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Biomedical subjects

W Strauss

Publications and source records attributed to W Strauss.

At least 37 records · Page 2Linked to original sources
PubMed1997

Xist-deficient mice are defective in dosage compensation but not spermatogenesis.

The X-linked Xist gene encodes a large untranslated RNA that has been implicated in mammalian dosage compensation and in spermatogenesis. To investigate the function of the Xist gene product, we have generated male and female mice that carry a deletion in the structural gene but maintain a functional Xist promoter. Mutant males were healthy and fertile. Females that inherited the mutation from their mothers were also normal and had the wild-type paternal X chromosome inactive in every cell. In contrast to maternal transmission, females that carry the mutation on the paternal X chromosome were severely growth-retarded and died early in embryogenesis. The wild-type maternal X chromosome was inactive in every cell of the growth-retarded embryo proper, whereas both X chromosomes were expressed in the mutant female trophoblast where X inactivation is imprinted. However, an XO mouse with a paternally inherited Xist mutation was healthy and appeared normal. The imprinted lethal phenotype of the mutant females is therefore due to the inability of extraembryonic tissue with two active X chromosomes to sustain the embryo. Our results indicate that the Xist RNA is required for female dosage compensation but plays no role in spermatogenesis.

Animals↗
PubMed1997

A population-based coprological study of human fascioliasis in a hyperendemic area of the Bolivian Altiplano.

The community of Chijipata Alta, at an altitude of 3850 m, near the southern coast of Lake Titicaca in the northern Altiplano of Bolivia, was surveyed for human fascioliasis. The global prevalence (66.7%) and intensity (eggs per gram of faeces--epg: range: 24-4440; arithmetic mean: 1001; geometric mean: 390) proved to be the highest known in the world by means of coprological techniques. These results suggest the existence of highly hyperendemic subzones among the large human fascioliasis-endemic zone of the Bolivian northern Altiplano. Despite the decrease in prevalence and intensity from children (75.0%, 24-4440 epg) to adults (41.7%, 144-864 epg), our findings show that in an hyperendemic zone adult subjects either maintain the parasites acquired when young or are newly infected as the consequence of inhabiting a zone of high infection risk.

Adolescent↗
PubMed1995

An outbreak of acute fascioliasis among Aymara Indians in the Bolivian Altiplano.

Fasciola hepatica is a common and important parasite of sheep, cattle, and other ruminants. In May 1991, 30 persons with possible acute fascioliasis were identified by health care providers at a district hospital in the Bolivian Altiplano, and two deaths were associated with this illness. A cross-sectional survey of a random sample of 30 (20%) of the 148 households in the community and a case-control study were performed to determine the extent of the outbreak and the vehicle of transmission. Ninety-one members from 23 of the 30 selected families participated in the cross-sectional survey. Twenty-one of the 91 members met the case definition for acute fascioliasis (illness since 16 February 1991 that was characterized by fever and abdominal pain plus serum IgG antibodies to F. hepatica), and 38 (49%) of 78 members had serum IgG antibodies to F. hepatica. If this rate is extrapolated to the entire community, an estimated 116 individuals (23% of 504) would have acute fascioliasis and 247 individuals (49% of 504) would have evidence of current or previous infection. Case-control analysis indicated that the only factor associated with illness was eating kjosco (an aquatic plant) while tending animals in the fields; 27 (52%) of the 52 case-patients vs. 9 (14%) of the 66 controls ate kjosco (OR = 6.84; 95% CI = 2.60, 18.44). The cause of the two deaths attributed to fascioliasis could not be firmly established. Fascioliasis is a significant human health problem and is highly endemic in the Aymara Indian community in the Bolivian Altiplano. Efforts to prevent fascioliasis should include educating people to avoid eating uncooked aquatic plants such as kjosco.

Acute Disease↗
PubMed1992

Fluorescence formation during photodynamic therapy in the nucleus of cells incubated with cationic and anionic water-soluble photosensitizers.

