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Biomedical subjects

T Gerber

Publications and source records attributed to T Gerber.

30 records · Page 2Linked to original sources

[Experimental evaluation of the accuracy and safety of intraluminal ultrasound].

In this in vitro investigation, we studied the feasibility and accuracy as well as the safety of intravascular ultrasound imaging. Plastic cylinders were used in order to validate measurements of luminal area, perimeter, diameter, and wall thickness. Fifty-nine segments of human arteries were also examined by intravascular ultrasound; then the results regarding the luminal area, perimeter, and wall thickness were compared with the corresponding histopathologic section. Close correlations were found in plastic cylinder studies (r = 0.999, 0.999, 0.998, and 0.994 for area, perimeter, diameter, and wall thickness, respectively). There was also an excellent correlation between intravascular ultrasound imaging and pathologic measurements (r = 0.993, 0.994, and 0.915 for luminal area, perimeter, and wall thickness). Five different cylinders, with a volume of 2, 5, 10, 20, and 50 mls, were employed to evaluate the effect of ultrasound on temperature. Ten blood samples anticoagulated with EDTA were used to detect the effects of ultrasound on blood elements. In the course of time, the ultrasound caused a slight increase of solution temperature (from 23.9 degrees C to 24.6 degrees C after 1-h examination in a 2-ml cylinder) and the temperature change became less obvious as the solution volume increased (the temperature raised 0.3 degrees C in the 2-ml cylinder, 0.1 degrees C in the 20-ml cylinder, but no change was detectable in the 50-ml cylinder after 10 min). No significant differences about WBC, RBC, and platelet counts were found between test and control group (p greater than 0.1) before and 5, 10, 15, 30, and 60 min after ultrasound examination.(ABSTRACT TRUNCATED AT 250 WORDS)

Arteriosclerosis↗

Novel features of retroviruses associated with human diseases.

The last decade has witnessed a new chapter in the history of retrovirology. As of now, four human retroviruses have been identified and molecularly characterized. They are associated with a wide spectrum of human diseases including cancer, immunodeficiency and neurological disorders. By virtue of their clinical relevance, their novel genes and regulatory mechanisms these viruses have become the focal point of research in retrovirology. The study of these viruses is of fundamental importance in understanding the mechanisms leading to transformation of human cells and distortion of the immunological state.

Genes, Viral↗

A host-mediated in vivo/in vitro assay with peritoneal murine macrophages for the detection of carcinogenic chemicals.

We have developed a host-mediated assay system for the detection of the transforming action of chemical carcinogens on peritoneal macrophages. Directly as well as indirectly acting carcinogenic substances administered intraperitoneally to NMRI mice could be examined in this way. Resident macrophages were recovered by peritoneal lavage from treated and untreated mice and were cultured in soft agar. After 5-6 days normal and transformed cells could be distinguished. Statistical analysis comparing cells, for example, from alpha-naphthylamine or diphenylhydantoin-treated animals with those from control mice proved that the test is positive at least on a significance level of 5% using the t-test. Further substances revealing a cell-transformation potential were benzene, benz(a)pyrene, 2,3,7,8-tetrachlorodibenzodioxin, N-nitrosodimethylamine, ethidium bromide, aflatoxin B1,N-methyl-N-nitrosourea, 1-methyl-3-nitro-1-nitrosoguanidine, 2-naphthylamine, dieldrin, suramin and trichloroethylene. A weak transforming potential was found for chlorambucil as well as for tetrachloroethylene. With toluene or azidothymidine no cell transformation could be observed. Several immortal cell lines could be established form NMRI mice treated with alpha-naphthylamine or N-methyl-N-nitrosourea. Athymic nu/nu mice injected subcutaneously with these cells developed tumors, establishing the oncogenic potential of these cell lines.

1-Naphthylamine↗

Epitope mapping of the low-molecular-mass subunits of reverse transcriptase in human immunodeficiency virus type 1 by monoclonal antibodies.

