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Biomedical subjects

D Green

Publications and source records attributed to D Green.

At least 415 records · Page 23Linked to original sources

Platelet-binding of the von Willebrand factor.

The aggregation of platelets by the antibiotic, ristocetin, requires a plasma cofactor (VIII:vWF) and one or more specific binding sites on the platelet membrane. The interaction between VII:vWF and the platelet was examined using VIII:vWF labelled with 125I. In the presence of ristocetin (1.5 mg/ml), from 70 to 90% of the 125I-VIII:vWF became platelet-bound. By contrast, only 21% was bound with thrombin (2.5 microgram/ml), and 2.2% with buffer alone. Fractionation of the platelets revealed that peak radioactivity was present in the membrane fraction. Treatment of ristocetin-reacted platelets with either chymotrypsin, 100 microgram/ml, or trypsin, 75 microgram/ml, resulted in the partial release of the membrane-bound radioactivity. It is concluded that VIII:vWF binds to the platelet membrane in the presence of ristocetin.

Binding Sites↗

The role of radiation therapy in the treatment of soft tissue sarcomas of childhood.

The treatment of soft tissue sarcomas in children at the Joint Center for Radiation Therapy, Children's Hospital Medical Center, and the Sidney Farber Cancer Institute from 1970 to 1976 has been reviewed. Twenty-seven patients were diagnosed with rhabdomyosarcoma, and twenty patients were diagnosed with soft tissue sarcomas of other histologies. An aggressive, combined modality therapeutic approach was applied in the treatment of all patients with emphasis placed on conservation of function. Of irradiated patients, local control was achieved in 96% of those with rhabdomyosarcoma and 85% in other sarcomas. Cumulative relapse-free survival (actuarial) at 5 years is projected at 65% for the rhabdomyosarcoma patients and at 63% for the other sarcoma patients. Although there were differences in chemotherapy regimens (vincristine, actinomycin-D and cyclophosphamide for rhabdomyosarcoma and adriamycin and DTIC for other soft tissue sarcomas), the surgical and radiation therapeutic approaches are similar for both groups. The high probability of local control using function-conserving surgery and high dose radiation therapy supports this emerging approach. Improvements in survival will require better control of metastatic disease.

Adolescent↗

Phase I studies on chlorozotocin.

A phase I investigation of chlorozotocin, a new-water soluble chloroethylnitrosourea, was undertaken to define its pharmacologic effects in man. Forty-three patients received single intravenous doses ranging from 5 to 175 mg/m2 every 6 wk. No signs of toxicity were observed at doses of under 120 mg/m2, but thrombocytopenia occurred at higher doses. The thrombocytopenic nadir appeared to be dose-dependent and occurred 4 wk after treatment. Platelet transfusions were required in 2 patients who had previously received intensive chemotherapy. No significant leukopenia occurred. A mild reversible and delayed elevation of hepatic transaminases was found in 25% of courses of 120 mg/m2 or more. No renal toxicity was observed and gastrointestinal toxicity was mild. Investigation of clinical pharmacology revealed a rapid triphasic plasma clearance with initial t1/2S of 3, 15, and 30 min. The concentration of N-nitroso intact drug at 1 hr was 10% of the initial peak level. Renal excretion accounted for half of the dose. No significant concentration of N-nitroso intact or radiolabeled drug was detected in the cerebrospinal fluid of 2 patients in whom it was examined. There were objective signs of therapeutic activity in 5 patients, 3 of whom had melanoma. Based on these studies, the recommended dose for phase II investigation of chlorozotocin is 120 mg/m2 every 6 wk.

Adolescent↗

Plutonium-239 deposition in the skeleton of the mouse.

Using the technique of neutron-induced autoradiography, together with computer-based methods of data reduction, the distribution of intravenously injected plutonium-239 in the skeleton of the female CBA mouse, 24 hours after injection, has been investigated. With these techniques, it is possible to measure the localization of 239Pu on the endosteal and periosteal surfaces of the bone to an accuracy of approximately +/- 2 x 5 micrometer. Results are reported for the distribution of 239Pu in the third lumbar vertebra, a central caudal vertebra, the right ilium and the right femur. Radiochemical analyses of the 239Pu in other comparable bones of the skeleton are also reported.

Animals↗

Cross-sectional echocardiographic characterization of aortic obstruction. 1. Supravalvular aortic stenosis and aortic hypoplasia.

Cross-sectional echocardiographic and cineangiographic studies of the left ventricular outflow tract and ascending aorta were performed in five patients with supravalvular aortic stenosis (four hourglass and one hypoplastic). Visualization of the area of obstruction was possible in each patient using the cross-sectional system. In each case the echocardiographically determined diameter at the level of obstruction was within 3 mm of the similar angiographic value. Assessment of the extent of the lesion was possible in four of five cases. In three of these four cases the echocardiographic measurement was within 5 mm of the angiographic measurement while in the fourth the obstruction was felt to involve the total ascending aorta by both techniques. Determination of percent decrease in LVOT diameter from the aortic anulus to the level of obstruction was useful in defining obstruction and estimating severity. Cross-sectional echocardiography is a valuable noninvasive method for evaluating the ascending aorta in patients with supravalvular aortic stenosis.

Adolescent↗

Cross-sectional echocardiographic detection of aortic obstruction. 2. Coarctation of the Aorta.

Cross-sectional echocardiographic studies of the aortic arch and proximal descending aorta were performed in 18 patients with coarctation of the aorta and 20 normal subjects. In normals the aortic arch and proximal descending aorta appeared as an arcuate, echo-free structure curving across the plane of the scan. There were no localized changes in aortic diameter and the amplitude of aortic systolic pulsation was symmetrically maintained throughout the scan plane. Visualization of this region was possible in 16 of 18 patients with coarctation. In each of these cases there was a localized area of decrease in aortic diameter in the region of the left subclavian artery which corresponded to the angiographic appearance of the coarctation. In addition prominent systolic pulsation of the aortic arch proximal to the region of obstruction was evident. Cross-sectional echocardiography may offer a useful noninvasive method for direct visualization of aortic coarctation.

Adolescent↗

Pharmacologic disposition of chlorozotocin in mice.

Cholorozotocin is a water-soluble chloroethylnitrosourea with the cytotoxic group attached to the C2 position of glucose. The distribution of the alkylating and carbamoylating moieties of the chlorozotocin molecule was determined in mice following the ip administration of an LD10 dose: 20 mg/kg. The half-life (T 0.5) for the plasma disappearance of intact drug was 5 minutes. The plasma disappearance of the ethyl-14C group was biphasic up to 120 minutes after administration; the T 0.5 of the initial phase was 17.5 minutes and the T 0.5 of the prolonged second phase was107 minutes. The disappearance of glucose-14C chlorozotocin followed kinetics similar to the chloroethyl-labeled compound. Fifteen minutes after administration, ethyl-14C drug concentrated maximally in the liver (194 nmols/g of tissue) and the kidney (131 nmols/g of tissue). Uptake into the bone marrow at 60 minutes after ip administration of the ethyl-labeled drug was 6.6 pmols of the ethyl-14C group covalently bound to proteins and nucleic acids per 10(7) nucleated cells. The concentration of ethyl-14C drug in the brain remained at 4 mnols/g of tissue up to 2 hours after administration, reflecting the water-soluble property of this new nitrosourea.

Animals↗

Sulindac.

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Anti-Inflammatory Agents↗