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Biomedical subjects

M Steinberg

Publications and source records attributed to M Steinberg.

At least 19 recordsLinked to original sources

Induction of Cyp1a-1 and Cyp1a-2 gene expression by a reconstituted mixture of polynuclear aromatic hydrocarbons in B6C3F1 mice.

The potential non-additive interactions of polynuclear aromatic hydrocarbon (PAH) mixtures as inducers of Cyp1a-1 and Cyp1a-2 gene expression were investigated in B6C3F1 mice using a reconstituted PAH mixture. The chemical composition (% by weight) of the reconstituted PAH mixture was: 2-ring PAHs--indan (0.22), naphthalene (23.8), 2-methylnaphthalene (23.2) and 1-methylnaphthalene (13.3); 3-ring PAHs--acenaphthylene (7.7), acenaphthene (0.6), dibenzofuran (0.7), fluorene (4.3), phenanthrene (10.5) and anthracene (3.4); > or = 4-ring PAHs--fluoranthene (2.4), pyrene (4.3), benz[a]anthracene (1.4), chrysene (1.5), benzo[b]fluoranthene (0.8), benzo[k]fluoranthene (0.9) and benzo[a]pyrene (0.9). The composition of the 2-, 3- and > or = 4-ring PAH fractions were based on the relative concentration of individual PAHs as noted above. The > or = 4-ring PAH fractions were based on the relative concentration of individual PAHs as noted above. The > or = 4-ring PAH fraction and reconstituted mixture induced hepatic microsomal ethoxyresorufin O-deethylase (EROD) activity and Cyp1a-1 mRNA levels, whereas the 2- and 3-ring PAHs were only weakly active. Direct comparison of the potencies of the reconstituted mixture and > or = 4-ring PAHs showed that the Cyp1a-1 induction activity of the reconstituted mixture was due to the > or = 4-ring PAHs. The reconstituted PAH mixture and > or = 4-ring PAHs also induced Cyp1a-2 hepatic mRNA levels and microsomal methoxyresorufin O-deethylase (MROD) activity; however, their dose-response curves indicated that the reconstituted PAH mixture was more potent as a Cyp1a-2 inducer than the > or = 4 ring PAHs. The differences in potency were due to 3-ring PAHs which were found to be strong inducers of hepatic Cyp1a-2 mRNA levels and microsomal MROD activity at the lowest dose administered (37 mg/kg). The 3-ring mixture caused a maximal 29-fold increase in hepatic MROD activity at a dose of 292 mg/kg, but only 28% of maximal induction of EROD activity. Northern analysis of liver mRNA from mice treated with 3-ring PAHs showed that there was minimal induction of Cyp1a-1 mRNA levels. The 3-ring PAHs did not competitively bind to the mouse hepatic cytosolic aryl hydrocarbon (Ah) receptor suggesting that 3-ring PAHs are a new class of Cyp1a-2 inducers which do not act through the Ah receptor.

Animals

Halogenated aromatic hydrocarbon-induced suppression of the plaque-forming cell response in B6C3F1 splenocytes cultured with allogenic mouse serum: Ah receptor structure activity relationships.

The immunosuppressive effects of halogenated aromatic hydrocarbons (HAHs) were investigated in B6C3F1 female mice and in mouse splenocytes cultured with allogenic mouse serum using the Mishell-Dutton model for in vitro immunization to trinitrophenyl-lipopolysaccharide (TNP-LPS). Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 2,3,4,7,8-pentachlorodibenzofuran (PeCDF), 1,2,3,7,8-PeCDF, 1,3,6,8-tetrachlorodibenzofuran (TCDF), 3,3',4,4',5-pentachlorobiphenyl (pentaCB), or 3,3',4,4',5,5'-hexaCB resulted in a dose-dependent suppression of the splenic plaque-forming cell (PFC) response both in vivo and in vitro. The effective dose required to decrease 50% (ED50) of the response to 2,3,7,8-TCDD, 2,3,4,7,8-PeCDF, 1,2,3,7,8-PeCDF, 1,3,6,8-TCDF, 3,3',4,4',5-pentaCB, or 3,3',4,4',5,5'-hexaCB in vivo was 14.1, 5.5, 1695, 34,800, 21, and 19 nmol/kg, respectively, and in vitro was 7.0, 10.6, 149, 2325, 9.1 and 9.1 nM, respectively. There was an excellent rank order and linear correlation between the in vivo versus in vitro activities for these HAHs (r < 0.99) and the relative immunosuppressive potencies of these compounds paralleled their binding affinities for the aryl hydrocarbon (Ah) receptor. These results show that splenocytes cultured with allogenic mouse serum is an Ah-responsive in vitro assay which can be used for quantitating the immunosuppressive effects of HAHs.

