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Biomedical subjects

B Schwartz

Publications and source records attributed to B Schwartz.

At least 217 records · Page 12Linked to original sources

Anti-HIV-1 activity of recombinant and hybrid species of interferon-alpha.

To identify candidate interferons (IFNs) for the treatment of human immunodeficiency virus type 1 (HIV-1) infection and to investigate sequence-function relationships, the antiviral activities of nine species of recombinant IFN-alpha [IFN-alpha A, IFN-alpha B, IFN-alpha C, IFN-alpha D, IFN-alpha J, [Ser116]IFN-alpha J1, IFN-alpha K, IFN-alpha J/C(Fnu4HI), and IFN-alpha A/D(BglII)] were evaluated against HIV-1. MT-2 cells were exposed to various concentrations of each IFN and were then infected with HIV. Protective effect was determined by cell viability using a tetrazolium dye assay. Activity against vesicular stomatitis virus (VSV) was assessed on MDBK and WISH cells. The 50% inhibitory concentration against HIV was 37 +/- 14 pg/ml for IFN-alpha A, and ranged from 15 +/- 3 pg/ml for IFN-alpha J/C(Fnu4HI) to > 90,000 pg/ml for IFN-alpha D. In general, relative activity against HIV was similar to relative activity against VSV on WISH cells. IFN-alpha D was notable for its decreased activity on human cells. The observations suggest that it may be possible to produce IFNs-alpha with more favorable therapeutic indices than currently available IFNs. Furthermore, the anti-HIV activity of IFNs-alpha is not determined solely by their linear amino acid sequence.

Acquired Immunodeficiency Syndrome↗

Clusters of invasive group A streptococcal infections in family, hospital, and nursing home settings.

The spread of group A streptococcal infection to close contacts of infected persons is well recognized. With the resurgence of invasive group A streptococcal infections, there is an increased potential for clusters of patients with invasive disease. We reviewed data collected since December 1988 at the Centers for Disease Control (Atlanta) to identify clusters of infection in which one or more patients had invasive disease. Twelve family clusters were identified. Infection in index cases included the toxic shock-like syndrome and septicemia. Infection in family contacts included invasive infections, pharyngitis, or asymptomatic carriage. Most invasive disease occurred in adults, while the majority of noninvasive infections were in children. Five nosocomial clusters with spread of infection from patients to hospital personnel were documented. All index patients had the toxic shock-like syndrome; secondary infections included the toxic shock-like syndrome, pneumonia, bullous cellulitis, lymphangitis, and pharyngitis. Clusters of invasive infections also were identified in five nursing homes. Pneumonia, cutaneous infections, and the toxic shock-like syndrome occurred most commonly. Clustering by nursing home unit occurred in three outbreaks. In hospitals and nursing homes, improved infection control will likely decrease secondary spread; in families, spread of disease may be prevented by identifying and treating those harboring the organism or by chemoprophylaxis. Studies that characterize the rate of secondary infection are needed before definitive recommendations can be made.

Adult↗

Morphological aspects of normal optic disc and early signs of glaucomatous alterations.

A group of 110 eyes with untreated ocular hypertension, 94 being non-exfoliative and 16 exfoliative and in addition 10 glaucomatous eyes were selected for this study. The optic nerve head was examined by ophthalmoscopy and a drawing was made of the estimated cupping. The disc pallor was measured from disc photographs in a double masked manner at the same time. The possibility to detect early glaucomatous damage by a single examination will be discussed and the two methods will be compared. This study indicates that an increasing vertical diameter of disc pallor might have a predictive value.

Aged↗

Measurement of retinal nerve fiber layer thickness and its functional correlations with the visual field.