The variations of fluorescence during light exposure of the cationic sensitizers methylene blue (MB) and meso-tetra(4N-methylpyridyl)porphyrin (T4MPyP) as well as the anionic meso-tetra(4-sulphonatophenyl)porphyrin (TPPS4) were measured at different intracellular sites using video-intensified microscopy in combination with microspectrofluorometry. Before light exposure the sensitizers were localized in distinct parts of the cytoplasm, especially in fluorescent organelles. During irradiation a drastic fluorescence formation and increase in the cytoplasm and nucleus, which was most pronounced in the nucleoli, could be observed for the cationic sensitizers as well as TPPS4. In the case of MB the increase in fluorescence was concomitant with a spectral shift in the emission spectra. For TPPS4 and T4MPyP the formation of a second species with a Soret band shifted towards longer wavelengths was observed and correlated with the fluorescence increase in the nucleoli. Cell deformations also took place.

Animals↗
PubMed1992

Intracellular localization of meso-tetraphenylporphine tetrasulphonate probed by time-resolved and microscopic fluorescence spectroscopy.

The effects of solvent pH on spectral properties and fluorescence decay kinetics were investigated in order to characterize the microenvironment of meso-tetraphenylporphine tetrasulphonate (TPPS4) taken up by cells. Steady-state absorption and fluorescence spectra of TPPS4 in buffer solutions of different pH were used to identify a ring protonated species at pH less than or equal to 4. This dictation could also be distinguished from the unprotonated form by its altered fluorescence decay time (3.5 vs. 11.4 ns). In addition, time-resolved spectroscopy gave some evidence of a monocationic species existing at pH 6-9. This was concluded from the occurrence of another component with a decay time of 5 ns. Measurements of the spectral and kinetic properties of the fluorescence emission of single epithelial cells (RR1022) incubated with TPPS4 indicated that the sensitizer was mainly localized in a microenvironment with a pH of 5, a value which occurs intracellularly only within lysosomes. Cells kept in the dark exhibited the characteristic spectra of both the dication and the neutral form. The fluorescence decay showed two components with decay times of 2.6 ns and 10.6 ns. Irradiation of the cells changed the decay times to 4.6 ns and 13.4 ns and the dication fluorescence emission peak vanished, which is in accordance with the results obtained from buffer solutions at pH greater than or equal to 6. Therefore, we deduce that the photodynamic action leads to a rupture of the lysosomes and that the sensitizer is released into the surrounding cytoplasm.

Animals↗
PubMed1991

Vascularity, perfusion rate and local tissue oxygenation of tumors derived from ras-transformed fibroblasts.

Tumors derived from ras-transformed rat fibroblasts were investigated in order to gain insight into possible interrelationships between oncogenic transformations and therapeutically relevant parameters of the metabolic micromilieu of solid tumors in vivo. Tumors grew in nude mice after injection of in vitro-passaged cells. Growth rates, early stages of angiogenesis, perfusion and tissue oxygenation were assessed. Compared with the parental cell line, both ras transformants grew very rapidly and exhibited an early onset of angiogenesis. Perfusion rates of one ras-transformed tumor line were similar to those of the parental tumors whereas reduced flow values were detected in tumors of the other ras line. The better perfused tumors exhibited more adequate tissue oxygen levels whereas reduced oxygen levels were obvious in the poorly perfused ras line. These results indicate that ras transformation alters therapeutically relevant parameters of the tumor micromilieu. However, the tumor phenotype cannot be predicted even if the transforming oncogene is known.

Animals↗
PubMed1989

In vivo expression of two novel tumor-associated antigens and their use in immunolocalization of human hepatocellular carcinoma.

