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Biomedical subjects

C W Young

Publications and source records attributed to C W Young.

At least 73 records · Page 4Linked to original sources
PubMed1985

Correlated response of udder dimensions to selection for milk yield in Holsteins.

Response to selection for milk yield in Holsteins was examined by a controlled selection experiment initiated in 1964. Foundation cows were paired by sire and divided randomly into two breeding groups, selection and control. Selection group was mated to four sires each year highest for Predicted Difference milk. Twenty bulls selected in 1964 as near breed average for milk sired all control cows. Milk yield was recorded for each lactation, and height of udder from ground, distances between teats, and perimeter and area bound by the four teats were measured at 30 to 75 days postpartum on 153 selection and 202 control cows over 14 yr. Most estimates of repeatability and heritability of udder dimensions before and after milking were .45 or larger. Correlations with milk yield were negative for udder height and positive for other udder measurements. Selection cows exceeded controls for lactational milk yield. Daughters of high milk bulls had greater distances between teats, greater perimeters, and larger areas of udder floor. Selection cows did not differ from controls in udder height for first parity but were below controls in udder height and had udders that collapsed more for all parities.

Animals↗
PubMed1985

Animal health and management and their impact on economic efficiency.

Relationships between animal health and economic efficiency were examined using data from genetic investigations and management studies. Genetic investigations have indicated that cows bred for high production do require more health care, but that increased costs for health care negate only a small fraction of the greater returns from cows that are genetically superior for yield traits. These same studies have identified age of cow and stage of lactation as important sources of variation in health care costs. Health care costs increase with age and are highest at parturition and immediately thereafter, and decrease to much lower levels as lactation progresses. Animal health issues considered from a management perspective were macro-environment (climate, housing, facilities), nutrition-reproduction complex, replacement management, mastitis and udder health, and herd health preventive medicine programs. Most advances in management of animal health were beneficial, but some are economical only for large herds. Improvement of udder health through continued and expanded research on milking procedures and equipment design is an area of unusual promise. Additional research appears needed to cope with stress and fatigue to legs and feet in modern facilities. Preventive medicine programs become more cost effective as herds become larger and should be used by a larger percentage of dairy producers. The economic efficiency of many management practices is uncertain due to a paucity of data. Animal scientists should plan to incorporate economic comparisons into much more of their research.

Animal Husbandry↗
PubMed1985

Growth hormone response to growth hormone-releasing factor in selected and control Holstein heifer calves.

Holstein heifer calves from selected and control lines were treated with growth hormone-releasing factor to determine whether the magnitude of the pituitary growth hormone response is associated with genetic potential for milk yield. Cows in the selected line were bred to highest Predicted Difference milk sires available each year, while control line cows were bred to bulls that were average for 1964 milk production. Eight calves from each line of similar age (206 to 210 days) and weight (205 kg average) were injected intravenously with .1 microgram/kg growth hormone-releasing factor. Dams' first lactation 305-day mature equivalent records were 10,192 +/- 495 kg for selected calves and 6,908 +/- 376 kg for control calves. Before treatment, GH tended to be higher in selected than control calves (mean +/- SE: selected = 7.5 +/- 1.8, control = 4.6 +/- .4 ng/ml). After injection, peak GH were reached within 20 min and were similar in selected and control calves, averaging 66 +/- 16 and 73 +/- 13 ng/ml, respectively. Results indicate that the magnitude of the growth hormone response to growth hormone-releasing factor is not related to future performance of dairy calves.

Animals↗
PubMed1985

Phase I trial of 1-(2'-deoxy-2'-fluoro-1-beta-D-arabinofuranosyl)-5-methyluracil (FMAU).

1-(2'-Deoxy-2'-fluoro-1-beta-D-arabinofuranosyl)-5-methyluracil (FMAU), a new pyrimidine nucleoside, is of potential clinical interest both as an anticancer and as an antiviral drug. FMAU is active in vitro and in vivo against P815 and L1210 cell lines resistant to cytarabine. Moreover, in mice inoculated ic with herpes simplex virus Type II, FMAU is 100-fold more potent than vidarabine or acyclovir. We have conducted a phase I trial of FMAU in 17 patients with advanced cancer. The dose levels studied were 2, 4, 8, 16, 32, 64, and 128 mg/m2/day iv for 5 days. The dose-limiting toxic effect was drug-induced central nervous system dysfunction. Although 32 mg/m2/day for 5 days produced only transient, mild symptoms, severe encephalopathy with extrapyramidal dysfunction occurred at 64 and 128 mg/m2/day for 5 days and contributed to two deaths. No toxicity was observed at less than 32 mg/m2. A dose of 32 mg/m2/day for 5 days is suggested for phase II study. Because of its potent and selective antiviral activity, future trials of low doses of FMAU in immunosuppressed patients with herpes virus infections are under consideration.

