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Biomedical subjects

S Smith

Publications and source records attributed to S Smith.

At least 829 records · Page 46Linked to original sources

Effects of thyroxine on mitochondrial morphology and uptake of 35S in embryonic chicken livers.

Ultrastructural analyses of reactions of mitochondria in hepatocytes of chicken embryos to low levels of exogenous thyroxine (T4) reveal that such reactions (overall swelling accompanied by disruption of crest geometry) first take place at about 10 days of incubation, T4 having been administered on the 6th day. Physically altered mitochondria may be seen after 11-12 days of incubation but are no longer evident by 13 days. Correlated with the initial evidence of T4 effects on mitochondria at 10 days of incubation is a spurt in hepatocyte proliferation. The time correlation observed between T4 induced mitochondrial changes in morphology and abrupt increases in rates of cell proliferation, suggests that liver nuclear receptors for thyroxine are unavailable prior to 9-10 days of incubation. Golgi complexes within the hepatocytes appear to be especially active in the production of electron-opaque vesicles from at least the 8th day of incubation to 11-12 days. Uptake of 35S (probably into chondroitin sulphates) was found to be fifteen times greater on the 8th day of incubation than at 15 days. This correlates with the period of heightened activity of the Golgi complex. In livers exposed to T4 on the 6th day, uptake of 35S was higher on the 9th and 10th days of incubation as compared to controls.

Animals↗

Metabolic and hormonal effects of 25-mg and 50-mg 17 beta-estradiol implants in surgically menopausal women.

A prospective study involving 12 surgically menopausal women was undertaken to determine whether 17 beta-estradiol pellets could maintain bone mineral content without inducing adverse cardiovascular side effects. Surgically menopausal women were randomly selected to have either 25-mg or 50-mg pellets implanted subcutaneously. The bone mineral content of the midshaft of the nondominant radius in the combined group--measured by single photon absorptiometry--increased by 1.8% over the two-year period of observation (P less than .03); the distal bone mineral content of the radius was maintained at 0.8% per annum. No adverse effects were noted in the coagulation profiles or in the coagulation inhibition and fibrinolysis assays of both groups. Serum high-density lipoprotein cholesterol and triglycerides were unaltered, but serum cholesterol values decreased during the six-month period of observation by 14 mg/dL (P less than .05) and 11 mg/dL in the 25- and 50-mg groups, respectively. Carbohydrate and insulin metabolism was unaffected, as was the systolic and diastolic blood pressure. There were no significant intergroup differences in any of the parameters measured. The serum estradiol/estrone ratios of 1.45 and 1.59 reflected a physiologic estrogen milieu at the 25- and 50-mg dosages. Subcutaneous 17 beta-estradiol pellets can effectively maintain the bone mineral content of surgically menopausal women without inducing adverse cardiovascular side effects.

Adult↗

Murine autoimmune oophoritis, epididymoorchitis, and gastritis induced by day 3 thymectomy. Autoantibodies.

In adult mice thymectomized at age 3 days (D3TX), increased incidences and/or levels of organ-specific antibodies to oocytes and/or zona pellucida, to testicular cell-sperm-differentiation antigens (TSDA), and to gastric parietal cells were detected, and these correlated significantly with oophoritis, orchitis (not epididymovasitis), and gastritis, respectively. The autoantibodies occurred in mice with the corresponding endogenous antigens. Thus, anti-oocyte/zona antibodies were detected in female, anti-TSDA antibodies in male, and anti-parietal cell antibodies in both sexes. Anti-oocyte/zona antibodies were first detected at age 5-6 weeks and were absent by 25 weeks. Serum antizona antibodies, but not anti-oocyte antibodies, inhibited mouse fertilization in vitro. In contrast, antibodies to sperm acrosome and antibodies to sperm surface did not correlate with testicular or epididymal disease. Moreover, both male and female mice had increased levels of anti-sperm surface antibodies, indicating that the sperm antigens detected may not be organ-specific. In addition, sera from 5-10% of D3TX mice reacted with a wide spectrum of epididymal and testicular antigens with defined cellular locations but of yet unknown specificity. Although the incidence of antibodies to cytoskeletal antigens was not significantly elevated after D3TX, anti-nuclear antibodies were more frequently detected in (SWR/J X A/J) F1 (SWRAF1) and (C57 BL/6J X A/J) F1 (B6AF1) mice after D3TX.

