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Biomedical subjects

B Schwartz

Publications and source records attributed to B Schwartz.

At least 19 recordsLinked to original sources
PubMed1992

Structural analysis of the human interferon gamma receptor: a small segment of the intracellular domain is specifically required for class I major histocompatibility complex antigen induction and antiviral activity.

Mutations of the human interferon gamma (IFN-gamma) receptor intracellular domain have permitted us to define a restricted region of that domain as necessary for both induction of class I major histocompatibility complex antigen by IFN-gamma and protection against encephalomyocarditis virus. This region consists of five amino acids (YDKPH), all of which are conserved in the human and murine receptors. Tyr-457 and His-461 are essential for activity. Approximately 80% of the amino acids of the intracellular domain of the receptor is not required for major histocompatibility complex class I antigen induction or for antiviral protection against encephalomyocarditis virus. The observation that there was no protection by IFN-gamma against vesiculostomatitis virus indicates that other factors, in addition to chromosome 21 accessory factor(s), are required to generate the full complement of transduction signals from the human IFN-gamma receptor.

Amino Acid Sequence↗
PubMed1992

Prevention of Lyme disease after tick bites. A cost-effectiveness analysis.

BACKGROUND: In areas of endemic disease, the probability of Lyme disease after a tick bite ranges from about 0.012 to 0.05. Early treatment with oral antibiotics prevents most complications of Lyme disease, but antibiotics are generally not prescribed until rash or other symptoms develop. METHODS: We used decision analysis to evaluate the outcomes, costs, and cost effectiveness of three alternative strategies to treat patients bitten by ixodes ticks in areas of endemic Lyme disease: empirically treat all patients with two weeks of doxycycline, treat only patients in whom erythema migrans develops, and treat only patients with erythema migrans or a positive serologic test for Lyme disease one month after exposure. RESULTS: Empirical treatment is the least expensive strategy and results in the fewest cases of Lyme disease and the fewest complications when the probability of Borrelia burgdorferi infection after a tick bite is 0.036 or higher. For probabilities of infection below 0.036, empirical therapy prevents most major complications, sequelae, and adverse events, but it incurs additional minor complications, especially as the probability of infection falls below 0.01. CONCLUSIONS: Empirical treatment of patients with tick bites is indicated when the probability of B. burgdorferi infection after a bite is 0.036 or higher, and this treatment may be preferred when the probability of infection ranges from 0.01 to 0.035. When the probability of infection after a tick bite is less than 0.01, empirical therapy is not warranted.

Animals↗
PubMed1992

The role of mucin in colon-cancer metastasis.

Mucinous colorectal cancer often presents at an advanced stage. We have previously observed that mucin production by human colon-cancer cells correlates with their ability to colonize the liver in experimental animal models. The present study was undertaken in order to further elucidate the mechanisms by which production of mucin by colon-cancer cells affects metastasis. Cell lines showing high mucin production (HMP) (HM 7, HM 3 and LS LiM 6) demonstrated increased adherence to basement membrane proteins and invaded a reconstituted basement membrane to a greater extent than their counter-part cell lines showing low mucin production (LMP) (LS174T and LM 12). Adherence of the LMP parental cell line LS174T to various matrix proteins was potentiated by the addition of purified human colon-cancer mucin in a dose-dependent fashion. HMP cell lines secreted more proteolytically active type-IV collagenase than LMP lines, and collagenase activity was further stimulated by purified mucin in a dose-dependent manner. Specific inhibition of mucin O-glycosylation by benzyl-alpha-N-acetylgalactosamine significantly affected each of the metastasis-related events, with the greatest effect on the HMP cell lines. The present data further indicate that mucin may play an important role in the metastatic process.

Animals↗
PubMed1992

Retinal vessel autoregulation in sickle cell patients.

