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Biomedical subjects

M Seligman

Publications and source records attributed to M Seligman.

At least 19 recordsLinked to original sources
PubMed1999

[Deficiency of the CD3-TCR signal pathway in three patients with idiopathic CD4+ lymphocytopenia].

Idiopathic CD4+ lymphocytopenia (ICL) is a rare syndrome affecting adults and defined by a stable loss of CD4+ T cells in the absence of any known cause of immune deficiency. Defective T-cell proliferations to mitogens and antigens have been described in some of such patients displaying clinical signs of immune deficiency such as opportunistic infections. We investigated here the hypothesis that T-cell depletion and dysfunction could be due to biochemical defects of the CD3-TCR pathway in CD4+ and/or CD8+ subsets from three patients with severe stable ICL (below 150 CD4+ T cells/microliter) and opportunistic infections. Patient 1 had a general T lymphocytopenia, whereas patients 2 and 3 displayed a selective loss of CD4+ T cells. We observed in all patients a major reduction of the proliferative response to CD3-TCR stimulation that affected only the depleted T-cell subpopulation. Moreover, in two cases, impaired early biochemical events of the CD3-TCR pathway were detected. In patient 1 and 3, we found a defect (of distinct intensity) of CD3-induced protein tyrosine phosphorylation in CD4+ cells compared to control cells, whereas this process was normally induced in CD4+ T cells from patient 2. Taken together, this study reveals that the heterogeneity of the ICL syndrome was situated at the cellular level, and involved in two cases abnormalities of transducing molecules of the CD3-TCR pathway.

Aged↗
PubMed1996

Sequential parenteral and oral ciprofloxacin regimen versus parenteral therapy for bacteremia: a pharmacoeconomic analysis.

OBJECTIVE: To compare, in patients with gram-negative bacteremia, a course of parenteral antibiotic therapy alone with initial parenteral therapy followed by oral ciprofloxacin in terms of the length of hospitalization, clinical effectiveness, toxicity, and cost. DESIGN: A prospective, controlled, randomized, open trial in select hospitalized patients. SETTING: Large metropolitan teaching hospital. PATIENTS: Fifty hospitalized patients with proven gram-negative bacteremia were randomized to receive either oral ciprofloxacin (group 1) following a 72-hour initial intravenous antibiotic regimen or to continue parenteral therapy alone (group 2). To compare the length of hospitalization, an additional group of 50 hospitalized patients with bacteremia (not enrolled in the study, group 3) were analyzed. INTERVENTION: Parenteral antibiotics for 72 hours followed by continuation of a parenteral regimen or oral ciprofloxacin 750 mg bid. MAIN OUTCOME MEASURES: Clinical response, toxicity, and length of hospitalization. RESULTS: Clinical resolution was comparable in the 24 group 1 patients receiving intravenous antibiotics followed by oral ciprofloxacin (83%), the 26 group 2 patients receiving parenteral therapy alone (77%), and the 50 comparison patients (76%). There was little toxicity noted in any group, and the initial parenteral antibiotic regimens were similar. The mean numbers of hospital days on antibiotics were 9.1, 11.2, and 10.6 days in groups 1,2, and 3, respectively (p < 0.05 for group 1 vs. group 2 or 3), and the lengths of hospitalization were 9.8, 15.7, and 12.1 days, respectively (p < 0.05 for group 1 vs. group 2 or 3). Shortening the length of hospitalization and days of antibiotic therapy was associated with a cost savings of up to $78 000 for group 1 patients. CONCLUSIONS: Parenteral therapy for 72 hours followed by oral ciprofloxacin significantly shortened both the number of hospital days taking antibiotics and the length of stay compared with parenteral therapy alone. Both regimens were equally effective and safe in the therapy of gram-negative bacteremia, and initial parenteral therapy followed by oral ciprofloxacin was cost-effective.

Administration, Oral↗
PubMed1996

Video techniques with chemically-dependent patients.

This paper describes the use of videotaping as an adjunctive intervention in the treatment of substance-dependent patients. In the context of a cognitive-behavioral treatment extensively modified to work with inner-city, methadone-maintained cocaine users, videotaping in both individual and group formats is described. Video sessions create an opportunity for patients to reflect on their experience, enhance their self-esteem, aid in teaching social skills, and help hard-to-engage patients begin to participate in treatment. In order to compete with both the powerfully reinforcing qualities of cocaine and the extreme degree of avoidance exhibited by this population, therapy has to provide intense capturing experiences at the outset of treatment. Patient's reactions indicate that the experience they have is captivating and stimulating more than most other early therapy experiences. It is additionally concluded that the use of video can be instrumental in addressing the severe psychological deficits of this population that otherwise impede treatment efforts. While the role of video was not independently evaluated for its contribution to patient retention, 62% of patients were retained through completion of an intensive 6-month protocol.

Adult↗
PubMed1991

Cross-resistance of an amsacrine-resistant human leukemia line to topoisomerase II reactive DNA intercalating agents. Evidence for two topoisomerase II directed drug actions.

