Search PubMed⌕ Search

Biomedical subjects

M Steinberg

Publications and source records attributed to M Steinberg.

At least 19 recordsLinked to original sources
PubMed1995

Oral iloprost as a treatment for Raynaud's syndrome: a double blind multicentre placebo controlled study.

OBJECTIVE: To compare the efficacy, tolerance and safety of 50-150 micrograms orally administered iloprost given twice a day versus placebo in patients with Raynaud's syndrome. METHODS: The study was multicentre (n = 3), double blind and placebo controlled. Sixty three patients who had eight or more vasospastic attacks per week were enrolled. After a one week run-in period, all patients received either iloprost or placebo treatment to a maximum tolerated dose of 150 micrograms twice a day for 10 days. Diary cards assessed the duration and severity of the vasospastic attacks. Side effects were monitored by direct questioning. A global assessment of treatment efficacy was made by the patient at the end of treatment and two weeks later. RESULTS: Patient opinion tended to favour iloprost at the end of the 10 day treatment phase (p = 0.09) and this was significant at day 24 (the follow up visit) (p = 0.011). Although the duration and severity of attacks tended to decrease in the iloprost treated group, these results tended not to reach statistical significance (for severity p = 0.06 at end of treatment, p = 0.09 on day 24). CONCLUSION: Iloprost administered intravenously has been shown to be of benefit in the treatment of the Raynaud's syndrome associated with systemic sclerosis, but this route of administration is inconvenient. This study evaluated the use of iloprost administered orally to patients with Raynaud's syndrome. Patient documented improvement was significantly improved by iloprost. Diary card analysis showed a trend in favour of iloprost, but these results did not reach statistical significance.

Administration, Oral↗
PubMed1995

Characterization of an additional articular cartilage vesicle fraction that generates calcium pyrophosphate dihydrate crystals in vitro.

OBJECTIVE: We previously identified a unique fraction of porcine articular cartilage vesicles, sedimentable at 8 x 10(6) g/min, which generate calcium pyrophosphate dihydrate crystals (CPPD) in vitro. We sought to identify and characterize other fractions of articular cartilage digest, sedimentable at lower g forces, which may also contain mineralizing vesicles. METHODS: Electron microscopy and alkaline phosphatase and nucleoside triphosphate pyrophosphohydrolase (NTPPPH) assays were used to analyze each fraction. Radiometric mineralization assays, Fourier transform infrared (FTIR) spectroscopy, and compensated polarized light microscopy were used to analyze crystals formed by these fractions. RESULTS: Vesicles of varying sizes identical to epiphyseal cartilage matrix vesicles were seen in all sedimentable fractions examined, but were the exclusive component of fractions sedimentable at 3 x 10(6) g/min, termed the heavy vesicle fraction (HVF), and at 8 x 10(6) g/min, now termed the light vesicle fraction (LVF). All vesicle containing fractions supported ATP dependent calcium pyrophosphate precipitation. The HVF and LVF precipitated 30 x more calcium than vesicle poor supernatant (p < 0.01) and 1.5-4 x more than cell-free unfractionated digest (p < 0.01). HVF differed from LVF in that it contained 3-4 x higher NTPPPH specific activity (p < 0.05). HVF resembled LVF in that both precipitated crystals consistent with CPPD by FTIR spectroscopy and compensated polarized light microscopy. CONCLUSION: These data expand our previous estimate of the total number of vesicles available for biologic mineralization and demonstrate heterogeneity of vesicle fractions. They support a key role for vesicles in CPPD crystal formation.

Alkaline Phosphatase↗
PubMed1992

Orthophosphate-promoted ouabain binding to Na/K pumps of resealed red cell ghosts. Evidence for E*P preferentially binding ouabain.

