PubMed Health⌕ Search

Biomedical subjects

J Ostermann

Publications and source records attributed to J Ostermann.

At least 19 recordsLinked to original sources
PubMed2006

Association of unmet needs for support services with medication use and adherence among HIV-infected individuals in the southeastern United States.

Unmet needs for services, such as housing and psychiatric treatment, are relatively common among HIV-infected individuals; however, the effects of different types of unmet needs on health-care outcomes are not well understood. This study describes unmet psychosocial needs and their relationship with health-care outcomes among individuals receiving HIV care in the southeastern US (n=526). We used multivariate logistic regression to examine the association of seven categories of unmet needs with HIV medication use and adherence. Most participants (84.5%) reported at least one service need in the past year. Nearly half (47%) of participants with service needs reported that at least one need was not met. Participants with one or more unmet needs were less likely to be taking any HIV medications (p = 0.007) and reported poorer medication adherence (p=0.013). The specific unmet needs for benefits (including Social Security, health insurance and prescription coverage) (p = 0.006) and a support group (p=0.040) were associated with being less likely to be taking any HIV medications. Unmet need for mental health-related counseling was associated with poorer medication adherence (p=0.003). Study findings regarding the high level of unmet need and the association of unmet need with poorer outcomes illustrate the importance of interventions to address these needs.

Adult↗
PubMed2006

Improving health outcomes among individuals with HIV, mental illness, and substance use disorders in the Southeast.

Providing behavioral treatment for mental health and substance use disorders among HIV-infected individuals is critical because these disorders have been associated with negative outcomes such as poorer medication adherence. This study examines the effectiveness of an integrated treatment model for HIV-infected individuals who have both substance use and mental disorders. Study participants (n = 141) were recruited through routine mental health and substance abuse screening at tertiary Infectious Disease clinics in North Carolina. The study participants received integrated mental health and substance abuse treatment for one year and were interviewed at three-month intervals. Using linear regression analyses, we detected statistically significant decreases in participants' psychiatric symptomatology, illicit substance use, alcohol use, and inpatient hospital days. Participants also reported fewer emergency room visits and were more likely to be receiving antiretroviral medications and adequate psychotropic medication regimens at follow-up. No changes in sexual risk, physical health, or medical adherence were detected after treatment participation. This integrated treatment model offers an option for treating HIV-infected individuals with mental health and substance use disorders that can be adapted for use in a variety of psychiatric and medical treatment settings.

Adult↗
PubMed2005

Sociodemographic and clinical characteristics of clients presenting for HIV voluntary counselling and testing in Moshi, Tanzania.

HIV voluntary counselling and testing (VCT) reduces high-risk sexual behaviour. Factors associated with HIV infection in VCT clients have not been well characterized in northern Tanzania. We prospectively surveyed 813 VCT clients in Moshi, Tanzania. Clients were administered a questionnaire on sociodemographic characteristics, sexual behaviour, and health status. Blood was taken for rapid HIV antibody testing. Factors associated with HIV seropositivity were identified using multivariate logistic regression analysis. Of 813 clients, the seroprevalence was 16.7%. The strongest associations with seropositivity were reporting diarrhoea (odds ratio [OR] 10.4, 95% confidence interval [CI] 3.6-29.9), an ill sexual partner (OR 6.3, 95% CI 3.0-12.9), or being a woman (OR 3.5, 95% CI 2.0-6.3). In a separate regression, the number of symptoms also predicted HIV infection (OR 2.1, 95% CI 1.6-2.6). VCT clients who tested positive had more HIV-related symptoms suggesting presentation at a later stage of HIV infection.

AIDS Serodiagnosis↗
PubMed2002

Visualization of auditory habituation by fMRI.

The aim of this study was to measure and quantify habituation phenomena within the auditory cortex of 18 healthy subjects by means of fMRI. Auditory stimulation was done by digitally generated pulsed (nu = 5 Hz) 800-Hz sine tones with three alternating ON (duration 2 min) and OFF (1 min) periods. Binaural stimulation resulted in symmetrical bihemispheric activation of the auditory cortex. Our data revealed a characteristic signal decay to repeated acoustic stimulation: the response to the second was even more pronounced, and the third stimulation block significantly lower compared to the first. Thus, our data clearly demonstrate habituation phenomena, probably due to reduced neuronal activity with increased duration and/or frequency of stimuli.

