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Biomedical subjects

J T Weber

Publications and source records attributed to J T Weber.

At least 19 recordsLinked to original sources
PubMed2001

Traumatic injury of cultured astrocytes alters inositol (1,4,5)-trisphosphate-mediated signaling.

Our previous studies using an in vitro model of traumatic injury have shown that stretch injury of astrocytes causes a rapid elevation in intracellular free calcium ([Ca2+]i), which returns to near normal by 15 min postinjury. We have also shown that after injury astrocyte intracellular calcium stores are no longer able to release Ca2+ in response to signal transduction events mediated by the second messenger inositol (1,4,5)-trisphosphate (IP3, Rzigalinski et al., 1998). Therefore, we tested the hypothesis that in vitro injury perturbs astrocyte IP3 levels. Astrocytes grown on Silastic membranes were labeled with [3H]-myo-inositol and stretch-injured. Cells and media were acid-extracted and inositol phosphates isolated using anion-exchange columns. After injury, inositol polyphosphate (IPx) levels increased up to 10-fold over uninjured controls. Significant injury-induced increases were seen at 5, 15, and 30 min and at 24 and 48 h postinjury. Injury-induced increases in IPx were equivalent to the maximal glutamate and trans-(1S,3R)-1-amino-1,3-cyclopentanedicarboxylic acid-stimulated IPx production, however injury-induced increases in IPx were sustained through 24 and 48 h postinjury. Injury-induced increases in IPx were attenuated by pretreatment with the phospholipase C inhibitors neomycin (100 microM) or U73122 (1.0 microM). Since we have previously shown that astrocyte [Ca2+]i returns to near basal levels by 15 min postinjury, the current results suggest that IP3-mediated signaling is uncoupled from its target, the intracellular Ca2+ store. Uncoupling of IP3-mediated signaling may contribute to the pathological alterations seen after traumatic brain injury.

Animals↗
PubMed2000

Traumatic injury of cortical neurons causes changes in intracellular calcium stores and capacitative calcium influx.

Using an in vitro traumatic injury model, we examined the effects of mechanical (stretch) injury on intracellular Ca2+ store-mediated signaling in cultured cortical neurons using fura-2. We previously found that elevation of [Ca2+](i) by the endoplasmic reticulum Ca2+-ATPase inhibitor, thapsigargin, was abolished 15 min post-injury. In the current studies, pre-injury inhibition of phospholipase C with neomycin sulfate maintained Ca2+-replete stores 15 min post-injury, suggesting that the initial injury-induced store depletion may be due to increased inositol trisphosphate production. Thapsigargin-stimulated elevation of [Ca2+](i) returned with time after injury and was potentiated at 3 h. Stimulation with thapsigargin in Ca2+-free media revealed that the size of the Ca2+ stores was normal at 3 h post-injury. However, Ca2+ influx triggered by depletion of intracellular Ca2+ stores (capacitative Ca2+ influx) was enhanced 3 h after injury. Enhancement was blocked by inhibitors of cytosolic phospholipase A2 and cytochrome P450 epoxygenase. Since intracellular Ca2+ store-mediated signaling plays an important role in neuronal function, the observed changes may contribute to dysfunction produced by traumatic brain injury. Additionally, our results suggest that capacitative Ca2+ influx may be mediated by both conformational coupling and a diffusible messenger synthesized by the combined action of cytosolic PLA2 and P450.

Animals↗
PubMed1999

Alterations in calcium-mediated signal transduction after traumatic injury of cortical neurons.

Calcium influx and elevation of intracellular free calcium ([Ca2+]i), with subsequent activation of degradative enzymes, is hypothesized to cause cell injury and death after traumatic brain injury. We examined the effects of mild-to-severe stretch-induced traumatic injury on [Ca2+]i dynamics in cortical neurons cultured on silastic membranes. [Ca2+]i was rapidly elevated after injury, however, the increase was transient with neuronal [Ca2+]i returning to basal levels by 3 h after injury, except in the most severely injured cells. Despite a return of [Ca2+]i to basal levels, there were persistent alterations in calcium-mediated signal transduction through 24 h after injury. [Ca2+]i elevation in response to glutamate or NMDA was enhanced after injury. We also found novel alterations in intracellular calcium store-mediated signaling. Neuronal calcium stores failed to respond to a stimulus 15 min after injury and exhibited potentiated responses to stimuli at 3 and 24 h post-injury. Thus, changes in calcium-mediated cellular signaling may contribute to the pathology that is observed after traumatic brain injury.

Animals↗
PubMed1998

Effect of HIV reporting by name on use of HIV testing in publicly funded counseling and testing programs.

