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Biomedical subjects

D Metzger

Publications and source records attributed to D Metzger.

At least 73 records · Page 4Linked to original sources
PubMed1994

The basic domain of the lentiviral Tat protein is responsible for damages in mouse brain: involvement of cytokines.

The HIV and visna lentiviruses induce an inflammatory reaction in the central nervous system (CNS) of the infected hosts leading to dysmyelination, demyelination, and neuronal loss. The basic domain of the transactivating Tat protein has been involved in CNS damage. Infusion of basic containing domain Tat peptides in the lateral ventricle (systemic injection) or in the grey matter, i.e., hippocampus and thalamus (local injection), induced an inflammatory process characterized by the formation of an edema and invasion of macrophage accompanied by reactive astrogliosis. Control peptides originating from either lentiviral proteins or irrelevant protein as ovalbumin did not lead to any inflammatory reaction or cell death. The inflammation led to the loss of ependymal cells in the lateral ventricles and neurons in the grey matter. RNA extracted from the Tat-injected hemisphere reacted with TNF-alpha, IL-1 alpha and beta, and IL-6 probes. The macrophage/microglia inducible nitric oxyde synthase was also expressed. Blockade of TNF-alpha by a pentoxifylline treatment led to the decrease of IL-1 and iNOS expression accompanied by a reduction of the volume of the lesions indicating that the Tat-induced lesions might be mediated by TNF production.

Amino Acid Oxidoreductases↗
PubMed1994

Anti-neutrophil cytoplasm antibodies (ANCA) in rheumatoid arthritis: relationship to HLA-DR phenotypes, rheumatoid factor, anti-nuclear antibodies and disease severity.

To investigate a possible relationship between the presence of anti-neutrophil cytoplasm antibodies (ANCA), rheumatoid factors (RF), anti-nuclear antibodies (ANA), disease severity and HLA-DR phenotypes, 46 consecutive ANCA+ and 48 ANCA-, clinically well-documented RA patients were studied for RF, ANA and HLA-DR phenotypes. The 46 ANCA+ patients showed predominantly an atypical perinuclear staining pattern (89%). ANCA positivity was associated with higher RF titres (P < 0.005) and advanced functional Steinbrocker grades III/IV (P < 0.015). ANCA+ patients were also more often positive for ANA than ANCA- patients (P < 0.008). There was no correlation between ANCA positivity and certain HLA-DR phenotypes although the frequency of DR4+ (67% vs 52%) and, in particular, of DR4+ blanks (phenotypically homozygous) was increased in ANCA+ as compared to ANCA- patients (20% vs 8%). DR4-DR1-RA patients were twice as frequent in the ANCA- than in the ANCA+ group (22.9% vs 8.7%). Correspondingly, the DR4+DR1- phenotype was increased among ANCA+ RA patients. Regarding functional Steinbrocker grades, the DR4+ phenotypes were slightly but not significantly increased in grades III and IV whereas ANCA positivity was significantly associated with severe functional Steinbrocker grades III/IV (66% ANCA+ vs 39% ANCA-, P < 0.015). ANCA positivity identified a population of RA patients with a long-standing and severe clinical course of the disease. There was no correlation between ANCA positivity and certain HLA-DR phenotypes.

Adult↗
PubMed1994

Involvement of alpha- and beta-noradrenergic receptors in the effects of hippocampal vasopressinergic treatment on retrieval and relearning.

Biochemical investigations show that vasopressin interacts with noradrenalin to potentiate noradrenalin-induced accumulation of cyclic-AMP in the hippocampus, via the beta-adrenergic receptors. We previously showed in BALB/c mice that the effects of vasopressin (bilaterally injected at a 25-pg dose) in the ventral hippocampus were more effective than in the dorsal hippocampus on the retrieval and relearning of a Go-No Go visual discrimination task. Considering our results and those reported by biochemical investigations, we evaluated possible noradrenergic-vasopressinergic interaction in the ventral hippocampus under our behavioral conditions. To do so, we first explored the effects of propranolol and phentolamine, antagonists of beta- and alpha-adrenergic receptors, respectively. Second, we assessed the modifications in the vasopressin-induced improvement of retrieval and relearning by pretreating the subjects with either propranolol or phentolamine. Third, we tested the treatments in a locomotor activity task to determine whether the effects demonstrated in the two preceding experiments could be partially due to locomotor alterations by the drug. The results indicated that bilateral injection of propranolol (1 microgram on each side), which did not appear to affect the retention performance itself, completely blocked the enhancement of retrieval and relearning resulting from the vasopressin treatment. In contrast, bilateral injection of phentolamine (1 microgram on each side), which moderately improved retrieval, enhanced the vasopressin effect. The present results lend further support to the view that both noradrenalin and vasopressin play important roles in retrieval and relearning processes. More importantly, they provide additional support for the functional interaction of the noradrenergic and vasopressinergic hippocampal systems.

