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Biomedical subjects

K Meyers

Publications and source records attributed to K Meyers.

At least 37 records · Page 2Linked to original sources
PubMed1996

Immunohistochemical staining of fixed tissue using antigen retrieval and a thermal cycler.

The use of monoclonal antibodies to identify antigens in perfused fixed tissue is currently very challenging. Recently, many antigen retrieval methods have been described that require heating the tissue on slides using a microwave oven. Here, we describe a protocol for antigen retrieval that uses a commercially available solution called Citra and a DNA thermal cycler to heat the tissue sections. This method (i) allows for precise control of the temperature and time (unlike the microwave oven), (ii) uses very small quantities of the antigen retrieval solution, (iii) stains either free-floating sections or sections mounted on slides and (iv) achieves uniform staining throughout the tissue. In the paraformaldehyde-perfused fixed rat cerebellum, the monoclonal antibody glial fibrillary acidic protein conveys the clarity of the Bergmann and stellate glia in the strata. Scanning confocal images through the center of the tissue demonstrates the depth of antibody penetration achieved using this method. Finally, using a monoclonal antibody against the simian virus 40 (SV40) T antigen allowed positive, unequivocal identification of a grafted cell line, immortalized using SV40 T protein, thus demonstrating the true value of this method in an experimental paradigm.

Aldehydes↗
PubMed1995

Will preventive HIV vaccine efficacy trials be possible with female injection drug users?

This article examines whether preventive HIV vaccines trials will be viable among female injection drug users (IDUs). Of the 137 women who completed baseline serologic and behavioral assessments, 121 (88%) were seronegative; all enrolled in Project Jumpstart in Philadelphia (PA, U.S.A.), a vaccine preparedness initiative cosponsored by NIAID and NIDA. Subjects were seen every 3 months for risk and vaccine opinion assessment, risk reduction counseling, and HIV antibody testing. The baseline prevalence rate of HIV infection was 12% (16 of 137) with an annual incidence rate of 3.5% (4 of 114) during the first year. Of the 121 baseline seronegative women, 28% shared needles and 52% engaged in unprotected intercourse. Sixty percent of the baseline seronegative women reported being willing to be one of the first people to try an HIV vaccine. According to logistic regression, needle sharers were 12.8 times more likely, women who engaged in sex for drugs or money 6.6 times more likely, out-of-treatment women 3.5 times more likely, and those who believed that vaccines can prevent disease acquisition 3 times more likely to report willingness to try an HIV vaccine than their respective counterparts. At 1-year postbaseline assessment, 98% of the women had behavioral data collected and 95% had serologic specimens collected. Given that seroconversions occur and that these women engage in risk behaviors, report willingness to try an HIV vaccine, and can be retained for longitudinal assessment, they appear to be suitable participants for preventive HIV vaccine efficacy trials. Nonetheless, work is required to insure that these women make informed and knowledgeable decisions regarding trial enrollment.

AIDS Vaccines↗
PubMed1995

Cancer awareness and self-examination practices in young men and women.

Participants in this study (N = 178) were poorly informed about risk factors, warning signs, and self-examination (SE) practices for two common cancers in young adults, testicular cancer in men and breast cancer in women. Compared to women, men were less likely to know about, see the importance of, or practice SE. We found no relationship between internal locus of control, hypochondriasis, and loneliness, on the one hand, and cancer knowledge and SE, on the other. The best predictors of cancer awareness and SE were fear of developing cancer and self-rated confidence that SE was being done correctly. The results are consistent with a health belief model and self-efficacy theory of health behavior.

Adolescent↗
PubMed1995

Long-term changes in psychological symptomatology associated with HIV serostatus among male injecting drug users.