CONTEXT: Policies requiring confidential reporting by name to state health departments of persons infected with the human immunodeficiency virus (HIV) have potential to cause some of them to avoid HIV testing. OBJECTIVE: To describe trends in use of HIV testing services at publicly funded HIV counseling and testing sites before and after the implementation of HIV reporting policies. DESIGN AND SETTING: Analysis of service provision data from 6 state health departments (Louisiana, Michigan, Nebraska, Nevada, New Jersey, and Tennessee) 12 months before and 12 months after HIV reporting was introduced. MAIN OUTCOME MEASURE: Percent change in numbers of persons tested at publicly funded HIV counseling and testing sites after implementation of confidential HIV reporting by risk group. RESULTS: No significant declines in the total number of HIV tests provided at counseling and testing sites in the months immediately after implementation of HIV reporting occurred in any state, other than those expected from trends present before HIV reporting. Increases occurred in Nebraska (15.8%), Nevada (48.4%), New Jersey (21.3%), and Tennessee (62.8%). Predicted decreases occurred in Louisiana (10.5%) and Michigan (2.0%). In all areas, testing of at-risk heterosexuals increased in the year after HIV reporting was implemented (Louisiana, 10.5%; Michigan, 225.1 %; Nebraska, 5.7%; Nevada, 303.3%; New Jersey, 462.9%; Tennessee, 603.8%). Declines in testing occurred among men who have sex with men in Louisiana (4.3%) and Tennessee (4.1%) after HIV reporting; testing increased for this group in Michigan (5.3%), Nebraska (19.6%), Nevada (12.5%), and New Jersey (22.4%). Among injection drug users, testing declined in Louisiana (15%), Michigan (34.3%), and New Jersey (0.6%) and increased in Nebraska (1.7%), Nevada (18.9%), and Tennessee (16.6%). CONCLUSIONS: Confidential HIV reporting by name did not appear to affect use of HIV testing in publicly funded counseling and testing programs.

AIDS Serodiagnosis↗
PubMed1998

Invasive cervical cancer in human immunodeficiency virus-infected and uninfected hospital patients.

OBJECTIVE: To compare the prevalence of invasive cervical cancer in women with, and in women without, human immunodeficiency virus (HIV) infection, so as to evaluate the inclusion of invasive cervical cancer in the AIDS surveillance case definition. METHODS: The Sentinel Hospital Surveillance System for HIV Infection collected data and serum specimens that remained after clinical testing of persons who received inpatient or outpatient care at 14 hospitals with high HIV prevalence. We analyzed data on invasive cervical cancer obtained from medical record review and HIV serostatus from white, black, and Hispanic women in the age groups 20-34, 35-44, and 45-54 years. RESULTS: In 1994 and 1995, 2684 (6.6%) of the 40,524 women sampled were HIV infected. Of the HIV-positive women, 28 had invasive cervical cancer (10.4 per 1000 women) and of the HIV-negative women, 236 had invasive cervical cancer (6.2 per 1000 women, relative risk [RR] 1.7, 95% confidence interval [CI] 1.1, 2.5). The prevalence of invasive cervical cancer was higher for HIV-positive than for HIV-negative black women aged 20-34 (RR 3.8; CI 1.7, 8.5) and Hispanic women aged 20-34 (RR 7.3; CI 1.4, 37.1) and 35-44 (RR 3.9; CI 1.1, 14.7) years. Twenty-six of the 28 cases of invasive cervical cancer in HIV-positive women were in women known to be HIV-positive during admission. CONCLUSION: The prevalence of invasive cervical cancer was higher for women who were HIV positive than for women who were HIV negative. This lends support to the inclusion of invasive cervical cancer in the revision of the surveillance case definition for AIDS in 1993.

Adult↗
PubMed1998

Trends in HIV seropositivity in publicly funded HIV counseling and testing programs: implications for prevention policy.

INTRODUCTION: We describe trends in seropositivity among clients attending publicly funded HIV counseling and testing sites across the United States and discuss implications for prevention policy. METHODS: The present analysis used client-level data from 1990 through 1994 for 26 of 65 state, territorial, and local health departments receiving Centers for Disease Control and Prevention funds. Logistic regression was used to predict the proportion of HIV tests that were positive. Curves were created representing adjusted HIV seropositivity trends for 1990 through 1994. RESULTS: HIV seropositivity rates were higher before 1992. Throughout, rates were higher among men, most racial/ethnic minorities tested, and persons 30 years or older. Although rates for men remained higher than those for women, the gap has narrowed in recent years. For both men and women, rates remained low for those reporting heterosexual activity as their only potential risk for HIV. Over time, more high-risk seronegatives are being repeatedly tested. CONCLUSIONS: Lower, stabilized seropositivity rates after 1992 reflect large increases in testing volume, increasing frequency of repeat testing, and fewer asymptomatic-infected persons entering this public system. Various program innovations including enhanced outreach, improved access, rapid testing, and client-centered counseling should be considered as strategies to increase the number of infected persons who learn their serostatus early and enter into medical care.