Analysis of Variance

Immunosuppressive activity of polychlorinated biphenyl mixtures and congeners: nonadditive (antagonistic) interactions.

The dose-response inhibition of the splenic plaque-forming cell (PFC) response and serum IgM units to the antigen, trinitrophenyl-lipopolysaccharide, was determined for several polychlorinated biphenyl (PCB) mixtures and congeners in female B3C3F1 mice. The ED50 values for Aroclor 1260-, 1254-, 1248-, and 1242-induced immunotoxicity varied by less than twofold from 355 to 699 mg/kg. The range of ED50 values for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 3,3',4,4'-tetrachlorobiphenyl, 3,3',4,4',5-pentaCB, 3,3',4,4',5,5'-hexaCB, 2,3,3',4,4'-pentaCB, 2,3',4,4',5-pentaCB, 2,3,3',4,4',5-hexaCB, 2,3,3',4,4',5,5'-heptaCB, 2,2',3,3',4,4',5-heptaCB, and 2,2',3,4,4',5,5'-heptaCB were 4.6 to 4.9, 134 to 245, 4.7 to 7.0, 6.9 to 11.1, 88,000 to 121,000, 122,000 to 132,000, 99,000 to 157,000, 89,000 to 129,000, 117,000 to 240,000, and 132,000 to 238,000 micrograms/kg, respectively. The immunotoxicity-derived toxic equivalency factors (TEFs) for these congeners could be calculated from the ED50 (TCDD)/ED50 (congener) ratios and the TEF values were within the range of those previously determined for other aryl hydrocarbon receptor-mediated responses. Based on the known concentrations of these congeners in the PCB mixtures, TCDD or toxic equivalents (TEQs) in the mixture were calculated [i.e., TEQ = sigma (PCBcongener x TEF)] using the immunotoxicity-derived TEFs (plaque-forming cells/10(6) viable cells). TEQ values for Aroclors 1260, 1254, 1248, and 1242 were 16.0, 54.4, 260.4, and 197 ppm, respectively. Based on the ED50 value for the immunosuppressive activity of TCDD (4.8 micrograms/kg), the calculated ED50 values for immune suppression by Aroclors 1260, 1254, 1248, and 1242 were 300, 88, 18, and 24 mg/kg, respectively. The ED50 (observed)/ED50 (calculated) ratios were 1.2, 5.9, 21, and 22.0 for Aroclors 1260, 1254, 1248 and 1242, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

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

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

Using the SCID-D to assess dissociative identity disorder in adolescents: three case studies.

The authors report on the diagnostic assessment of dissociative identity disorder in three adolescents using the Structured Clinical Interview for DSM-IV Dissociative Disorders (SCID-D; Steinberg, 1993b), a semistructured instrument for the diagnosis and assessment of dissociative symptoms and disorders. Although the SCID-D has received good-to-excellent ratings for reliability and validity in the adult population, these three cases are the first reports of the results of its administration to younger patients. Comparison of the three adolescent SCID-D interviews with findings in adults indicates that the profiles of the five dissociative symptoms measured by the SCID-D are virtually identical in adolescents and adults. The authors conclude with suggestions for future research regarding dissociative symptomatology in adolescents and outcome studies.

Adolescent

An enzyme-linked immunosorbent assay (ELISA) specific for antibodies to TNP-LPS detects alterations in serum immunoglobulins and isotype switching in C57BL/6 and DBA/2 mice exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin and related compounds.

