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Biomedical subjects

C M Wilson

Publications and source records attributed to C M Wilson.

At least 145 records · Page 8Linked to original sources
PubMed1985

Plasma bupivacaine levels associated with extradural anaesthesia for caesarean section.

Plasma bupivacaine levels were measured in 47 women undergoing extradural Caesarean delivery. They were divided into four groups according to the following dose regimens using 0.5% bupivacaine. Group A were given a bolus of 20 ml with increment after 20 minutes. Groups B and C were given 10 ml initially with further increments if required at 10 minutes (group B) and 20 minutes (group C); Group D consisted of patients who had an extradural block extended for emergency Caesarean delivery. In the elective groups the highest and most rapidly achieved values were associated with group A and the lowest levels found in group C. The highest levels of all were found in the emergency group. The investigation indicates that slow controlled induction of extradural anaesthesia for Caesarean section greatly reduces the risk of local anaesthetic toxicity.

Anesthesia, Epidural↗
PubMed1985

The interaction of androgen and thyroid hormones in the submandibular gland of the genetically hypothyroid (hyt/hyt) mouse.

The development and maintenance of granular convoluted tubule cells in the mouse submandibular gland (SMG) and the production of renin-1, renin-2, and epidermal growth factor (EGF) by these cells are under complex hormonal control. Hypophysectomy causes profound involution and loss of renin activity in this gland. We have shown previously that T4 acts synergistically with 5 alpha-dihydrotestosterone (DHT) to restore SMG morphology and renin-2 activity in hypophysectomized female mice. Investigating the mechanism of T4 and DHT interaction in the hypophysectomized mouse proved impractical, and in the present study we have used genetically hypothyroid (hyt/hyt) mice that carry the structural gene for renin-1 but not for renin-2. Levels of SMG renin-1 and EGF in hyt/hyt mice were less than 4% of those in euthyroid (hyt/+) littermates. Administration of a pharmacological dose of T4 (2.5 micrograms/g BW X day, ip) to male hyt/hyt mice for 18 days restored SMG renin-1 and EGF to near-normal levels. The weights of SMG, seminal vesicle, and epididymis were also lower in hypothyroid mice and increased in response to T4. The effect on SMG renin-1 and EGF of either DHT (150 micrograms/g BW every other day, sc) or T4 (0.025-2.5 micrograms/g BW.day, ip) was blunted in female hyt/hyt mice. A combination of DHT and T4 (0.1 microgram/g BW.day) that restored total circulating T4 and T3 to physiological levels acted synergistically to increase SMG renin-1 and EGF. The administration of 2.5 micrograms T4/g BW.day plus DHT for 7 days increased the specific activity of SMG renin-1 and EGF to levels approaching those in euthyroid littermates given the same treatment. T4 (0.1 microgram/g BW.day) did not alter the quantity or sedimentation characteristics of high affinity androgen-binding protein in SMG from female hyt/hyt mice and induced SMG renin-1 in Tfm/Y mice. Thus, T4 does not appear to exert its effect via the androgen receptor. The administration of DHT and T4 to female hyt/hyt mice produced lower circulating levels of both T3 and T4 than the same dose of T4 given alone, suggesting that DHT does not act by enhancing the conversion of T4 to T3. This study demonstrates that the interaction of T4 and DHT is not a pharmacological phenomenon, but occurs at doses of T4 that restore serum T3 and T4 in female hyt/hyt mice to normal or near-normal levels.(ABSTRACT TRUNCATED AT 400 WORDS)

Androgens↗
PubMed1985

Delayed pulmonary maturation in the fetus of the streptozotocin-diabetic rat.

