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Biomedical subjects

H Sussman

Publications and source records attributed to H Sussman.

12 recordsLinked to original sources
PubMed1992

Intracellular glutathione levels in T cell subsets decrease in HIV-infected individuals.

The authors have shown previously that intracellular glutathione (GSH) plays an important role in the regulation of human immunodeficiency virus (HIV) transcription and replication in vitro, through modulation of signal transduction by inflammatory cytokines. Moreover, intracellular GSH levels are known to regulate T-lymphocyte function. In multiparameter FACS studies presented here, we show that relative GSH levels in CD4+ and CD8+ T cells from HIV+ individuals are significantly lower than in corresponding subsets from uninfected controls. These studies define the relative intracellular glutathione (GSH) levels in CD4+ T cells, CD8+ T cells, B cells, and monocytes from 134 HIV-infected individuals and 31 uninfected controls. The greatest decreases in intracellular GSH occur in subsets of T cells in individuals in the later stages of the HIV infection. In AIDS patients, GSH levels are 63% of normal in CD4+ T cells (p less than 0.0001) and are 62% of normal in CD8+ T cells (p less than 0.0001). Similarly, in AIDS-related complex (ARC) patients, GSH levels are 66% of normal in CD4+ T cells (p less than 0.003) and are 69% of normal in CD8+ T cells (p less than 0.003). These findings suggest that low intracellular GSH levels may be an important factor in HIV infection and in the resulting immunodeficiency.

AIDS-Related Complex↗
PubMed1990

A clinical and biochemical assessment of a nonthiol ACE inhibitor (pentopril; CGS-13945) in active rheumatoid arthritis.

Captopril, which is a thiol containing angiotensin converting enzyme (ACE) inhibitor that has a close structural similarity to D-penicillamine, behaves as a disease modifying antirheumatic drug (DMARD) in rheumatoid arthritis (RA). In order to ascertain whether the DMARD-like properties of captopril reside in its ability to inhibit ACE or in the thiol group, we evaluated pentopril (CGS-13945) in patients with active RA. This recently synthesized drug is a nonthiol containing ACE inhibitor. Pentopril produced little clinical improvement and no biochemical improvement in a group of 15 patients with RA, many of whom were unable to tolerate it because of in-effect or side effects. A reduction in serum ACE activity and a modest fall in blood pressure suggested that the drug was exerting its pharmacological effect. Our study strengthens the argument that the therapeutic benefit of captopril in RA probably lies in its thiol group rather than in its enzyme inhibition properties, and that the thiol group may be the effective moiety in some other DMARD.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1989

A clinical and biochemical assessment of prinomide in patients with rheumatoid arthritis.

Prinomide (CGS-10787B), a potential disease modifying drug, was evaluated clinically and biochemically in 15 patients with active rheumatoid arthritis. The single group study design included monthly assessments of 7 clinical measures and 22 laboratory measures. Twelve patients completed 24 weeks' therapy with prinomide 1.2 g/day. All clinical variables showed improvement which consistently reached statistical significance for articular index from Week 8 (p less than 0.01), for summated change score from Week 12 (p less than 0.01) and for pain score from Week 16 (p less than 0.05). Sustained significant improvement in laboratory variables was seen by Week 2 for erythrocyte sedimentation rate and platelet count (both p less than 0.05), and by Week 4 for plasma viscosity (p less than 0.01), IgG, IgA, IgM (all p less than 0.05).

Aged↗
PubMed1989

[Impotence of vascular origin].

Between 1977 and 1986, 3,500 patients were examined for the symptom of impotence; 1,250 of them received multidisciplinary investigation permitting the diagnosis of a pure organic or mixed disorder in 85% of cases, including 62% of vascular disease subdivided into arterial (40%) and venous (22%). For 1,062 patients, 1 or several of the following therapies were used: intracavernous infusion of vasoactive drugs (N = 725), auto-injections (N = 235), vascular surgery (N = 357) and prostheses (N = 23). The diagnostic approach, formerly analytical and making use of multiple non-invasive methods, such as nocturnal erection plethysmography (NPT) and invasive methods (artificial erection, arteriography) have been transformed by the use of pharmacological tests associated with visual sexual stimulation (VSS) which enable, together with Doppler velocimetric examination, simple screening of vascular impotence based on the study of 4 parameters: penile pressure index (PPI) when less than 0.91 is always a sign of an arterial problem, the severity of which is directly proportional to the lowering of this index and the association with maintenance insufficiency; the initial intracavernous flow rate (IICF) depends overall on the maintenance flow and the state of erectile tissue, resulting from pharmacological stimulation by a low dose of papaverine (8 mg); penile rigidity attained by the combined action of pharmacological and visual sexual stimulation, reflecting the functional erectile capacity; the duration of the rigidity thus obtained on stoppage of VSS indicating the capacity for maintenance of erection. In the event of suspicion of an isolated venous leak or in association with arterial problems, it is the artificial erection with cavernosography, carried out after pharmacological stimulation, which enables the severity of the leak to be assessed. The following specific investigations are carried out to investigate a specific associated etiology: electromyogram for neurological disorders, hormone assay for endocrine disorders and psychological study using the MMPI questionnaire (Multiphasic Minnesota Personality Inventory). One can thus distinguish several groups of patients suffering from vascular impotence depending on the degree of arterial involvement: minor (PPI between 0.75 and 0.9), moderate (PPI between 0.65 and 0.75) and severe (PPI less than 0.65); depending on the degree of venous leaking: absent (MI less than 0.3 and/or MF less than 25 ml/min), minor (MI between 0.3 and 0.5 and MF between 30 and 50 ml/min), moderate (MI between 0.5 and 75 ml/min) and severe (MI greater than 0.75 and/or MF greater than 75 ml/mn).(ABSTRACT TRUNCATED AT 400 WORDS)