We have developed a technique for stereophotogrammetric measurements of retinal nerve fiber layer thickness at the disc margin. This technique has a reproducibility ranging from 3.9% to 6.0% in normal, ocular hypertensive and high pressure open angle glaucomatous eyes. The presence of a halo or scleral crescent had no effect on the reproducibility of the measurements. The measurements have shown that ocular hypertensive eyes have about an 18% decrease of retinal nerve fiber layer thickness compared to normals. High pressure open angle glaucomatous eyes have about a 43% decrease in retinal nerve fiber layer thickness compared to normals. This technique allows the development of maps of retinal nerve fiber layer thickness so that localized changes at the disc margin can be detected. The thinnest nerve fiber layer occurs primarily in the temporal segment. This technique has also correlated measurements of nerve fiber layer thickness with other measurements of the optic disc, particularly showing a significant correlation with area of pallor as well as measurements of the width of optic disc cup at about halfway between surface and the bottom of the cup. A significant correlation with visual field loss has been shown in high pressure open angle glaucomatous eyes, primarily with the temporal quadrant of the retinal nerve fiber layer and the nasal visual field. The rate of the visual field change in primary open angle glaucoma has been correlated with the initial nerve fiber layer thickness, with the greater the retinal nerve fiber layer thickness the greater the rate of the visual field loss during follow-up. These findings suggest that retinal nerve fiber layer thickness discriminates between normal, ocular hypertensive eyes as well as those with open angle glaucomas and may be useful in following patients with open angle glaucoma prior to development of the visual field loss.

Glaucoma, Open-Angle↗

Outbreak of invasive group A streptococcal infections in a nursing home. Lessons on prevention and control.

OBJECTIVE: Nine outbreaks of group A streptococcal (GAS) infections in nursing homes were reported to the Centers for Disease Control (Atlanta, Ga) during the past two winters. We conducted an intensive epidemiologic and laboratory investigation of one of these outbreaks to determine clinical characteristics, risk factors for transmission and infection, and methods of control and prevention. METHODS: Cases were detected using cultures and serologic tests. Matched case-control and retrospective cohort studies were performed to determine risk factors for infection. RESULTS: Between December 13, 1989, and January 31, 1990, 16 (20%) of 80 residents, and three (7%) of 45 staff, were infected with GAS. Eleven of the residents had invasive disease and four died. Isolates were available from four persons; all were serotype M-1, T-1. There was strong spatial clustering of cases within the nursing home; having a roommate with prior infection was the most important risk factor. Residents with preexisting decubiti had a reduced risk of infection, perhaps because of stricter infection control practices in their care. No evidence was found for common-source transmission of infection. No further cases occurred after improvement of infection control practices and administration of prophylactic antimicrobials to all residents and staff. CONCLUSIONS: Invasive GAS disease is increasing nationwide, and is a potentially serious problem in the growing and high-risk setting of nursing homes. These data suggest that, in this outbreak, a virulent GAS strain was introduced, with subsequent person-to-person transmission. Adherence to infection control practices can prevent or control GAS outbreaks. Prophylactic antimicrobials may be an effective adjunct to control severe or ongoing outbreaks.

Aged↗

Invasive group B streptococcal disease in adults. A population-based study in metropolitan Atlanta.

OBJECTIVE: To define the incidence and clinical spectrum of group B streptococcus infection in adults. To characterize groups at increased risk for infection. DESIGN: Retrospective population-based surveillance of group B streptococcus infections occurring in adults. Patients were identified by review of microbiology records at all surveillance area hospital laboratories. Demographic and clinical data were abstracted from patient medical records. SETTING: Metropolitan Atlanta, Ga, 1982 through 1983. PATIENTS: We identified 70 adult patients with invasive group B streptococcus infections; 14 infections occurred in pregnant women and 56 in nonpregnant adults. RESULTS: The annual incidence of group B streptococcus infection in men and nonpregnant women was 2.4 cases per 100,000 population. Incidence increased with age and was higher in blacks than in whites. The case-fatality rate was 32%. Group B streptococcus was most often isolated from blood (71%) and soft tissue (16%). Common clinical presentations included skin and soft-tissue infection (36%), bacteremia without focus (34%), pneumonia (11%), arthritis (9%), and endocarditis (9%). Compared with the general population's risk of infection, the risk of infection in persons with diabetes mellitus was increased 10.5-fold (95% confidence interval [CI], 7.8 to 14.4); in persons with cancer, it was increased 16.4-fold (95% CI, 11.5 to 23.3). CONCLUSIONS: Group B streptococcus infections cause serious disease in adults as well as in neonates, providing an additional rationale for vaccine development. Determining the incidence of adult disease and groups at greatest risk will help in focusing prevention efforts.

Female↗

Human monocytes bind to two cytokine-induced adhesive ligands on cultured human endothelial cells: endothelial-leukocyte adhesion molecule-1 and vascular cell adhesion molecule-1.