With the aid of monoclonal antibodies to the reverse transcriptase (RT) of human immunodeficiency virus type 1 (HIV-1), low-molecular-mass subunits (p29, p32, and p40) were identified in HIV-1 RT purified from HIV (HTLV-IIIB) virions by isoelectric focusing. Epitope mapping with synthetic polypeptides from various regions of the pol gene suggests that the low-molecular-mass subunits result from N-terminal cleavage of the p51 subunit. The subunits could be separated only by SDS-polyacrylamide gel electrophoresis and detected by immunoblotting. They could not be separated on chromatographic columns, suggesting that the subunits are complexed or conformationally arranged in such a way that their separation on the basis of molecular mass is not possible. The molecular mass of the active enzyme eluted from a chromatographic column (Sephacryl S-300) loaded with a mixture of the subunits was estimated to be 100 kDa.

Animals↗

The care of diabetic patients by ophthalmologists in New York State.

All ophthalmologists in New York State whom the authors could identify through state sources and professional societies (n = 1655) were surveyed about eye care of diabetic patients. Over 90% recommended at least annual retinal examinations for the presented hypothetical patients. Ninety-four percent said they "usually" (31%) or "almost always" (63%) recommend laser treatment for proliferative retinopathy, while 6% said they "occasionally" or "almost never" recommend such treatment. Almost all the latter physicians were general ophthalmologists. The decision to treat macular edema was highly dependent on the quality of the patient's vision. The percentage who "usually" or "almost always" recommend laser treatment for macular edema was 24% when the patient's vision was excellent, 63% when vision was mildly compromised, but 73% when vision was significantly compromised. General ophthalmologists and retina specialists differed significantly in their recommendations for follow-up and treatment of diabetic retinopathy. Ophthalmology 96:739-745, 1989.

Diabetes Complications↗

A state population-based statutory reporting of dementias.

Dementia registries have been legislated or are under discussion in at least seven states (California, Florida, Maryland, Michigan, South Carolina, Illinois, and Virginia). Future reporting requirements and recommendations for state mandated reporting systems were discussed in February 1988 at the first Alzheimer's Disease Registry Workgroup Meeting, sponsored by the University of South Carolina; Centers for Disease Control; and Alzheimer's Disease and Related Disorders Association (ADRDA). The discussion clearly demonstrated the involvement of medical record professionals in influencing future reporting decisions. As the first state population-based statutory dementia registry, the New York State Alzheimer's Disease and Other Dementias Registry has faced unique problems and developed unique solutions. Both the problems and solutions have been defined with the help of medical record professionals from a variety of reporting institutions. This input occurred through phone calls, correspondence, participation in field trials and through professional organizations. Medical record personnel will continue to play a vital role in both supplying data to the New York State registry and in conceptualizing the needs of future registries in other states.

Alzheimer Disease↗

Serological relationship between reverse transcriptases from human T-cell lymphotropic viruses defined by monoclonal antibodies. Evidence for two forms of reverse transcriptases in the AIDS-associated virus, HTLV-III/LAV.

The immunological relationship between reverse transcriptases purified from human T-cell lymphotropic viruses (HTLV-I, HTLV-II, HTLV-III) was defined using monoclonal antibodies specific for HTLV-III reverse transcriptase, secreted by a mouse/mouse hybridoma clone (4F8) developed in our laboratory. The viral proteins from HTLV-I and HTLV-II do not bear any cross-reactive epitope to antibodies secreted by this clone. These antibodies specifically cross-react with HTLV-III reverse transcriptase. The antibodies failed to neutralize the catalytic activity of reverse transcriptase; however, after immunoprecipitation with a magnetic conjugate of goat anti-mouse IgG, the residual activity was completely inhibited. This shows that the antibodies are not directed towards the catalytic active center of the enzyme. Using an immunoblotting technique (Western blotting), we have found two cross-reactive proteins with HTLV-III lysate with molecular masses of 53 and 66 kDa. This suggests that HTLV-III possesses two reverse transcriptase activities with a common determinant recognized by the same epitope.

