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Biomedical subjects

A Lerner

Publications and source records attributed to A Lerner.

At least 19 recordsLinked to original sources
PubMed1992

Differential regulation of T-cell receptor processing and surface expression affected by CD3 theta, an alternatively spliced product of the CD3 zeta/eta gene locus.

The T-cell receptor (TCR) is a multisubunit complex consisting of the clonotypic Ti alpha and beta (or Ti gamma and delta) subunits and the invariant CD3 gamma, CD3 delta, CD3 epsilon, CD3 zeta, and CD3 eta subunits. Herein, we describe an additional product from the CD3 zeta/eta gene locus which we have termed CD3 theta. The cDNA derives from the first seven exons common to CD3 zeta and CD3 eta, 94 base pairs (bp) of the CD3 eta-specific exon 9 and an additional exon 10 encoding the carboxyl-terminal 15 amino acids and the 3'-untranslated region. The expression of CD3 theta is equivalent to that of CD3 eta in tissue distribution and level of expression as judged by RNase protection analysis. Despite the identity of the amino-terminal 121 amino acids of CD3 zeta, CD3 eta, and CD3 theta and an additional 31 amino acids shared between CD3 eta and CD3 theta, transfection of CD3 theta into the CD3 zeta- eta- T-cell hybridoma, MA5.8, failed to restore detectable surface TCR expression in contrast to transfection with CD3 zeta or CD3 eta. Analysis of the CD3 theta protein in transfectants indicated that CD3 theta is associated with the TCR intracellularly. However, unlike with CD3 zeta, Ti alpha-beta chains remain endoglycosidase H sensitive, suggesting a role for the unique COOH-terminal segment of CD3 theta in mediating TCR retention and/or degradation in a pre-Golgi compartment.

Alternative Splicing↗
PubMed1992

Human genomic sequences corresponding to murine CD3 eta-related transcripts: lack of conservation or expression of homologous human products.

We have cloned and sequenced human genomic DNA homologous to exons 9 and 10 of the CD3 zeta/eta/theta locus. Although there are open reading frames within the human sequences corresponding to the translated portions of murine exons 9 and 10, we find no evidence of conservation of the encoded polypeptide product. Furthermore, using oligonucleotides derived from these homologous sequences, we are unable to detect human CD3 eta- or CD3 theta-like transcripts by polymerase chain reaction amplification of reverse-transcribed RNA from a variety of human lymphoid tissues. Despite the absence of evidence for conservation of human CD3 eta and CD3 theta, there is a surprising degree of similarity between human and murine nucleotide sequences, not only for exons 9 and 10 (78% and 70%, respectively), but also for the 9/10 intron (71%). A possible mechanism for this conservation is discussed.

Animals↗
PubMed1992

[3H]dopamine uptake by platelet storage granules in schizophrenia.

[3H]Dopamine (DA) uptake by platelet storage granules was determined in 26 schizophrenic male patients, paranoid type (14 acute stage; 12 in remission) and 20 age-matched, normal controls. Maximum velocity (Vmax) of DA uptake was significantly higher in acute patients, than patients in remission or controls (p less than 0.05). The apparent Michaelis constant (Km) of DA uptake in acute patients was also significantly different from chronic patients (p less than 0.05). Preincubation with reserpine (10(-4), 10(-5) M) produced a substantial diminution of DA uptake, while haloperidol (10(-4), 10(-5) M) did not affect the assay. Considering that a DA dysequilibrium in schizophrenia may be expressed not only in the brain, but also in the periphery and that an increased amount of DA accumulated in the vesicles, implies that an increased quantity of catecholamine is available for release, our findings suggest additional evidence for the role of DA overactivity in the pathophysiology of this disorder.

Adult↗
PubMed1992

Etoposide, doxorubicin, and cisplatin chemotherapy for advanced gastric adenocarcinoma: results of a phase II trial.

