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Biomedical subjects

S Pearlman

Publications and source records attributed to S Pearlman.

At least 19 recordsLinked to original sources
PubMed1999

Species differences in cis-elements of the proalpha1(I) procollagen promoter and their binding proteins.

Previous studies suggest that there may be species differences in the utilization of cis-elements of the type I collagen genes. The present study was designed to examine this possibility by focusing on two regions of the proalpha1(I) collagen promoter. One is the GC-rich A1 region (-194/168) that modulates transcriptional activity of the mouse promoter. The other contains a glucocorticoid response element (GRE) implicated in negative glucocorticoid regulation of the rat promoter. Unlike mouse A1 probes, probes representing the analogous human (-195/-168) and rat (-193/-179) regions failed to bind nuclear proteins in gel shift assays. Binding assays with mouse A1 probes containing base substitutions indicated that this behavior could be ascribed to five bases in the human, and two in the rat sequences. In addition, the pattern of expression of c-Krox, a protein that alters transcriptional activity via the mouse A1 element, differed in mouse and human tissues. Computer analysis revealed differences in the arrangement of GRE half-sites in human and rat proalpha1(I) collagen promoters. In a region of the human promoter (-700/673) analogous to the rat (-672/-633), there are three half-sites, each separated by two nucleotides, that cooperate in binding of glucocorticoid receptor. There also is a proximal half-site at position -335 of the human promoter that binds glucocorticoid receptor, but it is not present in the rat promoter. This study has defined several species-specific differences in the sequences and nuclear protein binding activity of regions involved in transcriptional activity of the proalpha1(I) collagen promoter. The results suggest that the A1 regions of the human and rat promoters examined here are unlikely to function as regulatory cis-elements, and they provide a framework for investigating the role of GREs in transcriptional regulation. They also suggest that species differences in cis-elements and transcription factors should be taken into consideration when using heterologous systems to study collagen gene regulation.

3T3 Cells↗
PubMed1998

The test-retest reliability of the frequency of multiple drug use in young drug users entering treatment.

Assessment of multiple drug use relies primarily on self-report. Several studies support the reliability of client self-reports of drug use but these studies have not involved assessment of the actual frequency of drug use. This test-retest reliability study assessed the frequency of drug use in a clinical sample of 103 multiple drug users, aged 16-25 years. At initial assessment, all participants completed the Drug Use History Form (DUHF) that inquired about the number of drug-using days and the daily frequency of use for 13 drug classes during four time intervals. The DUHF was readministered 2-4 weeks later. Reliability was assessed using Intra-class correlations (ICC's). The results indicated that clients do, in general, reliably report both the number of days of use and daily frequencies. The two frequency measures were not highly correlated. Reliability estimates declined over time but most markedly after 90 days, suggesting that assessments of drug use can be reliably extended beyond 30 days. Frequency estimates based solely on the number of days of use of a substance may be unreliable estimates of actual drug consumption, indicating limitations to this commonly used outcome measure.

Adolescent↗
PubMed1997

Characteristics of 73 patients, 1984-1993, treated by plasma exchange for Guillain-Barre syndrome.

Acute Guillain-Barre syndrome (GBS) is a demyelinating polyneuropathy which responds readily to plasma exchange (PEX). According to the North American Acute GBS PEX study there is a 50% or more reduction in the recovery time if PEX is initiated early in the course of the disease. Demyelinating antibodies are usually IgM. IgA antibodies require prolonged PEX. Patients with predominant IgG antibodies have chronic inflammatory demyelinating polyneuropathy (CIDP), which requires an even longer course of PEX, over weeks to months or years. We reviewed records of 73 patients with the initial diagnosis of GBS treated with PEX. Among these patients, 55 had classic GBS, three had the Miller-Fisher variant, two had CIDP, and 13 had demyelinating-like polyneuropathies associated with other conditions including malignancy, vaccine-related myelitis, steroid-induced myopathy, polymyositis, botulism, gram-negative sepsis, Sjogren's, and AIDS. Hughes grading system was used. Patients were graded 3 to 5, with grade 3 patients being unable to walk 5 m without support, grade 4 patients being bed or chair bound, and grade 5 patients being ventilator dependent. Of 60 unassociated (GBS) demyelinating cases receiving a mean of 6.5 PEX procedures, 13 (21%) were intubated early in the treatment, with four (6%) remaining ventilator dependent post-PEX. Of 51 non-intubated patients, 15 became ambulatory post-PEX. Patients with the Miller-Fisher variant showed improvement within 6 hours of PEX initiation. We did not investigate correlation of GBS with infection; however, we did observe a rise in CMV titer among 15% of the 58 patients with acute GBS. Considering our results we believe that intensive PEX on a daily basis for a few days is necessary for severely affected individuals. We advise five to nine procedures at consultation unless early, rapid recovery occurs.

