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Biomedical subjects

B Schwartz

Publications and source records attributed to B Schwartz.

At least 181 records · Page 10Linked to original sources

Immortalization of multiple cell types from transgenic mice using a transgene containing the vimentin promoter and a conditional oncogene.

Differentiated clonal cell lines were obtained from transgenic mice carrying a recombinant gene composed of DNA coding for a temperature-sensitive mutant of the simian virus large T antigen under the control of regulatory elements of the human vimentin gene. In response to mitogenic factors the vimentin promoter is activated in the presence of serum in almost all cultured cells independently of their origin. The expression of the T antigen could be controlled both at the level of transcription since the vimentin promoter is growth-regulated and at the level of the protein structure through the temperature stability of the T antigen. Indeed, the switch-off of the oncogene protein is obtained by serum deprivation of the culture and achieved with enhancement of the growth temperature. From transgenic mice several types of clonal differentiated cell lines were established and characterized including melanocytes, macrophages, mesangial, muscle, and endothelial cells. Melanocytes displayed melanin while endothelial cells from brain and heart expressed the related factor VIII and low density lipoprotein absorption capacities. Mesangial cells from kidney exhibited numerous desmosomes. Typical markers of macrophages from bone marrow were observed while skeletal muscle cells fused and contracted.

Animals↗

Intrasubject reliability and validity of somatosensory source localization using a large array biomagnetometer.

Neuromagnetic fields were evoked by tactile stimuli and detected with a multi-channel biomagnetometer through 72 independent repetitive measurements on a single subject. Each measurement consisted of a somatosensory evoked response (N = 256 stimuli) using a single probe placement. These fields were then analyzed for source localization using an equivalent current dipole model and demonstrated highly reliable localizations. The 3 major neuromagnetic somatosensory response components peaking at 35, 65 and 110 msec all localized to the same area of cortex. The relative contributions of intrinsic brain activity, habituation, probe placement, and choice of fiduciary points for headframe determination were quantified. Intrinsic factors were found to constitute the major source of inter-measurement error. Sources localized by magnetic source imaging (MSI) appeared valid relative to neuroanatomical estimation of the central fissure on MRI. Non-invasive presurgical biomagnetic localization of somatosensory cortex produces reliable and valid functional localizations which can be of potential value in risk assessment and may provide a useful guide for invasive functional mapping.

Adult↗

Circulatory defects of the optic disk and retina in ocular hypertension and high pressure open-angle glaucoma.

Studies using fluorescein angiography have shown that two types of circulatory defects occur in the optic disk and retina of open-angle glaucomatous eyes. The first is a defect of the microcirculation of the optic disk characterized as a fluorescein defect. Such defects begin as small areas of relatively little filling of the small vessels of the disk with fluorescein. The areas of defect show leakage for both fluorescein and indocyanine green. These defects increase in size and number with the progression of the disease. Fluorescein defects are significantly correlated with visual field loss and retinal nerve fiber layer loss. The second circulatory defect is a decrease of flow of fluorescein in the retinal vessels, especially the retinal veins, so that the greater the age, diastolic blood pressure, ocular pressure and visual field loss, the less the flow. Both the optic disk and retinal circulation defects occur in untreated ocular hypertensive eyes. These observations indicate that circulatory defects in the optic disk and retina occur in ocular hypertension and open-angle glaucoma and increase with the progression of the disease.

Blood Flow Velocity↗

Detection of malignancy-associated metabolites in the sera of cancer patients by electron capture gas chromatography.

A reliable test that detects malignancy and indicates response to therapy is needed. Frequency-pulsed electron-capture gas-liquid chromatography (FPEC-GLC), a selective analytical technique that is sensitive to 15 fmol quantities of metabolites, was used to analyse derivatised acidic chloroform extracts of sera from patients with biopsy-proven cancer, non-malignant infectious and non-infectious disease, and healthy controls. Two peaks designated P1 and P10, not found in serum from healthy controls (n = 7) or patients with non-malignant disease (n = 85), were detected in biopsy-proven samples (n = 52) from cancer patients. P1 and P10 were later shown by chemical and mass spectral studies to be carboxylic acids. When one or both of these peaks were detected in the sera of non-treated patients they were always associated with malignancy. In patients responding to therapy, a reduction or disappearance of these peaks was observed. Further, it was noted that P10 persisted or increased in sera of patients with progressive cancer not responding to therapy. We conclude that this test has potential in diagnosis and for following the response of the disease to therapy.