Pulmonary maturation was studied in fetuses in streptozotocin-diabetic rats on the final four days of gestation. Diabetes was induced prior to conception by the intravenous injection of streptozotocin. Fetuses were hyperglycemic but did not manifest hyperinsulinemia. Whole lung total phospholipid, phosphatidylcholine, and disaturated phosphatidylcholine were significantly decreased in the diabetic group on day 21 (term = 22 days), but not prior to or after that point in gestation. Morphologic analysis also revealed a decreased number of type II cells and lamellar bodies per alveolar lining cell in the diabetic group only on day 21, coincident with the changes in phospholipid analysis. Activities of enzymes involved in fetal pulmonary phospholipid synthesis were measured to see if differences could account for the observed developmental delay. No significant differences between diabetic and control lungs were noted in any of the enzymes studied from days 20-22, with the exception of an increase in cholinephosphate cytidylyltransferase activity in the diabetic fetuses on day 22. Immaturity in both biochemical and morphologic indices of lung development was present at a specific time late in the diabetic rat gestation. This maturational delay could not be accounted for by changes in the activities of enzymes involved in phospholipid synthesis. The fetus of the streptozotocin-diabetic rat provides a useful model to study the effects of hyperglycemia on fetal lung development.

Animals↗
PubMed1984

The major core histone antigenic determinants in systemic lupus erythematosus are in the trypsin-sensitive regions.

Antibody responses against nucleosome core histones in systemic lupus erythematosus have been shown, by immunoblotting, to be directed largely against the trypsin-sensitive regions of the histones. These occur at the N-terminal regions of all 4 core histones and at the C-terminal ends of H2A and H3. Since these regions are often not the most antigenic when individual histones are used as immunogens, and appear to be exposed in the nucleosome, the active immunogens in systemic lupus erythematosus seem likely to be chromatin-bound, rather than free, histones.

Amino Acid Sequence↗
PubMed1984

Corticosteroid binding by fetal rat and rabbit lung in organ culture.

To further characterize glucocorticoid action in fetal lung cells, we investigated corticosteroid metabolism and binding in explants of fetal rat and rabbit lung. Cortisone (E) was concerted to cortisol (F) and bound by receptor with a time course only somewhat slower than for F. Production of F (0.243 pmol/min/mg DNA) was the same in male and female rabbits and was not affected by prior exposure to glucocorticoid in utero or in culture. The t 1/2 for dissociation of nuclear-bound [3H]F was 84 min on changing the culture medium and 21 min on addition of excess non-labeled dexamethasone. Dissociation of [3H]dexamethasone was approx 5-fold slower by both procedures. The KD for nuclear binding of dexamethasone, F, E, and corticosterone in rabbit lung were 0.7, 7.3, 6.8 and 70.6 nM, respectively. In rat lung, the KD for dexamethasone was 6.8 nM. The concentrations of dexamethasone and F required for half-maximal stimulation of phosphatidylcholine synthesis were similar to the KD values. Dexamethasone binding capacity (sites/mg DNA) increased with age in both rat (+103% increase from day 16 to 22) and rabbit (+47% between day 23 and 30). Receptor concentration was the same in both sexes, and there were no developmental changes in non-specific binding, nuclear:cytoplasmic distribution, or KD. In 27-day rabbit fetuses, the rate of choline incorporation was higher in lungs with greater binding capacity. We conclude that (1) E is rapidly converted to F in rabbit lung to become an active glucocorticoid, whereas corticosterone probably has little physiologic activity, (2) there is a species difference in the affinity of dexamethasone binding which is reflected in responsiveness (3) there is no difference between sexes in E conversion, receptor capacity, or phosphatidylcholine synthesis, and (4) the concentration of binding sites per lung cell increases during fetal development. We suggest that developmental increases in both F production and receptor may be important factors in the expression of endogenous glucocorticoid effects.

Animals↗
PubMed1984

Evolution and variation of renin genes in mice.