PURPOSE: A phase II study of etoposide, doxorubicin, and cisplatin (EAP) therapy in patients with advanced gastric carcinoma was performed in an attempt to confirm encouraging results reported by German investigators using an identical EAP regimen. PATIENTS AND METHODS: Thirty-six consecutive, previously untreated patients with surgically unresectable, measurable gastric carcinoma were treated every 28 days with etoposide (120 mg/m2, days 4, 5, and 6), doxorubicin (20 mg/m2, days 1 and 7), and cisplatin (40 mg/m2, days 2 and 8). A total of 108 courses of treatment was given. RESULTS: Therapy was associated with myelosuppression (median granulocyte nadir, 239/microL; median platelet nadir, 81,000/microL), which reached its maximum 14 days after the start of therapy and necessitated hospitalization after 24 of 108 (22%) treatment courses. Four of 36 (11%) patients died of treatment-related toxicity: three from sepsis and one from hemorrhage. Objective responses were observed in 12 of 36 (33%) patients; three (8%) patients experienced a clinical complete response. The median time to progression was 4 months for all 36 patients and 8 months for the 12 responding patients. Of the 13 patients with localized but unresectable disease, five subsequently underwent surgical resection; only one of these five was rendered disease-free. CONCLUSION: The EAP regimen is highly toxic and results in response rates and survival times no better than those of more easily tolerated treatment programs.

Adenocarcinoma↗
PubMed1992

T-cell-receptor isoforms.

Early work on T-cell hybridomas lacking the T-cell-receptor (TCR) sub-unit CD3 eta had suggested a correlation between the presence of CD3 zeta-eta heterodimers and signalling leading to phosphatidyl-inositol (PI) turnover as well as activation-induced cell death. The cloning of CD3 eta has now allowed thorough and direct analysis of the signal transduction properties of CD3 zeta-zeta-, CD3 zeta-eta- and CD3 eta-eta-containing TCRs. We have found that all forms of the TCR are capable of transducing signals leading to PI turnover, Ca2+ mobilization, IL-2 production and cell-cycle arrest. CD3 zeta and CD3 eta utilize the same promoter which yields coordinate expression of both products, so that restricted CD3 eta expression in a sub-population of thymocytes is unlikely. Immunohistochemical methods employing an anti-CD3 eta-specific monoclonal antibody (MAb) show no detectable staining of thymic sections from adult mice, implying at best a low level of constitutive CD3 eta expression. In contrast, CD3 eta expression is readily detected in the majority of cortical thymocytes of CD3 eta transgenic mice using a Thy-1 promoter construct. However, over-expression of CD3 eta in mice transgenic for this polypeptide does not result in increased negative selection in vivo, consistent with the in vitro findings that induction of cell death is not strictly dependent on CD3 eta. Despite earlier reports of the detection of human CD3 eta protein, we find no CD3 eta message in human thymus or T cells. Cloning of the human CD zeta-eta genomic locus has demonstrated approximately 70% homology between the mouse and human genomic sequence, corresponding to the mouse CD3 eta-specific exon. However, translation of the DNA sequence does not result in a homologous amino acid sequence. Thus, there does not appear to be a CD3 eta protein in humans.

Animals↗
PubMed1992

Short term versus long term psychotherapy in opioid dependence: a pilot study.

A multicenter prospective open study was performed in order to compare the effectiveness of 2 modalities of individual dynamic psychotherapy in a group of recently detoxified opioid dependent patients. Thirty four patients were assigned to receive either short-term dynamic psychotherapy (ST) or long-term dynamic psychotherapy (LT); both modalities were offered along with drug counselling. At the end of the treatment, the short term therapy group was followed up for 2 years, while the long term therapy group continued the follow up for one year, due to the different time span of the treatment approaches. Dropout rates for ST (47%) and LT (53%) patients were similar, and the re-entry rate for the ST group was superior (62.5% vs. 28.5%). Short term interventions appear to be at least as effective as long term interventions, and have the advantage of a high rate of program re-entry. Further studies conducted on larger samples are needed.

Adult↗
PubMed1992

A naltrexone double blind placebo controlled study in Israel.

In a double blind study, out of 31 newly abstinent patients who underwent opioid free detoxification, 15 were started on the opiate antagonist Naltrexone for 2 months, and 16 were put on placebo for the same period. Given Naltrexone's known efficacy in blocking euphorigenic effects of opioid intake, and in decreasing cravings for the drug, the authors have tried to assess eventual drug taking, specifically in the context of suburban housing projects, and evaluate the rate of retention in a rehabilitative program for both the Naltrexone and placebo groups. An Opioid free condition was followed up for a year, also respecting double blind conditions. Naltrexone did not appear to be superior to the placebo with regards to retention rate. In the Naltrexone group (n = 15), 9 finished the two-month treatment, and 8 remained opioid-free for a year. In the placebo group (n = 16), 8 finished the 2 month trial and 6 remained opioid-free for a year. Naltrexone blocked opioid-induced euphoria and decreased the craving for opium, but it did not inhibit drug usage. The retention rate registered during the course of the study, as well as an opioid-free condition in the follow-up year, correlated with a patient profile defined by good social functioning and stable relationships. The inherent methodological limitations of this study did not allow for the discrimination of the role of non-pharmacological factors, such as psychotherapy, supportive family framework, community assistance, and staff motivation, concerning the clinical results. Further investigation of Naltrexone in larger samples is needed.

