Biomedical subjects
Publications and source records attributed to P Thompson.
The treatment of children suffering from cerebral paresis differs widely from that of children with poliomyelitis, since we deal with active spastic muscles which are influenced by many factors. We discuss these factors and present the results in a series of patients who were operated on with these factors borne in mind.
Chromatography of crude and purified human fibroblast interferon on activated thiol Sepharose 4B yielded two classes of material exhibiting different stability to inactivation by mechanical stress. Interferon which bound to the gel accounted for 20--30 per cent of recoverable activity, could be eluted with reducing agents and was unstable. Unbound material did not bind on subsequent rechromatography and was stable to shear forces. Leucocyte interferon did not bind, nor did fibroblast interferon treated with thiol blocking reagents. Peak eluted fractions had a specific activity of up to 10(7.9) units per milligram of protein, representing a 1700 fold purification.
Two random samples, each constituting 0.5% of the institutionalized elderly (over 65) in the cities of New York and London have been compared. This preliminary report of a collaborative study demonstrates the similarity of the 2 samples. Institutions in the 2 cities are shown to differ in size, type of ownership and the frequency that skilled nursing is provided. Some implications of these 2 findings are raised now, and will be discussed later when the full data for the study are presented.
In a series of chronic renal and congenitally deaf patients 24 were identified as having inborn renal and otologic disease. Sixteen patients, representing 14 families, had genetic disorders. Only two had the features of Alport's syndrome. The patients were classified as follows: 1) Probable Alport's--2 patients (1 family); 2) Atypical hereditary nephritis and sensorineural hearing loss--7 patients; 3) Renal and inner ear anomalies--1 patient; 4) Renal, inner ear and multiple anomalies--4 patients. The temporal bone pathology in one case showed primary neural atrophy and a mild Mondini malformation. In another a Scheibe defect and unusual calcific structures were found in the cochlear duct. 5) Renal, external or middle ear and multiple anomalies--6 patients (5 families); 6 Renal, middle and inner ear anomalies and multiple anomalies--2 patients. A temporal bone obtained from one case showed combined middle and inner ear defects. In the other, who had a chromosome defect, predominantly middle ear anomalies were found. 7) Nephrotic syndrome and congenital hearing loss--1 patient; 8) Unclassified--1 patient. Some cases represent entities apparently not previously described. Probably most interesting is the delineation of hereditary nephritis and deafness distinct from Alport's disease.
The operation of soft-tissue release and calcaneocuboid fusion, published by Dillwyn Evans in 1961, is described in detail and a long-term review of 118 club feet is presented. The average age of the patients at review was nearly seventeen years. All were resistant cases and in all the Dillwyn Evans "collateral operation", deliberately delayed by a policy of prolonged conservative treatment, had been the main surgical procedure.
The experiments in this paper show for the first time that CCNU, a nitrosourea, inhibits transglutaminase (an enzyme believed to be involved in tissue proliferation) on account of its cyclohexyl-isocyanate moiety.
Four families with a variety of renal tract abnormalities including reflux, cortical scars, atrophy and duplex systems are described. Cystometrograms in eight with reflux and scars did not show any evidence of outflow high pressure systems. Tissue typing was carried out in a proportion of affected and unaffected family members, and with the addition of another reported family that had been tissue typed, showed an increase in A9, B8 and homozygosity in the families with these abnormalities. A retrospective survey of transplanted patients with tissue type A9 showed a higher prevalence of pyelonephritis and associated abnormalities than other diseases leading to end stage renal failure.
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We have described a 25-year-old man with hyperthyroidism and normal levels of serum T3 and reverse T3, but with abnormalities in serum T4I, T3U, FTI, FT4, and T3 suppression and TRH stimulation tests consistent with the diagnosis of T4 toxicosis. Serum total iodine was elevated several-fold, and the observed response to iodine depletion and loading suggested that the T4 toxicosis in this patient probably resulted from an increased iodine load, with production of T4 preferentially to T3. There appeared to be no evidence of a defect in peripheral conversion of T4 to T3.
The HLA types of 133 patients with cleft lip and/or cleft palate were determined. Caucasian patients with isolated cleft palate showed a possible association with HLA. Ten of 11 male patients had HLA--A2 as compared to one out of eight female patients (P less than 0.005). Caucasian males with cleft lip and cleft palate had a slight increased frequency of HLA--Aw24 (P = 0.07) and Mexican-American males with cleft lip and/or cleft palate showed an increase of antigen HLA-A28 (P = 0.07), though neither were statistically significant. Females with cleft lip and/or cleft palate from either racial group had no differences from the controls. The serum from 90 mothers of patients with cleft lip and/or cleft palate were reacted against their child's lymphocytes. Of these crossmatch tests, 12% were found to be positive. These preliminary results suggest that male patients with isolated cleft palate are worthy of further studies with respect of HLA associations.
The central importance of elevated blood cholesterol levels in the process of atherosclerotic heart disease (ASHD) is firmly established. Cholesterol is transported in the blood in conjunction with protein as a lipoprotein complex. The low-density lipoproteins (LDL) carry the bulk of the blood cholesterol. The high-density lipoproteins (HDL) occur in much smaller amounts. Recently it has been demonstrated that not only is the cholesterol carried in the HDL fraction not harmful, but appears to be protective against the development of ASHD. Data from Framingham and elsewhere seem consistent with this observation. The HDS apparently represent the fraction concerned with the efflux of cholesterol from the tissues, so that higher levels may represent a heightened cholesterol-riddance mechanism. Thus far, two circumstances seem to be associated with elevated levels of HDL--physical exercise and ethanol ingestion. The importance of these observations in the clinical management of the patient at risk is discussed.
