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Biomedical subjects
Publications and source records attributed to R Wilson.
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Among 2123 premature infants monitored during a large multicenter study of patent ductus arteriosus, necrotizing enterocolitis (NEC) was diagnosed in 121 (5.7%) of these infants. Rates ranged from 13.5% among infants with a birth-weight (BW) of 500 to 749 g to 2.9% among infants whose BW was between 1500 and 1750 g. The presence of a hemodynamically significant patent ductus arteriosus did not alter the incidence of NEC. Of a large number of perinatal events and conditions considered, only BW and maternal toxemia were found to be associated with the rate of NEC, both relating inversely. Thus, these data do not support a relationship between NEC and a variety of perinatal factors previously postulated as potential determinants of the disorder.
The efficacy of irradiated tumor cells combined with chemotherapy or non-specific immunostimulation with complete Freund's adjuvant was tested in a model of minimal residual tumor-bearing syngeneic mice. Male C57BL/6J mice were innoculated in the right rear leg with live tumor cells from a methylcholanthrene induced fibrosarcoma. The tumor was resected when it reached 0.7 cm in diameter and animals were treated with doses of irradiated tumor cells (XTC) from the primary tumor ranging in number from 1 X 10(3) to 9 X 10(3). Best survival was noted using 5 X 10(3) XTC combined with irradiated tumor cells of liver or pulmonary metastases origin, complete Freund's adjuvant or cytoxan. The combination of irradiated tumor cells of metastatic origin did not enhance the therapeutic effect of XTC alone. Freund's adjuvant was not of benefit in enhancing the efficacy of XTC. However, improved survival was noted when chemotherapy in the form of cytoxan was used to supplement XTC. Our data suggests that XTC is more efficacious as a mode of immunotherapy than are live tumor cells. The dose of XTC used is critical in determining its effect. Chemotherapy appears to enhance the benefit of XTC.
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We have observed the occurrence of focal segmental glomerulosclerosis in all three siblings of a single Hispanic family. Each of the children had the onset of significant proteinuria on or before the age of 10. The two oldest children have had progression of their disease to end-stage with subsequent successful transplantation. The youngest sibling continues to have normal renal function. All three patients had renal biopsies prior to the onset of renal insufficiency and each of the biopsies showed the presence of focal segmental glomerulosclerosis with mild diffuse mesangial hypercellularity. Finally, HLA-typing revealed the presence of DRw8 in all three siblings and the father. This report further suggests that genetic factors may be quite important in the development of the lesion of focal segmental glomerulosclerosis.
It has been suggested that the good correlations found between carcinogenic potency in mice and in rats could be an artifact. The artifact suggested arises because there are four correlations to consider--interspecies correlations of toxicity, interspecies correlations of carcinogenic potency, and two intraspecies correlations between toxicity and carcinogenic potency--and the existence of any three implies the fourth. It was argued that the intraspecies correlations between toxicity and potency were due to criteria for data selection. Here we discuss the correlations in detail and show that they are principally due to the experimental observation that there are few cases where most or all animals in a bioassay get cancer. We conclude that the correlations between carcinogenic potency are valid.
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Granulomatous disease of the stomach is a rare disorder with multiple causes. We successfully treated a patient who had granulomatous disease that was confined to the gastric antrum with corticosteroids. We believe this is the first such report.
From a study population of 208 consecutive first cadaver renal transplant recipients a proportional hazard model was used to simultaneously quantify the role in graft failure of matching for specific HLA antigens and constitutional factors (age, sex, duration of dialysis (Dt), and pre- (PTr) and peri-(PerTr) operative transfusions) that influence nonspecific immune response. A comparison was also made of graft survival in patients treated by the two principal methods of dialysis, hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD). The advisability of including nonimmunological failures in studies of graft survival was also considered. The analysis indicated that factors influencing a patient's innate nonspecific immune response (e.g., Dt and PTr) are important determinants of graft survival and should be taken into account when considering matching for specific HLA-B or DR antigens prior to transplantation. While there was no overall effect of dialysis type on graft survival, the influence of other risk factors depended on the method of dialysis. Failure to identify and exclude graft loss for nonimmunological reasons can give rise to misleading conclusions in analysis of immunoregulatory factors in organ transplantation.