Adenocarcinoma↗

Transcription of a human neurotropic virus promoter in glial cells: effect of YB-1 on expression of the JC virus late gene.

We have isolated a partial recombinant cDNA clone from a HeLa expression library which encodes a protein capable of binding to the central region of the human neurotropic JC virus (JCV) enhancer/promoter, termed the B region. Sequence analysis revealed a complete homology of the partial cDNA clone to the N-terminal region, of a previously described DNA-binding protein, termed YB-1. Band shift analyses have indicated that the bacterially produced YB-1 interacts specifically with the double-stranded B oligonucleotide as well as the corresponding single-stranded DNA fragment representing the early promoter sequence. Further analysis indicated that the YB-1 protein binds specifically to the C/T-rich sequence of the B domain, which is located in close proximity to the TATA box within the virus enhancer/promoter. Results from cotransfection experiments demonstrated that the full-length (YB-1) but not the partial cDNA enhances expression of the JCV late (JCVL) promoter in glial cells. Cointroduction into glial cells of a recombinant expressing the YB-1 and JCVL deletion mutants indicated that removal of the C/T-rich sequence of the B domain reduces the level of activation of the virus promoter by YB-1. Further cotransfection experiments revealed that the virus transactivating protein T antigen appears to diminish the ability of YB-1 to activate JCVL gene expression. RNA studies indicated that YB-1 is expressed in several cell types and tissues. Examination of YB-1 RNA from mouse brain at various stages of development revealed high levels of YB-1 RNA at early stages of development and lower levels at all subsequent developmental stages.

Antigens, Viral, Tumor↗

Invasive group A streptococcus carriage in a child care centre after a fatal case.

After a fatal case of invasive group A streptococcal disease, serotype T-1, in a child care centre, group A streptococcal T-1 prevalence was measured and risk factors for carriage were determined. A total of 87% (224/258) had throat culture tests. Group A streptococcus was isolated from 57 (25%), and of the 50 isolates serotyped, 38 (76%) were T-1. Group A streptococcal T-1 prevalence was 18% (38/217) and six of nine rooms had children with group A streptococcal T-1 isolates. The risk of group A streptococcal T-1 carriage was increased for children who shared the index case's room (odds ratio (OR) = 2.7; 95% confidence interval (CI) = 0.8 to 9.4) and for each additional hour per week in child care (OR = 1.03; 95% CI = 1.001 to 1.061); and decreased in children taking antibiotics in the preceding four weeks (OR = 0.2; 95% CI = 0.1 to 0.9). Carriage of the invasive group A streptococcal strain could not be determined by identified risk factors alone.

Adult↗

Case management of substance abusers with HIV disease.

Case management is a promising intervention that has been used widely in many settings but is not well evaluated with substance abusers. This article describes a case management approach for substance abusers with human immunodeficiency virus (HIV) disease. Clients are enrolled from emergency and outpatient clinics of a general hospital. Case management focuses on encouraging a substance-free lifestyle, linking clients with needed services, and reducing their risk of transmitting HIV. A research project is currently underway to determine the effect of case management on client outcomes, assess its cost-effectiveness, and identify predictors of treatment participation and retention. Innovative models, such as case management approaches, can link drug abuse treatment with health care. These approaches may reduce the costs of care and improve the health care delivery system.

Adult↗

Identification of a yeast artificial chromosome clone encoding an accessory factor for the human interferon gamma receptor: evidence for multiple accessory factors.

Human chromosomes 6 and 21 are both necessary to confer sensitivity to human interferon gamma (Hu-IFN-gamma), as measured by the induction of human HLA class I antigen. Human chromosome 6 encodes the receptor for Hu-IFN-gamma, and human chromosome 21 encodes accessory factors for generating biological activity through the Hu-IFN-gamma receptor. A small region of human chromosome 21 that is responsible for encoding such factors was localized with hamster-human somatic cell hybrids carrying an irradiation-reduced fragment of human chromosome 21. The cell line with the minimum chromosome 21-specific DNA is Chinese hamster ovary 3x1S. To localize the genes further, 10 different yeast artificial chromosome clones from six different loci in the vicinity of the 3x1S region were fused to a human-hamster hybrid cell line (designated 16-9) that contains human chromosome 6q (supplying the Hu-IFN-gamma receptor) and the human HLA-B7 gene. These transformed 16-9 cells were assayed for induction of class I HLA antigens upon treatment with Hu-IFN-gamma. Here we report that a 540-kb yeast artificial chromosome encodes the necessary species-specific factor(s) and can substitute for human chromosome 21 to reconstitute the Hu-IFN-gamma-receptor-mediated induction of class I HLA antigens. However, the factor encoded on the yeast artificial chromosome does not confer antiviral protection against encephalomyocarditis virus, demonstrating that an additional factor encoded on human chromosome 21 is required for the antiviral activity.

