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Biomedical subjects

J M Ostrove

Publications and source records attributed to J M Ostrove.

At least 19 recordsLinked to original sources
PubMed2000

Viral shedding and biodistribution of G207, a multimutated, conditionally replicating herpes simplex virus type 1, after intracerebral inoculation in aotus.

G207 is a multimutated, conditionally replicating herpes simplex virus type 1 (HSV-1) that is currently in clinical trial for patients with malignant glioma. G207 exhibits an efficient oncolytic activity in tumor cells, yet minimal toxicity in normal tissue when injected into the brains of HSV-susceptible mice or nonhuman primates. In this study, we evaluated the shedding and biodistribution of clinical-grade G207 after intracerebral inoculation (3 x 10(7) pfu) in four New World owl monkeys (Aotus nancymae). Using PCR analyses and viral cultures, neither infectious virus nor viral DNA was detected from tear, saliva, or vaginal secretion samples at any time point up to 1 month postinoculation. Analyses of tissues obtained at necropsy at 1 month from two of the four monkeys, plus one monkey inoculated with laboratory-grade G207 (10(9) pfu) 2 years earlier, showed the distribution of G207 DNA restricted to the brain, although infectious virus was not isolated. Histopathology revealed normal brain tissues including the sites of inoculation. A measurable increase of serum anti-HSV antibody titer was observed in all monkeys, as early as 21 days postinoculation. The results ascertain the safety of G207 in the brain and indicate that strict biohazard management may not be required for G207-treated patients.

Animals↗
PubMed2000

Objective and subjective assessments of socioeconomic status and their relationship to self-rated health in an ethnically diverse sample of pregnant women.

A new measure of subjective socioeconomic status (SES) was examined in relation to self-rated physical health in pregnant women. Except among African Americans, subjective SES was significantly related to education, household income, and occupation. Subjective SES was significantly related to self-rated health among all groups. In multiple regression analyses, subjective SES was a significant predictor of self-rated health after the effects of objective indicators were accounted for among White and Chinese American women; among African American women and Latinas, household income was the only significant predictor of self-rated health. After accounting for the effects of subjective SES on health, objective indicators made no additional contribution to explaining health among White and Chinese American women; household income continued to predict health after accounting for subjective SES among Latinas and African American women.

California↗
PubMed1999

Socioeconomic status and health: what we know and what we don't.

In the past 15 years, we have seen a marked increase in research on socioeconomic status (SES) and health. Research in the first part of this era examined the nature of the relationship of SES and health, revealing a graded association; SES is important to health not only for those in poverty, but at all levels of SES. On average, the more advantaged individuals are, the better their health. In this paper we examine the data regarding the SES-health gradient, addressing causal direction, generalizability across populations and diseases, and associations with health for different indicators of SES. In the most recent era, researchers are increasingly exploring the mechanisms by which SES exerts an influence on health. There are multiple pathways by which SES determines health; a comprehensive analysis must include macroeconomic contexts and social factors as well as more immediate social environments, individual psychological and behavioral factors, and biological predispositions and processes.

Causality↗
PubMed1998

Women's personality in middle age. Gender, history, and midcourse corrections.

This article examines several key features of the course of adult development in the cohort of women born during the baby boom. By focusing on the women in this group and comparing their experience with that of older cohorts and research on men, the authors demonstrate the need for models of aging that take account of the inter-sections of history, gender, and individual development. Concepts proposed as universal features of middle age (midlife crisis, generativity, aging), as well as those proposed as specific to women (empty nest, menopause) are examined. Perhaps most important, certain features not commonly viewed as particularly important in women's middle aging (midlife review, identity, confident power) are shown to be central. The need for further research examining these same processes among men and different groups of women is underscored.

Adult↗
PubMed1998

Psychological predictors of good health in three longitudinal samples of educated midlife women.