Inbred strains of mice carry Ren-1, a gene encoding the thermostable Renin-1 isozyme. Ren-1 is expressed at relatively low levels in mouse submandibular gland and kidney. Some strains also carry Ren-2, a gene encoding the thermolabile Renin-2 isozyme. Ren-2 is expressed at high levels in the mouse submandibular gland and at very low levels, if at all, in the kidney. Ren-1 and Ren-2 are closely linked on mouse chromosome 1, show extensive homology in coding and noncoding regions and provide a model for studying the regulation of gene expression. An investigation of renin genes and enzymatic activity in wild-derived mice identified several restriction site polymorphisms as well as putative variants in renin gene expression and protein structure. The number of renin genes carried by different subpopulations of wild-derived mice is consistent with the occurrence of a gene duplication event prior to the divergence of M. spretus (2.75-5.5 million yr ago). This conclusion is in agreement with a prior estimate based upon comparative sequence analysis of Ren-1 and Ren-2 from inbred laboratory mice.

Animals↗
PubMed1984

Combined treatment with ranitidine and saline antacids prior to obstetric anaesthesia.

Ranitidine 150 mg was given to 126 patients requiring elective Caesarean section under general anaesthesia: 43 women had ranitidine alone, 43 had this supplemented by a pre-induction dose of sodium citrate and 40 patients had ranitidine plus sodium bicarbonate. All three sub-groups provided satisfactory gastric pH and volume. Ranitidine 150 mg was given orally every 6 hours to women in labour. Of 221 patients requiring general anaesthesia during labour, 103 women received 30 ml 0.3 M sodium citrate and 118 women, 20 ml of 8.4% sodium bicarbonate 10 minutes before induction of anaesthesia. In the citrate sub-group there was one patient with a gastric pH less than 2.5 (mean pH 6.2, SEM 0.13 range 2.1-8.4). In the bicarbonate sub-group the lowest gastric acidity was 3.8 (mean pH 8.3, SEM 0.11 range 3.8-9.83).

Anesthesia, General↗
PubMed1984

Steroid effects on uveal transport.

Hydrocortisone (10(-4)M) causes a significant depression of cholic acid accumulation by the isolated rabbit ciliary body-iris while causing little, if any, depression of p-aminohippuric acid uptake and not affecting alpha-aminoisobutyric acid uptake. Because no lag period is present for this inhibition and because cyclohexamide pretreatments fails to eliminate it, the hydrocortisone effect does not appear to be mediated by a protein synthesis mechanism. Deoxycorticosterone (10(-4)M) not only inhibits cholic acid uptake but also depresses p-aminohippuric acid uptake; no deoxycorticosterone effect on alpha-aminoisobutyric acid uptake is seen.

Aminoisobutyric Acids↗
PubMed1984

Glucocorticoid-thyroid hormone interactions in fetal rat lung.

Previous studies have shown that triiodothyronine (T3) enhances the effect of dexamethasone on phosphatidylcholine (PC) synthesis in organ cultures of fetal rat lung. The aim of this study was to investigate whether similar interactions occurred in vivo and to explore possible mechanisms for this phenomenon. Injection of 7.0 mg/kg T3 into pregnant rats on d 18 and 19 of gestation resulted in a mean fetal serum T3 level of 2380 ng/dl on d 20 (control, 84 ng/dl) and in maximal (34%) stimulation of choline incorporation into PC. Injection of 1.0 mg/kg betamethasone using the same protocol as for T3 resulted in maximal stimulation of 33% and administration of both hormones together produced a 69% increase, an additive affect. The percentage of PC that was disaturated was increased with betamethasone, but decreased with T3. Betamethasone treatment resulted in an increase in the whole lung disaturated PC content, but treatment with T3 did not. Betamethasone administration also increased fetal serum T3 levels, but T3 injection did not produce elevated fetal serum corticosterone levels. Injection of T3 in vivo, or exposure of explants of 18-d fetal lung to 100 nm T3 for up to 48 h did not result in an increase in cytoplasmic glucocorticoid binding or nuclear translocation of the receptor steroid complex. Exposure of explants to glucocorticoid or T3 in vivo or in culture (dexamethasone, 100 nM and T3, 100 nM; for 48 h) resulted in a significant increase in the activity of cholinephosphate cytidylyltransferase, an enzyme in the choline incorporation pathway of PC synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Educating the older cancer patient: obstacles and opportunities.

