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Biomedical subjects

C L Smith

Publications and source records attributed to C L Smith.

At least 343 records · Page 19Linked to original sources

Genotoxicity of N-acetylarylamines in the salmonella/hepatocyte system.

Coincubation of isolated, intact rat hepatocytes with Salmonella typhimurium tester strain TA 98 (Salmonella/hepatocyte system) has been employed to determine both bacterial mutagenicity and DNA damage in the hepatocytes following treatment with 2-acetylaminofluorene (AAF) and other AAF derivatives. In vivo pretreatment of rats with either 2,3,7,8,-tetrachlorodibenzo-p-dioxin (TCDD) or 3-methylcholanthrene (MC) markedly increased both DNA damage and bacterial mutation frequency upon incubation of AAF or 2-aminofluorene (AF), in this system. The increase in damage to the hepatocyte-DNA was more pronounced after AAF treatment than by that for AF, while the increase in bacterial mutation frequency was greater after AF treatment. Hepatocytes treated with paraoxon prior to exposure to N-hydroxy-2-acetylaminofluorene (N-OH-AAF) or N-acetoxy-2-acetylaminofluorene (N-OAc-AAF) partially inhibited the DNA damage caused by these agents, as well as inhibiting the bacterial mutagenicity of N-OAc-AAF (50% inhibition) and N-OH-AAF (80% inhibition). These data indicate that metabolic processes other than those involved in activating AAF and its derivatives into a bacterial mutagen(s) may contribute to the genotoxic effects of these compounds. Thus, the Salmonella/hepatocyte system may provide a useful model in which to study the relative role of the various metabolic processes associated with the carcinogenic effects of N-acetylarylamines.

Animals↗

Surgical treatment of renal hyperparathyroidism.

Renal hyperparathyroidism can be a major clinical problem in those receiving dialysis treatment and in those having renal transplants. This review of 66 patients during a five year period has led us to believe that laboratory data are useful for confirming the clinical diagnosis or for following the outcome of medical or surgical therapy. The screening for renal hyperparathyroidism should be on clinical grounds and not on isolated biochemical tests. All patients with renal failure, whether receiving dialysis therapy or renal transplantation, are at risk for having renal hyperparathyroidism develop. A careful assessment of the clinical and biochemical data is required to ensure proper patient selection for operation. Bone disease and persistent pruritus unresponsive to medical management remain the principle clinical indications for operation. Our preferred procedure is the standard subtotal parathyroidectomy.

Adenoma↗

Is purified poly(ethylene glycol) able to induce cell fusion?

Preparations of poly(ethylene glycol) 6000 (PEG) from five different commercial sources have been purified, and their ability to fuse hen erythrocytes has been investigated. Quantitative assessments of cell fusion showed that before purification one of the preparations (PEG Wako), was able to induce limited fusion (5-6%) of erythrocytes with conditions (1 min incubation with 50% w/w PEG) under which the other four unpurified preparations of PEG were inactive. On purification, PEG (Wako) became inactive. By contrast, when erythrocytes were incubated with 45% w/w PEG for 15 min, extensive fusion (23-27%) occurred with all five unpurified preparations of PEG. Under these conditions, the fusogenic properties of four of the preparations of PEG were unaffected by purification: fusion induced by PEG (Wako) was, however, decreased on purification from 27% to 19%. It appears that polymeric poly(ethylene glycol) is itself able to fuse cells, but that some commercial preparations, e.g. PEG (Wako), have enhanced fusogenic properties resulting from the presence of contaminating substances. No relationship between the absorbance at 290 nm of PEG and its fusogenic properties was found in this study. The addition of small quantities of fusogenic lipid-soluble compounds to PEG was, however, observed to enhance cell fusion by up to 50%.

Animals↗

Effects of thymosin and evidence of monocyte suppression of both T- and B-cell functions in two cases of 'common variable immunodeficiency'.

We have studied two patients with common variable immunodeficiency (CVID), impaired cell-mediated immunity, and high percentages of monocytes in their peripheral blood. Removal of monocytes from cultures of peripheral blood mononuclear cells from both patients increased the in vitro responses to phytohaemagglutinin (PHA) and concanavalin A (Con A) but not to purified protein derivative (PPD), as measured by [3H]thymidine uptake. Similarly, supernatants of monocyte cultures from both patients, unlike supernatants of normal monocytes, suppressed the in vitro responses to PHA and Con A but enhanced the response to PPD by cultured mononuclear cells from the patients and from normal donors. Addition of unfractionated mononuclear cells from both patients to normal mononuclear cells suppressed both pokeweed mitogen (PWM) stimulation and IgG production; this effect was abrogated by removal of monocytes from the patients' mononuclear cell populations. This effect of thymosin on both patients' mononuclear cells was assayed in vitro. Thymosin was ineffective in vitro with cells from the first patient; for the other patient, [3H]thymidine uptake by mononuclear cells stimulated with PPD increased, whereas uptake by Con A-stimulated cells decreased, as did the percentage of E rosette-forming cells, providing further evidence of heterogeneity of the CVID syndrome. The effects of thymosin were also dependent on monocytes.

