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Biomedical subjects

G C White

Publications and source records attributed to G C White.

At least 145 records · Page 8Linked to original sources

Soil plutonium and cesium in stream channels and banks of Los Alamos liquid effluent-receiving areas.

Stream channel sediments and adjacent bank soils found in three intermittent streams used for treated liquid effluent disposal at Los Alamos, New Mexico were sampled to determine the distribution of 238Pu, 239,240Pu and 137Cs. Radionuclide concentrations and inventories were determined as functions of distance downstream from the waste outfall and from the center of the stream channel, soil sampling depth, stream channel-bank physiography, and the waste use history of each disposal area. Radionuclide concentrations in channel sediments were inversely related to distances up to 10 km downstream from the outfalls. For sites receiving appreciable waste effluent additions, contaminant concentrations in bank soils decreased with perpendicular distances greater than 0.38 m from the stream channel, and with stream bank sampling depths greater than 20-40 cm. Concentrations and total inventories of radionuclides in stream bank soils generally decreased as stream bank height increased. Inventory estimates of radionuclides in channel sediments exhibited coefficients of variation that ranged 0.41-2.6, reflecting the large variation in radionuclide concentrations at each site. Several interesting temporal relationships of these radionuclides in intermittent streams were gleaned from the varying waste use histories of the three effluent-receiving areas. Eleven yr after liquid wastes were added to one canyon, the major radionuclide inventories were found in the stream bank soils, unlike most of the other currently-used receiving areas. A period of time greater than 6 yr seems to be required before the plutonium in liquid wastes currently added to the canyon is approximately equilibrated with the plutonium in the bank soils. These observations are discussed relative to waste management practices in these southwestern intermittent streams.

Cesium Radioisotopes↗

Cirrhosis, variceal bleeding, and distal splenorenal shunt in hemophilia A.

Chronic liver disease has become a significant complication of the therapy of hemophilia disorders. We describe two patients with hemophilia A and hepatitis B virus hepatitis who progressed to cirrhosis with bleeding esophageal varices. Each underwent distal splenorenal shunt under plasma concentrate therapy without difficulty. One patient died 19 months after operation and unsuspected hepatocellular carcinoma was found at autopsy. These cases illustrate the potential severity of liver disease in hemophilia and the ability to safely perform surgery for portal hypertension if required.

Adult↗

Chronic hepatitis in patients with hemophilia A: histologic studies in patients with intermittently abnormal liver function tests.

Recent studies in multiply transfused patients with hemophilia A and persistent liver function abnormalities have shown a high incidence of chronic active hepatitis. The purpose of the present study was to determine the severity of liver disease in multiply transfused patients with intermittent liver enzyme abnormalities. Fifteen patients with elevated enzymes on two or three out of four determinations at 6-mo intervals were studied. None had signs or symptoms of chronic liver disease. Thirteen had serologic evidence of prior exposure to the hepatitis B virus. Liver biopsy performed on these patients after replacement therapy with factor VIII showed chronic persistent hepatitis or other mild forms of liver disease in 14 of the 15 patients. Patients with chronic persistent hepatitis had significantly higher mean liver enzymes at time of biopsy than patients with milder forms of hepatic inflammation, but there was no relationship between liver histology and hepatitis B serology or the amount of factor VIII used in the 6 mo preceding biopsy. These findings support the continued use of factor VIII concentrates in patients with hemophilia.

Adolescent↗

Structure-function relations in platelet-thrombin reactions. Inhibition of platelet-thrombin interactions by lysine modification.

