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Biomedical subjects

D C Young

Publications and source records attributed to D C Young.

At least 127 records · Page 7Linked to original sources
PubMed1986

Chemotherapy of drug-resistant ovarian cancer: a Southwest Oncology Group Study.

We present a final analysis, including pathology review, of a cooperative group study of drug-resistant ovarian cancer. Of 200 patients registered, 112 were eligible and evaluable, with a response rate of 26% and median survival of 7 months. Because these results are poorer than those reported in the preliminary and interim analyses of this study, we scrutinized the 88 excluded patients, most of whom failed to meet our strict pathologic criteria for a diagnosis of ovarian cancer of epithelial type, and who, as a heterogeneous group, fared better than patients who did meet the eligibility criteria. We believe this analysis provides insight into the spectrum of diseases that are frequently called ovarian cancer, but might be more properly labeled abdominal carcinomatosis.

Adult↗
PubMed1986

Autocrine secretion of GM-CSF in acute myeloblastic leukemia.

Three cases of acute myeloblastic leukemia (AML) were identified in which clonogenic cells proliferated autonomously in vitro. Cells from two of these cases were found to secrete a colony-stimulating factor (CSF) that was immunologically and molecularly related to GM-CSF. Growth of AML-CFU could be blocked by the addition of a neutralizing antiserum to GM-CSF. Northern blot hybridization of leukemic cell mRNA with a cDNA probe for the GM-CSF gene revealed a 1-kb message identical in size to the normal GM-CSF message in stimulated T cells. No GM-CSF message was detected in the third case. These results indicate that constitutive expression of the GM-CSF gene, apparently by leukemic cells, can result in autonomous in vitro proliferation of AML-CFU in some cases of AML.

Cell Division↗
PubMed1986

Phase I trial of homoharringtonine administered by prolonged continuous infusion.

Cephalotaxine alkaloids have been extensively used in the Peoples Republic of China for treatment of acute leukemias and solid tumors (Yu-hua, L., Shu-fen, G., Fu-ying, Z., Shu-zhi, X., and Hui-lin, Z. Chin. Med. J., 96: 303-305, 1983). Several Phase I trials of homoharringtonine have been completed in the United States using either bolus administration or continuous infusion over a 5-day period. The major toxicities have been hypotension following rapid administration and myelosuppression when lower doses are infused over 5 to 7 days. None of these studies, however, reproduce the schedule used in China which is i.v. infusion of approximately 1 mg/day over 4-8 h for a period of 14-28 days or more, followed by a rest period of approximately 7-14 days. This study more closely reproduces that schedule as a Phase I trial by decreasing the daily dose of homoharringtonine and using a continuous infusion schedule to allow escalation of total days of treatment. Forty-eight patients entered the study. The final recommended dose of homoharringtonine is 1 mg/m2/day for 30 days followed by a 2-week rest period. The dose limiting toxicity of myelosuppression was severe and prolonged in some patients. Nonhematological toxicities were minimal and generally well tolerated. Patients should be followed with at least weekly blood counts and treatment interrupted pending full marrow recovery if the granulocyte count falls below 1,000/mm3 or the platelet count falls below 100,000/mm3.

Adult↗
PubMed1985

Virion conformational forms and the complex inactivation kinetics of echovirus by chlorine in water.

Aberrant inactivation kinetics were observed when monodispersed echovirus type 1 (Farouk) was inactivated with chlorine. An initial 1- to 2-log10-unit decrease in titer was followed by lag period, during which the titer stayed the same or increased, and this was followed by a final decline in titer. First-order kinetics were obtained with poliovirus type 1 under the same conditions. Isoelectric focusing studies of echovirus before chlorine treatment showed that the virus distributed into two pH-dependent and interconvertible isoelectric forms. After chlorine treatment all remaining virus infectivity was associated with a third pH-independent isoelectric form. The complex inactivation kinetics appeared to be due to shifts between these conformational forms during inactivation in certain ionic environments. Under certain conditions the conformational shifts resulted in substantial resistance of monodispersed echovirus to chlorine.

Capsid↗
PubMed1985

Poliovirus RNA-dependent RNA polymerase and host cell protein synthesize product RNA twice the size of poliovirion RNA in vitro.

