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Biomedical subjects

C A Clarke

Publications and source records attributed to C A Clarke.

At least 37 records · Page 2Linked to original sources
PubMed1989

Morphological and physiological effects of beta-hydroxybutyrate on rat embryos grown in vitro at different stages.

Diabetic women are more likely to give birth to infants with congenital malformations than are nondiabetic women. Rodent embryos have been used as a model for the study of abnormal fetal development associated with maternal diabetes, and some of the metabolic factors which are altered in diabetes, such as raised glucose and ketones, have been shown to cause abnormal development of rodent embryos in vitro. The present work explores further the teratogenicity of beta-hydroxybutyrate to rat embryos. To determine the sensitivities of rat embryos at different stages of their development, rat embryos at 9.5 days of gestation have been cultured in vitro for 24 or 48 h, with or without 4 x 10(-2) M beta-hydroxybutyrate for all or part of the culture period. The embryos have been examined by scanning electron microscopy, and a detailed morphometric analysis of one tissue, the neuroepithelium, has been undertaken. The results confirm that beta-hydroxybutyrate causes abnormal development of rat embryos. The results of experiments in which embryos were exposed to beta-hydroxybutyrate for only part of a 48 h culture show that embryos exposed to beta-hydroxybutyrate for a complete 48 h culture are more severely affected than embryos exposed to beta-hydroxybutyrate for only part of the culture and that embryos are more vulnerable to beta-hydroxybutyrate during the first half of a 48 h culture (equivalent to 9.5 to 10.5 days of gestation) than during the second half of a 48 h culture (10.5 to 11.5 days of gestation). The results of experiments in which embryos were cultured with beta-hydroxybutyrate from 9.5 days of gestation for 24 h (equivalent to 9.5 to 10.5 days of gestation) showed that some effects of beta-hydroxybutyrate are already apparent after 24 hours in culture. Many of the abnormalities produced by beta-hydroxybutyrate can be classified as embryonic retardations rather than malformations--that is, embryos show features characteristic of normal, but younger, embryos. Embryos exposed to beta-hydroxybutyrate for the complete 48 h culture period consume less glucose and produce less lactate than control embryos on a per embryo basis, but not on a per microgram protein basis, suggesting that the reduced metabolism is an effect of beta-hydroxybutyrate-induced developmental delay rather than a cause of it.(ABSTRACT TRUNCATED AT 400 WORDS)

3-Hydroxybutyric Acid↗
PubMed1987

The effects of mannose on rat embryos grown in vitro.

Rat embryos have been cultured in vitro from 9.5 days of gestation for different times in serum containing mannose, and the embryos have been observed by scanning electron microscopy. Embryos cultured in 3 mg/ml (1.7 X 10(-2) M) or 6 mg/ml (3.3 X 10(-2) M) mannose for 48 h showed inhibition of the expansion of the yolk sac and were smaller than the control embryos. Mannose-treated embryos also showed delayed development according to morphological criteria, and a range of abnormalities including abnormalities of the neural tube. Embryos cultured in 6 mg/ml mannose for 24 h also showed significant inhibition of yolk-sac expansion and were smaller and less advanced than the control embryos. Abnormalities were seen, including a delay in the closure of the neural folds. Abnormalities were also observed in embryos cultured in mannose for 10 h; embryos at the neural groove stage showed irregularities in the neural groove. Mannose did not inhibit the re-elevation of neural folds which had been caused to collapse by exposure to medium containing low calcium. These results are compatible with the idea that mannose retards development and thereby perturbs the morphogenesis of the neural tube.

Animals↗
PubMed1987

Oral administration of erythrocyte membrane antigen does not suppress anti-Rh(D) antibody responses in humans.

The effects of prior oral administration of erythrocyte membrane preparations (Oral Rh antigen) on the serum anti-Rh(D) antibody response has been evaluated in non-sensitized Rh(D)-negative male volunteers, and in female volunteers sensitized previously by Rh(D)-positive fetal blood during pregnancy. Sixty-one percent (11/18) of males who received oral Rh antigen (either D-positive or D-negative) before intravenous challenge with Rh(D)-positive cells produced detectable antibodies; of these 11, six received oral Rh(D)-negative antigen and five received oral Rh(D)-positive antigen. Seventy-two percent (13/18) of control males, who had received no prior oral Rh antigen, produced antibodies following challenge with Rh(D)-positive cells. Three out of six pre-sensitized females who received oral D-positive or D-negative Rh antigen for 4 weeks, but without intravenous challenge, increased their anti-Rh(D) antibody levels which peaked after 11-18 weeks: two had received Rh(D)-positive antigen, and one Rh(D)-negative antigen. These data indicate that administration of oral Rh antigen before parenteral immunization does not significantly suppress the anti-Rh(D) antibody response. Indeed, oral administration of either Rh(D)-positive or Rh(D)-negative antigen can boost systemic antibody in pre-sensitized females. These results do not support the rationale of treating Rh-sensitized pregnant women with oral Rh antigen.

Administration, Oral↗
PubMed1987

Effect on rat embryos of in vitro culture in sera from human diabetic patients.