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Six patients with vasopressin-responsive diabetes insipidus (DI) received clofibrate and chlorpropamide, singly and in combination. Decrease in urinary output averaged (mean +/- SEM): (1) clofibrate 2 g/day, 47% +/- 6%; (2) chlorpropamide 250 mg/day 59% +/- 5%; (3) clofibrate 2 g/day plus chlorpropamide 125 mg/day, 54% +/- 7%; (4) clofibrate 2 g/day plus chlorpropamide 250 mg/day 61% +/- 4%. Water deprivation tests before and during treatment showed significantly higher basal, final, and peak urinary osmolalities (Uosm) and lower free water clearance (CH20) on chlorpropamide, singly and in combination: clofibrate raised Uosm less but significantly decreased CH2O. Water load tests before and during treatment showed that chlorpropamide, singly and in combination, markedly decreased maximal urinary flow, maximal CH2O, percentage water load excreted, and increased minimal Uosm; clofibrate significantly decreased maximal urinary flow and CH2O only. One patient responded only to combination therapy. Chlorporpamide caused serious hypoglycemia in three of six patients. Clofibrate had no significant side effects.
The pyruvate dehydrogenase complex from pea (Pisum sativum L.) mitochondria was purified 23-fold by high speed centrifugation and glycerol gradient fractionation. The complex had a s(20,w) of 47.5S but this is a minimal value since the complex is unstable. The complex is specific for NAD(+) and pyruvate; NADP(+) and other keto acids give no reaction. Mg(2+), thiamine pyrophosphate, and cysteine are also required for maximal activity. The pH optimum for the complex was between 6.5 and 7.5.Continuous sucrose density gradients were used to separate castor bean (Ricinus communis L.) endosperm proplastids from mitochondria. Pyruvate dehydrogenase complex activity was found to be coincident with the proplastid peak on all of the gradients. Some separation of proplastids and mitochondria could be achieved by differential centrifugation and the ratios of the activities of the pyruvate dehydrogenase complex to succinic dehydrogenase and acetyl-CoA carboxylase to succinic dehydrogenase were consistent with both the pyruvate dehydrogenase complex and acetyl-CoA carboxylase being present in the proplastid. The proplastid fraction has to be treated with a detergent, Triton X-100, before maximal activity of the pyruvate dehydrogenase complex activity is expressed, indicating that it is bound in the organelle. The complex had a sharp pH optimum of 7.5. The complex required added Mg(2+), cysteine, and thiamine pyrophosphate for maximal activity but thiamine pyrophosphate was inhibitory at higher concentrations.
A steady-state kinetic analysis has been performed on the pyruvate dehydrogenase complex from pea (Pisum sativum L.) mitochondria and castor bean (Ricinus communis L.) proplastids. Substrate interaction kinetics for all substrates gave parallel lines consistent with a multisite ping-pong mechanism. Product inhibition studies showed uncompetitive inhibition between acetyl-CoA and pyruvate and competitive inhibition between NADH and NAD(+), both of which are also consistent with this mechanism. In the mitochondrial complex, acetyl-CoA showed noncompetitive inhibition versus CoA which suggests that the intermediate complex is kinetically important in the lipoamide transacetylase component of this complex. In contrast, the proplastid complex showed competitive inhibition in this interaction. NADH is a noncompetitive inhibitor versus CoA in both complexes indicating that these complexes, like the mammalian complex, may have protein-protein interactions between the second and third enzymes of the complex. Since NADH also shows noncompetitive inhibition versus pyruvate, this interaction may extend to all components of the complex. Acetyl-CoA shows noncompetitive inhibition versus NAD(+) which may also be a result of interaction between the second and third enzymes of the complex. The limiting Michaelis constants for substrates and the inhibitor constants for both complexes were determined.
The activity of the pyruvate dehydrogenase complex from pea (Pisum sativum L.) mitochondria is inhibited when MgATP is added to the reaction mixture; 50% inhibition occurs at 4 mm ATP. The inhibition does not increase with time and is higher in the more highly purified preparations. Crude preparations of the complex show a time-dependent inactivation when incubated with 7.5 mm MgATP alone but this is not found with the more highly purified complex. This inactivation does not occur at 0 C. The complex could not be reactivated by high concentrations of Mg(2+). It is suggested that a phosphorylation-dephosphorylation mechanism may occur in plants, but the phosphatase and kinase are not tightly bound to the complex and are lost on isolation. The complex does not respond in a significant manner to energy charge. The NAD(+) to NADH ratio is the principal means of regulation of the complex, NADH being competitive with NAD(+) for the dihydrolipoamide component. The CoA to acetyl-CoA ratio is not important in regulation.The castor bean (Ricinus communis L.) proplastid complex is inhibited by the addition of 2 mm MgATP to the assay mixture. The inhibition is immediate, suggesting that phosphorylation of the enzyme is not involved or must be very rapid. Incubation of the complex with 20 mm MgCl(2) causes an activation of the complex. Maximum activity is not expressed in this case for 30 minutes. A similar activation can be achieved by preincubating the complex with 1 mm pyruvate. These data suggest that the complex is not fully activated on isolation.