Animals↗
PubMed1994

Preparations for AIDS vaccine trials. An automated version of the Risk Assessment Battery (RAB): enhancing the assessment of risk behaviors.

Our primary objective during this pilot work has been to determine if the computerized RAB can be used in place of the paper-and-pencil version with an IDU population. As stated, reliability estimates in the form of correlations of risk scores between the two versions ranged from .82 to .94, and percentages of exact agreement of the scoreable items ranged from 88% to 100%. These correlations indicate that the C-RAB is comparable to the RAB in its psychometric properties. Further, subjects' positive ratings of the computer program and perceptions that it would better protect confidentiality indicate that this population would participate in assessments involving computer interactions. While these self-reports may be biased on clients' desire to be cooperative and the novelty of the assessment approach, the high level of approval ratings suggest that a majority of participants do prefer completing assessments on the computer. Similarly, participants' demonstrated ability to use the computer and their rating of the program as easy to use suggest that the C-RAB has potential to be a reliable and efficient tool in assessing risk behaviors among IDUs enrolled in HIV vaccine trials.

AIDS Vaccines↗
PubMed1993

Modulation of transcriptional activation by ligand-dependent phosphorylation of the human oestrogen receptor A/B region.

Using a transient co-transfection system, we show that the human oestrogen receptor (hER) becomes phosphorylated in the presence of oestradiol (E2) as well as in the presence of the anti-oestrogens 4-hydroxy-tamoxifen (OHT) and ICI 164, 384 (ICI), although at lower efficiencies than with E2. There are multiple sites of phosphorylation in hER; using deletion and point mutants one of these sites has been mapped in the N-terminal A/B region at serine 118. Mutation of this serine to alanine caused, in a number of cell types, a significant reduction in transcriptional activation by hER from reporter genes containing an oestrogen response element (ERE), but did not affect the DNA binding properties or nuclear localization of hER. Thus phosphorylation of serine 118 is important for the action of the transcription activation function 1 (AF-1) located in the A/B region of the oestrogen receptor.

Amino Acid Sequence↗
PubMed1993

Effect of changes in the intrahippocampal vasopressin on memory retrieval and relearning.

Previous results have indicated the involvement of the hippocampus in the behavioral effect of vasopressin, with a better effect when the peptide was injected in the ventral part rather than in the dorsal part of this structure. The purpose of the present study was to determine, in mice, whether the injection of vasopressin or vasopressin antisera into the ventral hippocampus has an effect on retrieval and relearning of a Go-No Go visual discrimination task and, if so, to what extent this involvement of the vasopressin system depends on the integrity of the medial amygdaloid nucleus, the main source of vasopressin innervation in the ventral hippocampus in rats. In the first experiment, we showed that pretest microinjection of Arg8-vasopressin (25 pg per animal) in the ventral hippocampus alleviated forgetting observed after a prolonged interval of 24 days between the acquisition of information and its retrieval. This enhancing effect was characterized by better retrieval and relearning in vasopressin-treated mice than those in control mice. Conversely, an immunoneutralization of endogenous vasopressin in the ventral hippocampus by the microinjection of vasopressin antisera (1/10 dilution) resulted in the drastic impairment of retrieval and relearning. Since the lack of an observable change in a locomotor activity test might explain these results, we postulated that the vasopressin system in the ventral hippocampus is involved in retrieval processes. Moreover, the effects of these treatments in a nonassociative context suggest that the effect of vasopressin could be dependent on the contextual paradigm used. In the second experiment, we localized vasopressin immunoreactive fibers in the CA1-CA2 ventral hippocampal fields and CA4-gyrus dentatus region, and vasopressin perikarya in the medial amygdaloid nucleus. Then, the projection of vasopressin cells from the medial amygdaloid nucleus to the ventral hippocampus was evaluated by studying changes in vasopressin immunoreactive fiber density in the ventral hippocampus after a lesion of the medial amygdaloid nucleus. The results showed the almost complete disappearance of vasopressin fibers in the CA1-CA2 hippocampal fields after the medial amygdaloid lesion. In contrast, vasopressin fibers in the CA4 and gyrus dentatus region remain unchanged. On the basis of our immunohistochemical results, our third experiment tested the repercussions of the change in vasopressin innervation in the ventral hippocampus, due to the medial amygdaloid lesion, on the effects of exogenously administered vasopressin on both retrieval and relearning processes. The medial amygdaloid lesion induced a deleterious effect on retrieval without really affecting the ability to relearn. No observable change in locomotor activity could explain this impairment.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1993

