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Biomedical subjects

S Wolff

Publications and source records attributed to S Wolff.

At least 19 recordsLinked to original sources

Both cross-links and monoadducts induced in DNA by psoralens can lead to sister chromatid exchange formation.

The relative importance of DNA-DNA cross-links and bulky monoadducts in sister chromatid exchange (SCE) formation was investigated in three human fibroblast cell lines with different repair capabilities. These cell lines included normal cells, which can repair both classes of lesions; xeroderma pigmentosum (XP) cells, which cannot repair either psoralen-induced cross-links or monoadducts; and an XP revertant that repairs only cross-links and not monoadducts. SCEs were induced by two psoralen derivatives, 4'-hydroxymethyl-4,5',8-trimethylpsoralen (HMT) and 5-methylisopsoralen (5-MIP). After activation with long-wave ultraviolet light, HMT produces cross-links and monoadducts in DNA, whereas 5-MIP produces only monoadducts. In normal human cells both psoralens induced SCEs, but if cells were allowed to repair for 18 h before bromodeoxyuridine (BrdUrd) was added for SCE analysis, the SCE frequency was significantly reduced. XP cells showed an SCE frequency that remained high regardless of whether SCEs were analyzed immediately after psoralen exposure or 18 h later. In the XP revertant that repairs only cross-links, both psoralens induced a high yield of SCEs when BrdUrd was added immediately after psoralen treatment. When XP revertant cells were allowed 18 h to repair before addition of BrdUrd, the SCEs induced by HMT were greatly reduced, whereas those induced by 5-MIP were only slightly reduced. These observations indicate that both cross-links and monoadducts are lesions in DNA that can lead to SCE formation.

Bromodeoxyuridine

'Schizoid' personality in childhood and adult life. II: Adult adjustment and the continuity with schizotypal personality disorder.

In a controlled follow-up study into adulthood of 32 children diagnosed 'schizoid', three-quarters fulfilled DSM-III criteria for schizotypal personality disorder and two developed schizophrenia. Overall their psychosocial adjustment was somewhat, but not markedly, worse than that of other attenders at a child psychiatry clinic, although as a group they remained more solitary, lacking in empathy, oversensitive, with odd styles of communicating, and often with circumscribed interests.

Adolescent

'Schizoid' personality in childhood and adult life. III: The childhood picture.

The childhood case records of 32 'schizoid' children and 32 matched controls were analysed. 'Schizoid' children were characterised by solitariness, unusual fantasies, special interests, and specific developmental delays, especially of language-related skills. They were of average or above-average IQ, and half presented with other, common, child psychiatric syndromes. It is important to distinguish 'schizoid' children from children with reactive psychiatric disorders.

Adolescent

Biological dosimetry with cytogenetic endpoints.

The induction of chromosome aberrations in the lymphocytes of people who have been exposed to ionizing radiation has provided a much-used quantifiable biological dosimeter with which it is possible to obtain a reliable estimate of the dose of radiation to which the people have been exposed. The induction of aberrations by truly radiomimetic (non-S-dependent) chemicals should also be capable of leading to an estimate of the amount of the chemical that has reached the nuclei of the target cells, and thus give a measure of the damage inflicted. In this case, however, it is not yet possible to relate aberration yield to the initial exposure in a quantifiable manner. Other cytogenetic endpoints, such as micronuclei and sister chromatid exchanges (SCEs), can also be used to estimate whether or not exposures have occurred. Since micronuclei are the result of broken or lagging chromosomes, they too can be used to estimate the dose of ionizing radiation to which a person has been exposed. The use of aberrations or micronuclei for estimating the dose of S-dependent chemicals, however, still remains problematical. SCEs, which are not readily induced by ionizing radiations, have proved to be the most sensitive mammalian endpoint for determining exposure to such S-dependent chemicals. Nevertheless, the utility of SCEs, or any cytogenetic endpoint for that matter, for estimating the dose of any S-dependent chemical has not been shown because of dosimetric problems and because DNA repair can remove many of the adducts before the cells enter S, both of which preclude the use of these endpoints as biological dosimeters for such agents.

Chromosome Aberrations

Long-term efficacy of nitroglycerin patch in stable angina pectoris.

Subchronic and chronic efficacy of a 10 mg of nitroglycerin (NTG) patch was studied in 30 patients with stable angina pectoris. The trial consisted of 2 periods of study: 1 period of 2 months with a double-blind, crossover, placebo-controlled design and a second period of open treatment with verum patch. Two 7-day washout periods were performed at entry and at the end of the study. Efficacy was evaluated by clinical assessment of anginal attacks and NTG consumption and by means of multistage treadmill exercise testing. Exercise tests were performed at time 0 (24 hours from application of last patch), at 4 and 12 hours after dosing at the end of first 7-day washout, at the end of the first month of treatment, at the end of the second month of treatment after crossover, at the end of 3 months of treatment with active patch and at the end of the second 7-day washout period. Statistics were obtained by multivariate analysis of difference. In 27 patients whose records were available for final analysis the daily attacks of angina and NTG consumption decreased significantly during both the subchronic and chronic phases of the trial compared with placebo (p less than 0.001). Subchronic study showed significant improvement of maximal exercise duration, time to onset of angina, time to ST-segment depression of 1.0 mm, time to regression of angina and time to regression of ST depression, compared with placebo.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Cutaneous

Family characteristics of autistic children: a further report.