Animals↗

Prognostic importance of hypodiploid hemopoietic precursors in myelodysplastic syndromes.

It has been suggested that a poor prognosis and the development of leukemia in patients with myelodysplasia may be related to chromosomal abnormalities. We measured the DNA content of bone marrow cells with flow cytometry in 19 hematologically normal subjects and in 70 patients who had recently been diagnosed as having myelodysplasia. Thirty-four of the patients were found to have aneuploidy. This was not related to the percentage of blast cells in the bone marrow, and there was no demarcation in terms of DNA content between patients with a high percentage of blast cells and those with a low percentage of such cells. Patients with hypodiploid marrow cells had a significantly shorter survival time than other patients (P = 0.001). Patients with hyperdiploid marrow and those whose marrow had a normal DNA content had similar survival times. Hypodiploidy appears to be a better indicator of poor survival than the marrow blast-cell count. Patients with sideroblastic anemia invariably had cells with a normal or high DNA content; none of these patients died during the study. Our data suggest that there is a relation between the loss of chromosomal material and progression toward a leukemic phenotype. It is tempting to speculate that this process may involve a loss of negative regulatory genes ("anti-oncogenes").

Aneuploidy↗

Cyclophosphamide in the seminal fluid of treated males: transmission to females by mating and effect on pregnancy outcome.

Cyclophosphamide is an anticancer and immunosuppressant drug administered to men of reproductive age. In the present study the ability of cyclophosphamide and/or its metabolites to enter secretions of the male reproductive tract, to be transmitted to the female partner upon mating, and to alter progeny outcome was assessed. [14C]Cyclophosphamide was given intravenously to adult male Sprague-Dawley rats; radiolabel (greater than 96% cyclophosphamide) was first found in seminal vesicle fluid within 10 min and equilibrated with plasma radioactivity within 30 min. Furthermore, radiolabel from cyclophosphamide given to the male was transmitted to the female upon mating up to 5 hr post-drug treatment. To study possible consequences of paternal treatment with cyclophosphamide on pregnancy outcome, male rats were administered a single dose of cyclophosphamide, 10, 30, or 100 mg/kg, or saline immediately prior to cohabitation with females in proestrus. There was no effect on the number of pregnant females per sperm-positive females but there was a significant decrease in the number of implantations per pregnant female per male and in the number of live fetuses per pregnant female per male. There was a twofold increase in preimplantation loss. There was no increase in postimplantation loss or number of abnormal fetuses. These results demonstrate that cyclophosphamide not only penetrates the male reproductive tract but that it can be transmitted to the female partner and can affect progeny outcome.

Animals↗

Oral ibuprofen: evaluation of its effect on peritendinous adhesions and the breaking strength of a tenorrhaphy.

In a study of 21 primates, treatment with oral ibuprofen significantly reduced the force required for tendon gliding following flexor tendon injury in zone II. Tendons that were partially lacerated but not repaired required less force for tendon motion than those repaired. Ibuprofen also reduced the breaking strength of completely divided and repaired extensor tendons. The addition of a piece of chromic suture buried across the extensor tenorrhaphy site significantly increased the breaking strength of the repair in control and treated animals alike. These findings were observed at 4 and 6 weeks after tendon injury and repair. No adverse reactions to the medication were observed.

Administration, Oral↗

The basis of Stroop interference involving the multimodal correlates of auditory pitch.

A pure auditory tone has a range of multimodal qualities that are determined by its pitch. A reaction-time task was used to demonstrate that subjects respond immediately and automatically to these qualities. Subjects were required to press one of two keys depending on which word, from a limited set, appeared on a microcomputer screen. The words were antonyms that represented multimodal stimulus qualities, and they were assigned to alternative responses so that the two words that shared the same response were correlated in the same way with pitch. As an incidental stimulus, either a 50 Hz tone or a 5500 Hz tone accompanied the presentation of each word. Subjects were found to respond more slowly when the multimodal qualities of the tone were incongruent with the qualities represented by the test word. When the stimulus-response mapping rules were changed, however, the Stroop effect did not occur; suggesting that a polarised semantic code of the incidental tone, that embraces its multimodal features, accesses the same semantic register as the equivalent code for the test word itself.