Concurrent and longitudinal associations between cognitive and affective personality variables--intellectual efficiency (IE), anxiety, and hostility--and observer ratings of physical health were examined in 3 longitudinal samples of women: Mills Longitudinal Study (n = 101); Radcliffe Study (RS, n = 118); and University of California, San Francisco Study (n = 44). Observer ratings of health were based on participants' reports of health problems. The California Psychological Inventory (H. G. Gough, 1996) IE, Hostility, and Anxiety Scales were used in all studies at Times 1 and 2, except in RS, when at Time 1 the Zung Anxiety (W. K. Zung, 1971) and the Profile of Mood States (D. M. McNair, M. Lorr, & L. F. Droppleman, 1971) Hostility Scales were used. In the majority of analyses, IE was positively associated with good health, and Anxiety and Hostility were negatively associated with health. IE was the strongest independent predictor of health, indicating that cognitive characteristics may have an important role in health and should be examined further.

Adult↗
PubMed1997

A rapid and simple procedure to detect the presence of MVM in conditioned cell fluids or culture media.

During the manufacture of biopharmaceuticals, numerous adventitious agents have been detected in Master Cell Banks, end-of-production cells as well as bulk harvest fluid. Recently, a number of large-scale production bioreactors have become infected with Minute Virus of Mice (MVM) during cGMP (current good manufacturing practices) operations, and this has resulted in both the loss of product and the need for major cleaning validation procedures to be put in place. We have developed a simple DNA extraction/PCR assay to detect the presence of MVM in cell culture supernatant (conditioned cell fluids). This highly specific assay can detect 10 or fewer genome equivalents (copies) of MVM following PCR and gel electrophoresis visualization. For routine high-throughput detection, 300-100 copies could be consistently detected. The extraction procedure was shown to reliably detect MVM at a concentration of 1 TCID50/ml. The combination of the extraction/PCR procedure establishes a powerful, sensitive, specific assay that can detect the presence of MVM sequences with a 1-day turnaround time.

Animals↗
PubMed1997

Development of an improved product enhanced reverse transcriptase assay.

A PCR based reverse transcriptase (RT) assay was developed that has 10(4)-fold higher sensitivity than conventional nucleotide incorporation assays and allows discrimination between false positive results generated by cellular polymerases and positives resulting from authentic RT activity. Recently, several reverse transcriptase (RT) assays have been developed where a reverse transcriptase reaction is performed on an RNA template/DNA primer combination. A specific region of the cDNA product is then amplified by the polymerase chain reaction to increase the sensitivity of cDNA detection. These reverse transcriptase assays up to 10(6)-fold more sensitive at detecting retroviruses than conventional methods. The drawback to these assays with increased sensitivity is the increased incidence of false positive results generated by cellular polymerases that can reverse transcribe. The MS2 bacteriophage RNA template and primers from one of the recently developed assays were used as the basis to develop the assay. A simple high resolution agarose gel was used as the endpoint for the assay without compromising sensitivity. In addition, the pH of the RT reaction was lowered to pH 5.5, the RT incubation was 1 h, and protease inhibitors were added to the RT reaction components. These modifications yield an assay that can discriminate between authentic RT activity and contaminating cellular polymerases.

3T3 Cells↗
PubMed1997

Predicting women's well-being in midlife: the importance of personality development and social role involvements.

Theories of adult development suggest that both personality and social roles are sources of adult well-being, but most research has examined only social roles. An integrated model was used, including personality, number of roles, and role quality, to predict well-being in 2 longitudinal studies of college-educated women. Results for both samples indicated that role quality and personality development were important components of the path to well-being, whereas number of roles, occupied was important mainly in early adulthood. Moreover, the results provided support for E. Erikson's (1968) notion of the importance of the sequencing of personality development for later well-being. Path analyses indicated that engagement in multiple roles during early adulthood facilitated the development of identity, which predicted generativity and role quality, which in turn predicted well-being.

Adaptation, Psychological↗
PubMed1996

Results of MDR-1 vector modification trial indicate that granulocyte/macrophage colony-forming unit cells do not contribute to posttransplant hematopoietic recovery following intensive systemic therapy.