Animals↗

The changing epidemiology of invasive group A streptococcal infections and the emergence of streptococcal toxic shock-like syndrome. A retrospective population-based study.

OBJECTIVE: To determine disease incidence and changes in the epidemiology of invasive group A streptococcal infections in a community in Arizona. DESIGN AND SETTING: We retrospectively surveyed microbiology records from all 10 hospitals in Pima County, Arizona, to identify patients who had Streptococcus pyogenes isolated from blood, sterile body fluid, or tissue biopsy specimens between April 1985 and March 1990. Demographic and clinical information was abstracted from the medical records of these patients. PATIENTS: A total of 128 patients with a median age of 53.5 years (range, 6 months to 96 years). OUTCOME MEASURES: Racial/ethnic differences in disease incidence; mortality and changes in the clinical spectrum of disease over the study period. RESULTS: The annual age-adjusted incidence was 4.3 per 100,000 but was 46.0 per 100,000 among Native Americans. Advanced age, age less than 5 years, hypotension, and multi-organ system involvement were significantly associated with increased mortality. From 1985 to 1990, the proportion of infections with hypotension, rash, desquamation, renal impairment, and gastrointestinal involvement increased significantly (chi 2 for trend P < or = .02 for each feature). A toxic shock-like syndrome occurred in 8% of infections since 1988, compared with none of the infections between 1985 and 1987 (P = .04). Patients with the syndrome were younger than patients with other invasive infections (median age 15 vs 54 years, P = .02), and were less likely to have underlying medical conditions (P = .008). CONCLUSIONS: Significant changes occurred in the spectrum of invasive group A streptococcal infections in Pima County, Arizona, between 1985 and 1990. Native Americans were at increased risk of acquiring these infections. Patients with the streptococcal toxic shock-like syndrome had epidemiologic features that distinguished them from patients with other invasive infections, including younger age and less underlying illness.

Adolescent↗

Cell adhesion markers are expressed by a stable human endothelial cell line transformed by the SV40 large T antigen under vimentin promoter control.

Markers of endothelium have been studied in a new endothelial cell line derived from human umbilical cord vein cells by microinjection of a recombinant gene that includes a deletion mutant of the human vimentin gene regulatory region controlling the large T and small t antigen coding region of the SV40 virus. In culture, this immortalized venous endothelial cell line (IVEC) demonstrated morphological characteristics of endothelium; uptake of acetylated low density lipoprotein and presence of the Factor VIII-related antigen. Treatment of IVEC cells with Interleukin-1 beta (IL-1 beta) at 10 U.ml-1 activates the expression of cell adhesion molecules such as endothelial leucocyte adhesion molecule (ELAM-1), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1), as observed in primary culture. Prostacyclin secretion was induced in the IVEC cells by 100 nM PMA treatment and thrombin at 0.5 U/ml. Angiotensin converting enzyme (ACE) activity detected in IVEC cells was present but lower than ACE activity in primary endothelial cells and was completely blocked by enalaprilat (1 microM), a specific ACE inhibitor. The presence of ACE mRNA was also demonstrated in IVEC cells by RT-PCR amplification. Our data demonstrate that endothelial cells immortalized by use of this recombinant gene retain the morphological organization and numerous differentiated properties of endothelium.

Antigens, Polyomavirus Transforming↗

Laser scanning tomography and stereophotogrammetry in three-dimensional optic disc analysis.