Modulation of phosphoenzyme forms of the Na/K pump by Na+ and K+ was studied by measuring the rate of Pi-promoted ouabain binding to resealed ghosts made from human red cells. This system permits distinguishing the effects of the ions at intracellular and external binding sites. Internal K+, Ki, inhibited the rate of Pi-promoted ouabain binding, contrary to a prediction based on a current model of the pump. External K+, Ko, failed to inhibit ouabain binding in the absence of Ki. However, Ko enhanced the inhibition by Ki. Nai also inhibited ouabain binding; this inhibition was much less affected by Ko than was inhibition by Ki, suggesting that Ki and Nai affect ouabain binding at different internal sites. Nao inhibited ouabain binding in the absence of Ki or Ko, so Nao and Ko also act at different sites. With Nao present, Ki stimulated ouabain binding. Thus a condition was found in which the predicted stimulation of binding by Ki was observed. The results of this study are interpreted in terms of three phosphoenzyme forms of the pump: E1P, E*P, and E2P. E*P is the form binding ouabain with highest affinity. Ki promotes E*P----E2P, thereby inhibiting ouabain binding. Ko binds only to E2P, therefore Ki is required for inhibition by Ko, and there is little E2P present with no Ki. Nao inhibits binding by stabilizing E1P whereas Nai inhibits by stabilizing E1. The stimulation by Ki with Nao present means that Ki and Nao together favor formation of E*P. Furthermore, Ki and Nao may bind to the pump simultaneously. Ki may play a role in the normal pump cycle, binding at allosteric sites to promote E*P----E2P.

Adenosine Triphosphate↗
PubMed1992

Laboratory profile of sickle cell disease: a cross-sectional analysis. The Cooperative Study of Sickle Cell Disease.

We have collected steady-state laboratory data for over 2600 patients, age 2 years and over, with sickle cell anemia (HbSS), HbSC disease, and HbS-beta(+)-thalassemia. The packed cell volume (PCV) is lower in males than in females until 17 or 18 years of age in HbSS and ages 13 to 15 in HbSC, but then becomes consistently higher in males. After age 40, the PCV falls in HbSS. The steady-state leukocyte count in HbSS is higher than that in normals, blunting the utility of this measurement in the assessment of infection. In HbSC and HbS-beta(+)-thalassemia, the leukocyte counts are more often within the range of normal. Platelet counts in HbSS are often found to be above normal and show a downward trend with age. There is a progressive rise in creatinine with age. In HbSS, this rise begins at age 14 and may be accounted for by the increased muscle mass that occurs with puberty. The further deterioration of renal function in patients over 20 may be a result of the known adverse effects of sickle cell disease upon the kidney. Our data provide a basis to compare perturbations caused by intercurrent complications and new therapies, as well as to contrast with similar information from other populations of patients with sickle cell disease.

Adolescent↗
PubMed1992

Dust exposure and pneumoconiosis in a South African pottery. 2. Pneumoconiosis and factors influencing reading of radiological opacities.

A cross sectional radiological survey of workers exposed to pottery dust during the manufacture of wall tiles and bathroom fittings was conducted in a South African factory. Roughly one third of workers with 15 or more years of service in high dust sections of the factory had pneumoconiosis. Previously undiagnosed advanced cases, including two with progressive massive fibrosis, were working in dusty occupations. A firm diagnosis of potters' pneumoconiosis was made in 11 of the 358 workers radiographed; all had served more than 10 years suggesting that radiography of workers with more than 10 years service would be a successful case finding strategy in South Africa. A combination of rounded and irregular opacities was the most common radiological finding in the workers with pneumoconiosis (55%). Three readers reported on the chest radiographs, and all found an association between small radiological opacities, which were usually irregular or a combination of irregular and rounded, and exposure to pottery dust. The occurrence of irregular radiological opacities in workers exposed to pottery dust deserves further study. The least experienced reader significantly associated age with small opacities when duration of service (years) was used to measure exposure to dust. Sex was not an important predictor of radiological changes consistent with pneumoconiosis. Breast shadows were not an important cause of false positive readings and participating women did not develop pneumoconiosis after less exposure than men.

Humans↗
PubMed1991

Employee assistance program compliance: impact of contrasting insurance coverage.

Employee assistance programs are offered by employers to assist employees with personal problems through professional evaluation of the problem and referral to an appropriate treatment source. Although some research has been conducted to document the effect of these programs on such variables as absenteeism and disciplinary action, little information is available regarding compliance with clinical recommendations, ie, initiating and remaining in prescribed treatment. The present study evaluated the effect of two different rates of insurance coverage for outpatient mental health services offered by two comparable blue-collar organizations. Employees from the organization with a higher rate of payment were significantly more likely to initiate treatment and to remain in treatment longer. This outcome was not accounted for by demographic differences between the groups or by differences in diagnostic categories or treatment approaches. Implications of this finding are discussed as well as the utility of an employee assistance program to prepare employees for treatment.

Adult↗
PubMed1991

Detection of dissociative disorders in psychiatric patients by a screening instrument and a structured diagnostic interview.