Production and characterization of monoclonal antibodies recognising defined regions of the human oestrogen receptor.

Mouse monoclonal antibodies were raised against the N-terminal (amino acids 151-165) and the very C-terminal (amino acids 578-595) regions of the human oestrogen receptor (hER). These antibodies recognise the hER by enzyme-linked immunosorbent assay, immunocytochemistry, immunoblotting, immunoprecipitation and gel retardation assays. The presence of hER is used prognostically in human breast cancer. We have tested the reactivity of our monoclonal antibodies on breast cancer sections, comparing with the commonly used Abbott rat monoclonal antibody H222. These studies show that the two monoclonal antibodies described here are highly versatile and will be useful tools for in vivo and in vitro studies of hER function. Furthermore, we show that the corresponding epitopes can be used as molecular "tags" for heterologous proteins and offer a powerful means of purifying and/or characterizing over-produced fusion proteins containing these regions.

Amino Acid Sequence↗
PubMed1993

Determinants of condom use among intravenous drug users.

OBJECTIVE: To examine the factors associated with condom use among a cohort of sexually active intravenous drug users (IVDU). DESIGN: Data were collected via personal interview at the fourth-month assessment point of a longitudinal study monitoring HIV infection and risk behaviors among IVDU. SETTING: A community-based methadone clinic. PARTICIPANTS: A total of 158 sexually active heterosexual male and female IVDU, including both methadone patients and out-of-treatment individuals with a history of opiate abuse. MAIN OUTCOME MEASURES: We describe a new approach to identify the determinants of condom use. Previous studies have described subjects as either 'condom users' or 'condom non-users', using an individual's overall behavior as the unit of analysis. By analyzing condom use during the most recent sexual encounter, we avoided the problem of interpreting inconsistent condom use. Data were analyzed using forward stepwise logistic regression. RESULTS: Thirty-four per cent of the heterosexual subjects (n = 160) reported using a condom during their last sexual encounter. Being HIV-positive and having either a causal or commercial partner were each associated with increased probability of using a condom (odds ratio, 10.6, 4.4 and 12.1, respectively). No interactions with sex were found. CONCLUSIONS: Our results suggest that knowing that one is HIV-positive is an important determinant of condom use; HIV testing may therefore increase the use of condoms. In addition, interventions to change sexual behaviors may need to focus on the type of sexual partner.

Adult↗
PubMed1993

[Anti-neutrophil-cytoplasmic antibodies in rheumatoid arthritis: specificity and clinical relevance?].

Sera of 90 patients fulfilling the criteria of the American Rheumatism Association for the rheumatoid arthritis (RA) were screened for antibodies against neutrophil cytoplasmic antigens (ANCA) by an indirect immunofluorescence test. All sera were also tested for rheumatoid factor (Waaler-Rose-Test, WRT), C-reactive protein (CRP), antinuclear autoantibodies (ANA) on HEp-2 cells. 40% of the 90 sera showed ANCA-positive reactions. c-ANCA and p-ANCA types were both observed but the latter was by far more common (91%). The peculiarity of the p-ANCA pattern was a fine granular perinuclear staining. Antibodies against myeloperoxidase (MPO) were negative in all RA sera tested. So far we found a significant relationship between positive ANCA staining, functional Steinbrocker grades, and rheumatoid factor. No significant correlation was observed with extraarticular manifestation, CRP, therapeutic modalities (gold) or MHC antigens. Currently the nature of the neutrophil antigen involved is under investigation.

Arthritis, Rheumatoid↗
PubMed1992

Promoter specificity of the two transcriptional activation functions of the human oestrogen receptor in yeast.