Cancer is a serious health problem among the elderly, with over 50% of all cancers occurring in the 11% of the population over age 65. Little research, however, has focused on the educational needs of elderly cancer patients and little is known about the emotional and psychological impact of cancer in this population. This paper describes two surveys which provide baseline data on the knowledge, attitudes, and beliefs of older people about cancer. These findings have implications for programs directed both at the healthy elderly and at older cancer patients.

Age Factors↗
PubMed1983

Effect of inoculation sequence and nutrients upon Streptococcus mutans BHT and Streptococcus mitior LPA-1 growing on human teeth in an artificial mouth.

Human teeth in an artificial mouth were inoculated with Streptococcus mutans BHT, Streptococcus mitior LPA-1, or sequentially with both organisms. Incubation was continued for 90 h. Mixed populations were largest when a nutrient supplement containing 5.0% (w/v) sucrose was supplied. Fewer organisms were recovered from experiments with synthetic saliva only, or when a supplement containing 0.05% (w/v) glucose was available. The inoculation sequence determined the total viable count and a larger population resulted when Strep. mutans was the initial colonizer (P less than 0.01). Strep. mutans was always able to become established even when super-infected on to a 24 h plaque of Strep. mitior. The final proportion of Strep mutans was lower when it was the superinfecting organism and the sucrose (P less than 0.01) or glucose (P less than 0.05) nutrient supplement was provided. This work confirms the importance of inoculation sequence and presence of sugars in plaque accumulation and demonstrates the fundamental role of microbial interactions in this process.

Ecology↗
PubMed1983

Fetal rat lung maturation: initiation and modulation.

The purpose of this study was to determine whether a rise in the level of circulating hormones is responsible for initiating fetal lung maturation. Explants of 13- to 20-day fetal rat lung were cultured in a constant chemically defined medium containing 0 or 1% serum. Growth, morphological maturation, and two biochemical markers of lung development, disaturated phosphatidylcholine (DSPC) synthesis and specific nuclear glucocorticoid binding, showed evidence of continuing development in culture. There is normally a marked increase in DSPC content and in the rate of choline incorporation into DSPC after 20 days gestation. Regardless of the gestational age of the fetal lungs used, there was a similar increase in culture at an equivalent gestational age of 20 days (e.g., 14-day lung after 6 days, 16-day lung after 4 days). Removal of 50 or 75% of the lung mesenchymal tissue at the initiation of the culture period did not prevent the increase in choline incorporation. Since the culture environment was constant and contained virtually no hormones, we conclude that the stimulus for the initiation of fetal lung maturation is most likely located in the lung tissue itself. The role of circulating hormones is probably later modulation of the maturational process.

Animals↗
PubMed1983

Corticosteroid stimulation of phosphatidylcholine synthesis in cultured fetal rabbit lung: evidence for de novo protein synthesis mediated by glucocorticoid receptors.

To investigate further the mechanism whereby glucocorticoids accelerate the maturation of the pulmonary surfactant system, we studied both binding of glucocorticoids and their effect on phosphatidylcholine synthesis in organ cultures of fetal rabbit lung grown in serum-free medium. The greatest effect of dexamethasone (100 nM for 48 h) occurred at 24 days gestation when there was a 103% increase in the rate of choline incorporation into phosphatidylcholine and a 24% increase in the tissue content of disaturated phosphatidylcholine. Stimulation by corticosteroid was first observed after 12 h of exposure. Choline incorporation increased in a linear fashion for 36 h and then began to plateau; removal of the steroid after 24 h prevented any further increase in stimulation. The presence of other hormones in the culture medium was not a prerequisite for the corticosteroid action. Fetal sex had no influence on dexamethasone-induced phosphatidylcholine synthesis or on nuclear binding of dexamethasone. There was a striking similarity between the Kd values for specific nuclear binding of dexamethasone and cortisol (0.6 +/- 0.1 and 7.3 +/- 0.1 nM, respectively) and the concentrations for half-maximal stimulation of phosphatidylcholine synthesis (0.7 +/- 0.1 and 6.8 +/- 0.5 nM). The relative potencies of a number of steroids (100 nM) for both nuclear binding and stimulation of choline incorporation were the same: dexamethasone greater than cortisol greater than cortisone greater than corticosterone greater than dehydrocorticosterone, with no effect by progesterone, testosterone, or estradiol at this dose. Actinomycin D and cycloheximide blocked dexamethasone-induced phosphatidylcholine synthesis in a dose-dependent fashion. Actinomycin D had a marked effect if added at the initiation of hormone exposure, but little effect when added after 24 h, whereas cycloheximide was primarily effective between 24-48 h. These findings suggest that glucocorticoid stimulation of phosphatidylcholine synthesis in fetal lung is mediated by binding to specific receptors, with subsequent de novo synthesis of RNA and protein.