OBJECTIVE: To examine long-term changes in psychological symptomatology from 6 to 24 months after notification of HIV serostatus among male injecting drug users (IDU). DESIGN: Self-report and interview data were collected at 6-month intervals as part of a longitudinal study monitoring HIV infection and risk-associated behaviors among IDU. SETTING: A community-based methadone-maintenance clinic. PARTICIPANTS: Ninety-seven male IDU (81 HIV-seronegative, 16 HIV-seropositive), including both methadone-maintained and out-of-treatment IDU. MAIN OUTCOME MEASURES: Analyses of long-term changes in psychological symptomatology associated with HIV serostatus among male IDU. RESULTS: Analyses of long-term changes in psychological symptomatology between groups revealed no significantly greater levels of overall psychological distress or significant elevations on subscales of the Symptom Checklist-90 for HIV-seropositive compared with HIV-seronegative male IDU. Also, no significantly higher scores on the Beck Depression Inventory or the psychiatric composite score of the Addiction Severity Index were observed between groups. CONCLUSIONS: Our results suggest that HIV-seropositive male IDU do not express greater levels of psychological symptomatology from 6 to 24 months following notification of seropositivity compared with HIV-seronegative male IDU. Several explanations for these findings are considered. Future work should examine why male IDU do not report significant and long-term elevations in symptoms post-notification of HIV seropositivity. Also, studies of changes in psychological symptomatology as a function of HIV serostatus among female IDU need to be conducted to assess implications for treatment interventions among this underserved population.

Adult↗
PubMed1995

Formation of the arterial media during vascular development.

We are still in the earliest stages of studying the molecular biology of vascular development. Key questions, even simple questions, such as the origin of endothelial precursors from the epiblast or the mesoderm, remain largely unanswered. For the smooth muscle cell, we do not even have a satisfactory molecular definition of cell type, because the known cell type-specific markers generally disappear when these cells are placed in vitro, and even in vivo smooth muscle cells identified by location can be very undifferentiated. A few bright spots illuminate this cloudy prospect. We do have endothelial lineage markers, and, given the powerful tools of promoting analysis, it seems likely that we will soon known a lot more about the identification of the endothelial lineage. It is hoped that this will help us understand how patterns of development of the vessel wall are controlled. Similarly, the failure of our early studies to identify molecules responsible for investment by smooth muscle can be seen as an exciting finding. If platelet-derived growth factor, fibroblast growth factor, and transforming growth factor beta are not expressed until after smooth muscle investment, still other as yet unidentified factors must be present to account for this stage of development of the vessel wall.

Animals↗
PubMed1995

Comparison of the nitric oxide synthase inhibitors methylarginine and aminoguanidine as prophylactic and therapeutic agents in rat adjuvant arthritis.

OBJECTIVE: To compare the nitric oxide synthase (NOS) inhibitors NG-methyl-L-arginine (L-NMA) and aminoguanidine (AG) as prophylactic and therapeutic agents in rat adjuvant induced arthritis (AIA). METHODS: Arthritis was induced in male Lewis rats by the injection of adjuvant into the base of the tail. L-NMA or AG was administered twice daily by gastric intubation starting at the time of adjuvant injection, just before the onset of clinical symptoms, or after the onset of clinical symptoms. Paw swelling, plasma fibrinogen levels and urinary NO2-/NO3- excretion were measured to assess the effect of the inhibitors on the arthritis response and whole body NO biosynthesis. Selected joints were also evaluated histopathologically. The abilities of L-NMA, AG and another NOS inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), to inhibit NO production by chondrocytes and synoviocytes were also compared. RESULTS: Treatment with L-NMA (400 mg/kg/day) or AG (500 mg/kg/day) reduced the urinary excretion of NO2-/NO3- to the control level. L-NMA suppressed the development of AIA when administered prophylactically; however, its antiarthritic properties declined with increasing delay of application. It was only weakly effective against established AIA. AG had neither a prophylactic nor a therapeutic antiarthritic effect. AG and L-NAME were much weaker inhibitors of NO production by chondrocytes and synoviocytes than L-NMA. CONCLUSION: Although L-NMA completely suppresses the development of AIA when administered prophylactically, it is much less effective when administered therapeutically. Furthermore, not all inhibitors of NOS show equal prophylactic activity against AIA. In addition, NOS inhibitors may be only weakly therapeutic, or even detrimental, in established disease. These findings should be considered when evaluating NOS inhibitors as potential therapeutic agents for the treatment of established human arthritis.