The poliovirus RNA-dependent RNA polymerase required an oligouridylate primer or a HeLa cell protein (host factor) to initiate RNA synthesis on poliovirion RNA in vitro. The polymerase synthesized template-sized product RNA in the oligouridylate-primed reaction. In the host factor-dependent reaction, the largest product RNA synthesized by the polymerase was twice the size of the template RNA. About half of the product RNA recovered from this reaction was shown to exist in the form of a snapback sequence. Time-course reactions and pulse-chase experiments showed that the product RNA was only slightly larger than the template RNA at early reaction times and that with time it increased in size to form the dimer-sized product RNA. Inhibition of the elongation reaction by adding only [alpha-32P]UTP and ATP resulted in the formation of template-sized product RNA. The dimer-sized product RNA was unaffected by phenol extraction or proteinase K treatment but was converted to template-sized molecules by S1 nuclease. Dimer-sized poliovirus RNA that was sensitive to S1 nuclease was also isolated from poliovirus-infected cells. The results from this study indicate that the labeled negative-strand product RNA synthesized in vitro was covalently linked to the positive-strand template RNA. Thus, in vitro, the primer-dependent poliovirus RNA polymerase may initiate RNA synthesis in the presence of the host factor by using the 3' end of the template RNA as a primer.

Base Sequence↗
PubMed1985

Adverse effect of exercise on immune complex-mediated glomerulonephritis.

To assess the effect of strenuous daily exercise on immune complex-mediated glomerulonephritis (GN), rabbits were randomly assigned to one of three experimental groups: Group I (n = 12): treadmill exercise for 28 days plus twice weekly intravenous injections of saline. Group II (n = 10): treadmill exercise for 28 days plus twice weekly intravenous bovine serum albumin (BSA) injection. Group III (n = 9): intravenous doses of BSA, as in group II, but no exercise. Blood and urine samples were collected from each animal periodically during the 28-day experimental period. On the 29th day of the study all animals were sacrificed and tissue taken for renal histopathologic studies. We found that in group II (exercise + GN) abnormal albuminuria was more frequent (p less than 0.001), blood urea nitrogen (BUN) levels rose significantly with time (p less than 0.02) and hematuria (blood in renal tubules) was more common (p less than 0.05), compared to group III (GN only). The differences between groups II and III could not be explained by the effect of exercise alone since group I (exercise only) developed no abnormal albuminuria, BUN levels or hematuria during the course of the study. These findings suggest that strenuous exercise superimposed on active immune complex-mediated GN results in worsening of the abnormal glomerular function.

Animals↗
PubMed1985

Effect of monensin and tylosin on average daily gain, feed efficiency and liver abscess incidence in feedlot cattle.

Fourteen trials were conducted to evaluate the effects of feeding monensin at 33 ppm alone, tylosin at 11 ppm alone and the two feed additives in combination on the average daily gain, average daily feed intake, feed:gain ratio and the incidence of liver abscesses in feedlot cattle. Monensin reduced feed intake and improved feed efficiency (P less than .05), and had no effect on average daily gain. Tylosin improved average daily gain (P less than .05) and had no effect on daily feed intake. The effect of tylosin on feed efficiency approached significance. The interaction of monensin and tylosin was nonsignificant for daily gain, daily feed intake and feed:gain ratio. Monensin had no effect on liver abscess incidence, while tylosin reduced abscess incidence from 27 to 9%.

Animal Feed↗
PubMed1984

Ca2+-activated proteinase in the rat. Quantification by immunoassay in the uterus during pregnancy and involution, and in other tissues.

Rat uteri were taken at various stages of pregnancy and involution post partum, and several other tissues were taken from pregnant and non-pregnant animals. Portions of each tissue were homogenized in the presence of proteinase inhibitors, and the amounts of the high-Ca2+-requiring Ca2+-activated proteinase in the supernatants were measured by a two-site immunoradiometric assay using 125I-immunoglobulin G. The proteinase was shown, by protein blotting, to be immunologically identical in all tissues. The amounts in the various tissues, expressed in units of proteinase activity/g wet wt., were: lung, 95; kidney and small intestine, 42; liver, 20; brain, heart and skeletal muscle, 13. Uterine wet weight increased at the end of pregnancy by about 8-fold, but the amounts of proteinase per uterus increased by about 22-fold; alternatively, expressed in units of proteinase activity/g wet wt., the mean uterine values were: non-pregnant, 28.6; term-pregnant, 77.0. As the wet weight of the uterus fell rapidly during involution, the amounts of proteinase activity remained relatively high. The data suggest that the Ca2+-activated proteinase may have some role in tissue resorption during uterine involution, but the high proteinase activity present before parturition must be regulated in ways which are not yet clear.

