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Biomedical subjects

R Weil

Publications and source records attributed to R Weil.

At least 55 records · Page 3Linked to original sources

Repression of nuclear lamin A and C gene expression in human acute lymphoblastic leukemia and non-Hodgkin's lymphoma cells.

The lamins A, B and C which are differentially expressed during ontogenesis and differentiation are karyoskeletal proteins forming a polymeric meshwork at the inner nuclear membrane. Using Northern blot analyses we investigated the steady state levels of the three lamin specific RNA transcripts in neoplastic cells derived from 16 untreated patients with acute lymphoblastic leukemia (ALL) or non-Hodgkin's lymphoma (NHL) and in ALL and NHL established cell lines. Whereas lamin B mRNA was present in all, lamin A and C transcripts were observed in none of the malignant cell samples except one of a common-ALL patient (precursor B-ALL, cytoplasmic mu chain negative). All three lamin mRNAs were detected in normal peripheral blood lymphocytes, however, only after mitogenic stimulation with concanavalin A. Our results provide evidence that expression of lamin A and C is repressed in neoplastic blast cells derived from patients with ALL or NHL and suggest that lamin A and C gene repression is not related to cell proliferation but might be relevant to the differentiated stages of the lymphoid cells in vivo.

Actins↗

Labeling of ethambutol with 99mTc using a new reduction procedure. Pharmacokinetic study in the mouse and rat.

Certain 99mTc-labeled derivatives of ethylene diamine substituted in NN', when labeled with 99mTc, have been proposed for studying renal excretion, and others for brain imaging. Ethambutol, a well known antituberculosis drug, possesses a structure very similar to these derivatives. We prepared a complex of [99mTc]ethambutol using hypophosphorus acid as the reducing agent. The complex was then analyzed by paper and cellulose F chromatography and by FAB mass spectrometry. A pharmacokinetic study in the mouse and rat indicated that the complex is eliminated by the kidney faster than DTPA, slower than [131I]hippuran and without significant renal retention. The [99mTc]ethambutol complex is easy to prepare and shows good stability in water at physiological pH, making it potentially useful in renal excretion studies.

Animals↗

Immunogenotyping with antigen receptor gene probes as a diagnostic tool in childhood acute lymphoblastic leukaemia.

13 cases of childhood acute lymphoblastic leukaemia (ALL) were studied combining cell surface marker analysis with immunogenotyping by Southern blot hybridisation with a panel of antigen receptor gene probes. The immunophenotypes were unequivocal: 7 patients had B-phenotype and 6 patients T-phenotype ALL. In several patients immunogenotypes were not fully consistent with the respective phenotypes. For example, 2 B-cell precursor ALL had rearranged TCR beta chain genes and 2 T-ALL rearrangement of Ig heavy-chain genes. All cases showed clonal rearrangement or deletions within the TCR delta gene locus. TCR delta gene rearrangements might, therefore, serve as markers of clonality but not of B- or T-lineage in immature lymphoid neoplasms. We conclude that in current diagnostic practice immunogenotyping is a supplement rather than an alternative to immunophenotyping by surface marker analysis.

Adolescent↗

Radioimmunological determination of total thyroxin by antibodies immobilized on polystyrene tubes coated with styrene-maleic anhydride copolymers.

In this new technique for preparing activated polystyrene tubes for assay of human thyroxin (T4) we coated plastic with styrene-maleic anhydride copolymers. The quantity of antibodies immobilized on these tubes was considerably greater than on non-activated polystyrene tubes, and the time required for immobilization was shortened. Calibration curves were plotted, and determination of total T4 in 200 serum samples confirmed the expected increase in sensitivity as compared with a commercial (Gammacoat) method. The manufacturing procedure is simple and could easily be automated. Thus, such copolymer-coated tubes constitute an advantageous and reliable component in the assay of total T4 that can be used to improve the sensitivity of this and various other radioimmunological determinations.

Antibodies↗

Case-control study of colorectal cancer and fecal mutagenicity.

Fecal mutagenicity was measured in 68 patients with colorectal cancer and in 114 controls, using Salmonella tester strains TA98 and TA100 with and without S9 activation. Samples were also tested for fecapentaenes by high-performance liquid chromatography, to permit the separation of fecapentaene and non-fecapentaene mutagenicity. Overall, no significant case-control differences in fecal mutagenicity were observed. However, when samples containing high concentrations of fecapentaenes were excluded, non-fecapentaene TA98 mutagenicity was observed in eight cases (12%) and only four controls (4%), resulting in an estimated relative risk of 4.4 (95% confidence interval = 1.0-21.1). The association of colorectal cancer risk with non-fecapentaene TA98 mutagenicity could not be explained as an artifact of diagnostic workup or gastrointestinal bleeding among the cases. Smoking could also be excluded as a source of the TA98 mutagenicity seen, but possible dietary origins are still being explored.

Adenocarcinoma↗

Case-control study of colorectal cancer and fecapentaene excretion.