Laser scanning tomography (LST) and computed stereophotogrammetry (CSP) are sophisticated diagnostic tools for the three-dimensional analysis of optic nerve head topography. The two methods are based on different physical principles. To compare the information about the shape of the cup of an optic nerve head obtained by LST and CSP, we evaluated the volume profile (VP; i.e., the cross-sectional area of the cup from top to bottom) in 36 discs of 36 patients (20 control group discs C, 16 glaucoma discs G). The Spearman correlation coefficient between the photogrammetric and the laser scanning VP-slope measurements was rs = 0.931; P < 0.001 (rs = 0.935 G, P < 0.001; rs = 0.910 C, P < 0.001). The results suggest that confocal laser scanning provides readings of the shape of the optic disc cup that are similar to the measurements of computed stereophotogrammetry.

Adolescent↗

Determination of the degree of cure of dental resins using Raman and FT-Raman spectroscopy.

FT-IR spectroscopy has traditionally been used to determine the degree of conversion of dental resins. FT-Raman scattering provided an alternate method of obtaining degrees of conversion for these systems and was particularly useful for measuring spectra of materials without any sample preparation. Raman and FT-Raman spectroscopy gave identical results, but the latter technique was preferred for the highly fluorescent samples often encountered in commercial composites. Linear calibration curves were obtained for the aromatic mixtures Bis-GMA/TEGDMA and Bisphenol-A/TEGDMA using C = C/phi, and for the wholly aliphatic mixture EGDMA/EGDA using C = C/C = O, over a wide range of mole ratios. If both the mole and intensity ratios [C = C/phi or C = C/C = O] were known for an uncured dental resin, then the degrees of conversion could be obtained for the cured materials using Raman spectroscopy. However, if the mole ratios for the uncured resin were unknown, then the degree of conversion depended on the calibration curve, since the Raman scattering cross section of the vibrational modes depended on the molecules to which they were attached.

Benzhydryl Compounds↗

Prophylaxis for recurrent acute otitis media: a Brazilian study.

We enrolled 60 children with recurrent acute otitis media (AOM) in a study of the effectiveness of antimicrobial prophylaxis. All children were entered into the study following an acute episode of infection treated with amoxicillin (AMX) for 10 days. Following therapy, the children were re-examined, and then randomly assigned to receive either trimethoprim-sulfamethoxazole (TMP-SMX), amoxicillin (AMX) or a placebo (PLA). Twenty children were included in each group. Each drug was administered once a day at bedtime, at 1/3 the therapeutic dose, for 3 months. Children were re-evaluated with pneumootoscopy during episodes of acute illness and with pneumootoscopy and impedance tympanometry (TYMP) at monthly intervals. We observed a significantly increased rate of recurrent AOM in children receiving placebo compared with those who received antibiotics (50% vs. 17% P < 0.005). Both prophylactic antibiotics were equally effective in preventing recurrent AOM (recurrence rate 20% TMP-SMX, 15% AMX). We also observed that recurrences in children receiving placebo occurred earlier in the study period than in those receiving antibiotics. These results suggest that antimicrobial prophylaxis in children with recurrent acute otitis media is effective in reducing subsequent disease. The similar efficacy of both antibiotics tested suggests that the less expensive agent should be used.

Amoxicillin↗

Anti-rhinoviral activity of recombinant and hybrid species of interferon alpha.

To define further differences in antiviral activity as well as to identify candidate interferons for study in the prevention of rhinovirus colds, the antiviral activities of nine species of recombinant interferon alpha (IFN-alpha A, IFN-alpha B, IFN-alpha C, IFN-alpha D, IFN-alpha J, [Ser-116]IFN-alpha J1, IFN-alpha K, IFN-alpha J/C(Fnu4HI), and IFN-alpha A/D(BglII)) were evaluated against rhinovirus types 39 (RV 39) and 1A (RV 1A). WI-38 cells were exposed to various concentrations of each interferon and were then infected with RV 39, RV 1A, or VSV. Efficacy was determined by protection from cytopathic effect using a tetrazolium dye assay. The 50% inhibitory concentrations ranged from 4 +/- 3 pg/ml for IFN-alpha C to > 3000 pg/ml for IFN-alpha D against RV 39, and from 6 +/- 4 pg/ml for IFN-alpha J/C(Fnu4HI) to > 3000 pg/ml for IFN-alpha D against RV 1A. IFN-alpha J/C(Fnu4HI), [Ser-116]IFN-alpha J1, and IFN-alpha C were the most active of the interferons, and were all more active than IFN-alpha A, against RV 39, RV 1A, and VSV. These interferons warrant further study against rhinoviruses and other viruses.

Amino Acid Sequence↗