Auditory Perception↗

Chromatographic purification and identification of polar metabolites of benazolin-ethyl from soybean.

The metabolism of benazolin-ethyl (4-chloro-2-oxobenzothiazolin-3-ylacetic acid ethyl ester), a post emergence herbicide, has been studied in soybean using (14C)-phenyl labelled compound. Preliminary studies were performed on excised soybean leaves. Following hydrolysis of the ethyl ester to benazolin acid (4-chloro-2-oxobenzothiazolin-3-ylacetic acid), extensive metabolism to polar conjugates was observed. The polar fraction from a Bligh-Dyer extraction was purified by solvent partitioning, preparative TLC and reverse phase HPLC with ion suppression. The two major metabolites were characterised by fast atom bombardment mass spectrometry with accurate mass determination as an aspartate conjugate and a malonyl-beta-glucose ester of benazolin acid. Subsequent experiments were performed by spraying intact plants at growth stage V4. The major polar metabolite isolated one month after treatment was identified as the aspartate conjugate by mass spectrometry and high resolution nuclear magnetic resonance spectroscopy.

Aspartic Acid↗

The influence of oxygen tension on the long-term growth in vitro of haematopoietic progenitor cells from human cord blood.

Growth of low density human cord blood cells in long-term suspension culture was evaluated at incubation conditions of 5% carbon dioxide in approximately 20% (normal incubator) oxygen tension or in 5% (low) oxygen tension. During the first 5 weeks there was no difference in the numbers of morphologically recognizable cells grown at either oxygen tension, while growth was superior from weeks 5 to 8 at approximately 20% oxygen tension. For the first 5 weeks, growth of granulocyte-macrophage progenitors (CFU-GM) was superior at 5% oxygen tension during the long-term and semi-solid culture phases and least impressive in the long-term and semi-solid cultures incubated at approximately 20% oxygen. This trend was reversed after 5 weeks and after 8 weeks there were no detectable CFU-GM in suspension cultures at 5% oxygen while steady state levels of CFU-GM were maintained for greater than 12 weeks in suspension cultures at approximately 20% oxygen. Semi-solid cultures for erythroid (BFU-E) and multipotential (CFU-GEMM) progenitors were incubated at approximately 20% oxygen only. During the first 4 weeks, the growth of BFU-E and CFU-GEMM was superior at 5% oxygen during long-term culture. Numbers of these cells decreased by week 5 and at this time growth was better in the long-term cultures grown at approximately 20% oxygen. By week 6, no BFU-E or CFU-GEMM were detectable. Thus, growth of cord blood at low oxygen tension gives an initial enhancement in output of progenitor cells, but this appears to be at the expense of continued production.

Cells, Cultured↗

Role of atrial natriuretic peptide in adaptation of sodium excretion with reduced renal mass.

The kidney maintains constancy of body fluid volume by regulating urinary sodium (Na) excretion. In chronic renal failure, the reduction in glomerular filtration rate (GFR) is accompanied by an increase in Na excretion per nephron if dietary Na intake is not changed. Reduction in Na intake in proportion to reduced GFR obviates this adaptive increase in tubule Na excretion. To examine the potential role of endogenous atrial natriuretic peptide (ANP) in modulating the enhanced Na excretion per nephron in chronic renal failure, we studied rats subjected to 5/6 nephrectomy or sham operation on low, normal, and high Na intakes. Urinary Na excretion increased with increasing dietary Na in all groups, and Na excretion per nephron was increased in 5/6 nephrectomized rats as compared with sham-operated rats on the higher Na intakes. Plasma ANP levels were unaffected by dietary Na manipulations in sham-operated rats, but rose progressively in 5/6 nephrectomized rats with increasing Na intake. Despite extensive nephron reduction, however, plasma ANP levels failed to rise in uremic rats on low Na diets and in this group Na excretion per nephron also failed to rise. We conclude that enhanced ANP secretion may play an important role in promoting the adaptive increase in Na excretion per nephron in chronic renal failure. Restriction of dietary Na in the setting of reduced GFR obviates the stimulation of ANP secretion as well as the adaptive increase in Na excretion rate per nephron.