The fecapentaenes are potent mutagens found in high concentrations in the stools of some individuals. These compounds are produced in vivo by common species of the colonic microflora, from precursors of unknown origin. The fecapentaenes have been postulated to increase the risk of colorectal cancer. To test this hypothesis, we measured fecapentaene excretion in 69 patients with adenocarcinoma of the colon or rectum, newly diagnosed at three Washington, DC area hospitals. The cases were compared with 114 surgical controls, frequency matched to the cases on age, sex, and hospital. We attempted to measure fecapentaene excretion 4 times for each subject: before surgery; and at 1 mo; 3 mo; and 6 mo following surgery. Contrary to our study hypothesis, we found fecapentaene excretion during the four study periods to be similar or even lower in cases compared to controls. An indirect measurement of fecapentaene precursors also tended to be lower in cases. The case-control differences could not be explained as effects of bleeding or of the colorectal diagnostic workup, which was assessed in a separate group of 86 patients. We conclude from these data that the excretion of fecapentaenes does not increase the risk of colorectal cancer, at least when measured near the time of diagnosis.

Aged↗

[Protein-calorie malnutrition in the elderly patient].

Protein-energetic malnutrition is frequent in geriatric practice and particularly among hospitalized patients. It has many different causes and its consequences frequently hinder medical and surgical treatments. It is difficult to diagnose and the measures to take belong to the field of social medicine, nutrition, biological research and education. A multidisciplinary approach is therefore essential in this field which needs to be developed.

Aged↗

SV40-induced expression of mouse gene 24p3 involves a post-transcriptional mechanism.

SV40 and polyoma virus induce a mitotic host reaction in confluent, Go-arrested primary mouse kidney cell cultures. To define the primary effects of infection we constructed a cDNA library corresponding to polyA+ mRNA isolated shortly after onset of polyoma T-antigen synthesis. By differential screening of the library we have isolated and then sequenced cDNA recombinant 24p3; determined by Northern blotting, 24p3 mRNA steady state levels increased in parallel with polyoma and SV40 T-antigen synthesis. Since this rapid and early increase was particularly striking (14-20 fold) in SV40-infected cells, we studied the molecular mechanism of induction in this virus-cell system. We show that wt SV40 large T-antigen is required for the increase in 24p3 mRNA levels. The results tend to exclude that this increase is due to an SV40-induced stabilization of the 24p3 mRNA, or to an SV40-induced stimulation of transcription of the 24p3 gene; they are compatible with the working hypothesis that SV40 large T-antigen increases the efficiency of processing, possibly splicing, of the 24p3 pre-mRNA. The biological implications of these results are discussed.

Amino Acid Sequence↗

31P nuclear magnetic resonance study of renal allograft rejection in the rat.

Phosphorus (31P) nuclear magnetic resonance (NMR) spectroscopy was used to serially evaluate heterotopic renal allograft rejection in the rat. Renal allografts transplanted to the groin of recipient animals were studied using a 1.89 Tesla horizontal bore magnet. The relative intracellular concentrations of phosphorus metabolites such as adenosine triphosphate and inorganic phosphate as well as intracellular pH were determined by 31P NMR on days 4, 7, 10, and 14 following transplantation across a major histocompatibility mismatch. Recipient rats chosen to be rejectors received no immunosuppression while animals chosen to be nonrejectors received cyclosporine during the first 7 days following transplantation. By day 7, all rejector rats could be distinguished from nonrejector rats by their higher relative concentration of inorganic phosphate and their lower relative concentration of adenosine triphosphate. These NMR findings correlated with histologic findings of renal infarction probably related to vascular rejection in the allografts. 31P NMR spectroscopy may have application as a noninvasive tool in the differential diagnosis of posttransplantation renal insufficiency.

Adenosine Triphosphate↗

A new microvascular model for noninvasive nuclear magnetic resonance spectroscopy of the transplanted kidney.

The cellular biology of graft rejection is not well understood. Phosphorus-31 nuclear magnetic resonance (31P NMR) spectroscopy is a new noninvasive technique for the measurement of intracellular pH and relative amounts of phosphorus-containing compounds, such as adenosine triphosphate (ATP), inorganic phosphate, phosphocreatine, and sugar phosphates, in any tissue from which a clear signal can be obtained. Biochemical analysis of such precision, without the need for tissue destruction, represents an unusual opportunity for analysis of in vivo cellular metabolism under varying conditions, including graft rejection. 31P NMR study of intra-abdominal viscera has not been feasible in most laboratories without laparotomy because of signal interference from abdominal wall muscle. In this study, to eliminate this interference, a rat kidney was transplanted to the groin, where it could be serially studied without overlying skeletal muscle. This new vascular technique was successful in 11 of 11 attempts and maintained normal serum creatinines in 10 chronic survivors after removal of both native kidneys. The 31P NMR spectroscopic signal from the groin kidney is clear and highly reproducible. This new microvascular model will make it possible to carry out noninvasive long-term spectroscopic studies that could potentially identify a reliable marker for allograft rejection.

Adenosine Triphosphate↗