the pulmonary circulation.     

ras and myc analysis in primary and metastatic colorectal carcinomas

Paired primary colorectal adenocarcinoma and normal frozen tissue samples from 60 patients were prospectively studied to determine the frequency of point mutations in K-ras and the occurrence of structural alterations in c-myc. Parallel investigations were performed on liver metastatic specimens from 16 of the patients. 47% of the primary tumors presented point mutations in K-ras; 71% of these were in codon 12. Significant associations were found between codon 13 ras mutations and Dukes' D stage (p<0.05), and between mutations in codon 12 and mucinous type (p<0.01). The c-myc gene structure was altered in 5/60 cases (8%). In 4/16 cases, the K-ras gene status in the primary carcinoma and in the metastatic tissue from the same patient was found to be different. Our results suggest that codon 13 I-as mutations may be associated with an increased invasive and metastatic potential, while codon 12 mutations may have a role in the mucinous differentiation pathway.     

Tumor-necrosis-factor and DNA topoisomerase-ii inhibitors in human ovarian-cancer - potential role in chemotherapy

Seven ovarian and one cervical human cancer cell lines were examined far their sensitivity or resistance to tumor necrosis factor, to three topoisomerase II inhibitors and to cisplatin. Only one line exhibited the multidrug-resistance phenotype and another one an 'atypical'-MDR phenotype. The combination of TNF and topoisomerase-II inhibitors produced enhanced cytotoxicity and overcame the MDR and the atypical resistance. No potentiation of cisplatin cytotoxicity was observed. These findings suggest that TNF enhances the activity of DNA topoisomerase II both in TNF resistant and sensitive cells.     

Genome scanning using endogenous LTR-like elements for rapid DNA-fingerprinting of breast-cancer and transformed human breast epithelial-cells

In the present work genomic DNAs from nine primary breast cancers and transformed human breast epithelial cell lines obtained by treatment of MCF 10F, a spontaneously immortalized human breast epithelial cell line, with benzo(a)pyrene (BP) or 7,12 dimethyl benz(a)anthracene (DMBA), were used for genomic scanning. The treatment of MCF 10F with BP gave rise to different clones designated BP1 and BP1E, the latter being a tumorigenic cell line. Treatment with DMBA gave rise to D3 and D3-1 clones. The clones D3-1 and BP1 have been transfected with the plasmid pH06T1 containing the mutated c-Ha-ras oncogene resulting in the D3-1Tras and BP1T-ras cell lines, that are highly tumorigenic in SCID mice. Genomic DNA are separately hybridized to two different probes representing different families of human endogenous retrovirus like sequences (RTLV-H and HERV-K LTR). The technique of genomic scanning allows the mapping of each tumor or cell line and comparison with its counterpart obtained from the adjacent normal tissue of the same patient or with the untreated MCF 10F cells. DNA changes such as deletions, amplifications and/or rearrangements were detected in 5 of the tumor pairs studied. We have identified genomic alterations that involved amplification of a 10 kb band in the transformed cell lines. The cell lines D3-1Tras and BP1T-ras show, in addition, the presence of a second band of 4.5 kb in size. A third band of 500 bp size was found in clones D3-1 and BP1E that have a more aggressive behavior in vitro than their precursors D3 and BP1 cells respectively. In conclusion the present report indicates that genomic scanning detects DNA aberrations in primary primary tumors and in human breast epithelial cells transformed with chemical carcinogens and/or oncogene transfection that are not present in their normal counterpart. These results further indicate that detection of endogenous retrovirus elements may help in genome mapping and can be a useful tool for detecting genomic changes in the preliminary screening of DNA extracted from primary breast cancer and transformed cells.     

Pharmacokinetics of thiopental after single and multiple intravenous doses in critical care patients

Thiopental was administered to neurosurgical patients for cerebral protection and its pharmacokinetic parameters were determined after a single bolus of 540, 1000 or 1500 mg (3 subjects) or after multiple doses of 250 mg (5 subjects) and 500 mg (2 subjects) every two hours for up to 7 days. The data were analysed by a two- or three- compartment model and linear kinetics. After a single IV bolus, the mean initial volume of distribution (V1) was 0.4811·kg^–1, and the steady-state volume of distribution (V_ss) was 2.16 1·kg^–1. The distribution (t_1/2) and elimination (t_1/2) half-lives were 0.590 and 5.89 h, respectively, and the mean residence time (MRT) was 7.44 h. The clearance was 5.41 ml·min^–1·kg^–1. With repeated injections, the pharmacokinetic parameters for each patient were estimated taking into account all administered doses and blood samples, which were taken whenever possible daily at steady state and after the last dose. The variability observed in the pharmacokinetic parameters of thiopental reflected by the coefficient of variation (CV%) was wide but was of similar magnitude within patients (CV_intra) as it was between patients (CV_inter). The steady-state trough plasma concentration (C_min obs) ranged from 4.8 to 30 mg·1^–1 (mean 16.0 mg·1^–1 and median 14.3 mg·1^–1). Peak concentrations (C_max obs) ranged from 8.35 to 45 mg·1^–1 (25.4 mg·1^–1, and median 23.3 mg·1^–1). The values of V1 and V_ss were similar to those obtained after a single dose. For V1, the mean was 0.333 1·kg^–1. The mean V_ss was 2.68 1·kg^–1, with a CV_intra of 12.6 to 56% and a CV_inter of 13.2%. A shorter distribution half-life t_1/2 was noted on multiple dosing; the mean value was 0.122 h. The elimination half-life t_1/2 and the mean residence time became longer due to a decrease in clearance. For t_1/2 the mean value was 16.3 h. The mean MRT was 21.9 h, CV_intra 9.19 to 48.5%, and the CV_inter 35.3%. The mean clearance was 2.16 ml·min^–1·kg^–1, CV_intra 7.28 to 25.5%, and the CV_inter 20.4%. This value is 50% lower than after a single dose.Identification of the kinetic parameters of thiopental allows simulation of the effects of doses on subsequent plasma levels and will permit a priori prediction of day to day adjustment of drug dosage.