Search PubMed⌕ Search

Biomedical subjects

R Resnick

Publications and source records attributed to R Resnick.

At least 19 recordsLinked to original sources
PubMed1989

Structural and functional characterization of the unusually short long terminal repeats and their adjacent regions of a novel endogenous avian retrovirus.

We have cloned the long terminal repeats and their flanking regions from four different proviruses belonging to a large, highly conserved, novel family of avian endogenous retroviruses. This family, termed the endogenous avian retrovirus (EAV) family, is distinct from the previously characterized avian endogenous and exogenous retroviruses. We have analyzed the sequences of the long terminal repeats and their adjacent noncoding viral sequences, including the gag leader region and the 3' noncoding region, of several different members of the EAV family and have found that the regulatory region of these novel viruses contains several unique features. The LTRs of the EAV proviruses are extremely short (243 bp long) but contain all of the essential regulatory features of longer avian retrovirus LTRs. The gag leader region and the 3' noncoding region of the novel EAVs are only weakly related to those of other avian retroviruses. Northern blot hybridization analysis of RNA from Line-0 chicken embryos reveals several transcripts derived from the EAV proviruses. Primer extension analysis indicates that all transcripts initiated from 5' proviral LTRs are initiated at the predicted +1 position within the EAV LTRs. The relative shortness, sequence divergence from other known LTRs, and the retention of the transcriptional integrity of the EAV LTRs make these LTRs an interesting model system for LTR function and for study of the potential involvement of such highly conserved retroviral elements in development.

Animals↗
PubMed1989

Decreased susceptibility of a 70-kDa protein to cathepsin L after phosphorylation by protein kinase C.

A 70-kDa protein is phosphorylated in cell-free preparations from rat or mouse fibroblasts by an endogenous protein kinase. This protein is immunologically related to a group of 68-kDa to 87-kDa proteins described in the literature as substrates for protein kinase C (PK-C). Although the phosphorylation of the 70-kDa protein by isolated plasma membranes takes place in the presence of EGTA, we conclude that the reaction is catalyzed by PK-C based on its inhibition by staurosporin. As shown previously, pure PK-C phosphorylates a synthetic random polymer of arginine and serine in the absence of Ca2+ and lipids, a reaction markedly stimulated by an endogenous unidentified activator of PK-C. When the 70-kDa protein from normal fibroblasts was exposed to the cytosol of chemically or ras-transformed fibroblasts, it disappeared as measured by phosphorylation by added PK-C. Cytosol of normal fibroblasts was much less effective (ca. 20%). Cathepsin L purified from rat kidney or from the medium of transformed cells had an effect similar to that of the cytosol of transformed cells. When the 70-kDa protein was phosphorylated by PK-C prior to exposure to cathepsin L or to the cytosol of transformed cells, there was a marked protection of the 70-kDa protein. We conclude that the 70-kDa protein is degraded by cathepsin L as ascertained by both immunological and biochemical assays and that it is protected by prior phosphorylation with PK-C. The possible role of this effect in signal transduction is discussed.

Alkaloids↗
PubMed1986

Naltrexone and Alzheimer's disease.

Naltrexone, an oral opiate antagonist, was administered to nine patients with a diagnosis of Alzheimer's-type dementia (ATD) in a two-phase design: an open dose-ranging phase and a double-blind placebo-controlled trial for patients who showed improvement during the open phase. After a three day placebo (baseline) period, patients received increasing doses of naltrexone over two weeks up to a maximum daily dose of 100 mg. Assessments were made at baseline and at daily dose of 5 mg, 50 mg and 100 mg. Testing was done 2 to 4 hours after medication was administered. Any patient who showed cognitive/behavioral improvement on a given dose of naltrexone was then treated with this dosage in a double-blind crossover comparison to placebo. Criteria for inclusion in the double-blind phase consisted of improvement on three behavioral scales and at least one cognitive test on a given dose of naltrexone. Each double-blind phase followed a one-week washout and was two weeks long. Two of the nine patients demonstrated apparent cognitive enhancement on 100 mg daily of naltrexone and were then tested in the double-blind crossover period. Only one of these patients improved during active naltrexone administration. We conclude that the opiate antagonist naltrexone in a dosage range of 5-100 mg daily is not efficacious in ATD.

Alzheimer Disease↗
PubMed1986

Molecular cloning and characterization of gag-, pol-, and env-related gene sequences in the ev- chicken.

Using less stringent hybridization conditions and cloned viral DNA probes representing the avian sarcoma virus gag, pol, env, and long terminal repeat (LTR) gene sequences, we detected related sequences in two avian species purportedly lacking all endogenous avian leukosis viruses, the ev- chicken and the Japanese quail. The blot hybridization patterns obtained with the various probes suggest the presence of between 40 and 100 copies of retrovirus-related sequences in the genomes of these two species. An ev- chicken genomic DNA library was prepared and screened with gag-specific and pol-specific DNA probes. Several different clones were obtained from this library and characterized. Analysis of these clones revealed that the retrovirus-related gene sequences are linked in the order LTR-gag-pol-env-LTR, a structure indicative of a complete provirus. These data indicate the presence of previously unidentified endogenous retrovirus species in avian cells, suggesting that under the appropriate conditions of hybridization additional, more distantly evolved families of endogenous retrovirus genes may be identified in vertebrate species.

Animals↗
PubMed1984

Alternative induction and crossover schedules for methadyl acetate.