We have previously demonstrated that the human oestrogen receptor (hER) contains two transcriptional activation functions located in the N-terminal region (TAF-1) and in the hormone binding domain (TAF-2), which can act both independently and synergistically in a promoter- and cell-specific manner in animal cells. We have also demonstrated that hER can activate transcription from chimaeric oestrogen-responsive GAL1 promoters in yeast, and shown that transcriptional activation was due to TAF-1, whereas TAF-2 showed little, if any, transcriptional activity on these promoters. By using a more complex promoter derived from the URA3 gene, we now show that TAF-2 is also active in yeast, and that the activities of TAF-1 and TAF-2 are promoter-context-specific in yeast. We also confirm that the agonistic activity of 4-hydroxytamoxifen (OHT) can be ascribed to the activity of TAF-1.

Base Sequence↗
PubMed1992

The Fifth Edition of the Addiction Severity Index.

The Addiction Severity Index (ASI) is 12 years old and has been revised to include a new section on family history of alcohol, drug, and psychiatric problems. New items were added in existing sections to assess route of drug administration; additional illegal activities; emotional, physical, and sexual abuse; quality of the recovery environment; and history of close personal relationships. No changes were made in the composite scoring to maintain comparability with previous editions. This article discusses the clinical and research uses of the ASI over the past 12 years, emphasizing some special circumstances that affect its administration. The article then describes the rationale for and description of the changes made in the ASI. The final section provides "normative data" on the composite scores and severity ratings for samples of opiate, alcohol, and cocaine abusers as well as drug abusing inmates, pregnant women, homeless men, and psychiatrically ill substance abusers.

Adolescent↗
PubMed1992

Mechanisms of antihormone action.

The mechanisms of action of two types of anti-hormones is discussed. Type I anti-hormones comprise the antiestrogen hydroxy-tamoxifen and the antiprogestin RU486, both of which promote DNA binding of the cognate receptors and, due to the activity of one of the two transcription activation functions of the estrogen and progesterone receptors, act as mixed agonist/antagonists. Evidence supporting that ICI 164,384 is also a member of the same group is presented. Type II antagonists impair DNA binding of the corresponding receptor in vitro and, in some cases, also in vivo. Ligand-mapping, an approach to identify the site of interaction of a steroid substitution within the hormone-binding domain of the receptor has been used to identify the 11 beta-pocket of the progesterone receptor and revealed that a single amino acid is responsible for the differential antagonistic effect of RU486 in man, chicken and hamster.

Animals↗
PubMed1992

A new measure of substance abuse treatment. Initial studies of the treatment services review.

This paper describes the development and initial testing of the Treatment Services Review (TSR). The TSR is a 5-minute, technician-administered interview that provides a quantitative profile of the number and types of treatment services received by patients during alcohol and drug abuse rehabilitation. Test-retest studies indicated satisfactory reliability administered either in person or over the phone. Tests of concurrent validity showed the ability to discriminate different levels of treatment services and good correspondence with independent measures of treatment provided. While additional studies are still needed with this instrument, the data collected thus far suggest that the TSR may serve two types of needs. First, at the programmatic level, the TSR may prove useful in describing and comparing programs in terms of the nature and number of services actually delivered to patients. At the individual patient level, the TSR may offer a means of evaluating the "match" between a patient's needs and the services actually provided.

Comprehensive Health Care↗
PubMed1992

High-risk sexual behaviors of intravenous drug users in- and out-of-treatment: implications for the spread of HIV infection.

This paper examines the sexual behaviors of 255 intravenous drug users (IVDUs) to assess the potential for the sexual transmission of HIV and to examine differences in sexual behaviors between in- and out-of-treatment IVDUs. In-treatment subjects (N = 152) were a random sample of clients at a large, publicly funded methadone maintenance program. Out-of-treatment subjects (N = 103) were recruited through a chain referral technique, using the in-treatment subjects. Forty-five percent of the study subjects reported multiple partners and 32% reported exchanging sex for money or drugs in the preceding 6 months. Fifty-three percent reported no use of condoms. After controlling for demographic differences between the in- and out-of-treatment groups, out-of-treatment IVDUs reported significantly more partners than in-treatment IVDUs (4.6 vs 2.3, significant t < 0.01), and more often had exchanged sex for money or drugs (44 vs 26%, relative odds 1.8, p < .05). In- and out-of-treatment subjects did not differ with respect to condom use. We conclude that IVDUs both in- and out-of-treatment continue to be at risk of contracting and spreading HIV infection through sexual behaviors, and that being in drug treatment is associated with a lower incidence of high risk sexual behaviors.

Acquired Immunodeficiency Syndrome↗