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Two nodule-specific Rhizobium loti compounds were identified in Lotus tenuis and Lotus pedunculatus nodules induced by strain NZP2037. One, a silver nitrate-positive cation called rhizolotine, has been characterized as the riboside of a novel alpha-hydroxyimino acid containing a 1,4,5,6-tetrahydropyrimidine ring (G. J. Shaw, R. D. Wilson, G. A. Lane, L. D. Kennedy, D. B. Scott, and G. J. Gainsford, J. Chem. Soc. Chem. Commun., p. 180-181, 1986), and the other, yellow-1, stains yellow with ninhydrin. Both compounds were degraded by R. loti NZP2037 but not by strains of Rhizobium meliloti, Rhizobium trifolii, or Agrobacterium tumefaciens. Under the conditions tested neither compound was able to serve as a sole source of C or N for growth of R. loti NZP2037. Rhizolotine and yellow-1 were found in nodules from a range of different legumes inoculated with NZP2037, suggesting that the Rhizobium and not the host plant determines their synthesis. Neither compound was found in nodulelike structures of L. pedunculatus induced by transposon Tn5-induced noninfectious (Inf-) mutants of NZP2037 or in similar structures induced by a transconjugant of NZP2037 containing the symbiotic (Sym) cointegrate plasmid pPN1 of R. trifolii. Both compounds were also absent in the ineffective nodules induced by the bacterial-release-negative (Bar-) mutant, strain PN239. However, both compounds were present in nodules induced by the fixation-negative (Fix-) mutant PN235 and in Fix+ nodules formed by a plasmid-cured derivative of NZP2037. These results would suggest that infection and bacterial release from the infection thread are necessary for nodule (symbiotic) synthesis of these compounds.
A well-nourished alcoholic patient developed a subacute myopathy which responded rapidly to correction of severe hypomagnesaemia. The finding of profound hypocalcaemia prompted the measurement of serum magnesium. Magnesium deficiency should be looked for in any alcoholic patient with a myopathy as the prognosis seems better than in many other forms of alcoholic myopathy. Correction of the magnesium deficiency corrects the hypocalcaemia without the need for calcium supplementation.
Serum thyrotrophin receptor antibody (TRAb) and thyroid stimulating hormone (TSH) (IRMA) levels were measured in 38 patients at one month after the end of a course of carbimazole/T3 therapy for Graves' disease. Despite the increased sensitivity of the IRMA assay a TSH measurement at this stage was found to be of no predictive value, in contrast to estimation of serum TRAb levels which correctly predicted relapse and remission in 90% of patients.
Patients with chronic bronchial sepsis have impaired mucociliary clearance. A study was carried out on the effect of sputum sol (obtained by rapid centrifugation of purulent sputum) from 20 patients with chronic bronchial sepsis on the beating of human nasal cilia in vitro by a photometric technique. Thirteen sols caused significant (p less than 0.001) ciliary slowing. Two patterns of slowing were observed: firstly, a gradual onset associated with epithelial disruption (inhibited by alpha 1 antiprotease) and, secondly, an immediate onset associated with ciliary dyskinesia and ciliostasis (inhibited by chloroform extraction). The ciliary slowing activity of sputum sols was associated with the isolation of Pseudomonas aeruginosa (p less than 0.01). It is concluded that purulent sputum contains at least two factors that impair ciliary beating--one a serine protease, which is probably a product released by the host's phagocytic defences, and the other, which is chloroform extractable and probably a bacterial product.
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Pseudomonas aeruginosa culture filtrates varied in their ability to slow human ciliary beat frequency (7-71%). This activity did not correlate with known virulence factors. However, a close correlation (r = 0.97) existed between ciliary slowing and pigment content. In a prolonged culture, the increase in activity correlated (r = 0.94) with pigment accumulation. Gel filtration of lyophilized filtrate yielded a single peak of activity corresponding to the pigment fraction. Pyocyanin extracted from an active strain, and 1-hydroxyphenazine were purified by high performance liquid chromatography, and characterized by ultraviolet absorbance spectra and mass spectrometry. Both slowed cilia in a dose-dependent manner, and were synthesized and shown to be indistinguishable from the biological compounds. Pyocyanin caused gradual onset of slowing and ultimate widespread ciliostasis with epithelial disruption. 1-hydroxyphenazine caused rapid onset of ciliary slowing associated with dyskinesia and ciliostasis. Pyocyanin assayed within filtrates accounted for a significant proportion of the bioactivity present.
A very low molecular weight heparin fragment (CY222) was administered by subcutaneous injection to a group of normal volunteers. This drug caused increased anti Xa activity with peak levels being observed two hours after injection. This coincided with changes in thyroid hormone levels especially with a fall in red cell thyroxine levels. Larger doses of CY222 caused a fall in serum total thyroxine and triiodothyronine, a rise in free thyroxine and a fall in TSH levels. It was thought that these findings may be due to the production of a circulating inhibitor of cellular uptake of thyroxine and that this might be related to the elevated levels of serum free fatty acids produced by the heparin.
We review the experimental evidence for various shapes of dose-response relationships for carcinogens and summarize those experiments that give the most information on relatively low doses. A brief review of some models is given to illustrate the shapes of dose-response curve expected from them. Our major interest is in the use of dose-response relationships to estimate risks to humans at low doses, and so we pay special attention to experimentally observed and theoretically expected nonlinearities. There are few experimental examples of nonlinear dose-response relations in humans, but this may simply be due to the limitations in the data. The several examples in rodents, even though for high dose data, suggest that nonlinearity is common. In some cases such nonlinearities may be rationalized on the basis of the pharmacokinetics of the test compound or its metabolites.