Acoustic Stimulation↗
PubMed2001

Stoichiometry and kinetics of transport vesicle fusion with Golgi membranes.

The in vitro complementation assay established by Rothman and co-workers continues to be an important tool to study intra-Golgi transport. In this study, kinetic modeling is used to identify four main parameters that, together, explain the basic features of an assay that is a modification of the original assay. First, the assay signal depends on the ratio of Golgi membranes to transport intermediates in the assay. Secondly, an inactivation rate describes how the activity of transport intermediates decreases over time. Thirdly, the rate at which transport intermediates irreversibly bind to Golgi membranes is measured independently of membrane fusion, thus allowing a quantitative distinction between these two steps. Fourthly, a single rate constant describes the remaining reactions, which result in membrane fusion. This approach of kinetic modeling of experiments is generally applicable to other in vitro assays of cell biological phenomena, permitting quantitative interpretations and an increased resolution of the experiments.

Animals↗
PubMed2001

Effects of alcohol consumption on disability among the near elderly: a longitudinal analysis.

Data from four waves of the Health and Retirement Study are used to analyze the effects of alcohol use on disability, mortality, and income transfers from public programs. Cross-sectional analysis reveals a complex relationship, with a history of problem drinking clearly leading to higher rates of limitations, and a nonmonotonic relationship between current drinking and disability. In longitudinal analysis, problem drinking was predictive of disability onset, but not of transfer receipt or mortality. Heavy drinkers and problem drinkers, if anything, were less likely to receive public income support than abstainers or moderate drinkers. The likelihood that heavy drinkers received public transfers did not decrease relative to others following statutory changes in 1996 that sought to limit eligibility of alcoholics and drug abusers.

Age of Onset↗
PubMed2000

Mouse hepatitis virus replicase proteins associate with two distinct populations of intracellular membranes.

The coronavirus replicase gene (gene 1) is translated into two co-amino-terminal polyproteins that are proteolytically processed to yield more than 15 mature proteins. Several gene 1 proteins have been shown to localize at sites of viral RNA synthesis in the infected cell cytoplasm, notably on late endosomes at early times of infection. However, both immunofluorescence and electron microscopic studies have also detected gene 1 proteins at sites distinct from the putative sites of viral RNA synthesis or virus assembly. In this study, mouse hepatitis virus (MHV)-infected cells were fractionated and analyzed to determine if gene 1 proteins segregated to more than one membrane population. Following differential centrifugation of lysates of MHV-infected DBT cells, gene 1 proteins as well as the structural N and M proteins were detected almost exclusively in a high-speed small membrane pellet. Following fractionation of the small membrane pellet on an iodixanol density gradient, the gene 1 proteins p28 and helicase cofractionated with dense membranes (1.12 to 1.13 g/ml) that also contained peak concentrations of N. In contrast, p65 and p1a-22 were detected in a distinct population of less dense membranes (1.05 to 1.09 g/ml). Viral RNA was detected in membrane fractions containing helicase, p28, and N but not in the fractions containing p65 and p1a-22. LAMP-1, a marker for late endosomes and lysosomes, was detected in both membrane populations. These results demonstrate that multiple gene 1 proteins segregate into two biochemically distinct but tightly associated membrane populations and that only one of these populations appears to be a site for viral RNA synthesis. The results further suggest that p28 is a component of the viral replication complex whereas the gene 1 proteins p1a-22 and p65 may serve roles during infection that are distinct from viral RNA transcription or replication.

Animals↗
PubMed1999

ER/Golgi intermediates acquire Golgi enzymes by brefeldin A-sensitive retrograde transport in vitro.

Secretory proteins exit the ER in transport vesicles that fuse to form vesicular tubular clusters (VTCs) which move along microtubule tracks to the Golgi apparatus. Using the well-characterized in vitro approach to study the properties of Golgi membranes, we determined whether the Golgi enzyme NAGT I is transported to ER/Golgi intermediates. Secretory cargo was arrested at distinct steps of the secretory pathway of a glycosylation mutant cell line, and in vitro complementation of the glycosylation defect was determined. Complementation yield increased after ER exit of secretory cargo and was optimal when transport was blocked at an ER/Golgi intermediate step. The rapid drop of the complementation yield as secretory cargo progresses into the stack suggests that Golgi enzymes are preferentially targeted to ER/Golgi intermediates and not to membranes of the Golgi stack. Two mechanisms for in vitro complementation could be distinguished due to their different sensitivities to brefeldin A (BFA). Transport occurred either by direct fusion of preexisting transport intermediates with ER/Golgi intermediates, or it occurred as a BFA-sensitive and most likely COP I-mediated step. Direct fusion of ER/Golgi intermediates with cisternal membranes of the Golgi stack was not observed under these conditions.