Adolescent↗
PubMed1998

Intracellular free calcium dynamics in stretch-injured astrocytes.

We have previously developed an in vitro model for traumatic brain injury that simulates a major component of in vivo trauma, that being tissue strain or stretch. We have validated our model by demonstrating that it produces many of the posttraumatic responses observed in vivo. Sustained elevation of the intracellular free calcium concentration ([Ca2+]i) has been hypothesized to be a primary biochemical mechanism inducing cell dysfunction after trauma. In the present report, we have examined this hypothesis in astrocytes using our in vitro injury model and fura-2 microphotometry. Our results indicate that astrocyte [Ca2+]i is rapidly elevated after stretch injury, the magnitude of which is proportional to the degree of injury. However, the injury-induced [Ca2+]i elevation is not sustained and returns to near-basal levels by 15 min postinjury and to basal levels between 3 and 24 h after injury. Although basal [Ca2+]i returns to normal after injury, we have identified persistent injury-induced alterations in calcium-mediated signal transduction pathways. We report here, for the first time, that traumatic stretch injury causes release of calcium from inositol trisphosphate-sensitive intracellular calcium stores and may uncouple the stores from participation in metabotropic glutamate receptor-mediated signal transduction events. We found that for a prolonged period after trauma astrocytes no longer respond to thapsigargin, glutamate, or the inositol trisphosphate-linked metabotropic glutamate receptor agonist trans-(1S,3R)-1-amino-1,3-cyclopentanedicarboxylic acid with an elevation in [Ca2+]i. We hypothesize that changes in calcium-mediated signaling pathways, rather than an absolute elevation in [Ca2+]i, is responsible for some of the pathological consequences of traumatic brain injury.

Animals↗
PubMed1998

An outbreak of Brainerd diarrhea among travelers to the Galapagos Islands.

In 1992, an outbreak of chronic diarrhea occurred among passengers on a cruise ship visiting the Galapagos Islands, Ecuador. Passengers (548) were surveyed, and stool and biopsy specimens from a sample who reported chronic diarrhea were examined. On completed questionnaires, returned by 394 passengers (72%), 58 (15%) reported having chronic diarrhea associated with urgency (84%), weight loss (77%), fatigue (71%), and fecal incontinence (62%). Illness began 11 days (median) after boarding the ship and lasted 7 to >42 months. Macroscopic and histologic abnormalities of the colon were common, but extensive laboratory examination revealed no etiologic agent. No one responded to antimicrobial therapy. Patients were more likely than well passengers to have drunk the ship's unbottled water or ice before onset of illness and to have eaten raw sliced fruits and vegetables washed in unbottled water. Water handling and chlorination on the ship were deficient. Outbreaks of a similar illness, Brainerd diarrhea, have been reported in the United States. Although its etiology remains unknown, Brainerd diarrhea may also occur among travelers.

Anti-Bacterial Agents↗
PubMed1998

A bioactive peptide from the transmembrane 5-intracellular loop 3 region of the human 5HT1a receptor.

15 amino acid peptide from the transmembrane 5-intracellular loop 3 region of the human 5HT1a receptor produced concentration-dependent decreases in agonist binding. This result is consistent with a competitive interaction between peptide, receptor, and G protein at the receptor-G protein interface. Bombesin and a 13 amino acid peptide from the carboxyl terminus region of the receptor were inactive. Additionally, the peptide decreased forskolin-mediated cAMP elevation. Overall, these results suggest that amino acid residues from this region of the receptor are involved in receptor-G protein coupling and that G protein is activated by the receptor.

Animals↗
PubMed1997

Tumor necrosis factor-alpha: a neuromodulator in the CNS.

In the central nervous system (CNS), the cytokine tumor necrosis factor-alpha (TNF alpha) is produced by both neurons and glial cells, participates in developmental modeling, and is involved in many pathophysiological conditions. There are activity-dependent expressions of TNF alpha as well as low levels of secretion in the resting state. In contrast to the conventional view of a cytotoxic effect of TNF alpha, accumulating evidence suggests a beneficial effect when TNF alpha is applied at optimal doses and at specific periods of time. The bimodal effect is related to subtypes of receptors, activation of different signal transduction pathways, and the presence of other molecules that alter the intracellular response elements such as immediate-early genes. TNF alpha may be an important neuromodulator in development of the CNS, diseases of demyelination and degeneration, and in the process of regeneration. It could induce growth-promoting cytokines and neurotrophins, or it could increase the production of antiproliferative cytokines, nitric oxide, and free radicals, thereby contributing to apoptosis.