Adolescent↗
PubMed1996

Moderate expansion of a normally biallelic trinucleotide repeat in spinocerebellar ataxia type 2.

The gene for spinocerebellar ataxia type 2 (SCA2) has been mapped to 12q24.1. A 1.1-megabase contig in the candidate region was assembled in P1 artificial chromosome and bacterial artificial chromosome clones. Using this contig, we identified a CAG trinucleotide repeat with CAA interruptions that was expanded in patients with SCA2. In contrast to other unstable trinucleotide repeats, this CAG repeat was not highly polymorphic in normal individuals. In SCA2 patients, the repeat was perfect and expanded to 36-52 repeats. The most common disease allele contained (CAG)37, one of the shortest expansions seen in a CAG expansion syndrome. The repeat occurs in the 5'-coding region of SCA2 which is a member of a novel gene family.

Amino Acid Sequence↗
PubMed1996

Time course of endothelial dysfunction and neutrophil adherence and infiltration during murine traumatic shock.

Traumatic shock in rats has been shown to induce endothelial dysfunction, and to increase intestinal myeloperoxidase activity (MPO) indicative of neutrophil infiltration. To examine the time course of endothelial dysfunction and neutrophil adherence and infiltration, pentobarbital anesthetized rats, subjected to Noble-Collip drum trauma, were studied prior to and 15, 30, 60, 90, 120, 150, and 180 min following drum trauma. Superior mesenteric artery rings obtained from traumatized rats were tested for responsiveness to acetylcholine (ACh), a receptor-mediated endothelium-dependent vasodilator, and to NaNO2 an endothelium-independent vasodilator. ACh-induced relaxation was not impaired immediately after the induction of trauma (time 0). However, 15-30 min after trauma, responses to ACh were significantly depressed (p < .05) and were further reduced (p < .01) 90-180 min after trauma. No significant changes occurred in response to the direct vasodilator NaNO2 at any of the times studied, indicating no vascular smooth muscle injury. Moreover, the adherence of polymorphonuclear leukocytes (PMNs) to the post-traumatic mesenteric vascular endothelium also showed an increase that peaked 30 min post-trauma. Intestinal MPO activity, indicative of neutrophil infiltration, was characterized by a continuous and sustained increase from 30-180 min. Our findings suggest that endothelial dysfunction resulting in reduced NO release occurs in the early phase of murine traumatic shock, and that this phenomenon is followed by a time-dependent increase in adhesivity of neutrophils to the vascular endothelium leading to a progressive accumulation of PMNs in injured tissues (e.g., intestine).

Animals↗
PubMed1994

Durable remissions following prolonged plasma exchange in thrombotic thrombocytopenic purpura.