To formally test the hypothesis that the granulocyte/macrophage colony-forming unit (GM-CFU) cells can contribute to early hematopoietic reconstitution immediately after transplant, the frequency of genetically modified GM-CFU after retroviral vector transduction was measured by a quantitative in situ polymerase chain reaction (PCR), which is specific for the multidrug resistance-1 (MDR-1) vector, and by a quantitative GM-CFU methylcellulose plating assay. The results of this analysis showed no difference between the transduction frequency in the products of two different transduction protocols: "suspension transduction" and "stromal growth factor transduction." However, when an analysis of the frequency of cells positive for the retroviral MDR-1 vector posttransplantation was carried out, 0 of 10 patients transplanted with cells transduced by the suspension method were positive for the vector MDR-1 posttransplant, whereas 5 of 8 patients transplanted with the cells transduced by the stromal growth factor method were positive for the MDR-1 vector transcription unit by in situ or in solution PCR assay (a difference that is significant at the P = 0.0065 level by the Fisher exact test). These data suggest that only very small subsets of the GM-CFU fraction of myeloid cells, if any, contribute to the repopulation of the hematopoietic tissues that occurs following intensive systemic therapy and transplantation of autologous hematopoietic cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1993

HSV-1 activation of HIV-1 transcription is augmented by a cellular protein that binds near the initiator element.

A cellular DNA binding protein, which we term Leader Binding Protein-2 (LBP-2), binds near the transcriptional initiation site of the human immunodeficiency virus type 1 (HIV-1) promoter. This protein recognizes a motif similar to that of LBP-1, a putative repressor of transcription (Kato, H., et al., Science, 251, 1476-1479, 1991). LBP-2 is associated with transcriptional activation of HIV-1 by herpes simplex virus type 1 (HSV-1). Electrophoretic mobility shift assays showed that nuclear levels of this protein increase markedly following HSV-1 infection. Mutations of the LBP binding motif eliminate LBP-2 binding and interfere with HIV-1 activation by HSV-1. When inserted into an unrelated promoter, this motif confers transcriptional responsiveness to HSV-1 infection. Proteins that bind near the initiator element may be important regulators of HIV-1 gene expression.

Base Sequence↗
PubMed1993

Herpes simplex virus type 1 transcription is not detectable in quiescent human stromal keratitis by in situ hybridization.

PURPOSE: The purpose of this study was to determine whether herpes simplex virus (HSV) transcripts are present in the corneas of patients with chronic herpetic stromal keratitis. METHODS: Corneal buttons from patients with a history of stromal keratitis, but no ongoing active disease, together with positive and negative control tissues, were analyzed by in situ hybridization using single-stranded RNA probes for all three classes of viral lytic cycle transcripts as well as for the latency-associated transcripts (LATs). Tissues also were screened for presence of HSV genomic DNA using the polymerase chain reaction (PCR). RESULTS: HSV DNA was detected in 7 of 13 quiescent corneas by PCR, but no viral transcripts were detected in any of these corneas by in situ hybridization. CONCLUSIONS: At the level of detection afforded by in situ hybridization, HSV persistent in scarred human corneas after stromal keratitis appears to be transcriptionally dormant. This contrasts with the situation in neurons of latently infected sensory ganglia, in which LATs are present at high levels.

Animals↗
PubMed1992

Transactivation of the HIV-1 LTR by HSV-1 immediate-early genes.

Herpes simplex virus type 1 (HSV-1) activates transcription from the long terminal repeat (LTR) promoter region of the human immunodeficiency virus type 1 (HIV-1). HSV-1 immediate-early (IE) genes ICP0 and ICP4 are thought to be important mediators of this process, which is known to involve the induction of the cellular activators NF-kappa B and Sp1. We demonstrate that ICP0 and ICP4 transactivation of the LTR is largely dependent on the presence of NF-kappa B and Sp1 binding sites. However, in Jurkat CD4-positive lymphocytes, HSV-1 activates LTR constructs lacking all NF-kappa B or Sp1 Binding sequences. This effect is still evident when all sequences upstream of the TATA motif are removed. Such enhancer-independent transactivation can be produced by cotransfection of ICP0 and ICP4. Thus HSV-1 IE genes transactivate the HIV-1 LTR both through the induction of NF-kappa B and Sp1 and through another as yet undefined cellular factor.