Animals↗
PubMed1997

Rabbit cerebral cortex 5HT1a receptors.

Selective 5HT1a agonist binding to membranes from rabbit cerebral cortex was concentration-dependent and saturable; the Kd was 1.1 nM and Bmax of 480 fmols/mg protein. Scatchard as well as Hill plots were linear; the Hill coefficient was 0.96, suggesting a single, non-interacting binding site. Agonist binding was inhibited in a concentration-dependent fashion by gamma S GTP, a result consistent with the coupling of this binding site to the G protein signal transduction system. In competition experiments involving agonist and a series of agents with known affinities and specificities at 5HT1a receptors, a rank order relationship was found consistent with this binding site being a 5HT1a binding site. Direct comparisons of agonist and antagonist binding at rat cerebral cortex 5HT1a receptors and cloned human 5HT1a receptors also suggested that the rabbit binding site belongs to the 5HT1a class. The only rank order anomalies were with methiothepin in rabbit cerebral cortex, where a comparatively high Ki was observed and with buspirone in cloned human 5HT1a receptor, where a low Ki was determined; these anomalies bear further study in light of the comparative pharmacology of 5HT1a receptors. Finally, the natural product parthenolide was tested for affinity in the rabbit, rat, and human systems, where it uniformly was unable to displace agonist, suggesting that the 5HT1a receptor is not a target for this compound. Overall, these results suggest that a functional 5HT1a receptor exists in rabbit cerebral cortex.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1997

Activity of Parthenolide at 5HT2A receptors.

Parthenolide displaces [3H]ketanserin from 5HT2A receptors from rat and rabbit brain and cloned 5HT2A receptors. Ki's are in the 100-250 microM range. These results suggest that parthenolide may be a low-affinity antagonist at 5HT receptors; it is unlikely that the entire mechanism of action can be explained by its modest 5HT2A receptor affinity.

Animals↗
PubMed1997

Presence of human immunodeficiency virus (HIV) type 1 subtype A infection in a New York community with high HIV prevalence: a sentinel site for monitoring HIV genetic diversity in North America. Centers for Disease Control and Prevention-Bronx Lebanon HIV Serosurvey Team.

To determine whether US residents are infected with subtypes of human immunodeficiency virus (HIV) type 1 other than subtype B (Western), the predominant North American subtype with a unique GPGR genetic sequence in the V3 loop, viruses from 22 HIV-infected adults were serotyped and subtyped. Twenty patients had subtype B (Western), of whom 15 had serotype B (Western), 3 had serotype A/C, 1 had serotype B (Thai), and 1 had a nontypeable serotype. Two had subtype A, both serotype A/C. Both subtype A-infected patients, only 1 of whom had been outside the United States, reported sex with persons traveling abroad, suggesting possible acquisition in the United States. Because US residents are infected with non-subtype B (Western) strains, US surveillance for HIV-1 diversity is needed to elucidate subtype-specific transmission patterns and pathogenesis and to guide evaluation and development of HIV diagnostic tests and vaccines.

Adolescent↗
PubMed1997

Publicly funded HIV counseling and testing in the United States, 1992-1995.

Data are collected and reported through the Centers for Disease Control and Prevention (CDC) Counseling and Testing System (CTS) on episodes of publicly funded counseling and HIV testing in the Unites States. The objective of this analysis is to describe testing data reported from 1992 through 1995. In 1992, 2,689,056 tests were performed, and 55,024 (2.0%) were positive; in 1995, 2,491,434 tests were performed, of which 40,605 (1.6%) were positive. Among tests reported with client-level data, the proportion of tests of men and women at higher risk for HIV infection remained stable or declined; the proportion of tests of persons who had been previously tested increased each year; and in 1995, the proportion of tests that included posttest counseling was 86% for anonymous and 70% for confidential tests. Although information collected through CTS could be improved by changing the system so that individuals could be distinguished from testing episodes, the CTS does provide important monitoring information to local and state health departments.

AIDS Serodiagnosis↗
PubMed1996

Performance characteristics of a rapid HIV antibody assay in a hospital with a high prevalence of HIV infection. CDC-Bronx-Lebanon HIV Serosurvey Team.