Animals↗
PubMed1982

Comparison of genetic and endocrine control of renin and kallikrein in mouse submandibular gland.

The effects of strain, sex, hypophysectomy and hormone treatment on mouse submandibular gland renin, kallikrein, S2266 hydrolase, and BAEe esterase activities have been examined. Renin activity is determined by the Rnr locus on mouse Chromosome 1. Female SWR/J mice (Rnrs/Rnrs) have 1000-fold higher submandibular gland renin activity than C57BL/6J mice (Rnrb/Rnrb). Both strains have similar kallikrein activity. Renin, BAEe esterase, and S2266 hydrolase are substantially higher in male mice compared to females of the same strain whereas kallikrein is not. Dihydrotestosterone and/or thyroxine treatment induces renin, BAEe esterase, and S2266 hydrolase in female mice with little effect on kallikrein. All four enzyme activities are profoundly reduced by hypophysectomy. Dihydrotestosterone and thyroxine are both required to restore renin, BAEe esterase, and S2266 hydrolase to induce levels. Dihydrotestosterone and/or thyroxine restores kallikrein to control levels. We conclude that renin and kallikrein in the mouse submandibular gland are under different genetic and endocrine control. In addition, the synthetic substrate S2266 is not a specific substrate for kallikrein activity in mouse submandibular gland cytosol.

Animals↗
PubMed1982

Genetic regulation of thermostability of mouse submaxillary gland renin.

Renin activity in the mouse submaxillary gland is under complex hormonal and genetic control. Basal and induced renin levels are regulated by Rnr, a gene located on Chromosome 1. Mice homozygous for Rnrs or Rnrb alleles have high or low levels of submaxillary gland renin, respectively. We have utilized inbred strain-specific differences in renin stability at 60 degrees C to determine the relationship between Rnr and the renin structural gene. Renin from 13 strains carrying the Rnrb allele is more stable (mean t1/2 = 13.6 +/- S.E. 0.9 min) than that from 24 strains carrying the Rnrs allele (mean t1/2 = 2.1 +/- 24 strains carrying the Rnrs allele (mean t1/2 = 2.1 +/- S.E. 0.04 min). Thermostability was not affected by purification or dilution of the enzyme, or by mixing labile and stable renin prior to heating. Fifty-five informative recombinant inbred mouse strains were also examined, and inactivation of renin at 60 degrees C in each instance resembled one or the other progenitor strain. Furthermore, when the Rnrs alleles is transferred to the genetic background of an Rnrb type strain, renin activity from the congenic inbred strain is both high and thermolabile. Thus, there is complete concordance between thermolability and Rnrs. Alloantibody elicited by submaxillary gland renin from an Rnrs/Rnrs strain blocks the activity of Rnrs but not Rnrb type renin. These results indicate close linkage or identity between a gene that regulates renin activity in the mouse submaxillary gland and a gene that influences the structure of the renin molecule. Such a relationship is compatible with several models for the genetic control of renin activity in this tissue.

Alleles↗