Erectile Dysfunction↗
PubMed1988

Modulation of the transferrin receptor during DMSO-induced differentiation in HL-60 cells.

When HL-60 cells are induced to differentiate by dimethyl sulfoxide along a granulocytic pathway there is a fivefold decrease in the total number of transferrin receptors within 3 days, as compared to untreated cells. This decrease is due primarily to a rapid decline in the synthesis of the receptor rather than an increase in the degradation of the receptor. The decrease in transferrin receptor synthesis is a specific and early event that precedes the cessation of cell proliferation, differentiation, and the decrease in total protein synthesis.

Cell Differentiation↗
PubMed1987

Characterization of a human osteoblastic osteosarcoma cell line (SAOS-2) with high bone alkaline phosphatase activity.

We characterized the alkaline phosphatase activity of the human osteogenic sarcoma cell line, SAOS-2, and studied the regulation of this enzyme and 3',5'-cyclic adenosine monophosphate levels by 1,25-dihydroxyvitamin D3 and triamcinolone acetonide. We report that the basal alkaline phosphatase activity of SAOS-2 cells was 100-1000 times greater than that of other established human osteogenic sarcoma cell lines. The enzymatic activity was thermolabile, could be inhibited by levamisole and L-homoarginine, but not by L-phenylalanine, and was immunoprecipitable with anti-bone/liver/kidney, but not with anti-placental antibody, confirming that it is the tissue-unspecific or bone/liver/kidney isoenzyme. However, in contrast to other established human osteosarcoma cell lines (TE-85, SAOS-1), in which alkaline phosphatase activity is stimulated several-fold by the steroid hormones 1,25-dihydroxyvitamin D3 and hydrocortisone, the alkaline phosphatase activity of SAOS-2 cells was not affected by 1,25-dihydroxyvitamin D3 treatment despite the presence of classical receptors for this hormone. Furthermore, administration of the potent glucocorticoid analogue, triamcinolone acetonide, induced only a modest increase in activity. The SAOS-2 cell line expressed low basal cAMP levels (28 pmol/10(6) cells) which could be increased 25-40 times by pretreatment with parathyroid hormone. However, unlike other osteoblastic models, in which PTH-induced cAMP stimulation is modulated by 1,25-dihydroxyvitamin D3 and glucocorticoids, neither of these hormones had an effect on the PTH-stimulated cAMP levels in SAOS-2 cells. We conclude that the SAOS-2 cell line is an osteoblastic cell model which expresses high levels of tissue-unspecific alkaline phosphatase activity and exhibits limited responsiveness to two steroid hormones.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaline Phosphatase↗
PubMed1986

Compensatory articulation in Broca's aphasia.

Thirteen patients clinically diagnosed as Broca's aphasics, were administered a vowel bite block task to ascertain their on-line compensatory articulation ability. Formant frequencies for F1 and F2 were obtained from a pitch-synchronous spectral analysis of digitized vowel waveforms. Bite block/i/productions were consistently characterized by higher F1 and lower F2 frequencies compared to normal vowel productions. Undershooting of tongue elevation and fronting explains this result. No consistent pattern of "off-target" productions were found for/a/tokens. A multiple correlation analysis among clinically derived quantitative measures (BDAE score, oral and verbal apraxia), experimentally derived measures (bite block performance, articulatory reaction time), and neurological measures (brain lesion volume) was highly successful despite a relatively small sample size. Compensatory articulation was significantly related to both oral apraxia scores (r = -.70) and the BDAE total score (r = -.51). A multiple regression analysis nearly reached statistical significance (p = .11) in predicting bite block performance, with oral apraxia the most powerful predictor variable. Descriptive accounts of loci of brain lesion vis-à-vis compensatory articulation ability are given to delimit brain areas thought to possibly mediate this articulatory adaptive skill. Preliminary speculation supports the notion that an intact Area 44 is a prerequisite for successful compensatory ability.

Adaptation, Physiological↗