Vascular cell adhesion molecule-1 (VCAM-1) and endothelial-leukocyte adhesion molecule-1 (ELAM-1) are adhesive proteins induced on endothelium by cytokines. We examined the contribution of these adhesive proteins to human peripheral blood monocyte adherence to endothelium using transfected Chinese hamster ovary (CHO) cells stably expressing these proteins and monoclonal antibodies (MoAbs) to ELAM-1, VCAM-1, or CD49d/CD29 (VLA-4), the leukocyte receptor for VCAM-1. Monocytes bound to CHO cells transfected with cDNA of ELAM-1 or VCAM-1. Binding to ELAM-1 was inhibited by MoAb to ELAM-1 and binding to VCAM-1 was inhibited by MoAb to VCAM-1 or the alpha-chain of very late activation antigen-4 (VLA-4) (CD49d). Additive inhibition of adherence to unstimulated human umbilical vein endothelium (HUVE) was observed when monocytes were pretreated with both MoAb to CD49d and MoAb to CD18, the common beta-chain of the leukocyte beta 2 integrin receptors. Adherence of monocytes to HUVE stimulated by recombinant human tumor necrosis factor-alpha was not reduced by MoAbs to CD18, CD49d, or ELAM-1 when used singly, but combinations of these MoAbs produced significant inhibition. We conclude that multiple receptor-ligand systems are involved in monocyte adherence to endothelium.

Animals↗

Intraocular pressure and the rate of visual field loss in chronic open-angle glaucoma.

We measured the rate of change of visual field threshold values over time (mean follow-up, 44.9 +/- 17.4 months) by trend analysis in 40 eyes of 40 patients with chronic open-angle glaucoma. Twenty-eight eyes had stable visual fields, and two eyes had significant visual field improvement. Ten eyes had significant visual field deterioration and showed a correlation between indices of intraocular pressure (standard error of the mean, P = .02; standard deviation, P = .04; and range, P = .05) and the rate of visual field loss in the superonasal region of the visual field, such that the greater the variation of intraocular pressure the greater the rate of loss. The group losing visual fields had a higher mean visual field threshold value and significantly less optic disk pallor and cupping at the start of the study than the stable visual field group. Thus, a significant rate of visual field loss occurred at an earlier stage of the disease and showed a correlation with intraocular pressure in this stage.

Aged↗

Optic nerve head and nerve fiber layer in Alzheimer's disease.

We compared (1) the differences in the retinal nerve fiber layer between 26 patients with Alzheimer's disease and 30 age- and race-matched normal controls with use of blue-light high-resolution photography, (2) the differences in disc pallor between 30 patients with Alzheimer's disease and 32 controls with use of a boundary-tracking program and fundus photographs, and (3) the topographic disc variables between 26 patients with Alzheimer's disease and 36 controls with use of an optic nerve head analyzer. A higher proportion of patients with Alzheimer's disease had detectable nerve fiber damage as seen by red-free photography compared with controls. Although the pallor area-to-disc area ratio was not significantly different between patients with Alzheimer's disease and controls, the patients with higher pallor area-to-disc area ratios had higher Alzheimer's Disease Assessment Scale (ADAS) scores and longer durations of disease. Patients had an increased cup-to-disc ratio and cup volume and decreased disc rim area compared with controls. These variables also correlated significantly with ADAS scores and the duration of disease. The correlation among the optic nerve head changes and the ADAS scores in patients with Alzheimer's disease suggests a potential role for optic nerve head analysis in monitoring the progression of Alzheimer's disease and in assessing the effectiveness of any treatments developed.

Aged↗

Enhanced ocular hypotensive response to epinephrine with prior dexamethasone treatment.

In 12 patients with ocular hypertension and similar pressures in each eye, one eye was randomly selected in a masked manner for pretreatment with three applications of topical 0.01% dexamethasone sodium phosphate drops prepared in artificial tears. The other eye was treated with three applications of drops of artificial tears alone. Both eyes were then treated with 0.1% epinephrine hydrochloride drops. Ocular pressures were measured for the next 2 hours at 20-minute intervals. When compared with eyes treated with epinephrine drops alone, eyes pretreated with dexamethasone drops showed a significantly greater decrease in pressure (mean [+/- SD] maximum difference, 3.1 +/- 2.1 mm Hg). Five patients had a difference of 1.0 to 4.0 mm Hg and five patients had a difference of 4.0 to 6.0 mm Hg. Two patients showed no response. Younger age was associated with the greater response. Adrenergic-glucocorticoid synergism resulting in the lowering of ocular pressure may offer a potential for therapeutic use in ocular hypertension and glaucoma.

