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Biomedical subjects

S J Freeman

Publications and source records attributed to S J Freeman.

At least 37 records · Page 2Linked to original sources

The occupational stress of judges.

This paper reports the results of what is believed to be the first systematic survey of the Canadian judiciary about work-related stress. County and District Court judges from four provinces who were attending an educational event on two successive years (N = 104) reported in writing, anonymously, their perceptions of the most stressful aspects of being a judge. A similar survey of their spouses (N = 48) added another perspective to the findings. The overwhelming majority of respondents reported aspects of the work itself (for example, sentencing, child custody cases, judgements, decision-making, and jury trials) as being their primary source of occupational stress. This is not in keeping with the results of most studies, which find that workers view job factors such as role conflict, employer/employee relationships, and career decisions as being more stressful than the actual work they perform. Qualitative material from individual and group interviews suggests that additional preparation and training for the bench and mechanisms for reducing isolation and improving communication might alleviate the stress experienced by judges, while helping them to cope more effectively with their increasingly complex and difficult roles.

Adult↗

Evaluation of the teratogenic potential of the dopamine agonist bromocriptine in rats.

Single subcutaneous injections of bromocryptine (BCR; 2 mg/kg) to rats on days 5, 7 or 10 of gestation caused a lowering of the serum prolactin (PRL) concentration and, on days up to and including day 8 of gestation, abortion of entire litters. Coincident with the end of the PRL-dependent phase of gestation (approximately day 9), BCR was no longer abortifacient, allowing higher doses of the drug to be administered from this time without the risk of abortion. Treatment at 50 or 100 mg/kg from day 10 to 16 of pregnancy, despite affecting the dams (increased water consumption), had no adverse effects on pregnancy or fetal development.

Abnormalities, Drug-Induced↗

Failure of zinc to prevent dysmorphogenesis of cultured rat conceptuses by anti-yolk sac antiserum.

Day 10 rat conceptuses were cultured for 48h in the presence of either cadmium or anti-visceral yolk sac antiserum (AVYS). Cadmium was embryotoxic at concentrations exceeding 0.25 micrograms/ml whilst AVYS caused embryonic dysmorphogenesis, particularly affecting the optic vesicles, at concentrations of 2 microliters/ml and above. The effect of pretreatment with zinc on embryotoxicity caused by cadmium or AVYS was studied. Zinc ameliorated the effects of cadmium but had no effect on AVYS-induced embryonic abnormalities. In a second set of experiments inhibition of 125I-labelled PVP uptake by the yolk sac of cultured whole conceptuses was studied. Cadmium and AVYS both inhibited uptake compared to control cultures. Zinc again ameliorated the effect of cadmium but had no action against AVYS-induced inhibition. These results are in contrast to our previous findings using isolated cultured yolk sacs in which zinc ameliorated the inhibitory effects on 125I-labelled PVP uptake of both cadmium and AVYS. These data show that in experiments using the isolated cultured yolk sac and the intact cultured conceptus, a qualitatively different response in yolk sac behaviour is observed under similar experimental conditions.

Animals↗

Anti-kidney antibody teratogenesis: evidence for a direct action on the rat conceptus by a mechanism involving the yolk sac.

IgG from anti-rat kidney antiserum (anti-K) was added to 48-h cultures of 9.5-day whole rat conceptuses. At concentrations of 25 micrograms/ml and above, dysmorphogenesis of embryos (optic vesicle defects) was observed. Significant embryonic growth retardation was apparent at 75 micrograms/ml and above. Other abnormalities (neural tube defects, deficits in axial rotation, reduced somite numbers) were seen at 100 and 150 micrograms/ml. In separate experiments, anti-K inhibited pinocytosis of 125I-polyvinylpyrrolidone by isolated yolk sacs. All of these effects of anti-K are similar to those produced by anti-visceral yolk sac antiserum suggesting a similar mechanism of teratogenic action, namely interference with yolk-sac-mediated embryotrophic nutrition.

Abnormalities, Multiple↗

Working in arctic and sub-arctic conditions: mental health issues.

As Canada expands its activities in the North, it becomes necessary to understand the mental, emotional and health consequences of working in harsh, isolated environments. This paper reviews the pertinent literature and reports on a study, commissioned by Environment Canada, of the working conditions of meterological technicians in 33 isolated stations who were surveyed by questionnaire. Numerous personal interviews and visits to five Arctic stations were also carried out. GHQ scores of psychological distress were significantly higher than in a Saskatchewan community sample but not higher than in male air transport shift workers in Ontario. Sleep disturbances and anergia were the two most prominent symptoms in our sample. The literature also stressed these symptoms as well as alcoholism and a number of curious cognitive phenomena. The importance and problems of group functioning are stressed. Our subjects showed fewer problems than the literature would have predicted, but it is generally agreed that there are few, if any, irreversible sequela of life in the North.

Adaptation, Psychological↗

A complex genetic locus, polyhomeotic, is required for segmental specification and epidermal development in D. melanogaster.