BACKGROUND: The delay between collection of blood samples and availability of test results may be as long as 3 weeks and is one barrier to the acceptance of voluntary testing for human immunodeficiency virus (HIV) infection. Serologic tests that provide results rapidly could overcome this barrier, but the accuracy and reliability of rapid tests have not been well characterized in the United States. OBJECTIVE: To evaluate, in a "real world" setting, the performance characteristics of a rapid HIV assay that reduces the need for patients to return for counseling after the test. DESIGN: Testing of HIV antibodies by rapid and nonrapid assays and survey about risk behaviors for HIV. SETTING: A hospital in Bronx, New York, with a high prevalence of HIV-seropositive patients. PATIENTS: 837 patients who were not known to be infected with HIV, had not been admitted for conditions related to the acquired immunodeficiency syndrome, and agreed to participate in HIV testing and an interview. MEASUREMENTS: Sensitivity and specificity of a rapid HIV antibody assay based on comparisons with nonrapid assay and Western blot assay. RESULTS: According to nonrapid assays, 5.4% of patients were infected with HIV. The rapid assay was highly accurate in this sample overall: its sensitivity was 1.00, its specificity was 0.991, its positive predictive value was 0.865, and its negative predictive value was 1.00. The assay was also highly accurate in various subgroups. CONCLUSIONS: Accurate, rapid tests for HIV infection may enhance testing programs by preventing the need for delayed counseling of seronegative patients and by providing preliminary results to seropositive patients. These preliminary results may encourage patients to return for confirmatory test results and to adopt risk-reducing behaviors sooner.

Adolescent↗
PubMed1996

Absence of human immunodeficiency virus type 2 infection among patients in a hospital serving a New York community at high risk for infection. Centers for Disease Control and Prevention/Bronx-Lebanon Hospital Center HIV Serosurvey Team.

BACKGROUND: Although human immunodeficiency virus type 2 (HIV-2) infection among United States residents is considered rare, there are US populations at high risk. Few studies have surveyed these populations with a high likelihood of infection, that is, those with high percentages of persons from HIV-2-endemic areas and high prevalences of behaviors that would allow for transmission. STUDY DESIGN AND METHODS: Patients (n = 832) enrolled in a confidential HIV serosurvey at a hospital that serves a community with a relatively high percentage of West African immigrants, drug injectors, and persons who practice high-risk sexual activity were evaluated. Sera were tested for HIV type 1 (HIV-1) and HIV-2 by rapid enzyme immunoassays, standard enzyme immunoassays and Western blots. RESULTS: Eight of 832 patients were weakly reactive to HIV-2 on rapid assay, but none was confirmed to be infected when tested by standard immunoassay and Western blot. Five of these eight were reactive to HIV-1. CONCLUSION: Weak reactivity to HIV-2 antibody on the rapid assay is best explained by cross-reactivity with HIV-1 antibody; thus, even in this population at high risk for infection, false-positive reactions are more likely than true infections. The finding that HIV-2 is absent in this population at potentially high risk for infection corroborates the findings of other studies that HIV-2 infection is rare among US residents. These results support previous recommendations that, in settings other than blood collection facilities, HIV-2 testing should be selectively offered to persons with epidemiologic risk factors.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Experience with the use of an investigational F(ab')2 heptavalent botulism immune globulin of equine origin during an outbreak of type E botulism in Egypt.

During an outbreak of type E foodborne botulism in Cairo in 1991, an investigational equine F(ab')2 "despeciated" heptavalent botulism immune globulin (dBIG) was provided to the Egyptian Ministry of Health by the U.S. Army. Of 54 patients known to have been treated with antitoxins, 4 received commercially available trivalent antitoxins, 45 received dBIG, and 5 received both commercial antitoxin and dBIG. Physicians recorded side effects in 10 (22%) of 45 patients who received dBIG; in nine cases, reactions were considered "mild," and in one case they were believed to be serum sickness. In contrast, possible serum sickness during hospitalization was recorded for two of four patients who were receiving commercial antitoxins. No complications of therapy were noted for any patient who was receiving both antitoxin types. In a separate study, 31 patients were contacted about their reactions to the antitoxin by telephone after discharge from the hospital. Seven (54%) of 13 patients attributed symptoms that they experienced while they were hospitalized to receipt of dBIG, while four (44%) of nine patients who indicated that they had received commercial antitoxins and one (20%) of five who received both commercial antitoxin and dBIG reported side effects before discharge. Data on the efficacy of the antitoxins were not obtained. In our experience, equine dBIG was at least as safe as commercially available antitoxins in treating type E foodborne botulism.

Antitoxins↗