Animals↗
PubMed1994

N-monomethyl arginine, an inhibitor of nitric oxide synthase, suppresses the development of adjuvant arthritis in rats.

OBJECTIVE: To test the hypothesis that nitric oxide (NO) is involved in the pathophysiology of arthritis. METHODS: Arthritis was induced in male Lewis rats by the injection of adjuvant into the base of the tail. The NO synthase (NOS) inhibitor, NG-monomethyl-L-arginine (L-NMA), was administered daily by the oral route for 19 days. Paw swelling, plasma fibrinogen levels, and urinary NO2/NO3 levels were measured to assess the effect of L-NMA on the arthritic response and whole-body NO production, respectively. On day 20, the ankle joints were processed for histopathologic evaluation. RESULTS: The onset of clinical symptoms was preceded by elevated biosynthesis of NO. In a dose-dependent manner, L-NMA inhibited both NO biosynthesis and paw swelling; histopathologic changes in the ankle joints were also prevented. D-NMA had no effect on the development of arthritis, while L-arginine reversed the effects of L-NMA. Fibrinogen levels in rats with arthritis were unaffected by L-NMA. CONCLUSION: NO is critical to the development of both the inflammatory and erosive components of adjuvant arthritis in rats. There may be a future clinical role for suitable inhibitors of NO production or activity.

Amino Acid Oxidoreductases↗
PubMed1994

Temporal patterns of human immunodeficiency virus type 1 transcripts in human fetal astrocytes.

Human immunodeficiency virus type 1 (HIV-1) infection of the developing central nervous system results in a dementing process in children, termed HIV-1-associated encephalopathy. Infection of astroglial elements of the pediatric nervous system has been demonstrated and suggests that direct infection of some astrocytes may contribute to the neurologic deficit. In this model, HIV-1 establishes a persistent state of infection in astrocytes, which can be reactivated by the cytokines tumor necrosis factor alpha (TNF-alpha) and interleukin 1 beta (IL-1 beta). To better understand the natural history of viral persistence in astroglial cells, we characterized infection at the transcriptional level. The most abundant viral transcript during the establishment of persistence was the subgenomic multiply spliced 2-kb message, similar to mononuclear cell models of HIV-1 latency. Following reactivation with TNF-alpha or IL-1 beta the multiply spliced 2-kb message remained the most abundant viral transcript, in contrast to infected mononuclear cells in which reactivation leads to the reemergence of the 9- and 4-kb transcripts. Further characterization of the persistent 2-kb transcript by PCR amplification of in vitro-synthesized viral cDNA showed that, in the absence of cytokine stimulation, the most abundant multiply spliced transcripts were the Nef- and Rev-specific messages. However, following cytokine stimulation, double- and triple-spliced Tat-, Rev-, and Nef-specific messages could be identified. Immunohistochemical staining demonstrated that, during viral persistence, astrocytes expressed Nef protein but few or no viral structural proteins. These results demonstrate that viral persistence in astrocytes at the transcriptional level is fundamentally different from that seen in mononuclear cells and could account for the virtual absence of astroglial expression of viral structural antigens in vivo.

Astrocytes↗
PubMed1994

HIV vaccine trials: will intravenous drug users enroll?

OBJECTIVES: The purpose of this study was to assess the willingness of intravenous drug users to participate in a preventive human immunodeficiency virus (HIV) vaccine efficacy trial. METHODS: Of the 347 intravenous drug users in methadone treatment who were approached for participation, 257 completed a battery of self-administered questionnaires assessing risk behaviors, interest in vaccine trials, and other vaccine-related information. Data from 16 known seropositives and 1 inconsistent responder were dropped from analyses (n = 240). RESULTS: Fifty-two percent of the subjects expressed a willingness to be one of the first individuals to participate in a preventive HIV vaccine efficacy trial. Subjects who had recently shared needles or works and subjects who trusted the government to ensure vaccine safety were both twice as likely to report interest in participation. Twenty-two percent of subjects reported that they would increase needle sharing if vaccinated. Thirty percent did not know what a vaccine was. CONCLUSIONS: These findings suggest that some in-treatment intravenous drug users would volunteer for a preventive HIV vaccine efficacy trial. Education and counseling will be required to ensure that subjects fully understand the trial's purposes, methods, risks and benefits.