Two mutagenic events are required to make null mutations of polyhomeotic (ph), which suggests that the locus is complex. Amorphic mutations (ph degrees) die in mid-embryogenesis and completely lack ventral thoracic and abdominal epidermal derivatives, whereas single-event mutations lead to transformations similar to those of known dominant gain of function mutants in the Antennapedia and bithorax complexes. After a chromosomal walk, the ph gene was localized using deficiencies and ph mutations that result from DNA rearrangements. Hybridization analyses show that there are two large, duplicated sequences in the ph region, and DNA lesions affecting either one of these repeats alter the function of the ph locus. We propose a model that may account for this unusual functional organization.

Alleles↗

Differential effect of zinc on teratogen-induced inhibition of pinocytosis by cultured rat yolk sac.

Pinocytosis as measured by the uptake of 125I labelled PVP by the isolated cultured day 12 rat yolk sac was observed to be linear over a 4 h incubation period and to proceed at a rate of approximately 2.5 microliters/mg protein/h. Cadmium, anti-visceral yolk sac antibody (AVYS) and trypan blue all inhibited pinocytosis in a concentration-dependent fashion when added to the culture medium, although at low concentrations trypan blue was slightly stimulatory. The effect of zinc on the inhibition of pinocytosis by these three teratogens was studied. It was observed that zinc ameliorated the inhibitory effects of cadmium and AVYS, but had no effect on inhibition by trypan blue. These results indicate that the previously demonstrated protective action of zinc against cadmium-induced yolk sac dysfunction is not specific to that agent but extends to inhibition of pinocytosis by AVYS, and further suggest that, because of its refractoriness to zinc, trypan blue-induced inhibition of pinocytosis by yolk sac occurs by a mechanism different from that effected by cadmium and AVYS.

Animals↗

Loss and depression. A controversial link.

Inconsistent findings in studies of loss and depression arise from methodological differences, lack of common definitions of depression and loss, and the failure to consider the interaction hypothesis: the effect of early loss on depression is partly conditional on the presence of a current loss. Data were collected from 744 university students. Only 15% of subjects without loss vs. 44% with both types of loss had Beck Depression Inventory scores indicative of moderate depression. Analysis of variance confirmed this strong interaction effect. These results provide empirical support for Freud's view that a recent loss can reactivate depressive feelings associated with earlier loss.

Adolescent↗

Evidence that suramin and aurothiomalate are teratogenic in rat by disturbing yolk sac-mediated embryonic protein nutrition.

Suramin (250 mg/kg) and sodium aurothiomalate (100 mg/kg) both induced congenital malformations in the offspring following treatment of pregnant rats at either 8.5 or 9.5 days of gestation. Conceptuses from 9.5-day pregnant rats were cultured for 48 h in homologous serum to which either suramin or sodium aurothiomalate was added for the final 6 h. The presence of suramin up to 5 mg/ml had no effect on the protein content of yolk sacs at harvesting, but at 10 mg/ml caused a significant decrease. In contrast sodium aurothiomalate increased the protein content of yolk sacs at harvesting, in a concentration-dependent manner up to 100 micrograms/ml. Neither suramin nor sodium aurothiomalate significantly affected embryo protein content. When 125I-labelled polyvinylpyrrolidone was added to the culture serum for the final 6 h of culture, radioactivity was found in the yolk sac at harvesting, but not in the embryo. When suramin (2-10 mg/ml) was present for the final 6 h of culture, the quantity of radioactivity measured in the yolk sac at harvesting was significantly decreased in a concentration-dependent manner. No radioactivity was detected in the embryos. Sodium aurothiomalate had no effect on the uptake of 125I-labelled polyvinylpyrrolidone. When rat serum whose proteins were labelled with [3H]leucine was used as culture medium, radioactivity was found in the conceptus (both yolk sac and embryo) at harvesting. Suramin (5 mg/ml), present for the final or penultimate 6 h, significantly decreased the uptake of radioactivity into conceptuses and caused a significant increase in the proportion of the captured radiolabel that was associated with the yolk sac. Sodium aurothiomalate (25 or 500 micrograms/ml) had no effect on the total uptake of radio-label but caused a significant increase in the proportion of total radioactivity captured that was associated with the yolk sac. These data indicate that suramin, by interfering with both the uptake and intralysosomal digestion of protein, and sodium aurothiomalate, by inhibiting digestion of captured protein, disturb the normal pathway of yolk sac-mediated protein utilization with a consequent diminution of the supply of amino acids to the conceptus. The effects of suramin are seen only at high concentration, those of sodium aurothiomalate at much lower concentrations. It is likely that the two drugs exert their teratogenic action by their effects on the yolk sac nutritional pathway with resultant amino acid deprivation of the conceptus at a critical stage of development.

Abnormalities, Drug-Induced↗

Psychosocial factors and depressive symptoms.