We evaluated the efficacy of prolonged plasma exchange (PEX) for attaining durable remissions in thrombotic thrombocytopenic purpura (TTP). A recent review using steroids or PEX in initial management showed an 80% response rate but produced a relapse rate of 67-84%. Records of 50 patients starting PEX treatment for TTP/HUS were reviewed to identify and select those whose course of treatment had ended over 1 year earlier, whether or not the result was satisfactory. Records were evaluated for outcome, especially remission associated with treatment by "prolonged" plasma exchange. "Prolonged" was defined as continuing PEX beyond the stage where a normal platelet count was attained and until evidence of hemolysis was "minimal or at least compensated." If disease activity as judged by the criteria of hemolysis became accelerated or resumed, PEX was increased by volume of FFP (e.g., from 3 to 4 L) or rate (from less than daily to daily). Of 50 consecutive patients treated by PEX for TTP/HUS there were 40 cases after which at least one year had passed since the end of treatment. These 40 patients were evaluated for the results of treatment by PEX. Eight failed to achieve remission, dying in hospital within 1 month of admission. Twenty-eight achieved remission, sustained for 1 year or more in all. These are the reasons for our enthusiasm about this report. Four achieved remission lasting less than 1 year. Splenectomy was performed to obtain a sustained remission in one patient following administration of three 2 mg doses of vincristine and two relapses.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Striatal implants of fetal striatum or gelfoam protect against quinolinic acid lesions of the striatum.

Previous studies in our laboratory have shown that intrastriatal implants of fetal striatum significantly attenuate excitotoxic damage resulting from a 240 nmol quinolinic acid (QA) challenge delivered 7 days later. In contrast, animals with intrastriatal implants of other tissue types (adipose tissue, peripheral nerve or adrenal medulla) demonstrate a more limited, but consistent trend in protection from QA excitotoxicity. The present study was designed to test the hypothesis that partial striatal protection found in animals receiving peripheral tissue grafts is due to the transplantation procedure eliciting a host response which attenuates excitotoxicity. Adult female Long-Evans rats received either cellular (fetal striatum) or acellular (gelfoam) implants followed 1 week later by a unilateral injection of 240 nmol QA into the grafted striatum. Animals were tested for rotational asymmetries before grafting, post-implantation, and after lesioning. Compared to baseline rotational behavior, rats which received implants did not show changes in ipsilateral turning after QA lesions. This protective effect was not limited to rotational behavior since improvements in spontaneous locomotor activity were evident. In addition, the adipsia and aphagia often associated with striatal lesions were ameliorated in both groups of grafted animals. Morphometric analysis demonstrated that endogenous dopaminergic, cholinergic and enkephalinergic systems in the two transplanted groups sustained less excitotoxic damage than in the QA lesioned, non-grafted animals. These results are consistent with the hypothesis that a host generated response activated by the implantation procedure provides a protective effect against QA excitotoxicity.

Animals↗
PubMed1993

Detection of simian immunodeficiency virus and human immunodeficiency virus type 2 capsid antigens by a monoclonal antibody-based antigen capture assay.

We have tested the ability of a monoclonal antibody-based simian immunodeficiency virus (SIV) p27 capsid antigen assay to detect SIV antigen in supernatants from a variety of infected cell cultures. The antigen capture assay has a sensitivity of approximately 30 pg of SIV p27 capsid antigen/ml. The assay detected SIV p27 capsid antigen in cell culture supernatants from all six strains tested, detected the replication of SIV following the inoculation of the virus in peripheral blood mononuclear cell cultures earlier compared to reverse transcriptase assay, and was more sensitive in detection of the SIV antigen compared to human immunodeficiency virus type 1 (HIV-1) antigen capture assays. The SIV antigen capture assay was used to detect SIV antigen from serum samples and tissue cultures from eight of eight SIVB670-infected rhesus macaques (Macaca mulatta). Similar samples from four control rhesus macaques were negative when tested by the assay. The SIV antigen was detected in virus-infected monkeys during early time periods following inoculation (1 to 3 weeks) or during episodes of CD4+ lymphocytopenia and clinically evident disease. In addition, the SIV antigen capture assay positively identified each of three different HIV-2 strains in cell culture supernatants. The SIV antigen capture assay provides a sensitive and specific method to monitor SIV and HIV-2 capsid antigen in cell cultures and from infected animals. The assay will be an important tool in the utilization of SIV and HIV-2 primate models for HIV-induced acquired immunodeficiency disease syndrome.

Animals↗
PubMed1992

Development of a monoclonal antibody-based p24 capsid antigen detection assay for HTLV-I, HTLV-II, and STLV-I infection.