Animals↗
PubMed1983

Evaluation of the immunological and toxicological properties of MVE-2 in phase I trials.

Pyran copolymer enhances resistance to infections and transplantable tumors in mice. It induces interferon, activates macrophages, increases antibody-dependent cellular cytotoxicity (ADCC), functions as an adjuvant, and has direct antitumor effects. MVE-2, a low-molecular-weight (15,000) component of pyran copolymer, exhibited less toxicity and essentially the same positive biological effects as pyran copolymer. MVE-2 was, therefore, chosen for clinical trials. This study was designed to determine the toxicity and immunological effects of MVE-2 in humans. Fourteen patients who received biweekly MVE-2 had lymphocyte and monocyte ADCC, natural killer activity, and monocyte to macrophage maturation measured 2, 3, 7, 10, and 13 days after each of the first three doses of MVE-2. Lymphocyte antibody-dependent cellular cytotoxicity and monocyte maturation increased significantly following MVE-2 administration and the effect persisted at least 4 weeks. Although numbers were small, the enhanced ADCC seemed related to both single dose and cumulative dose of MVE-2. Five of six patients receiving more than 2 g of MVE-2 had improvement in lymphocyte ADCC. Increases in lymphocyte and monocyte natural killer activity approached, but did not attain statistical significance. Proteinuria was the dose-limiting toxicity, but was reversible. MVE-2 induced a modest, but real enhancement of lymphocyte and monocyte function at doses that were well tolerated.

Adult↗
PubMed1983

Induced delivery prior to surgery for ruptured cerebral aneurysm.

Labor was induced by amniotomy at 34 weeks' gestation because of preeclampsia in a woman with a recent ruptured cerebral aneurysm prior to corrective neurosurgery. Neither labor nor vaginal delivery caused neurologic injury to the mother. Subsequent neurosurgery was successful and both mother and infant continued to do well several months later. These outcomes support management advised in the literature in circumstances not previously reported.

Adult↗
PubMed1983

The incidence of thromboembolic disease.

The incidence of thromboembolism was determined by a survey of 7986 orthopedic patients who had 5966 operations at a university hospital during a three-year period. Patients were analyzed to determine thromboembolic risks with respect to the orthopedic diagnosis to assist in providing the patient with informed consent and to identify patients who need prophylactic anticoagulation therapy. The patient population was divided into three risk classes: Class 1, low-risk patients, including children, all upper-extremity patients, and adult non-surgical ambulatory rehabilitation patients; Class 2, medium-risk patients, including all adult lower-extremity patients and patients with spine problems and no history of thromboembolic disease; Class 3, high-risk patients, including all patients with a previous history of thromboembolic disease or venous stasis disease. Class 1 patients require no prophylactic anticoagulation, Class 2 patients should be treated with dextran or aspirin, and Class 3 patients should be treated with warfarin. The calculated mortality for Class 2 patients, excluding hip problems, is 0.26%; mortality for acute spinal cord injuries is 2.9% and for hip surgery 2.2%.

Adolescent↗
PubMed1983

Phase I trial of homoharringtonine.

Homoharringtonine is one of a group of cephalotaxine esters reported by the Chinese to have significant antitumor efficacy, with particularly good activity in human leukemias. Preclinical antitumor activity against P388 leukemia, colon 38 carcinoma, and mammary carcinoma led to phase I trials which are currently nearing completion in this country. The phase I study reported here used a single infusion of homoharringtonine over 90 minutes given every 21 days. Dose-related and life-threatening hypotension, without significant myelosuppression, was the dose-limiting toxic effect. The mechanism of hypotension is not understood but it is not related to cardiac arrhythmias. Myelosuppression was not seen regularly. We do not recommend this schedule for phase II trials.

Adult↗
PubMed1982

Inhibiton of prostaglandin synthesis by human amniotic fluid: acute reduction in inhibitory activity of amniotic fluid obtained during labor.

Human amniotic fluid contains an inhibitor of prostaglandin synthesis. The activity of the inhibitor was measured in amniotic fluid obtained in early pregnancy, and at term both before and after the onset of labor. The inhibitory activity was greater in amniotic fluid taken in early pregnancy than in fluid taken at term before the onset of labor (P less than 0.05). There was a further significant reduction in inhibitory activity (P less than 0.01) in amniotic fluid collected during labor. These results are suggestive that the onset of labor is associated with a local withdrawal of inhibition of prostaglandin biosynthesis.

Albumins↗