Adult↗
PubMed1985

Cisplatin nephrotoxicity. Correlation with plasma platinum concentrations.

Plasma platinum concentrations were measured in 45 patients receiving 46 courses of cisplatin (DDP) 100-120 mg/m2 and in 21 patients receiving 35-60 mg/m2. Samples were drawn 5 minutes, 24, and 48 hours following completion of the DDP infusion. Nephrotoxicity was defined as a greater than 50% increase in serum creatinine measured at 24 and/or 48 hours when compared to the baseline pretreatment value. In patients receiving DDP 100-120 mg/m2, 5/20 with 5-minute plasma platinum concentrations greater than 6 micrograms/ml developed nephrotoxicity; 0/26 with concentrations less than 6 micrograms/ml became nephrotoxic (p less than 0.05). Concentrations at 24 and 48 hours in toxic and nontoxic patients were similar. Five-minute plasma platinum concentrations in excess of 6 micrograms/ml did not occur in the 21 patients receiving DDP 35-60 mg/m2. Only one of these 21 patients became nephrotoxic. The data suggest that an increased incidence of acute nephrotoxicity is related to high peak plasma platinum concentrations.

Cisplatin↗
PubMed1985

Gossypol, a hyperthermic sensitizer of HeLa cells.

Gossypol, a polyphenolic aldehyde extracted from cotton plants, is a potent antifertility agent in humans. Since we have previously reported that several male antifertility agents including 5-thio-D-glucose and lonidamine demonstrate hyperthermic sensitizing effects in HeLa cells, we wished to determine whether gossypol also exhibits the hyperthermic sensitization. Gossypol was not cytotoxic up to 4 h at 37 degrees C (10 micrograms/ml). When HeLa cells were exposed to gossypol at 41 degrees and 42 degrees C, significant potentiation of hyperthermia induced cytotoxicity was observed. The magnitude of the potentiation was dependent on the drug concentration, pH of the culture medium, glucose concentration, temperature, and duration of treatment. The hyperthermic sensitizing effect of gossypol was increased by an acidic pH and glucose deprivation. These data suggest that the sensitizing effect of the drug may be mediated through the lowering of cellular energy level by the inhibition of both glycolysis and oxidative phosphorylation.

Cell Division↗
PubMed1985

Phase II trial of 4'-deoxydoxorubicin in patients with advanced breast cancer.

4'Deoxydoxorubicin (25 mg/m2 iv every 3 weeks) was evaluated in 20 patients with advanced breast cancer. The patients had good performance status and had not been heavily pretreated. Although all patients experienced leukopenia, no major therapeutic responses were observed. Nonhematologic toxicity was mild. Further evaluation of 4'-deoxydoxorubicin at this dose and schedule is not warranted in patients with advanced breast cancer.

Adult↗
PubMed1984

NHL-3 protocol. Six-drug combination chemotherapy for non-Hodgkin's lymphoma.

Combination chemotherapy and radiotherapy (RT) were administered to 73 adults with non-Hodgkin's lymphoma (NHL). Ten cycles of the following drugs were given: intravenous Adriamycin (doxorubicin) (25 mg/m2), cyclophosphamide (700 mg/m2) and vincristine (1.5 mg/m2) on day 1; arabinosylcytosine (100 mg/m2) and methotrexate (10 mg/m2) on days 3 to 5; and oral prednisone (60 mg/m2) on days 1 to 5. Radiotherapy was given to resistant or initially bulky disease (2000 rad). Patients were also randomized to receive pseudomonas vaccine or no immunotherapy. Of 61 evaluable patients, 33 (54%) achieved a complete response (CR) and 18 (30%) a partial response (PR). Among 44 evaluable patients with diffuse histiocytic lymphoma (DHL), 22 (50%) had a CR, and 15 (34%) a PR. For 17 evaluable patients with nodular (4) and diffuse (11) mixed and poorly differentiated lymphocytic and diffuse "undifferentiated" (2) lymphomas, CR and PR rates were 65% and 18%, respectively. No statistically significant differences in response rate or duration and survival have been observed between the patients randomized to receive pseudomonas vaccine or no immunotherapy. Median follow-up time from start of treatment was 47.5 months. Median survival for all 73 patients (including inevaluables ) and for 52 DHL patients was 30.7 months. Poor prognostic features influencing survival included: female sex (P = 0.003), poor response to therapy (CR versus PR; P = 0.001), prior chemotherapy, (P = 0.01) and high levels of lactic dehydrogenase (P = 0.001). It can be concluded that this combination of cycle and phase-active agents is of similar efficacy to other reported regimens in inducing major responses and that it has the potential to prolong disease-free survival. The analysis of prognostic factors has been used to dissect poor prognostic categories that might require different modalities of treatment.