Adaptation, Physiological↗

Regional Review Boards of Ontario: a medico-legal review.

The functioning of the Regional Review Boards of Ontario (RRB) or their equivalents in other provinces has not been previously reviewed. This study reviews socio-demographic and clinical data of 248 patients seen between 1974 and 1983 by the RRB. The RRB heard 132 applications as 116 were withdrawn. The results are compared with 173 matched inpatient controls. Applications by psychiatrists were infrequently withdrawn or revoked. Long delays between the time of application and the hearing, and a trend towards increasing numbers of applications were noted. Schizophrenia and affective disorder were the most prevalent diagnosis with alcohol abuse and organic brain syndrome being less common among applicants. An increase in duration of stay and transfer to chronic care institutions were found among applicants. Results suggest that RRB's are not 'rubber stamping bodies' and should be more readily available and should have increased public accountability. Future changes to the Mental Health Act should be based on scientific data.

Commitment of Persons with Psychiatric Disorders↗

Ultrastructure of in-vitro oocyte maturation in cattle.

Cumulus-oocyte complexes were collected from cows at an abattoir by aspiration from small (1-6 mm) antral follicles. After different periods of culture the complexes were processed for electron microscopy. Cumulus expansion occurred at 12-18 h of culture and concomitantly enlargement of cumulus cell projections in the perivitelline space was seen. At 48 h the innermost cumulus cells flattened and adhered tightly to the zona pellucida. In the oocyte the following changes occurred: at 0-3 h of culture the perivitelline space developed; at 3-12 h disconnection of the junctions between cumulus cell projections and the oolemma, and the concomitant breakdown of the nucleus was observed; at 12-18 h the mitochondria moved from a peripheral location to a more even spatial distribution and the Golgi complexes decreased in size; at approximately 18 h the smooth endoplasmic reticulum formed large aggregates surrounded by mitochondria; at 18-21 h the first polar body was abstricted; at 24-40 h the cortical granules spread; at 30-40 h the polar body degenerated in some specimens; at 40-48 h the perivitelline space decreased in size; and at 48 h one oocyte was in the process of fragmentation. It is concluded that nuclear and cytoplasmic oocyte maturation is simulated in vitro. However, certain deviations were noticed compared to in-vivo maturation.

Animals↗

Multiple-angle, variable-interval, nonorthogonal MRI.

Multiple-angle, variable-interval, nonorthogonal (MAVIN) MRI is a new, time-saving technique that allows for the independent choice of slice angle and position for each slice in a multiangle pulse sequence. By appropriate adjustment of the slice-select radiofrequency pulse and the slice-select and readout magnetic-field gradients, the interval and angle of each slice may be individually chosen. MAVIN can reduce examination time in studies of the lumbar spine, orbits, knees, and heart, where nonparallel oblique scanning may be necessary and would otherwise require the use of additional pulse sequences. Loss of signal in the region of intersection of multiple planes due to local changes in effective repetition time is a practical limitation. For this reason, scan planes are chosen so that the intersection does not overlie the region of interest.

Humans↗

How useful is weight reduction in the management of hypertension?

A group of previously untreated obese hypertensive patients were started on a weight reduction programme supervised by two dietitians working in a general practice surgery. It was stressed from the beginning of the programme that reducing blood pressure was the purpose of the diet. The results of follow-up after six months are presented together with results for a control group of obese hypertensive patients not receiving dietary advice or drug therapy, but being followed by the general practitioner. The weight, systolic blood pressure and diastolic blood pressure of the dieting hypertensive group were significantly lower than those of the non-dieting group after six months. However, the drop-out rate was significantly higher for the dieting group than for the non-dieting group.The results of a separate comparison between a control group of obese normotensive patients following the same dietary programme and the group of dieting obese hypertensive patients are also presented. Attendance rates and weight loss achieved were significantly better for the hypertensive group than for the normotensive group after 12 months.Weight reduction appears to be an effective first-line therapy for approximately 50% of obese patients with mild to moderate hypertension, and raised blood pressure appears to provide motivation for such patients to attend a dietitian's clinic and to lose weight.

Adult↗