OBJECTIVE AND METHOD: Diagnosis and treatment of the dissociative disorders may be delayed for many years because of difficulties in detecting patients at high risk for dissociative disorders. This study investigates the utility of the Dissociative Experiences Scale (DES), a self-report instrument for dissociative experiences, in detecting patients at high risk for dissociative disorders. The clinician-administered Structured Clinical Interview for DSM-III-R Dissociative Disorders (SCID-D) was used as the diagnostic standard, and 36 outpatients with mixed diagnoses and nine normal subjects were evaluated for the presence and absence of a dissociative disorder. DES scores were then compared. RESULTS: Results indicate that a DES cutoff score of 15-20 yields good to excellent sensitivity and specificity as a screening instrument. However, for higher cutoff points the sensitivity can be much lower. CONCLUSIONS: Thus, although the DES can be used to identify some high-risk patients, they should be further evaluated with such diagnostic instruments as the SCID-D or by in-depth clinical follow-up.

Adult↗
PubMed1991

The role of oxygen in thermo-photodynamic processes leading to sunscald-like damages in green tissues.

Sunscald is a physiological disorder causing, in warm climates, severe damages to green tissues. Earlier studies established the essential role of heat, light and chlorophyll in the development of the disorder. In the present work, the role of oxygen in the development of the injury was investigated. Green cucumber fruit were exposed to heat and light under controlled atmosphere, and the development of the injury was followed. No damage occurred in the absence of either heat or light. Tissues exposed to heat, light and either nitrogen or air, suffered marked electrolyte leakage, indicative of membrane damage. Chlorophyll fluorescence values of cucumbers treated with high temperatures, oxygen and light, were considerably lower than those measured for the respective dark treated tissues. Irradiated cucumbers flushed with either 100% N2 or less than 2.5% O2, lost about 50% of their chlorophyll. These tissues turned olive-green but did not bleach. At higher conc., oxygen treated tissues lost their plastid pigments and bleached within 7 hr of exposure to heat and light. A significant decrease in chlorophyll was evident also in atmosphere containing 1% CO2 in nitrogen. Malondialdehyde conc was significantly higher in the presence of O2 as compared with N2 atmosphere. The results clearly show, that sunscald damage is a result of thermo-photooxidative processes.

Chlorophyll↗
PubMed1990

Epidermal cell-shape regulation and subpopulation kinetics during butyrate-induced terminal maturation of normal and SV40-transformed human keratinocytes: epithelial models of differentiation therapy.

Recent data indicate that malignant human epidermal cells may be appropriate targets for sodium butyrate (NaB)-mediated differentiation therapy. The response of pre- and post-crisis populations of SV40-transformed human keratinocytes (SVKs) to this differentiation-inducing agent was assessed, therefore, within the framework of NaB-directed normal human keratinocyte (NHK) maturation. NaB augmented cornified envelope (CE) production in NHK and pre-crisis SVK cultures; the time-course and efficiency of induced maturation were similar in the 2 cell systems. In NHKs, the percentage of amplifying ("B" substate) cells decreased with time in NaB correlating with increases in both "C" stage keratinocytes and CEs. The latter formed over one or 2 layers of nucleated basal-like cells. Inductions were accompanied by immediate cell cycle blocks (in both the G1 and G2/M phases), reorganization within the actin cytoskeleton, and transient early increases in cellular actin content. Increased NHK and pre-crisis SVK cytoskeletal-associated actin reached a maximum approximately 48 hr after NaB addition and preceded development of CEs. The CE precursors, thus, probably reside in the "B" substate. Post-crisis SVKs, in contrast, were refractive to NaB-induced terminal maturation or cell-cycle perturbation, failed to initiate actin filament rearrangements, and retained a basal cell-like phenotype. Stable transformation of human SVKs in post-crisis phase, therefore, appears to be associated with loss of maturation "competence" within the "B" keratinocyte subpopulation.

Actin Cytoskeleton↗
PubMed1990

Differential effects of substrates on three transport modes of the Na+/K(+)-ATPase.