Administration, Topical↗

The effect of intermittent scrotal hyperthermia on the Sprague-Dawley rat testicle.

Twenty-four mature male Sprague-Dawley rats were divided into 2 groups of 12. One group was exposed to intermittent hot baths for 1 month, while the other group was exposed to room temperature baths. The group that was exposed to the elevated temperature demonstrated histological testicular changes that included decreased tubular diameter, basement membrane thinning, and decreased spermatogenesis. Fertility rates were markedly reduced in the heat exposed group, but complete recovery of fertility occurred by 10 weeks after completion of the heat treatments.

Animals↗

Isolation and characterization of normal and neoplastic colonic epithelial cell populations.

The aim of the present study was to characterize rat mucosal colonic cells harvested from the crypt continuum during differentiation and dimethylhydrazine-induced neoplasia. The collection of colonocytes was performed using a modified nonenzymatic isolation procedure based on Ca2+ chelation and gentle mechanical dissociation. Light and electron microscopy histomorphological examinations, [3H]thymidine incorporation studies, and activity gradients of alkaline phosphatase, thymidine kinase, and cytoskeleton-associated protein tyrosine kinase indicated that distinct cell populations were harvested from the various crypt regions in a temporal sequence mirroring their zonal and functional distribution in situ. After dimethylhydrazine administration, marked protein tyrosine kinase activity was noted in colonic cells harvested from upper crypt zones. The misplaced and sustained kinase activity preceded the actual polyp or tumor formation. This observation is consistent with the expansion of colonic proliferative compartments beyond allowable boundaries during the preneoplastic period. Companion studies in human colonic epithelial specimens corroborate the findings observed in normal and transformed murine colonocytes. It is believed that the characterization and manipulation of colonocytes using our in vitro model will provide important clues to the molecular events underlying the differentiation program and carcinogenic process in the colonic cell.

Animals↗

House dust mite sensitization in children and residential characteristics in a temperate region.

House dust mite (Hdm) infestation used to be rare in Stockholm, but Hdm-sensitized children are now frequently observed, which probably indicates an increased infestation rate. This study was performed to elucidate determinants of Hdm sensitization in children living in the area. In a case-control study, 53 Hdm-sensitized children (cases), a group of non-Hdm-sensitized atopic children (N = 54), and a group of nonallergic neighborhood children (N = 53) were included. Mattress dust was analyzed with ELISA for content of Hdm allergens. Indoor humidity and temperature were measured, and questionnaire data were collected. Asthma was significantly more common in the Hdm-sensitized group than in the atopic control group. Hdm allergens were found in 40%, 19%, and 23% of the dust samples of the case group, atopic group, and neighborhood control groups, respectively. Only 15% of the dust samples of the Hdm-sensitized children contained Hdm allergens above the recommended threshold levels of sensitization of 2000 ng/gm of dust. Inadequate ventilation, which partly appeared to be a consequence of energy saving, appeared to be a risk factor for Hdm sensitization. This result may apply also to other temperate regions and suggests that the problem is preventable.

Adolescent↗

Mammalian cell lines can be efficiently established in vitro upon expression of the SV40 large T antigen driven by a promoter sequence derived from the human vimentin gene.

The aim of this study was to investigate a new method to enhance the efficiency to create mammalian cell lines. Cell immortalization was achieved by intranuclear microinjection of a recombinant DNA construct composed of a constitutive promoter controlling the genes encoding immortalizing proteins; the sequences coding for the large T and small t antigens were fused downstream of regulatory elements from the vimentin gene, the activation of which characterizes the vast majority of cells growing in vitro. Data show that the efficiency of the immortalizing procedures using the SV40 early genes could be enhanced by the control elements derived from the human vimentin (HuVim) 5' sequences that contained nucleotides -878 to +93 from the CAP site. This HuVim 830-T/t recombinant was used to create cell lines from numerous primary cultures of different origins: rabbit, porcine and human endothelial cells, rabbit and bovine epithelial cells. A set of large T-expressing cells was derived, and these cells retained characteristics of differential cells: binding of Ulex europaeus lectin and synthesis of Factor VIII for human endothelial cells; network of cytokeratin for bovine oviductal cells and rabbit mammary cells.

Animals↗