The chemical modification of lysine residues in human alpha-thrombin has been used to study the interaction of thrombin with human platelets. Phosphopyridoxylation of thrombin using pyridoxal 5'-phosphate (pyridoxal-P) has been shown to inhibit the fibrinogen clotting activity of thrombin but not the catalytic activity (Griffith, M. J. J. Biol. Chem. 254, 3401-3406). Phosphopyridoxylation resulted in marked inhibition of the platelet-activating activity of thrombin. The concentration of pyridoxal-P-thrombin required to induce half-maximal platelet aggregation and release was 60 times greater than that of unmodified thrombin. Binding studies using pyridoxal-P-125I-thrombin showed a loss of both high and low affinity binding of thrombin to the surface of intact gel filtered platelets. In contrast, thrombin modified with pyridoxal-P in the presence of heparin incorporated up to 1 mol of pyridoxal-P per mol of thrombin. The heparin-protected pyridoxal-P-thrombin was only slightly inhibited in its interaction with platelets, and binding studies with the heparin-protected pyridoxal-P-125I-thrombin showed selective loss of low affinity binding but preservation of high affinity binding. These results provide further support for the hypothesis that residues at the macromolecular binding site of thrombin are involved in the binding of thrombin to platelets and further separate this functional region of thrombin into two lysine-containing subregions, one which is protected from modification by heparin which is involved in high affinity binding, and another which is not protected by heparin which is involved in low affinity binding.

Blood Platelets↗

Platelet calcium-dependent proteins: identification and localization of the calcium-dependent regulator, calmodulin, in platelets.

The calcium-dependent regulator protein, calmodulin, is a 17,000 molecular weight polypeptide which binds calcium and has been shown to confer calcium sensitivity on contractile and other proteins. In the present study, we have examined the presence and subcellular distribution of this protein in preparations of human platelets. Calmodulin was quantified using a two-stage phosphodiesterase assay. Whole platelets contained 1.33 +/- 0.06 units calmodulin per 10(6) platelets or 26.5 +/- 3.4 fg calmodulin per platelet. The distribution of calmodulin in the platelet was predominantly soluble with over 80 percent of calmodulin activity in the soluble fraction of the cell. There was no apparent difference in the distribution of calmodulin between soluble and particulate compartments in recalcified platelet homogenates compared to homogenates in EDTA. Indirect immunofluorescent studies with monospecific antisera to dinitrophenylated calmodulin showed intense staining of platelets in a diffuse pattern. The identification of calmodulin in platelets raises the possibility that this protein may participate in calcium-dependent reactions important in platelet aggregation and release.

Animals↗

Occupations of fathers of children dying from neoplasms.

It has been suggested in a number of recent reports that there is a possible relationship between parental occupation and malignant disease in children. A proportional mortality analysis relating deaths among children in England and Wales in 1959-63 and 1970-72 to occupation of father as stated on the child's death certificate has not shown any convincing evidence for such associations. Earlier papers published on the subject are reviewed. Although there is some slight evidence for associations between childhood tumours and certain parental occupations there is little consistency between the results reported by different authors. A previously reported association between higher social class and deaths from neoplasms was found also in this study. The explanation for this finding is unknown, and it remains possible that it is an artefact.

Adolescent↗

Heterogeneity of membrane surface proteins in Glanzmann's thrombasthenia.

Studies in several laboratories have suggested that platelets from patients with Glanzmann's thrombasthenia are deficient in two major membrane glycoproteins and that this membrane defect is uniform from patient to patient. We have used an improved electrophoretic technique to study further the surface composition of normal and thrombasthenic platelets. Platelets from three unrelated thrombasthenic patients were labeled by either lactoperoxidase-catalyzed iodination or the neuraminidase-galactose oxidase-[3H]NaBH4 technique and the labeled proteins were separated by two dimensional isoelectric focusing SDS polyacrylamide gel electrophoresis. With both techniques, the major radiolabeled proteins were clearly separated from each other and were present as a horizontal collection of discrete spots that suggest charge heterogeneity. Most of the labeled proteins had an acidic isoelectric point. Compared to normal platelets, platelets from patients with Glanzmann's disease contained no electrophoretically identifiable fibrinogen. In two patients with thrombasthenia, there was total absence of surface glycoproteins GPIIb and GPIII, while a third patient with thrombasthenia, who was clinically indistinguishable from the previous two patients, had decreased, but detectable, amounts of GPIIb and GPIII. These studies suggest that there are at least two phenotypic patterns of membrane abnormalities in Glanzmann's thrombasthenia involving GPIIb and GPIII and may indicate genetic heterogeneity in this disease.