With a purified Na+/K(+)-ATPase preparation reconstituted into phospholipid vesicles, Na+/K+, Na+/Na+, and uncoupled Na+ transport were studied using three nucleotides and five substrates of the K(+)-phosphatase reaction that this enzyme also catalyzes. For Na+/K+ exchange, CTP was half as effective as ATP and GTP one-twentieth; of the phosphatase substrates only carbamyl phosphate and 3-O-methylfluorescein phosphate produced significant transport and at merely 1% of the rate with ATP. For Na+/Na+ exchange, comparable rates of transport were produced by ATP, CTP, carbamyl phosphate and acetyl phosphate, although the actual rate of transport with ATP was only 2.4% of that for Na+/K+ exchange; slower rates occurred with GTP (69%), 3-O-methylfluorescein phosphate (51%), and nitrophenyl phosphate (33%). Only umbelliferone phosphate was ineffective. For uncoupled Na+ transport results similar to those for Na+/Na+ exchange were obtained, but the actual rate of transport was still slower, 1.4% of that for Na+/K+ exchange. Thus, not only nucleotides but a variety of phosphatase substrates (which are phosphoric acid mixed anhydrides) can phosphorylate the enzyme at the high-affinity substrate site to form the E1P intermediate of the reaction sequence. Oligomycin inhibited Na+/K+ exchange with ATP by half, but with carbamyl phosphate not at all; with CTP the inhibition was intermediate, one-fourth. By contrast, oligomycin inhibited Na+/Na+ exchange by one-fifth with all three substrates. A quantitative, steady-state kinetic model accounts for the relative magnitudes of Na+/K+ and Na+/Na+ exchanges with ATP, CTP, and carbamyl phosphate as substrates, as well as the extents of inhibition by oligomycin. The model requires that even when Na+ substitutes for K+ a slow step in the reaction sequence is the E2 to E1 conformational transition.

Animals↗
PubMed1990

The Structured Clinical Interview for DSM-III-R Dissociative Disorders: preliminary report on a new diagnostic instrument.

The authors describe the Structured Clinical Interview for DSM-III-R Dissociative Disorders (SCID-D), which investigates five groups of dissociative symptoms (amnesia, depersonalization, derealization, identity confusion, and identity alteration) and systematically rates both the severity of individual symptoms and the evaluation of overall diagnosis of dissociative disorder. Preliminary findings from a study of 48 subjects with and without psychiatric diagnoses indicate good to excellent reliability and discriminant validity for the SCID-D as a diagnostic instrument for the five dissociative disorders and as a tool for the evaluation of dissociative symptoms encountered within nondissociative syndromes.

Adult↗
PubMed1990

[The reaction mechanism of Na, K-ATPase].

To help characterize the Na,K-ATPase active site with enzyme incorporated into phospholipid vesicles, the activities with alternative substrates were compared, 22Na/Na-transport was equivalent with ATP, CTP, carbamylphosphate and acetylphosphate, but slower with CTP, 3-O-methylfluoresceinphosphate (3-O-MFP), nitrophenylphosphate and umbelliferonephosphate. It indicates a slower rate of formation of phosphorylating enzyme complex in conformation position of E1 (E1P) when the second group of substrates is bound with enzyme active center. 22Na/K-transport was half as effective with CTP as with ATP and was far slower with the other substrates. It indicates a more stringent selectivity at the low-affinity site of enzyme in conformation E2 that accelerates the slow step of this transport mode. Although enzyme modification with fluoresceinisothiocyanate blocks the high-affinity site to ATP, the K-phosphatase reaction catalyzed by E2 is retained, even with a substrate, 3-O-MFP, that binds to the adenine pocket. Dimethylsulfoxide inhibits hydrolysis of the nucleotides and of the carboxylic phosphate substrates of the K-phosphatase reaction, but stimulates hydrolysis of the phenolic phosphate substrates (nitrophenylphosphate and umbelliferone phosphate) which normally are hydrolyzed more slowly than the other substrates. On the basis of these data the authors propose the model of Na,K-ATPase active center.

Alkaline Phosphatase↗
PubMed1989

Life after death--mortality statistics and the public health.

The process by which mortality statistics are compiled in the RSA and the potential impact on public health are discussed. The use of the international death certificate is outlined; this is compared with the South African death certificate to illustrate the importance of establishing the chain of events leading to death. The distinction between underlying and direct causes of death in compiling mortality statistics and planning public health intervention is considered. The major part played by medical practitioners in the death certification process is emphasised, and some of the areas in which mortality data could be improved are highlighted.

Cause of Death↗
PubMed1989

Studies on conformational changes in Na,K-ATPase labeled with 5-iodoacetamidofluorescein.