Animals↗
PubMed1999

GTP hydrolysis by arf-1 mediates sorting and concentration of Golgi resident enzymes into functional COP I vesicles.

Upon addition of GTPgammaS to in vitro budding reactions, COP I vesicles form but retain their coat, making them easy to isolate and analyze. We have developed an in vitro budding assay that reconstitutes the formation of COP I-derived vesicles under conditions where GTP hydrolysis can occur. Once formed, vesicles are uncoated and appear functional as they fuse readily with acceptor membranes. Electron microscopy shows a homogeneous population of uncoated vesicles that contain the medial/trans Golgi enzyme alpha1, 2-mannosidase II. Biochemical quantitation of vesicles reveals that resident Golgi enzymes are up to 10-fold more concentrated than in donor membranes, but vesicles formed in the presence of GTPgammaS show an average density of resident Golgi enzymes similar to that seen in donor membranes. We show that the sorting process is mediated by the small GTPase arf-1 as addition of a dominant, hydrolysis-deficient arf-1 (Q)71(L) mutant produced results similar to that of GTPgammaS. Strikingly, the average density of the anterograde cargo protein, polymeric IgA receptor, in COP I-derived vesicles was similar to that found in starting membranes and was independent of GTP hydrolysis. We conclude that hydrolysis of GTP bound to arf-1 promotes selective segregation and concentration of Golgi resident enzymes into COP I vesicles.

ADP-Ribosylation Factor 1↗
PubMed1999

Arfaptin 1, an ARF-binding protein, inhibits phospholipase D and endoplasmic reticulum/Golgi protein transport.

Class I ADP-ribosylation factors (ARFs) are essential for coatomer and clathrin coat assembly and vesicular transport in the Golgi apparatus. However, little is known about the in vivo regulation of ARF actions. Recently we cloned arfaptin 1, a 39 kDa protein that binds active, GTPgammaS-liganded ARF and translocates with it to Golgi membranes. Here we show that phorbol ester-stimulated phospholipase D (PLD) activity is inhibited in arfaptin 1-overexpressing NIH 3T3 cells and that arfaptin 1 inhibits ARF activation of Golgi-associated PLD. Since PLD activity is thought to play a role in regulating vesicular transport in the secretory pathway, we determined the rate of glycosylation of vesicular stomatitis virus glycoprotein as a measure of protein transport from the endoplasmic reticulum through the Golgi apparatus. Arfaptin 1 overexpression was found to decrease the rate of this reaction approximately two-fold. These data suggest that arfaptin 1 is a regulator of ARF action in the Golgi apparatus.

3T3 Cells↗
PubMed1998

Isolation of functional Golgi-derived vesicles with a possible role in retrograde transport.

Secretory proteins enter the Golgi apparatus when transport vesicles fuse with the cis-side and exit in transport vesicles budding from the trans-side. Resident Golgi enzymes that have been transported in the cis-to-trans direction with the secretory flow must be recycled constantly by retrograde transport in the opposite direction. In this study, we describe the functional characterization of Golgi-derived transport vesicles that were isolated from tissue culture cells. We found that under the steady-state conditions of a living cell, a fraction of resident Golgi enzymes was found in vesicles that could be separated from cisternal membranes. These vesicles appeared to be depleted of secretory cargo. They were capable of binding to and fusion with isolated Golgi membranes, and after fusion their enzymatic contents most efficiently processed cargo that had just entered the Golgi apparatus. Those results indicate a possible role for these structures in recycling of Golgi enzymes in the Golgi stack.

Adenosine Triphosphate↗
PubMed1994

ADP-ribosylation factor and coatomer couple fusion to vesicle budding.