AIDS Vaccines↗
PubMed1993

Transformation of NIH3T3 cells with ras oncogenes abrogates the retinoic acid induction of tissue transglutaminase.

Retinoic acid greatly increases enzyme activity and mRNA expression of the tissue-type transglutaminase enzyme in NIH3T3 cells. This response is blocked in cells transformed with activated H-ras, K-ras or N-ras oncogenes, but not in pSVneo vector transfected cells. Lack of induction by RA of the tissue-type TGase in these ras-transformed fibroblasts suggests intersecting pathways between retinoid action and the ras oncogene.

3T3 Cells↗
PubMed1993

Inpatient vs outpatient treatment for substance dependence revisited.

Miller and Hester's 1986 review of inpatient versus outpatient alcohol treatment studies concluded with no "justification" for inpatient treatment. Further examination of these studies revealed shortcomings such as the use of random assignment designs which excluded psychiatrically-complicated patients. Carrier Foundation's inpatient/outpatient study of private psychiatric patients with alcohol and/or cocaine dependence includes a patient-treatment matching design to address weaknesses in the existing literature. Patients with high psychiatric severity and/or a poor social support system are predicted to have a better outcome in inpatient treatment, while patients with low psychiatric severity and/or a good social support system may do well as outpatients without incurring the higher costs of inpatient treatment. Preliminary results from 183 inpatients and 120 outpatients indicated outpatients, regardless of level of psychiatric severity, were 4 times more likely to be early treatment failures (chi-square = 41.2, df = 1, p < .01). While the determination of long-term follow-up status of early treatment failures is currently underway, this finding underscores the potential risk of early treatment failure in outpatient compared to inpatient substance abuse treatment programs and the importance of addressing the issue of early attrition in conducting outcome analyses.

Ambulatory Care↗
PubMed1992

Detection of JC virus DNA in peripheral lymphocytes from patients with and without progressive multifocal leukoencephalopathy.

Progressive multifocal leukoencephalopathy (PML) results from lytic infection of oligodendrocytes by JC virus (JCV). Although JCV has been identified in mononuclear cells in bone marrow and hematogenous dissemination of the virus to the central nervous system has been suspected, JCV has never been clearly demonstrated in the peripheral circulation. Using polymerase chain reaction technology, we examined peripheral lymphocytes of 19 patients with brain biopsy-proven PML for the JCV genome. Two non-PML control groups, consisting of 26 patients seopositive for human immunodeficiency virus type 1 (HIV-1) and 30 immunocompetent patients with Parkinson's disease, were also examined for the presence of the JCV genome in lymphocytes. Cerebrospinal fluid from 10 patients with PML was examined for the presence of the JCV genome as well. The JCV genome was detected in the lymphocytes of 89% (17) of the patients with PML, 38% (10) of the HIV-1-seropositive patients without PML, and none of the patients with Parkinson's disease. Sequencing of the JCV regulatory region from the lymphocytes of three patients revealed the prototype MAD-1 strain of JCV in one patient with PML, a MAD-4 strain in a second patient with PML, and a slightly modified MAD-4 strain in an HIV-1-positive patient without PML. Only 3 of 10 patients with PML who had JCV detected in lymphocytes had the JCV genome in their cerebrospinal fluid. These results demonstrate that the JCV genome can be found in circulating lymphocytes from patients with PML and suggest that lymphocytes are an important vector for hematogenous dissemination of JCV to the central nervous system.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗
PubMed1991

Platelets and coagulation.

Hemostasis is a multiple-component system. In order to function properly it has become highly integrated with several strategies of control. Failure of the system or its control can result in life-threatening hemorrhage requiring transfusion. It is hoped that the information provided in this article has enhanced the reader's understanding of hemostasis in animals, and will enable the reader to make a more educated choice concerning transfusion therapy for the bleeding patient.

Animals↗