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Biomedical subjects

K Smith

Publications and source records attributed to K Smith.

At least 505 records · Page 28Linked to original sources

Effect of adrenalectomy and steroid treatment on rat skin cytosol glucocorticoid receptor.

Using an exchange assay to measure occupied and unoccupied binding sites, the glucocorticoid receptor in rat skin cytosol has been measured after adrenalectomy and parenteral steroid administration. Adrenalectomy increased the number of receptor sites with maximal effect after 5 days, after which numbers decreased to those of intact animals. Injection of adrenalectomized animals with the unlabelled agonist corticosterone resulted in a rapid dose-related decrease in the number of cytosolic receptor sites at 30 min whereas the antagonist progesterone had no effect. It is concluded that changes in glucocorticoid concentration lead to rapid inverse changes in cytosolic receptor.

Adrenalectomy↗

The usefulness of the Denver Developmental Screening Test to predict kindergarten problems in a general community population.

The Denver Developmental Screening Test (DDST) was administered to 2,569 children five to seven months prior to starting kindergarten in September 1980 in a geographically well-defined community. The test was administered by trained public health nurses. At the end of the 1980-1981 school year, all 163 kindergarten teachers in the area completed a rating form for each child in their class. The rating form determined global ratings of: 1) learning abilities; 2) classroom behavior; 3) amount of special attention required; and 4) referrals to special education services outside the classroom. The specificity of the DDST in predicting kindergarten teacher ratings was 99 per cent for all areas. Test sensitivity varied from 5 per cent to 10 per cent in detecting problems in the four areas. The predictive values of an positive test varied from 31 per cent for behavior problems to 62 per cent for extra attention required in the classroom. Negative test predictive values varied from 79 per cent to 93 per cent. These results based on kindergarten teacher ratings suggest that, because of the low sensitivity and modest predictive value, the DDST may be relatively inefficient to use in a school entry screening program in a general community population of children.

Child, Preschool↗

Dose, plasma concentration and response relationships of D-penicillamine in patients with rheumatoid arthritis.

Plasma concentrations were measured in 10 patients with rheumatoid arthritis taking 250 mg, 500 mg and 750 mg of D-penicillamine daily. A disproportionate rise in the dose adjusted area under the plasma concentration vs time curve suggested dose dependent kinetics for D-penicillamine. Marked interindividual variability was seen with pharmacokinetic parameters and no correlations were observed between side effects or response and plasma concentrations of reduced D-penicillamine.

Adult↗

Ectopic parathyroid hormone production by a squamous carcinoma of the tonsil.

A patient with recurrent squamous carcinoma of the neck showed hypercalcemia with the immunoreactive parathyroid hormone (PTH) level within the upper limits of normal range, this being inappropriate for the degree of hypercalcemia. An immunoreactive peak of PTH was found in the tumor tissue extract, which appeared on column chromatography to be in the region of elution of pure bovine PTH. The tumor tissue showed positive immunoperoxidase reaction for PTH compared with negative reaction when the patient had normocalcemia. These findings are strong evidence that the tumor produced a PTHlike substance.

Carcinoma, Squamous Cell↗

Maternal effects and temperature-sensitive period of mutations affecting embryogenesis in Caenorhabditis elegans.

We have used standard tests to investigate the nature of gene expression of a new set of temperature-sensitive mutants defining 30 emb genes (essential for embryogenesis) in the nematode Caenorhabditis elegans. The mode of gene expression as determined by progeny tests for parental effects divides the genes into four classes. For 18 genes maternal gene expression is necessary and sufficient for normal embryogenesis; for 2 genes zygotic expression is necessary and sufficient; for 7 genes either maternal or zygotic expression is sufficient; for 3 genes both maternal and zygotic expression are necessary. One mutant displayed partial paternal sufficiency. The results of temperature-shift experiments define two "execution stages," corresponding to the limits of the temperature-sensitive period (TSP), and indicate the nature and the time of action or synthesis of the gene products. Most of the maternally expressed genes have very early execution stages indicating translation before fertilization, but some are temperature sensitive late in embryogenesis. Early execution stages for 2 zygotically necessary genes demonstrate that the zygotic genome can be active in the earliest stages of embryogenesis. All taken together, the mode of gene expression, TSP, and arrest stage (terminal phenotype) allow us to classify functionally and begin to order the genes essential for embryogenesis. The results indicate a preeminent role for maternal genes and gene products in embryogenesis, in agreement with the results of others.