Adult↗

Ulcerative colitis: effect of sulphasalazine, its metabolites and indomethacin on the ability of human colonic mucosa to metabolize prostaglandins in vitro.

1 Homogenates of mucosa from human colon metabolize [3H]-prostaglandin E1 in the presence of nicotinamide adenine dinucleotide to 15-oxo prostaglandin E1 or 15-oxo, 13,14 dihydro prostaglandin E1. 2 Metabolic capacity of tissue from patients with active ulcerative colitis under treatment with sulphasalazine (0.021 +/- 0.004 nmol/Mg protein +/- s.e. mean) did not differ from mucosa of normal patients (0.02 +/- 0.004 nmol/mg protein) during 1 h incubation. 3 Sulphasalazine inhibits prostaglandin E1 metabolism by mucosal homogenates in a dose-dependent manner with an ID50 of 125 microM. Its therapeutically active metabolite, 5-aminosalicylic acid (2.6 mM) was without significant inhibitory activity. 4 Indomethacin inhibits prostaglandin E1 metabolism by colonic mucosa with an ID50 of 388 microM. 5 At present we cannot clearly relate the therapeutic benefit of sulphasalazine and its therapeutically active metabolite, 5-aminosalicylic acid, in ulcerative colitis to their effects on prostaglandin E synthesis or metabolism in vitro.

Alprostadil↗

The metabolic effects of moderately severe upper gastrointestinal haemorrhage in man.

The metabolic effects of moderately severe gastrointestinal haemorrhage were investigated in man. Before resuscitation, patients had raised circulating concentrations of glucose, lactate, alanine, glycerol and cortisol. After urgent operation for haemorrhage, metabolite concentrations were similar to those of control patients having elective abdominal surgery, but insulin concentrations were higher and cortisol lower in haemorrhage patients. There were no significant differences in nitrogen excretion between haemorrhage patients and their controls, but urinary 3-methyl-histidine excretion by haemorrhage patients was lower indicating decreased muscle protein breakdown. Decreased amino acid release from muscle might account for previously reported imparied wound healing after haemorrhage.

Alanine↗

Oesophageal motility in the irritable bowel syndrome.

Oesophageal motility was assessed in 30 patients with the irritable bowel syndrome and controls matched for age and sex. Lower oesophageal sphincter pressure was significantly lower in the patients than their controls (mean pressures 13.8 and 23.8 cm H2O respectively), and the same degree of difference between patients and controls was maintained in all age groups. In addition, spontaneous activity, repetitive contractions, and the presence of variable-amplitude and simultaneous waves were significantly more common in the patients, who were also more likely to have more than one abnormal pattern of motility. There was no difference in upper oesophageal sphincter pressure between the two groups. These findings may help to explain why patients with the irritable bowel syndrome may complain of upper gastrointestinal symptoms, including heartburn and dysphagia. The results suggest that the syndrome may be a more widespread disorder of smooth muscle, or its innervation, than was previously thought.

Adult↗

A double-blind controlled trial of the effect of sodium cromoglycate in preventing relapse in ulcerative colitis.

A double-blind controlled trial of the effect of sodium cromoglycate (SCG) in preventing relapse in ulcerative colitis has been completed in 100 subjects. In patients already taking sulphasalazine, SCG did not prove to be of any additional benefit. However, in patients not on any other maintenance therapy, the relapse rate was 40% for SCG as compared with 75% for placebo. A large study of the effect of SCG in patients intolerant of sulphasalazine is indicated.

Adult↗

Physical therapy management of patients with total ankle replacement.

Ankle arthrodesis has been the treatment of choice for patients who have arthritic or degenerative ankly disease with disabling pain and loss of motion. But the results of long-term retrospective studies show a significant percentage of arthrodeses are unacceptable to patients and considered to be clinically poor or failures by the physicians. Therefore, total replacement of the ankle joint is becoming recognized as an alternative to ankle arthrodesis. This procedure eliminates pain and provides suffient ankle motion for resumption of normal activities. Objectives and indications for the procedure, two types of prostheses, and the surgical procedure are discussed. Guidelines are provided for preoperative and postoperative physical therapy for patients having total ankle replacements.

Ankle Joint↗