We tested retinal vessel autoregulation in 16 sickle cell patients and 6 controls by computer-assisted measurements of constriction of the superior and inferior temporal veins and arteries after pure oxygen breathing. Compared to the controls and corrected for age, we found a decrease of vasoconstriction in three of the four vessels measured in the sickle cell group, which was statistically significant only for the superior temporal artery (P 0.009). The number of patients was too small to allow a separate analysis of possible contributory factors within the sickle cell group, such as sickle cell hemoglobin subtype and extent of retinal ischemia. Our findings indicate a factor not yet well known in the pathophysiology of sickle cell disease: an abnormality of local microvascular control.

Adult↗
PubMed1992

Neuroretinal rim area measurements by configuration and by pallor in ocular hypertension and glaucoma.

PURPOSE: The purpose of this study is to examine the differences between measurements of neuroretinal rim area of the optic disc defined by configuration and by pallor. METHODS: One hundred seventy-one patients were studied (59 with glaucoma, 96 ocular hypertensive patients, and 16 controls). The magnification-corrected neuroretinal rim area was measured from black-and-white stereoscopic paper prints. The central area of pallor was measured using computer-assisted image analysis techniques. The percentage of central area of pallor was converted into mm2, and an estimate of neuroretinal rim area defined by color was calculated. RESULTS: The correlation between the measurements of neuroretinal rim area by configuration and by pallor was statistically highly significant (r = 0.89, P less than 0.0001). No consistent differences between measurements were found in different diagnostic groups, or in different stages or types of glaucomatous optic disc abnormality. The correlation of changes of both measurements during a 9-year follow-up period also was statistically significant (r = 0.68, P less than 0.001). CONCLUSION: In clinical routine measurements of the neuroretinal rim area, using both configuration and pallor definition does not seem to add to the information.

Adult↗
PubMed1992

Role of the temporal cilioretinal artery in retaining central visual field in open-angle glaucoma.

The authors reviewed the optic disc photographs of 34 eyes with high-pressure open-angle glaucoma with advanced visual field loss. Thirteen eyes (38%) had one or two temporal cilioretinal arteries, and 21 eyes (62%) had no temporal cilioretinal artery. All 13 eyes with a temporal cilioretinal artery retained central visual field and had visual acuity of 20/40 or better. In the 21 eyes without a temporal cilioretinal artery, 8 eyes lost central visual field and 12 eyes had a visual acuity of less than 20/40, while 13 eyes retained central visual field and 9 eyes had a visual acuity of 20/40 or better. Significant differences were obtained when eyes with and without cilioretinal arteries were compared for retention of visual field (P less than 0.02) and visual acuity (P less than 0.01). The presence of a temporal cilioretinal artery may provide more circulation to the temporal rim of the optic disc and aid in retaining central field and visual acuity in advanced open-angle glaucoma.

Aged↗
PubMed1992

Engineered disulfide bond greatly increases specific activity of recombinant murine interferon-beta.

Unlike other species of interferon-beta (IFN-beta) mouse (Mu) IFN-beta has no naturally occurring intramolecular disulfide bond. When expressed in Escherichia coli, MuIFN-beta appears to exhibit instability and low activity. To increase its activity, we engineered a pair of cysteines into recombinant MuIFN-beta to test whether this change would improve its antiviral activity. In the absence of detailed structural data, the optimal placement of cysteines was determined by sequence comparison with other species of IFN-beta. While MuIFN-beta has only a single cysteine (at position 17), other species of IFN-beta have three cysteines, at positions 17, 31, and 141 (numbering based on consensus sequence), a disulfide bond being formed between the latter two residues. Thus, we introduced cysteines into MuIFN-beta at positions 29 and 136, which correspond to positions 31 and 141 of the consensus sequence. When the variant form of MuIFN-beta was expressed in bacteria and purified, we found that the additional cysteines greatly increased the antiviral activity. Further improvement was obtained by replacement of the Cys-17 with a serine. In this manner a specific activity approximately 15-fold that of the wild-type recombinant molecule was achieved.

Animals↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