The personality features of parents of a group of 21 well-functioning autistic children have been described previously. The main characteristics of these parents were social gaucheness and a tendency towards the single-minded pursuit of special, often intellectual, interests. We now present the agreement between research interviewers and clinician in the diagnosis of these parents as schizoid, together with clinical details of those parents rated by both as having definite schizoid traits. The educational functioning of the siblings of the autistic children compared with that of siblings of a matched control group is also reported.

Achievement

Direct evidence of a functional separation of alloreactive T lymphocytes from bystander cells infiltrating rat allografts. Interleukin 2 receptor-positive cells reacting with the monoclonal antibody ART 18 mediating second-set rejection.

In this study we examined the functional capacity of unseparated, IL-2R positive and IL-2R negative leukocytes infiltrating BN rat hearts or kidneys grafted into allogeneic LEW rats. Upon adoptive transfer into syngeneic LEW recipients, splenocytes or day-3 graft infiltrate cells of either cardiac or renal transplants were ineffective to alter BN cardiac test graft survival (controls 7.8 +/- 0.8 day). However, adoptive transfer of day-5 heart infiltrate cells resulted in a delay of test graft rejection (9.4 +/- 0.7 day, P less than 0.001), while day-5 kidney-graft-infiltrating cells produced second set rejection (6.2 +/- 0.5, P less than 0.001). Specificity controls of day-5 cells infiltrating DA heart or kidney grafts rejected at 7.8 +/- 0.8 or 7.7 +/- 0.5 days. Following separation into IL-2R positive and negative subpopulations by use of the mAB ART 18, IL-2R positive but not IL-2R negative cells caused second set rejection in both the renal and the cardiac model (6.2 +/- 0.4, respectively, 6.3 +/- 0.5 days, P less than 0.001 or P less than 0.005). Furthermore, in the kidney model IL-2R positive nylon-wool nonadherent cells also caused second set rejection (6.2 +/- 0.4, P less than 0.005) suggesting that IL-2R positive T cells present in the graft at maximal infiltration are the mediators of rejection. Thus, it appears that these cells can be phenotypically and functionally separated from bystander cells.

Animals

Linear drive birdcage coil for 23Na human head studies at 1.5 T.

Progress in the development of non-proton NMR applications in medical research has been hampered by the generally low sensitivity of these nuclides as well as the lack of instrumentation readily available for studying these spins. For example, custom head coils suitable for sodium imaging of the human head are either not available or very expensive, making research startup costs high or impossible. Herein the detailed design and construction of a research 23Na head coil for MRI imaging is presented. 23Na NMR images collected with the coil are presented as well as a discussion of design modifications for other nuclides.

Head

Intravenous amiodarone in acute anterior myocardial infarction: a controlled study.

A randomized, single-blind controlled study intended to assess the potential benefits of intravenous amiodarone in anterior myocardial infarction is presented. Three hundred nineteen patients entered the study, 159 received amiodarone infusion, and 160 received glucose-insulin-potassium (GIK) infusion. Basal characteristics were similar in the two experimental groups, who were randomized on a consecutive basis. Exclusion criteria were shock or pulmonary edema, hypotension, inferoposterior infarction, bradycardia, antrioventricular block, severe diabetes, and other major diseases. Patients aged 27 to 70 years, with a Q-wave anterior infarction, initiated 12-40 hours earlier at the time of admission, entered the trial. Other entry criteria were heart rate higher than 80 beats/min and systolic blood pressure higher than 100 mmHg. Amiodarone was administered in saline infusion 10-20 mg/kg, within 4 to 10 hours, through a central vein. GIK infusion consisted of 150-300 g of glucose, 25-50 IU of insulin, and 80-120 mEq of KCl in 1000 cc of water at a rate of 1.5-2.0 ml/g/hour. Both groups received digitalis, nitrates, sedatives, and diuretics as needed. Although individually the major endpoints of death, reinfarction, and sustained supraventricular and ventricular arrhythmias did not differ significantly, each was less in the amiodarone group than in the control, and the sum of all adverse events was significantly lower for the amiodarone patients (p less than 001). Heart failure and conduction disturbances were not different in the two groups. This study shows that amiodarone, with its vasodilating and antiarrhythmic properties, may be beneficial in acute anterior infarction, but further studies on larger populations will be necessary in order to show a reduction of mortality rate.

Acute Disease

Inhibition of the adaptive response of human lymphocytes to very low doses of ionizing radiation by the protein synthesis inhibitor cycloheximide.

When human lymphocytes are preirradiated with 1 cGy of X-rays, the cells become less sensitive to subsequent exposures to high doses of about 150 cGy in that approximately one-half as many chromatid aberrations are induced as expected. This adaptation has been attributed to the induction of repair enzymes (proteins) some 4-6 h after the initial low-dose exposure. Experiments have now been carried out showing that application of the protein synthesis inhibitor cycloheximide at this time, but not earlier, prevents the adaptive response.

Adaptation, Physiological