The coat proteins required for budding COP-coated vesicles from Golgi membranes, coatomer and ADP-ribosylation factor (ARF) protein, are shown to be required to reconstitute the orderly process of transport between Golgi cisternae in which fusion of transport vesicles begins only after budding ends. When either coat protein is omitted, fusion is uncoupled from budding-donor and acceptor compartments pair directly without an intervening vesicle. Coupling may therefore results from the sequestration of fusogenic membrane proteins into assembling coated vesicles that are only exposed when the coat is removed after budding is complete. This mechanism of coupling explains the phenomenon of "retrograde transport" triggered by uncouplers such as the drug brefeldin A.

ADP-Ribosylation Factors↗
PubMed1993

Stepwise assembly of functionally active transport vesicles.

Budding of COP-coated vesicles (the likely carriers of newly synthesized proteins from the endoplasmic reticulum through the Golgi stack) from Golgi cisternae requires ADP-ribosylation factor (ARF), coatomer proteins from the cytosol, GTP, and fatty acyl-coenzyme A (CoA). The assembly of coated buds on the membranes requires coatomer, ARF, and GTP. When palmitoyl-CoA is added, membrane fission occurs at the coated bud, releasing coated vesicles. We show that COP-coated vesicles can be generated stepwise in vitro and isolated in a functionally active form, demonstrating that the minimal set of cytosolic components required for their formation as well as principal steps in their assembly have been identified.

ADP-Ribosylation Factors↗
PubMed1992

Antifolding activity of hsp60 couples protein import into the mitochondrial matrix with export to the intermembrane space.

Cytochrome b2 reaches the intermembrane space of mitochondria by transport into the matrix followed by export across the inner membrane. While in the matrix, the protein interacts with hsp60, which arrests its folding prior to export. The bacterial-type export sequence in pre-cytochrome b2 functions by inhibiting the ATP-dependent release of the protein from hsp60. Release for export apparently requires, in addition to ATP, the interaction of the signal sequence with a component of the export machinery in the inner membrane. Export can occur before import is complete provided that a critical length of the polypeptide chain has been translocated into the matrix. Thus, hsp60 combines two activities: catalysis of folding of proteins destined for the matrix, and maintaining proteins in an unfolded state to facilitate their channeling between the machineries for import and export across the inner membrane. Anti-folding signals such as the hydrophobic export sequence in cytochrome b2 may act as switches between these two activities.

Base Sequence↗
PubMed1991

Etoposide in patients with previously untreated non-small-cell lung cancer: a phase I study.

In a phase I study, a range of doses of etoposide (200-370 mg/m2 given i.v. daily on 3 consecutive days) were evaluated for tolerance and response as first-line treatment in 26 patients with non-small-cell lung cancer. The dose-limiting toxicity was myelosuppression, especially leukopenia. At dose levels of 350 and 370 mg/m2 etoposide per day, leukopenia of WHO grade 4 occurred in two and one of seven patients, respectively. No thrombocytopenia of this degree was observed. Myelosuppression was quickly reversible and noncumulative. Apart from alopecia, nonhematologic organ toxicities above WHO grade 2 were not seen. Toxicity analysis suggests that the recommended dose of single-agent etoposide for phase II studies in untreated patients is 330-370 mg/m2 given i.v. daily for 3 days. At the dose levels tested, 6 (23%) major responses could be induced. All responses were seen at a starting dose of greater than 300 mg/m2 per day. The median duration of response was 4 months. The median survival for all patients was 8 months and that for responding patients was 15 months.

Aged↗
PubMed1990

Precursor proteins in transit through mitochondrial contact sites interact with hsp70 in the matrix.

We previously reported that hsp70 in the mitochondrial matrix (mt-hsp 70 = Ssclp) is required for import of precursor proteins destined for the matrix or intermembrane space. Here we show that mt-hsp70 is also needed for the import of mitochondrial inner membrane proteins. In particular, the precursor of ADP/ATP carrier that is known not to interact with hsp60 on its assembly pathway requires functional mt-hsp70 for import, suggesting a general role of mt-hsp70 in membrane translocation of precursors. Moreover, a precursor arrested in contact sites was specifically co-precipitated with antibodies directed against mt-hsp70. We conclude that mt-hsp70 is directly involved in the translocation of many, if not all, precursor proteins that are transported across the inner membrane.

Biological Transport↗