An enzyme-linked immunosorbent assay (ELISA) was developed to detect IgM and IgG antibodies specific for trinitrophenyl-lipopolysaccharide (TNP-LPS). Treatment of C57BL/6 and DBA/2 mice with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and other aryl hydrocarbon (Ah) receptor agonists followed by immunization with TNP-LPS resulted in a dose-dependent decrease in serum IgM which paralleled the decrease in the splenic PFC response. The ED50 values for the IgM and splenic PFCs in C57BL/6 mice for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 3,3',4,4',5-pentachlorobiphenyl (pentaCB) and 3,3',4,4',5,5'-hexaCB were 2.8 and 1.6, 11 and 14, and 25 and 20 micrograms/kg, respectively; in the less Ah-responsive DBA/2 mice, the ED50 values were 8.5 and 10, 61 and 69, and 73 and 71 micrograms/kg, respectively. In addition, treatment of C57BL/6 mice with TCDD resulted in alterations of serum IgG relative to IgM and a delay of isotype switching was observed after immunization and boosting with TNP-LPS. This ELISA may prove to be a useful tool in monitoring immune function during long-term exposure of mice to TCDD and related compounds and exploring the mechanism of Ah receptor-mediated immunosuppression.

Animals

Attrition from conjoint alcoholism treatment: do dropouts differ from completers?

This study addresses patient attrition in order to identify variables associated with retention in conjoint treatment for alcohol abuse and dependence. Subjects were 105 male alcoholics and their partners who participated in a randomized clinical trial of three approaches to conjoint treatment of alcoholism: (a) alcohol and behavioral marital therapy (ABMT); (b) ABMT plus Alcoholics Anonymous and Alanon (AA/ABMT); and (c) ABMT plus relapse prevention (RP/ABMT). Completers (n = 45) attended two assessment and 15-17 treatment sessions. Partial completers (n = 23) left treatment between the 5th and 15th treatment session. Thirty-seven dropouts left treatment between the first assessment session and the 5th treatment session; of these, 22 dropouts completed at least one treatment session (called early treatment dropouts). Of subjects who entered treatment, dropouts from early treatment were least compliant with treatment requirements in the first few sessions, less educated, and less committed to their relationship. Data indicate that therapists with more clinical experience were more likely to retain clients in treatment, regardless of treatment condition. The data do not reflect a linear relationship between most variables studied and a continuum of attrition status from assessment to completion of the program.

Adult

Participation of the school community in AIDS education: an evaluation of a high school programme in South Africa.

An AIDS education programme was developed and evaluated in a high school in a socio-economically disadvantaged, urban, African area in South Africa. The programme, which addressed the whole school community, aimed to raise awareness about AIDS using a variety of educational methods and operating through a number of channels. Students and teachers were actively involved in its design and implementation. Students' knowledge of and attitudes towards AIDS prevention were investigated before and after the AIDS programme, and compared to a neighbouring school, in which no AIDS education was conducted. The programme greatly improved student knowledge of HIV transmission and prevention. It increased levels of acceptance of people with AIDS and had a small impact on behavioural intentions. The process of involving the school community in the design of the AIDS education programme is discussed.

Acquired Immunodeficiency Syndrome

Distinguishing between multiple personality disorder (dissociative identity disorder) and schizophrenia using the Structured Clinical Interview for DSM-IV Dissociative Disorders.

The authors describe the systematic assessment of dissociative symptoms using the Structured Clinical Interview for DSM-IV Dissociative Disorders (SCID-D) in 50 psychiatric outpatients with a referring DSM-III-R diagnosis of either schizophrenia or schizoaffective disorder (N = 31) and subjects with multiple personality disorder (MPD [DSM-IV name change: dissociative identity disorder]; N = 19). Results indicate that patients with MPD experience significantly higher scores for five specific dissociative symptoms than patients with schizophrenia or schizoaffective disorder. The range, severity, and nature of the five dissociative symptom areas evaluated by the SCID-D distinguish MPD from the occasional occurrence of dissociative symptoms which may be seen in schizophrenia. Systematic assessment of dissociative symptoms using the SCID-D can assist in accurate differential diagnosis of MPD and schizophrenia.

Adult

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

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

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

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

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

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