We are investigating the antigenic changes on the cell surface of human hepatocytes that distinguish the normal from the transformed phenotype using monoclonal antibodies. In vivo expression of antigens has been directly assessed by in situ radioimmunohistology. This technique allows one to determine the distribution and density of antigen expression at the individual cellular level on fresh hepatoma and adjacent uninvolved liver tissue. We have found two antigens recognized by monoclonal antibodies XF-8 and AF-20 that are uniformly present on 15/15 hepatocellular carcinomas tested thus far. Most if not all tumor cells highly express these antigens. Such antigens were not evident on adjacent normal liver and the XF-8 epitope was not found on other normal human tissues. AF-20 antigen distribution revealed low-level expression on a subpopulation of cells in the zona glomerulosa of the adrenal gland and on crypt cells of the small intestinal tract. We have studied the capability of radiolabeled XF-8 and AF-20 monoclonal antibodies when administered either alone or in combination to localize a hepatitis B virus-related hepatocellular carcinoma cell line (FOCUS) grown as subcutaneous tumors in nude mice. Biodistribution experiments demonstrated an excellent localization to tumor of 15 to 22% of the injected dose of 125I-labeled antibodies. Indeed, it was possible to enhance the delivery of 125I to the tumor cell surface by the use of XF-8 and AF-20 in combination. Nuclear imaging studies showed sharp visualization of tumor and demonstrate that these monoclonal antibodies have sufficient specificity and sensitivity to be strongly considered as immunotargeting agents.

Adenocarcinoma↗
PubMed1989

Radioimmunolocation of hepatic and pulmonary metastasis of human colon adenocarcinoma.

We have established a large library of monoclonal antibodies against a human hepatoma cell line called FOCUS. One such monoclonal antibody (SF-25) detects a 125-kilodalton cell surface antigen found on FOCUS cells. As both the liver and the colon are of endodermal origin, we examined the possibility of expression in colon adenocarcinomas. This antigen was found in all 23 colon adenocarcinoma tissues surgically obtained but was absent in the adjacent normal mucosal counterpart as determined by a direct radioimmunohistologic technique. In the present study, we have established a model for human metastatic colon adenocarcinoma using the LS 180 cell line. Athymic mice were further immunosuppressed by intravenous injection of anti-NK cell antibodies (antiasialo GM1). After 24 h, mice were injected with LS 180 cells either via the tail vein or into the spleen followed by splenectomy. Macroscopic pulmonary and lymphatic metastasis developed within 2-3 wk after injection of cells and 9 of 10 mice died with advanced metastatic disease 2-3 wk later. In addition, macroscopic hepatic metastases were evident in 4 of 5 mice 3-4 wk after intrasplenic injection. Both hepatic as well as pulmonary and lymphatic tumor spread was localized by nuclear imaging with 125I-SF-25. Furthermore, micrometastases were detected by autoradiography 5-10 days later. Monoclonal antibody SF-25 is a potential candidate for tumor localization and the experimental metastatic colon cancer animal model may be useful for treatment evaluation of monoclonal antibody SF-25 either alone or in combination with other monoclonal antibodies when conjugated to radionucleotides and chemotherapeutic agents.

Adenocarcinoma↗
PubMed1988

In vivo localization of human colon adenocarcinoma by monoclonal antibody binding to a highly expressed cell surface antigen.

We have produced a monoclonal antibody (SF-25) against a human hepatoma cell line (FOCUS) that strongly reacts with an antigen shared by all six colon adenocarcinoma cell lines. This cell surface antigen was uniformly expressed in all 17 human adenocarcinomas of the colon obtained at surgery but not on the normal adjacent mucosa counterpart. Other normal tissues were negative except for a population of cells in the distal tubule of the kidney as shown by immunoperoxidase staining and direct binding to membrane preparations. Binding of this Mr 125,000 antigen to antibody is disrupted by detergents, sodium dodecyl sulfate, and paraformaldehyde fixation but not by treatment of FOCUS cells with trypsin. The SF-25 antibody when labeled with 125I shows a striking capacity by both biodistribution and nuclear imaging studies to localize human colon adenocarcinoma grown as solid tumors in nude mice. SF-25 may be useful in distinguishing between normal colon and the transformed phenotype.