HL-60/AMSA is a human leukemia cell line that is 50-100-fold more resistant than its drug-sensitive HL-60 parent line to the cytotoxic actions of the DNA intercalator amsacrine (m-AMSA). HL-60/AMSA topoisomerase II is also resistant to the inhibitory actions of m-AMSA. HL-60/AMSA cells and topoisomerase II are cross-resistant to anthracycline and ellipticine intercalators but relatively sensitive to the nonintercalating topoisomerase II reactive epipodophyllotoxin etoposide. We now demonstrate that HL-60/AMSA and its topoisomerase II are cross-resistant to the DNA intercalators mitoxantrone and amonafide, thus strongly indicating that HL-60/AMSA and its topoisomerase II are resistant to topoisomerase II reactive intercalators but not to nonintercalators. At high concentrations, mitoxantrone and amonafide were also found to inhibit their own, m-AMSA's, and etoposide's abilities to stabilize topoisomerase II-DNA complexes. This appears to be due to the ability of these concentrations of mitoxantrone and amonafide to inhibit topoisomerase II mediated DNA strand passage at a point in the topoisomerization cycle prior to the acquisition of the enzyme-DNA configuration that yields DNA cleavage and topoisomerase II-DNA cross-links. In addition, amonafide can inhibit the cytotoxic actions of m-AMSA and etoposide. Taken together, these results suggest that the cytotoxicity of m-AMSA and etoposide is initiated primarily by the stabilization of the topoisomerase II-DNA complex. Other topoisomerase II reactive drugs may inhibit the enzyme at other steps in the topoisomerization cycle, particularly at elevated concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Amsacrine↗
PubMed1991

A comparison of stress and coping by fathers of adolescents with mental retardation and fathers of adolescents without mental retardation.

This investigation was an attempt to provide comparative information regarding stress and coping in fathers of adolescents with mental retardation and fathers of adolescents without mental retardation. Subjects for the study were 40 fathers of adolescents with mental retardation and 31 fathers of adolescents without mental retardation.

Adaptation, Psychological↗
PubMed1987

Adaptation of children to a chronically ill or mentally handicapped sibling.

The presence of a chronically ill or mentally handicapped child in a family can be a stress for the child's siblings, who often are ill informed about the nature and prognosis of the illness, may be uncertain what is expected of them in the caregiving role, may feel their own identities threatened, and may experience ostracism by their friends and misunderstanding at school. Although individual reactions vary widely, feelings of anger, guilt, resentment and shame are commonly reported. Excessive responsibility and concern about one's identity may add to these feelings and culminate in psychologic problems in the sibling. The physician caring for the family must be alert for symptoms of emotional disturbance or social maladjustment among the siblings of chronically ill or mentally handicapped children and should be prepared to counsel the family or refer them to a counsellor experienced in this area. In general, the first step is to be sure that the sibling is fully informed about the condition and to encourage frank discussion between the parents and the handicapped child's siblings.

Adaptation, Psychological↗
PubMed1977

Role of ecdysone, pupariation factors, and cyclic AMP in formation and tanning of the puparium of the fleshfly Sarcophaga bullata.

Two pupariation factors, anterior retraction factor (ARF) and puparium tanning factor (PTF), are absent from the hemolymph of larvae at the time of tanning accelerated by ARF/PTF, cyclic AMP, or dopamine. ARF and PTF are not involved in derepression of dopa decarboxylase (aromatic L-amino-acid decarboxylase, aromatic L-amino-acid carboxy-lyase, EC 4.1.1.28) synthesis initiated by ecdysone. Tanning is entirely inhibited by injection of two transcriptional inhibitors, actinomycin and BrdUrd, and two translational inhibitors, puromycin and cycloheximide. Retraction activity is more severely inhibited by the transcriptional than by the translational inhibitors. A tanning response is initiated by cyclic AMP in the presence of the transcriptional but not the translational inhibitors. Dihydric tanning substances (dopa, dopamine) initiate tanning in the presence of both types of inhibitors. Release of ARF and PTF from the central nervous system is inhibited by the four inhibitors. ARF totally reverses the inhibitory effects on retraction, whereas PTF does not reverse inhibition of tanning. These data are interpreted to mean that PTF is concerned with the regulation of two components of the tanning response: (i) acceleration of synthesis of a particular protein (associated with the tyrosine hydroxylation complex), and (ii) activation via cyclic AMP of a component of the tyrosine hydroxylating system.

Journal Article↗
PubMed1975

Mineralization of elastin extracted from human aortic tissues.

Elastin was isolated from human aortic tissues by extraction with formic acid. The aortas came from individuals of both sexes with ages ranging from 18 to 67 years. The elastin was treated to remove pre-existing nuclei for hydroxyapatite and mineralized in vitro by incubation in a solution metastable to hydroxyapatite. The results showed an increased rate of mineralization in vitro as the age of the individual from whom the aorta was obtained increased. The lag period in mineral formation seen with elastin samples obtained from individuals below the age 40, disappeared with older elastin. Amino-acid analysis of the elastin samples confirmed earlier results by indicating an increase in the more polar amino acids in the older elastin samples. Exposure of the extracted elastin samples to several proteolytic enzymes including elastase confirmed the identity of the material as elastin.

Aging↗