A monoclonal antibody-based antigen capture enzyme-linked immunosorbent assay (ELISA) was developed and employed to detect p24 capsid antigen from human T-cell lymphotropic viruses type I and II (HTLV-I, HTLV-II), simian T-cell lymphotropic virus type I (STLV-I)-infected cell lines, and from mononuclear cell cocultures of HTLV-infected humans and STLV-I infected monkeys. A monoclonal antibody specific for HTLV p24 and p53 capsid antigens was coated onto 96-well microtiter plates to capture HTLV/STLV antigen. Captured antigen was then detected by the addition of a polyclonal, biotinylated human anti-HTLV-I antibody, and color developed with tetramethyl benzidine/H2O2 substrate. As little as 15 pg/ml of HTLV-I p24 antigen could be detected in this assay. Culture supernatants from HTLV-I-infected cell lines (HUT-102, MT-2, C5/MJ, HTLV-II-infected cell lines (Mo-T, Mo-B, PanG 12.1, NRA) and STLV-I-infected cell lines (Matsu, NEPC M39) were all positive in the assay. In addition, p24 was detected from peripheral blood mononuclear cell (PBMC) cocultures of 8 of 8 (100%) HTLV-I diseased patients, 14 of 20 (70%) HTLV-I and HTLV-II-infected, asymptomatic persons, and 8 of 8 (100%) STLV-I-infected, asymptomatic monkeys. Culture supernatants of cells infected with human immunodeficiency virus type (HIV-1), simian immunodeficiency virus (SIV), Chlamydia trachomatis, cytomegalovirus (CMV), herpes simplex I and II (HSV), feline leukemia virus (FELV), bovine leukemia virus (BLV), and bovine immunodeficiency virus (BIV) were all negative. Similarly, normal human peripheral blood mononuclear cells and uninfected, transformed human T cells, were also negative in the assay.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗
PubMed1989

The comparability of solicited versus clinic subjects in alcohol treatment research.

The increasing use of media advertisements to recruit subjects in alcohol treatment research has raised concerns about the comparability of such solicited subjects and subjects drawn from more traditional clinic populations. This paper, based on a study that involved both solicited and clinic subjects, identifies differences between the two types of subjects in terms of sociodemographic variables; pre-treatment drinking and marital adjustment; several dimensions of 'self-definition'; and three outcome measures. These findings suggest that there may be significant differences between solicited and clinic subjects and that these differences should be taken into account in the design of studies utilizing solicited subjects in order to determine the generalizability of the results.

Adult↗
PubMed1983

Reducing attrition from conjoint therapy with alcoholic couples.

Premature termination of treatment by the client has been a pervasive problem in the alcohol treatment field. This drop-out problem is compounded in conjoint therapy for alcoholic couples since most clients typically do not view the drinking problem from a systemic, interactional perspective. Within a short-term communication-interaction based conjoint therapy program offered to couples with an alcohol problem on an outpatient basis, specific mechanisms were developed to deal with client-initiated attrition from treatment. These procedures involve the systematic involvement of the spouse in all aspects of intake, assessment and treatment; the use of role induction in a pretherapy interview; and formal contracting during the beginning phase of therapy. Preliminary results suggest that these efforts may be effective in retaining more socially stable alcoholic clients. For the more transient, less socially stable group of individuals with alcohol-related difficulties, the above mechanisms may not be sufficient to forestall unplanned terminations. It is suggested that the latter group may require help to reduce stresses related to concrete concerns prior to receiving conjoint therapy for their alcohol problem.

Adult↗
PubMed1980

Cytology and colposcopy in the diagnosis and management of outpatients with cervical intraepithelial neoplasia.

One hundred consecutive outpatients seen in the colposcopy clinic of a private hospital had one or more Papanicolaou smears that suggested cervical atypia, dysplasia or carcinoma in situ. Of these 100 patients, 7% underwent a diagnostic cervical cone biopsy; 11% more had therapeutic conization. The accuracy of colposcopic examination with directed cervical biopsy within one level (under or over) of histologic findings was 88%; the cytologic accuracy within one level of histologic findings was 83%. The study showed that patients with cervical atypia at cytologic examination had dysplasia and carcinoma in situ at subsequent colposcopic cervical examination with directed biopsy.

Carcinoma in Situ↗