Adenocarcinoma↗
PubMed1988

Serial determinations of PF4 and beta TG: comparisons between multiple venipunctures vs a catheter infusion system.

Platelet factor 4 (PF4) and beta thromboglobulin (beta TG) are platelet-specific proteins which are released upon platelet aggregation and which can be accurately measured by radioimmunoassay. We devised a catheter-infusion system that enables serial determinations of these proteins. In 20 subjects (10 healthy volunteers and 10 patients with stable coronary artery disease), we compared samples collected by individual venipunctures with those simultaneously obtained by means of a simple catheter-infusion system. At least 5 samples were obtained over a period of time which was as long as 60 min, and at least 30 min. Subjects with stable coronary artery disease were selected so that they would be expected to have stable and normal PF4 and beta TG levels. Thus, elevations of either PF4 or beta TG would represent artifacts secondary to sampling technique. Analysis of the results demonstrated that the catheter-infusion system was equivalent to individual venipunctures for determination of PF4 and beta TG. 16.8% of samples obtained via the catheter and 17.2% of those obtained by individual venipunctures were spuriously elevated. A second series of studies were performed to refine the technique further by examining the impact of infusion rate and the addition of citrate phosphate dextrose (CPD) to the infusate. Ten additional subjects had catheter systems utilized in both arms simultaneously. The addition of CPD resulted in significantly less abnormal values at slower infusion rates (1 and 2.5 cc/min). At 5 cc/min D5/w or saline alone are suitable. These investigations confirm that this simple catheter system is equivalent to individual venipunctures for determination of PF4 and beta TG while avoiding patient discomfort.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1987

Relationship of the genes for Chediak-Higashi syndrome (beige) and the T-cell receptor gamma chain in mouse and man.

The genetic linkage of Chediak-Higashi syndrome and its murine analog, beige (bg), to the T-cell receptor (TCR-gamma) gamma chain gene is further defined. Previous studies using recombinant inbred strains of mice demonstrated that the murine bg gene is genetically linked to a murine TCR-gamma gene. We report that in the mouse the frequency of recombination between these two markers is 0.025. Further, we tested the hypothesis that these two genes are linked in the human genome by analyzing restriction fragment length polymorphisms (RFLPs) in five families with children afflicted with Chediak-Higashi syndrome. In three families, RFLPs in TCR-gamma genes were inherited discordantly from Chediak-Higashi syndrome, demonstrating nonlinkage. We postulate that there is an evolutionary chromosomal breakpoint between the bg gene and the TCR-gamma gene.

Animals↗
PubMed1986

Event-related potentials in patients with Huntington's disease and relatives at risk in relation to detailed psychometry.

Event-related potentials (ERPs) were studied in patients with Huntington's disease (HD) and their offspring at risk in a simple auditory oddball paradigm requiring the counting of the rarer of two stimulus categories. Group statistical analysis revealed prolongation of latencies of components P2, N2 and especially P3 in HD patients and to a lesser extent in at-risks. In a large population of normals the age-latency relationship for component P3 showed a non-linear shape with increasing slope and scatter in the older age groups. A bipartate linear regression analysis splitting the normal population at age 50 was used for detection of abnormalities of P3 latency in individual cases. Abnormal P3 latencies were present in the majority of HD patients and also in 25% of clinically normal at-risks. Correlation analysis of ERP components with detailed psychometry revealed a particularly high association of P3 latencies with measurements requiring speeded information processing in non-verbal tasks. P3 amplitude did not covary with performance scores but unlike P3 latency showed association with depression and psychosis scores. From the results it appears that analysis of ERPs is a useful electrophysiological tool for an objective assessment of cognition both in clinically definite and subclinical stages.

Adolescent↗
PubMed1985

Comparison of three semiautomatic methods for determination of left ventricular ejection fraction from gated cardiac blood pool images.