Animals↗

Treatment of sickle cell anemia with 5-azacytidine results in increased fetal hemoglobin production and is associated with nonrandom hypomethylation of DNA around the gamma-delta-beta-globin gene complex.

Increased production of fetal hemoglobin (HbF) was observed in a patient with sickle cell anemia treated with 5-azacytidine. Each of four courses of therapy resulted in a rapid and prolonged increase in the percentage of HbF containing reticulocytes (F reticulocytes) and HbF containing erythrocytes (F cells). The percentage of HbF in peripheral blood rose from 1.8 to 8.9%. The rise in HbF production was accompanied by an increase in peripheral blood hemoglobin concentration from 8 to 12 g/dl and an increase in mean erythrocyte volume. Treatment with 5-azacytidine resulted in hypomethylation of total genomic and a Y-chromosome-specific DNA fragment isolated from both peripheral blood and bone marrow. Of 15 restriction enzyme sites around the gamma-delta-beta-globin gene complex, only 2 became hypomethylated: one 107 bases 5' to the gamma G and the other 107 bases 5' to the gamma A globin genes.

Adult↗

The role of catheter surface morphology and extractable cytotoxic material in tissue reactions to urethral catheters.

Batches of urethral catheters associated with stricture formation during clinical usage were found to be amongst those causing marked acute and chronic inflammation after subcutaneous implantation in rats. The degree of inflammation did not correlate with the surface roughness of catheters assessed by scanning electron microscopy, but showed an excellent correlation with the cytotoxic effects of soluble extracts from catheters on macrophage monolayers in tissue culture. The findings suggest that stricture formation may be chemically induced and may not relate to surface roughness of catheters.

Animals↗

Family loss and hospital suicide.

In 19 consecutive cases of inpatient suicide occurring over many years, 18 out of the 19 cases (95 percent) were judged to have a significant "family" loss issue affecting the suicide. In five cases (26 percent), there seemed to be a powerful institutional attachment and loss threatened that attachment. In 13 cases (68 percent), a major family issue was involved which included events that estranged the patient from the family (real or imagined); divorce or separation issues; death or illness of a significant other; a family that insisted on continued treatment (and/or growth). In 13 cases (68 percent), significant communication from or about the "family" occurred which seemed to have an impact on the suicidal behavior often within days of the final event. In 10 cases (53 percent), an actual family visit had occurred within two weeks of the death. These issues are discussed and case examples presented.

Adult↗

Characterization of the glucocorticoid receptor in rat skin.

Using an exchange assay to measure occupied and unoccupied binding sites the interaction between [3H]triamcinolone acetonide and rat skin cytosol proteins was studied. A binding site with a high affinity (dissociation constant = 7 x 10(-10) mol/l) and a low capacity (400-600 fmol/mg protein) for triamcinolone acetonide was detected. The binding was specific to corticosteroids; fluorinated steroids showed a higher affinity than natural steroids. Non-corticosteroids, with the exception of progesterone, had little or no affinity for the binding site. At 0 degrees C the second-order rate constant of association was 2.23 x 10(6) mol/l per min and the first-order rate constant of dissociation was 1.6 x 10(-4) per min. In the absence of dithiothreitol and molybdate the specific binding was rapidly abolished. The binding was also labile to heating and proteolytic enzymes. One day after adrenalectomy there was a significant increase in the number of assayable binding sites in the cytosol. The results are consistent with the binding protein being the physiological glucocorticoid receptor in rat skin.