Adult↗
PubMed1991

The temporal bone in the Johanson-Blizzard syndrome. A CT study.

The findings of thin-section high-resolution CT of the temporal bone in two children with Johanson-Blizzard syndrome are reported. In both cases an anomaly of the inner ear was found, consisting of bilateral cystic dilatation of the cochlea and the vestibulum. The possible etiologic basis for the hearing loss in this syndrome is discussed and the literature is reviewed.

Child↗
PubMed1991

Pitfall in diagnosis of Crohn's disease in a cystic fibrosis patient.

Cystic fibrosis (CF) and Crohn's disease may both present as failure to thrive and recurrent intestinal obstruction. Proper treatment and adequate nutrition may reverse these manifestations and improve the patient's quality of life. We describe a girl with CF who, despite appropriate management, failed to grow and had several episodes of bowel obstruction. After the additional diagnosis of Crohn's disease was reached, the patient improved on antiinflammatory and nutritional therapy. This patient illustrates the pitfall in the diagnosis of Crohn's disease in a CF patient due to the clinical overlap between the two conditions. We suggest that therapeutic failure in a chronic disease justifies additional diagnostic efforts resulting in a completion of diagnosis and significant changes in management.

Child↗
PubMed1990

Immunology of celiac disease: tissue and species specificity of endomysial and reticulin antibodies.

Patients with celiac disease and dermatitis herpetiformis have circulating antibodies to reticulin and endomysium, the 'extracellular matrix' components as defined by their detection on rodent and primate tissues, respectively. Because both types of antibodies occur in both forms of gluten-sensitive enteropathy, studies were conducted to determine if the two types of antibodies can be distinguished by species and organ specificity. The results of these studies indicate that distinct endomysium-specific and reticulin-specific antibodies can be found and that these differ in their species specificity; i.e., endomysium antigen occurs in primate and not in rodent tissues while the reticulin antigen occurs in rodent and not in primate tissues. However, the activity of both endomysium and reticulin antibodies demonstrates similar tissue distribution, in that both react to antigens associated with gastrointestinal smooth muscles, peritubular and periglomerular areas of the kidney, and sinusoidal and periportal areas of the liver. Also, both antigens seem to be present in sheep and goat tissue. These studies indicate that the antigens reactive with endomysial antibodies are distinct from those reactive with reticulin antibodies.

Animals↗
PubMed1990

Transient inhibitory seizures mimicking crescendo TIAs.

Somatic inhibitory seizures are thought to occur rarely. We describe a patient with somatic inhibitory seizures who initially presented with a clinical picture of crescendo transient ischemic attacks. He did not improve with anticoagulation, but the episodes ceased promptly after the administration of an anticonvulsant.

Aged↗
PubMed1989

Pgp-1hi T lymphocytes accumulate with age in mice and respond poorly to concanavalin A.

Aging is associated with an accumulation of T cells functionally hyporesponsive to the effects of mitogens such as concanavalin A. Recent studies in mice and human have identified surface markers useful for distinguishing antigen-stimulated memory T cells from virgin T cells. In mice, memory T cells within the CD8+ cell population have been shown to express relatively high levels of the cell surface glycoprotein Pgp-1. On the theory that aging might diminish the supply of virgin thymic emigrants without compromising the production of memory T cells, we examined the proportion of Pgp-1hiCD4+ and CD8+ cells in the spleen, blood and lymph nodes of mice of varying age. We found a dramatic (2.5-fold) age-associated increase in the percentage of cells with the Pgp-1hi phenotype. By limiting dilution methods, the frequency of concanavalin A-responsive T cells was found to be significantly reduced in the Pgp-1hi cell pool, whether measured by interleukin 2-dependent proliferation, interleukin 2 production or generation of cytotoxic effectors. Pgp-1hi and Pgp-1lo T cells from young mice proliferate equally well when stimulated by optimal doses of phorbol myristate acetate and ionomycin suggesting that the poor responses to concanavalin A do not simply reflect low viability. Aging leads both to an increase in mitogen-hyporesponsive Pgp-1hi T cells, and also to lower responsiveness of cells in the Pgp-1hi subset.

Aging↗