Animals↗
PubMed1991

Detection and characterization of latent HSV RNA by in situ and northern blot hybridization in guinea pigs.

Following intravaginal infection of guinea pigs, herpes simplex virus establishes a latent infection in the sensory lumbosacral ganglia. Using the techniques of in situ and Northern blot hybridization, we have characterized this latent HSV-2 virus and compared it to latent HSV-1 at the same anatomical site. For HSV-2, a single 1.8-kb latency-associated transcript (LAT) was detected. In contrast, as described for latent HSV-1 in the trigeminal ganglia of rabbits and mice, two HSV-1 LAT species were detected in the lumbosacral ganglia, an abundant transcript of 1.8 kb and a less abundant transcript of 1.55 kb. Despite these differences in LAT expression, the clinical course of the acute and recurrent genital disease was similar for both viruses. LAT was detected in 0.3-6.0% of the sensory neurons of sacral but not in lumbar ganglia. The abundance of LAT correlated with the severity of the initial infection, but not with the frequency of recurrent disease. Thus, vaccination strategies that substantially reduced or eliminated symptomatic disease following challenge infection appeared to block the establishment of a latent infection.

Acute Disease↗
PubMed1991

Characterization of herpes simplex virus type 2 latency-associated transcription in human sacral ganglia and in cell culture.

The ability of herpes simplex virus type 2 (HSV-2) to establish latency in and reactivate from sacral dorsal root sensory ganglia is the basis for recurrent genital herpes. The expression of HSV-2 genes in latently infected human sacral ganglia was investigated by in situ hybridization. Hybridizations with a probe from the long repeat region of HSV-2 revealed strong nuclear signals overlying neurons in sacral ganglia from five of nine individuals. The RNA detected overlaps with the transcript for infected cell protein O but in the opposite, or "anti-sense," orientation. These observations mimic those made previously with HSV-1 in human trigeminal ganglia and confirm the recent findings during latency in HSV-2-infected mice and guinea pigs. Northern hybridization of RNA from infected Vero cells showed that an HSV-2 latency-associated transcript was similar in size to the larger (1.85 kb) latency transcript of HSV-1. Thus, HSV-1 and HSV-2 latency in human sensory ganglia are similar, if not identical, in terms of their cellular localization and pattern of transcription.

Adult↗
PubMed1991

Characterization of a potent varicella-zoster virus-encoded trans-repressor.

Using a transient expression assay in Vero cells, we have shown that the protein product from gene 61 of varicella-zoster virus (VZV) can repress the function of the VZV encoded trans-activators on putative viral immediate-early, early, and late gene promoters. The repression is exerted at the transcriptional level and requires functional gene 61 protein. This trans-repressor is the herpes simplex type 1 ICP0 (a trans-activator) homolog, as defined by gene location, the sharing of a cysteine-rich putative zinc-binding finger in the amino-terminal region, and limited amino acid homology. Open reading frame 61 (ORF61)-mediated trans-repression appears to be specific for VZV-encoded trans-activators in that it has no effect on simian virus 40 and Rous sarcoma virus promoters. Moreover, it does not inhibit trans-activation of the human T-lymphotropic virus type I and human immunodeficiency virus long terminal repeats by tax and tat genes, respectively. We constructed plasmids with mutations in ORF61 and tested them for their ability to inhibit trans-activator (VZV genes 4 and 62)-mediated activation of the viral thymidine kinase promoter-chloramphenicol acetyltransferase construct. Mutants containing interruptions in ORF61 lost their trans-repressing ability, as demonstrated at both the protein and steady-state RNA levels. These results suggest that the ORF61 protein product can mediate down-regulation of VZV gene expression.

Animals↗