The relationship of four psychosocial factors (family history of psychiatric illness, early loss of a nurturing relationship, stressful life events, and low social support) to depressive symptoms was investigated in university students using a cross-sectional design. A depressed group (N = 160), selected from a consecutive sample of students diagnosed depressed and attending a university psychiatric service, was contrasted with a nondepressed group (N = 206) randomly selected from the general university population within three strata (sex, academic level, and month of the year) to match the clinic group. Depression was measured by the Beck Depression Inventory. It was found that family history of psychiatric illness, stressful life events, and lack of a confidant all had a significant, independent direct effect on the occurrence of depressive symptoms, but early loss was not associated. An interaction effect among the psychosocial factors was not demonstrated.

Adolescent↗

Phosphatidylcholine and 4-methylumbelliferyl phosphorylcholine hydrolysis by purified placental sphingomyelinase.

We present evidence which indicates that highly purified placental acid sphingomyelinase hydrolyses [14C]phosphatidylcholine [( 14C]PC) and the synthetic phosphodiester 4-methylumbelliferyl phosphorylcholine (4-MUPC). Hydrolysis was achieved by phospholipase C phosphodiesterase action. Of the several detergents tested, sodium taurocholate alone was necessary for PC hydrolysis, while 4-MUPC was hydrolysed independent of any detergent requirement. The pH optima for the reactions were 4.6-4.8 for PC hydrolysis and 4.8-5.0 for 4-MUPC hydrolysis. As with sphingomyelin hydrolysis, degradation of both PC and 4-MUPC was inhibited by 5'-, 3'-, and 2'-AMP, 5'-AMP being the most effective of the three. Furthermore, the phosphodiesterase activity against PC and 4-MUPC copurified with sphingomyelinase from human placenta and cross-reacted with a specific anti-sphingomyelinase monoclonal antibody, strongly indicating identity of the phosphodiesterases. This explains phospholipase C deficiency in sphingomyelinase-deficient Niemann-Pick disease cells.

Adenine Nucleotides↗

Psychiatric aftercare in a metropolitan setting.

In the face of the trend toward brief hospitalization, rising re-admission rates and other indices of poor community adjustment, concern has developed about the adequacy of psychiatric aftercare services. The authors report on a comprehensive study of psychiatric aftercare in a large metropolitan area (population 2.5 million). The study followed prospectively a group of 747 patients, representative of a significant proportion of patients in the care system. The findings document inadequacies in hospital-based discharge planning, unbalanced use of aftercare services and poor patient outcomes six months and two years post-discharge. The study found heavy reliance on medical/therapeutic aftercare services with a relative neglect of housing, vocational/educational, financial and social/recreational services. Despite the large volume of medical/therapeutic service use, the patient group had a high readmission rate, high levels of symptomatology and poor social adjustment on follow-up. The authors suggest that community-based practitioners with specialized training in psychiatric rehabilitation would improve the system of aftercare.

Adult↗

Comparative effects of cathepsin inhibitors on rat embryonic development in vitro. Evidence that cathepsin D is unimportant in the proteolytic function of yolk sac.

The effects of two proteinase inhibitors, leupeptin and pepstatin on the development of 9.5-day rat conceptuses in vitro has been studied. All cultures were of 48 h duration and the inhibitors were present throughout the entire period. When pepstatin was added to the culture medium (5-25 micrograms/ml) conceptuses developed and grew to an extent that did not differ from untreated controls. However, leupeptin (1-4 micrograms/ml) caused severe growth retardation and abnormal development of conceptuses. The effects of the two inhibitors on the hydrolysis of 125I-labelled BSA and haemoglobin by homogenates of 10.5-day yolk sac indicated the biochemical basis for the differential toxic effects of the two inhibitors on development. Leupeptin was highly inhibitory of the degration of both substrates whereas pepstatin caused no inhibition of 125I-labelled BSA hydrolysis, and only a slight inhibition of haemoglobin hydrolysis. These observations demonstrate that cathepsin D, a lysosomal aspartic proteinase that is specifically inhibited by pepstatin is not involved in yolk-sac-mediated protein utilization by early organogenesis-phase conceptuses and that lysosomal cysteine proteinases, specifically inhibited by leupeptin, are of paramount importance in this yolk sac function.

Animals↗

Solid-phase assay for the detection of low-abundance enzymes, and antibodies to enzymes in immune reactions, using acid sphingomyelinase as a model.

The development of a solid-phase immunosorbent assay, suitable for use with enzyme antigens, is described. Acid sphingomyelinase and a mouse monoclonal anti-sphingomyelinase antibody have been used to determine optimal conditions for the assay. The assay involves immobilization of a second antibody (anti-mouse IgG) in the wells of a polyvinyl microtiter plate. Soluble immune complexes of first antibody (monoclonal anti-sphingomyelinase) and antigen (sphingomyelinase), incubated in separate vials, are then reacted in the anti-mouse IgG-coated assay wells, and the extent of the cross-reaction between antibody and antigen is measured by direct assay of enzyme retained in the well. A necessary condition of the assay is that antibody must not inhibit enzyme activity, which makes it especially suitable for monoclonal antibodies. The assay finds useful application in hybridoma fluid screening, equivalence point determination, and demonstration of cross-reacting enzyme from various tissue sources.

Animals↗