Adrenalectomy↗

Scope of scanning electron microscopy, transmission electron microscopy and freeze fracture technique in diagnostic cytology of effusions.

A review of the literature on the application of scanning electron microscopy (SEM) and transmission electron microscopy (TEM) to cytodiagnosis of neoplastic cells in effusion fluid reveals a lack of consensus as to which of the techniques is most beneficial to a cytologist for a satisfactory diagnosis. The purpose of this study is therefore to critically evaluate the relative merits of SEM, TEM and freeze-fracture (FF) techniques in enhancing the diagnostic "sensitivity" of ultrastructural cytology. Two cases of adenocarcinoma, one case of mesothelioma and one case of small cell undifferentiated carcinoma of the lung were studied in detail by SEM, TEM and FF techniques. A comparative analysis of the results demonstrates that SEM is a rapid and useful technique where the microvilli on the tumour cell surface is the most prominent feature especially in adenocarcinomas. The major handicap of SEM becomes evident in cases where the extreme variability of the surface morphology amongst tumour cells makes it difficult to establish a diagnosis with confidence. TEM along with light microscopy (LM) of toluidine blue sections gives us the most comprehensive method for cyto-diagnosis and is particularly useful in cases where LM cytology alone is inconclusive. It has the added advantage of revealing diagnostically significant nuclear and cytoplasmic features which are helpful in differentiating a benign from a malignant cell and in some instances the probable site of the primary neoplasm. FF technique, though not conducive to a routine diagnostic situation, is of benefit in demonstrating the organization of junctional complexes. From preliminary studies it appears that the tight junctions in adenocarcinoma are different from those seen in small cell carcinoma. In mesothelioma, gap junctions are invariably present, but they are not seen prominently in adenocarcinoma or small cell carcinoma. Thus in poorly differentiated tumours where LM and TEM are inconclusive, FF may prove useful. It is concluded that such coordinated studies in the future have the potential to better our understanding of the nature and behaviour of tumour cells in effusion fluid.

Adenocarcinoma↗

Laboratory model for infectious bovine keratoconjunctivitis: the pathogenicity of different strains of Moraxella bovis, pathology and ultrastructural observations.

Further studies were made using C57 mice pretreated with a corticosteroid and inoculated with Moraxella bovis by instillation, as a model for infectious bovine keratoconjunctivitis. Strains of M bovis which had previously been tested in cattle produced a generally similar range of pathogenicity when tested in mice. The pathology in the mouse model closely resembled that in cattle and the value of the model for studies on M bovis was confirmed.

Animals↗

Double-blind controlled trial of topical acyclovir in genital herpes simplex virus infections.

Sixty-nine patients with first episodes and 111 with recurrent episodes of genital herpes simplex virus (HSV) infection were enrolled in a double-blind trial comparing a 5 percent topical acyclovir ointment versus placebo, polyethylene glycol (PEG). Among acyclovir recipients with first episodes of genital herpes, the mean duration of viral shedding from genital lesions, 2.0 days, mean duration of local pain or itching, 3.6 days, and mean time to healing of lesions, 11.2 days, were less than in placebo recipients 4.6, 6.7, and 15.8 days, respectively (p less than 0.05 for each comparison). Among patients with recurrent genital herpes, the mean duration of viral shedding from genital lesions was 0.8 days in acyclovir recipients compared with 1.7 days in placebo recipients (p less than 0.001). Among men with recurrent genital herpes, the mean time to crusting and healing of lesions was 3.5 and 7.5 days in acyclovir recipients compared with 5.0 and 9.7 days in placebo recipients, p = 0.03 and 0.07, respectively. No significant differences in the duration of symptoms or healing times were noted between acyclovir- and placebo-treated women with recurrent genital herpes. Acyclovir therapy was not associated with a decrease in frequency of clinical recurrences or an increase in the time of the next recurrence in patients with either first or recurrent genital herpes. Topical acyclovir appears effective in shortening some of the clinical manifestations of genital HSV infections.

Acyclovir↗