Blood Platelet Disorders↗

Mortality of wives of men dying with cancer of the penis.

711 women were identified who in 1939 were married to men who died with cancer of the penis in England and Wales during the period 1964 to 1973. The records of women were traced through the National Health Service Central Register and, by January 1975, 378 (53%) were found to have died. Expected numbers of deaths from all causes, all cancers and from some specific cancers were calculated assuming the women to have the same mortality rates as the general population of England and Wales. The total number of deaths (378) was close to the number expected (366-8) but there was a slight excess of deaths from cancer (89 against 76.5 expected). Of the individual sites examined only cancer of the cervix showed a statistically significant excess (11 deaths against 3.9 expected, P = 0.002). This finding is similar to those reported in two other studies of the wives of men with cancer of the penis. On the basis of these studies it is suggested that some cases of cancer of the cervix and cancer of the penis may have a common aetiology. Other epidemiological characteristics of the two diseases do not show a marked similarity.

Adult↗

Medical complications of hemophilia.

The modern, comprehensive care of patients with hemophilia requires an awareness that complications other than those caused by acute hemorrhage can occur. The use of newer, more potent plasma concentrates has been accompanied by an increased incidence of liver disease in transfusion-requiring hemophiliacs. The progression to chronic active hepatitis and cirrhosis are particularly ominous developments in these patients. There is also a high incidence of urinary tract abnormalities in hemophiliacs, though the long-term consequences of these abnormalities are unknown. Furthermore, it must be remembered that urinary tract disorders unrelated to hemorrhage, such as nephrolithiasis, tumors, and nephritis, can occur in patients with hemophilia and may be mistaken for hemorrhage. Finally, hypertension occurs more frequently in patients with hemophilia than in the general population and may in part contribute to the occurrence of bleeding within the central nervous system. Methods for evaluating and treating these various disorders are discussed. Greater awareness of these potentially treatable medical complications will improve further the quality of care in hemophilia.

Acute Disease↗

Estimation and comparison of parameters in stochastic growth models for barn owls.

Alternative methods for parameter estimation and the incorporation of stochasticity into growth models are investigated and compared to the commonly used sampling error model in which error terms are simply added-on to the integrated form of the growth equation. A process error model, in which the process of growth is assumed to have stochastic variation or error incorporated within it, was found to be more appropriate for use with nonlinear estimation procedures based on a minimization of sigma ei2. The process error model tended to minimize and/or eliminate the autocorrelation of residuals, which were characteristic of the sampling error model. These analyses further suggest that while the commonly used sampling error growth model may indeed provide unbiased parameter estimates, the estimated variances of such estimates are likely to be unwarrantedly low, thus raising questions as to the validity of any statistical comparisons based on such analyses. The procedure is illustrated with growth data from captive-reared sibling nestling barn owls, using the Richards' growth curve. These analyses suggest that both growth rate and growth form are subject to a higher degree of genetic control than is asymptotic weight which showed a greater tendency to vary according to the hatching order of the nestlings.

Age Factors↗

Glanzmann's thrombasthenia. Report of two oral surgical cases using a new microfibrillar collagen preparation and EACA for hemostasis.

Glanzmann's thromboasthenia is a rare congenital platelet disorder characterized by a prolonged bleeding time, a qualitative platelet defect, and severe hemorrhagic episodes. Patients with this disorder have been managed by administration of blood and blood components (most recently, platelet-rich plasma and platelet concentrates) to control hemorrhage resulting from trauma or surgical procedures. The two case reports presented here illustrate the use of a local hemostatic agent (microfibrillar bovine collagen, Avitene) and a systemic fibrinolytic inhibitor (epsilon aminocaproic acid, Amicar) to control postoperative hemorrhage secondary to elective extraction of teeth. The clinical results demonstrate excellent postoperative hemostasis and support recent in vitro observation of platelet adherence to the collagen preparation. This provides an alternate therapeutic modality in the management of patients with Glanzmann's disease and possibly other disorders of platelet function.

Abscess↗