A number of computer programs exist for the determination of ejection fraction from gated blood pool images. Three commercially available algorithms were compared on the same radionuclide data from 50 catheterized patients. The methods used were: (1) simple thresholding, (2) second derivative edge determination, and (3) a combination of these two. There was good correlation with catheterization ejection fraction for all three methods using smoothed data [r = 0.781, 0.77, 0.84 respectively (P less than 0.01)]. However, interobserver variance was significantly decreased (P less than 0.01) by use of the second derivative method when compared with the other two methods and catheterization. Thus, if accuracy and low interobserver variance are required, then a combination of a second derivative and thresholding method is preferable.

Cardiac Catheterization↗
PubMed1985

An Ia-positive mouse T-cell clone is functional in presenting antigen to other T cells.

In this report we present data demonstrating the endogenous expression of I-region associated (Ia) antigens on a cloned line of mouse T cells, CTLL, as well as transcription of the invariant chain gene in these cells. We demonstrate further that this Ia-bearing T-cell clone, CTLL, can utilize the expressed Ia molecules to present antigen to Ia-restricted antigen-specific T cells.

Animals↗
PubMed1985

Antigenic characterization of human hepatocellular carcinoma. Development of in vitro and in vivo immunoassays that use monoclonal antibodies.

Several libraries of monoclonal antibodies have been produced by immunization of Balb/c mice with single cell suspensions of nontrypsin-treated human hepatocellular carcinoma cell (HCC) lines in order to study the antigenic properties of transformed hepatocytes. The antibodies were characterized with regards to specificity for hepatoma-associated antigens and their capability for use as reagents in radioimmunoassays (RIAs) and tumor localization in vivo. Three such antibodies namely, P215457, PM4E9917, P232524 of the IgG2a, IgG2a, and IgG1 isotypes, respectively, not only recognized separate and distinct antigenic determinants on four human hepatoma cell lines but also reacted with epitopes present on chemically induced rat hepatoma cell lines. In contrast, only 1 of 38 other human malignant and transformed cell lines demonstrated reactivity with the three antibodies; normal human tissues were also found to be unreactive. Monoclonal antibody P215457 densely stained the plasma membrane by indirect immunofluorescence, showed rapid binding activity to HCC cells in suspension, and precipitated a 50,000-mol wt cell surface protein; antibody PM4E9917 also stained the plasma membrane and precipitated a 65,000-mol wt protein, whereas P232534 recognized cytoplasmic antigenic determinants. With these antibodies "simultaneous sandwich" RIAs were established that detect soluble hepatoma-associated antigens in culture supernatants. Finally, the Fab fragment of P215457 was found to be useful in tumor localization in vivo. This antibody fragment when labeled with 131I was shown to localize by radionuclide-imaging studies in human hepatoma grown in nude mice. Thus, these investigations demonstrate that monoclonal antibodies may be produced against epitopes that reside almost exclusively on transformed hepatocytes and such antibodies may be successfully employed in the development of in vitro and in vivo immunoassays.

Animals↗
PubMed1982

Alcohol-chlordiazepoxide interaction.

The effects of chlordiazepoxide (CDP) or its N-demethyl metabolite (NDCDP) on ethanol-induced sleep time were investigated. The results indicate that CDP or NDCDP produced a supra-additive effect on the duration of sleep time induced by ethanol. These effects were not due to an alteration in the rate of elimination of blood ethanol levels. Mice which were administered CDP/ethanol had significantly higher blood and brain CDP levels than mice injected with CDP alone. The increase in CDP concentrations could be partly responsible for the supra-additive prolongation of ethanol sleep time. Our results also indicate that NDCDP and/or its metabolites were largely responsible for the supra-additive effect, because mice injected with CDP/ethanol or NDCDP/ethanol (ethanol 4 g/kg: CDP or NDCDP, 10 mg/kg) showed comparable increases in sleep time, and the blood and brain levels of NDCDP were comparable in these two groups.

Animals↗