The rates of individual steps in the reaction cycle of dog kidney Na,K-ATPase labeled with iodoacetamidofluorescein (IAF) were measured using the fluorescence stopped-flow technique. The maximal rate of the fluorescence quenching accompanying ATP hydrolysis at 20 degrees C in the presence of K+ is 66.3 s-1, while the turnover rate in the same conditions is 15.5 s-1. The rate without K+ is slightly lower. Unexpectedly, at very high ionic strength, K+ accelerates the rate 2-fold. The fluorescence change appears to be associated with the E1P----E2P transition. The results are consistent with the classical Albers-Post scheme but do not support recent criticisms that E1P is kinetically incompetent in the presence of Na+ plus K+. As expected, in the absence of ATP the rate of E2(K)----E1Na was very slow (0.2 s-1) but was greatly accelerated by ATP (maximal rate 15.9 s-1) with low affinity (K0.5 = 196 microM). It was concluded that E2(K)----E1 is the slowest step of the cycle, even at nonlimiting ATP concentrations. The rate of E1K----E2(K) for both IAF- and fluorescein 5'-isothiocyanate-labeled enzyme was stimulated by K+ acting with low affinity, but not at all by ATP at 5 microM. Whereas the maximal rate with IAF-enzyme (271 s-1) was similar to previous work, the K+ affinity was significantly higher. Fluorescence signals accompanying hydrolysis of acetyl phosphate with both IAF- and fluorescein 5'-isothiocyanate-labeled enzyme have similar rates, 5.25 s-1 and 4.06 s-1, respectively. A species difference was observed between dog and pig kidney Na,K-ATPase in that both enzymes are labeled with IAF but only in dog enzyme were conformational transitions associated with fluorescence changes. Therefore, the IAF-labeled dog kidney enzyme is the preparation of choice for measuring fluorescence changes accompanying ATP hydrolysis.

Animals↗
PubMed1989

Identification of the 5-iodoacetamidofluorescein reporter site on the Na,K-ATPase.

5-Iodoacetamidofluorescein (5-IAF) labels the catalytic (alpha) subunit of dog kidney Na,K-ATPase without inhibiting enzymatic activity and is thus a useful fluorescent reporter of enzyme conformation under conditions of enzyme turnover. In this study conditions for labeling a unique sulfhydryl group are described, and this residue is identified in the cDNA-derived sequence. Reaction with iodoacetate (IAA) prior to fluorescent labeling lowers the stoichiometry of 5-IAF incorporation from 2.1 to 1.2 mol/mol alpha beta protomer, and increases the conformationally dependent fluorescence changes by 40-50%, consistent with the elimination of nonspecific labeling. IAA/IAF-enzyme has the same catalytic activity as the IAF-enzyme. In contrast, treatment with iodoacetamide prior to labeling with 5-IAF abolishes all fluorescence responses, although activity is retained. IAA/IAF-enzyme was digested by extensive trypsinolysis, and the fluorescent peptides released from the membrane were purified by high performance liquid chromatography and sequenced. Several fluorescent peptides were found, containing all or part of the sequence Cys-Ile-Glu-Leu-Cys-Cys-Gly-Ser-Val-Lys, corresponding to residues 452-461 in the sheep alpha subunit. The major site of modification is the second of the vicinal cysteine residues, Cys-457. Phenylarsine oxide, a reagent specific for vicinal sulfhydryl groups, prevents fluorophore incorporation, thereby confirming the identification of the IAF site from the sequence data.

Amino Acid Sequence↗
PubMed1988

Sensation-seeking congruence in couples as a determinant of marital adjustment: a partial replication and extension.

The present study is a replication of an earlier one. There were 30 dysfunctional couples and 30 control couples matched with the clinic couples on age and education. Both partners independently took the Sensation Seeking Scale (SSS) and the Locke Marital Adjustment Questionnaire (MAQ). Control couples were significantly higher on the MAQ (better marital adjustment). Correlations between partners in the control couples were higher than those between partners in the dysfunctional couples on the SSS Total and Boredom Susceptibility scales, which replicated previous findings. Female partners of males who scored high on the SSS were more likely to initiate the contact for treatment than partners of low male sensation seekers. Female partners of low male sensation seekers and the low males themselves tended to report that sex between them was only tolerable or "disgusting," whereas female partners of high sensation seekers and their mates tended to report sex as pleasurable and apparently sought therapy for other reasons. Congruence on sensation seeking is an important factor in marital adjustment.

Adaptation, Psychological↗