Acquired Immunodeficiency Syndrome↗

Biochemical heterogeneity of reverse transcriptase purified from the AIDS virus, HTLV-III.

The reverse transcriptase from AIDS virus, HTLV-III, was purified and characterized. The purified enzyme has a very high affinity for template primers (rC)n X (dG)12 and (rCm)n X (dG)12 compared to that for (rA)n X (dT)12. In addition, the HTLV-III reverse transcriptase was able to transcribe (rAm)n X (dT)12 very efficiently. The ionic requirements are unique in the sense that HTLV-III reverse transcriptase prefers Mg2+ as divalent ions to transcribe (rC)n X (dG)12 and (rA)n X (dT)12. The Mr of the enzyme is 95 000-98 000. Unlike the HTLV-I reverse transcriptase, the HTLV-III enzyme is highly stable and has a much higher activity in the presence of (rC)n X (dG)12; the Vmax for HTLV-III reverse transcriptase is several-fold higher than that for HTLV-I enzyme. The enzyme activity of the purified reverse transcriptase from HTLV-III was resolved into two peaks on a preparative isoelectric column, one at pH 5.75 and the other at pH 6.25. This leads us to conclude that the reverse transcriptase of HTLV-III is biochemically heterogeneous.

Cations, Divalent↗

Inhibitors of retroviral DNA polymerase: their implication in the treatment of AIDS.

Compared to other T-lymphotropic human retroviruses, human T-cell leukemia (lymphotropic) virus I (HTLV-I) and HTLV-II, the acquired immunodeficiency syndrome (AIDS)-associated virus, HTLV-III, is a nontransforming cytopathic virus without immortalizing activity. Thus the virus replication is an important event in the manifestation of this disease, and the interruption of viral replication offers an important strategy for the control of AIDS. For this reason we have purified the reverse transcriptase (RT) from HTLV-III and from HTLV-III infected cells to study the structure-activity relationship of RT inhibitors developed in our laboratory. The cellular DNA polymerases from H9 cells were also purified to study the selectivity of RT inhibitors. Purified HTLV-III RT has several distinguishing features: (a) unlike the HTLV-I enzyme it is highly stable and can be kept for several weeks without any loss of activity; (b) using identical procedures of isolation the HTLV-III enzyme shows a much higher activity than does the enzyme from HTLV-I; (c) the Vmax for HTLV-III RT is by severalfold higher than that for the HTLV-I enzyme in the presence of (rC)n X (dG)12 and (rCm)n X (dG)12, and besides the usual template-primers used for RT assay this enzyme has a relatively high affinity for (rAm)n X (dT)12; and (d) the cationic requirements for the transcription of various template-primers are unusual. The purified enzyme has a molecular weight of 95,000-98,000, as judged by the gel filtration method. The purified HTLV-III RT was inhibited by a partially thiolated polycytidylic acid (5-mercaptopolycytidylic acid); the cellular DNA polymerase beta from H9 cells was not sensitive to 5-mercaptopolycytidylic acid. Germanin (synonym, suramin), an antiprotozoan drug, also inhibits HTLV-III RT activity, but the DNA polymerase alpha activity was also sensitive to Germanin. The nonspecific effect of Germanin is probably due to the high content of sulfonic acid residues. This paper describes new approaches for designing specific inhibitors of retroviral reverse transcriptases which may be useful in developing a potential drug against AIDS.

Acquired Immunodeficiency Syndrome↗

Characterization of the RNA dependent DNA polymerase of bovine leukemia virus.

The reverse transcriptase-RNA dependent DNA polymerase of Bovine Leukemia Virus (BLV) was isolated and characterized. The enzyme has a molecular weight of about 80kd and the isoelectric point is 7.6. The enzyme prefers magnesium, as a divalent cation using synthetic homopolymeric template primer poly (C) oligo (dG). Monoclonal antibodies directed against reverse transcriptase of human immunodeficiency virus type I (HIV-I) did not crossreact with the isolated polymerase.

Antibodies, Monoclonal↗