Various schedules exist for inducting heroin addicts newly admitted to treatment into methadyl acetate maintenance and crossover schedules for the transition from methadone maintenance to methadyl acetate maintenance. A sample of 255 street addicts was randomized to three induction schedules: methadyl acetate three times a week (tiw) with placebos on alternate days; methadyl acetate tiw supplemented with decreasing doses of methadone on alternate days; methadyl acetate six days a week with diminishing doses on three days. Treatment was double-blind for four weeks and single-blind for six. All schedules were considered feasible, but supplementation with methadyl acetate or methadone had no advantage. A sample of 310 patients receiving methadone maintenance was randomized to comparable supplementation groups, except that the group receiving supplementary methadyl acetate received it along with the regular dose. This schedule was not successful. Supplementing with methadone had no advantage.

Adolescent↗
PubMed1984

Evidence for involvement of an RNA primer in initiation of strong-stop plus DNA synthesis during reverse transcription in vitro.

Employing enzymatic reactions in vitro, we have identified the presence of oligoribonucleotides at the 5' end of strong-stop plus [(+)] DNA. Similar results were obtained whether the strong-stop (+) DNA was synthesized by preparations of detergent-disrupted avian sarcoma virus or reconstructed reactions containing purified reverse transcriptase and a template that mimics the purported natural template for strong-stop (+) DNA synthesis. The latter reactions provide a system to delineate more precisely the discrete requirements necessary for the initiation and synthesis of this species of (+) DNA.

Animals↗
PubMed1984

Involvement of retrovirus reverse transcriptase-associated RNase H in the initiation of strong-stop (+) DNA synthesis and the generation of the long terminal repeat.

Reconstructed enzymatic reactions containing purified reverse transcriptase and defined analog substrates which mimic those purported to be natural substances for reverse transcription in vivo were employed to delineate the mechanism of strong-stop (+) DNA synthesis. Our analysis of this system has indicated that strong-stop (+) DNA synthesis is initiated after the introduction of a nick in the viral RNA genome between a polypurine sequence and an inverted repeat that represents the end of the long terminal repeat. Since inhibitors of the reverse transcriptase-associated RNase H activity prevent the introduction of the nick and the synthesis of strong-stop (+) DNA synthesis, it appears that this particular reverse transcriptase-associated enzymatic activity is responsible for the initiation of strong-stop (+) DNA. Our data also indicated that the RNase H activity creates a second nick in the viral RNA genome 11 nucleotides upstream from the strong-stop (+) DNA initiation site since the strong-stop (+) DNA synthesized in these reactions is covalently linked to an oligoribonucleotide 11 residues in length. Nucleotide sequence analysis of the oligoribonucleotide primer molecule indicated that a single homogenous oligomer was associated with strong-stop (+) DNA exhibiting the sequence rArGrGrGrArGrGrGrGrGrA. The oligoribonucleotide primer can be removed from strong-stop (+) DNA by the purified reverse transcriptase, which creates a nick at the junction between the primer and strong-stop (+) DNA. These data demonstrate that the initiation of strong-stop (+) DNA synthesis is mediated by RNase H and that the site of initiation is exactly at the end of the long terminal repeat, providing evidence for yet another function of this reverse transcriptase-associated enzymatic activity in the synthesis of retrovirus DNA.

Animals↗
PubMed1978

Methadone dose, plasma level, and cross-tolerance to heroin in man.

The development of cross-tolerance between methadone and heroin was studied in postaddict volunteers who had been drug-free for at least 6 weeks. Two methadone dose schedules were used; each was employed in six subjects. One schedule brought the subjects to a dose of 40 mg, while the other brought them to 80 mg of methadone a day. Subjects received injections of heroin (0.214 mg/kg) and placebo at various times before and during methadone treatment. Pupillary and subjective effects of injections were measured. Plasma levels of methadone were determined concurrently. Subjects on both treatment schedules developed an incomplete cross-tolerance to this dose of heroin. As the dose and plasma level of methadone increased with time, the cross-tolerance to all heroin effects increased. Plasma levels did not affect the development of cross-tolerance independently of methadone dose. The most important contribution to the cross-tolerance to pupillary effects was made by the duration of methadone treatment. Furthermore, the cross-tolerance to the subjective effects of heroin developed earlier than that to the pupil effect.

Adult↗
PubMed1976

Clinical experiences with naltrexone in 370 detoxified addicts.

Our studies have shown no evidence of toxicity and few side effects from naltrexone. It is a valuable adjunct in treating addicts who wish to be opiate free. Patients who drop out and return to treatment tend to remain longer with each successive readmission. Naltrexone has special potential for persons, such as an opiate-abusing physician for whom methadone maintenance is clearly inappropriate. A double-blind study has suggested that it may have value as a transitional treatment for detoxified methadone maintenance patients. Differences between naltrexone and cyclazocine suggest that a treatment combining these drugs should be explored.

Clinical Trials as Topic↗
PubMed1975

Methadone in man: pharmacokinetic and excretion studies in acute and chronic treatment.

The biologic disposition of methadone in acute and during chronic administration was studied in 12 human volunteers. In the acute study a biexponential methadone plasma level decay was observed. The acute primary half-life (t1/2) of 14.3 hr in combination with the acute secondary t1/2 of 54.8 hr were longer than the single exponential chronic t1/2 of 22.2 hr determined in the same subjects. The urinary and fecal excretion of methadone and its mono-N-demethylated metabolite increased from 22.2% in the acute to 62.0% in the chronic phase of the study. The urinary metabolite 1 to methadone ratio tripled from the acute to the chronic phase. The pupillary effects of methadone monitored throughout 24 hr were nearly the same in magnitude in the acute and the chronic studies, whereas the plasma levels increased 3- to 8-fold following chronic methadone administration. These findings suggest that both dispositional and pharmacologic tolerance are involved in the development of tolerance following chronic administration of methadone.

Adult↗