Recently conditions have been established whereby rat embryos can be cultured in vitro in human serum over the period of their major morphogenesis. By standardizing the amount of glucose in sera from diabetic subjects prior to culture, it has been possible to investigate factors other than hyperglycemia which might account for the increased incidence of congenital defects seen in infants of diabetic mothers. The incidence of abnormalities in rat embryos cultured in sera from chlorpropamide-treated diabetics was not significantly different from that using control sera from normal subjects. On the other hand, sera from insulin-dependent diabetics produced more defects in rat embryos than sera from either normal subjects or diabetics on oral agents. The incidence of abnormal rat embryos does not appear to be correlated with patient age, with the original blood glucose concentration or with the concentration of hemoglobin A1 or, in the insulin group, with the total daily insulin dosage.

Animals↗
PubMed1986

Effect of cigarette smoking, pulmonary inflammation, and lung disease on concentrations of carcinoembryonic antigen in serum and secretions.

A specific radioimmunoassay for carcinoembryonic antigen was used to investigate aspects of its measurement in lung disease. The results confirm that serum carcinoembryonic antigen concentrations are higher in healthy smokers and patients with chronic obstructive bronchitis than in healthy non smokers (p less than 0.01). Corticosteroid treatment reduced the concentration in nine patients with bronchitis (p less than 0.05). Other inflammatory lung diseases (bronchiectasis, pneumonia, fibrosing alveolitis) are not associated with a raised serum carcinoembryonic antigen concentration. The sputum concentrations were about 100 times those found in serum and there was a positive correlation (r = 0.611 2p less than 0.01) between the concentrations in sputum and serum in patients with bronchitis. No preferential rise in sputum concentration was found in current smokers or patients with lung carcinoma (n = 16). A higher ratio of carcinoembryonic antigen to albumin concentration (p less than 0.05) was, however, found in lavage fluid obtained from the tumour site than in fluid from "normal" lung in the same patients, suggesting an increase in carcinoembryonic antigen secretion in the vicinity of the tumour. Despite this "local" effect the sputum concentration does not, however, appear to be a useful marker of lung carcinoma and the measurement could not be used as a screening test.

Bronchitis↗
PubMed1985

Deaths from rhesus haemolytic disease in England and Wales in 1982 and 1983.

Examination of death certificates and the clinical notes of the patients concerned showed that the number of deaths from rhesus (D) haemolytic disease in England and Wales was 44 and 34 during 1982 and 1983, respectively, a substantial decrease from the figure of 106 for 1977. Of the 78 women whose infants died in 1982 and 1983, 49 had not received anti-Rh immunoglobulin after previous pregnancies with Rh positive infants; most of these deaths would presumably have been prevented had postnatal anti-Rh immunoglobulin been given. In 13 women anti-D was detected during, or immediately after, a first pregnancy, and in 15 women rhesus immunisation developed despite administration of anti-Rh immunoglobulin postnatally. One or two apparent failures of treatment may have been due to underdosage, but it must be concluded that about one third of the deaths in 1982 and 1983 could have been prevented only by giving anti-Rh immunoglobulin antenatally as well as postnatally.

England↗
PubMed1985

Effects of beta-hydroxybutyrate on rat embryos grown in culture.

In order to investigate further the relationship between maternal diabetes and fetal malformation, rat embryos were grown in vitro in the presence of beta-hydroxybutyrate, one of the ketone bodies produced by diabetics. At 10 mM, beta-hydroxybutyrate produced minor abnormalities and at 20 mM it produced major abnormalities in rat embryos.

Abnormalities, Drug-Induced↗
PubMed1985

Identification of two complementation groups in Fanconi anemia.

Considerable variation can be observed in the clinical presentation of Fanconi anemia (FA) patients and in the degree of sensitivity of their cells to DNA damaging agents. We have examined the hypothesis that genetic heterogeneity underlies this variation by testing for complementation in somatic cell hybrids constructed from FA cells. Hybrids were formed by fusing lymphoblastoid cell lines derived from four different FA patients. Complementation of the cellular defects in FA was tested by examining sensitivity to growth inhibition by mitomycin C(MMC), spontaneous chromosome breakage, and MMC-induced chromosome breakage in the hybrid cells. These studies revealed the presence of at least two complementation groups, suggesting that there may be two or more different FA genes.

Anemia, Aplastic↗
PubMed1984

Is cytoplasmic Ca2+ in lymphocytes elevated in cystic fibrosis?

An increased cytoplasmic Ca2+ concentration ( [Ca2+]i) has been implicated in the pathogenesis of cystic fibrosis. We compared the [Ca2+]i levels of normal and cystic fibrosis peripheral blood lymphocytes and Epstein-Barr virus-transformed lymphoblasts using quin 2, an internally trapped indicator. The [Ca2+]i levels of normal and cystic fibrosis cells were not significantly different. The ionophore-releasable intracellular Ca2+ stores were also comparable in both types of individual.

Adolescent↗
PubMed1984

Vascular reactivity in rats with glycerol-induced acute renal failure.

The vascular reactivity of rats with glycerol-induced acute renal failure was assessed in vitro and in vivo. The contractile responses to noradrenaline, angiotensin and potassium chloride of aortic strips and portal vein segments from uraemic rats were significantly smaller than the responses obtained in vessels from control animals. The pressor responses to angiotensin were reduced significantly in rats with acute renal failure when compared to those in control rats. The reduced vascular responses to a range of spasmogens suggests that in this model of renal failure there is a defect in some mechanism of vascular contraction common to all three constrictor agents.

Acute Kidney Injury↗