Adult↗
PubMed1984

Relationships among dietary constituents and specific serum clinical components of subjects eating self-selected diets.

Sex- and age-related differences in dietary and blood chemistry factors were investigated in subjects adhering to their usual lifestyles. Diet records were examined daily and blood chemistry profiles were monitored five times during the 1-yr study. As expected, high-density lipoprotein cholesterol was significantly higher in women than in men. Values of creatine phosphokinase, aspartic aminotransferase, alanine aminotransferase, glucose, triglycerides, urea nitrogen, uric acid, and total bilirubin were higher in men than in women. Glucose was lower while high-density lipoprotein cholesterol, albumin, and total protein were higher in the younger women than in older women. Alcohol consumption by men correlated positively with aspartic aminotransferase and alanine aminotransferase but not with high-density lipoprotein cholesterol. Alcohol consumption by women did correlate positively with high-density lipoprotein cholesterol but not with the aminotransferase enzymes. Correlations between serum high-density lipoprotein cholesterol and vitamin C intake were positive and significant in women. In men, high levels of high-density lipoprotein cholesterol seems to be associated with very high vitamin C intakes, but no associations were apparent at normal levels of these parameters. Serum cholesterol did not correlate significantly with dietary cholesterol, saturated fat, linoleic acid, or P/S in men or women.

Adult↗
PubMed1984

Phase II trial of 1-(2-chloroethyl)-3-(2,6-dioxo-3-piperidyl)-1-nitrosourea in small cell cancer of the lung.

Nineteen patients with a histologically confirmed diagnosis of small cell carcinoma (SCCL) of the lung were entered on trial with a new nitrosourea, 1-(2-chloroethyl)-3-(2,6-dioxo-3-piperidyl)-1-nitrosourea (PCNU). All patients had had prior chemotherapy and 42% had received a nitrosourea. No patient had a major response to treatment with PCNU and only one patient had a minor response of short duration. Myelosuppression, particularly thrombocytopenia, was the major dose-limiting side effect. PCNU did not appear to be of benefit in patients with recurrent SCCL.

Adult↗
PubMed1984

Radiosensitization of Meth-A fibrosarcoma in mice by Lonidamine.

Isogenic male BALB/c mice bearing Meth-A tumors in the ascites form were used. The effects of Lonidamine and irradiation both alone and in combination were studied. Lonidamine administered intraperitoneally produced a significant enhancement of irradiation effects.

Animals↗
PubMed1984

Phase I and clinical pharmacologic evaluation of Lonidamine in patients with advanced cancer.

Lonidamine was studied in 31 patients with different types of advanced cancer. With one exception, patients were pretreated. Lonidamine was given at 6 dosage levels from 180 to 520 mg/m2 for at least 28 days. No toxicity on hematopoietic function was observed. Side effects consisted mostly in musculoskeletal discomfort, testicular pain in males and a reversible ototoxicity. In 2 patients conjunctivitis and photophobia occurred. Plasma Lonidamine levels were measured in 14 patients. Peak concentrations were observed from 1 to 2 h after administration and ranged from 3 to 35 micrograms/ml. Objective antitumoral effects were observed in only 2 patients with mycosis fungoides; a 3rd patient with mycosis fungoides was considered to have stable disease.

Adolescent↗
PubMed1984

Inbreeding and the gene pool.

The trend in the artificial insemination industry in recent years has been to sample larger numbers of sons sired by the most popular bulls. This trend has caused concern in the dairy industry regarding inbreeding and the gene pool. The known detrimental effects of inbreeding on economically important traits are one reason for this concern, and these are reviewed here. Also reviewed and discussed are estimates of inbreeding in dairy cattle populations. These estimates indicate that for the populations studied, inbreeding has increased little if at all during the period of widespread use of artificial insemination. During the 1970's average inbreeding in United States Holsteins and British Friesians was on the order of 3 to 6% relative to their foundations. A recent study of inbreeding in United States Ayrshires suggests little inbreeding in that breed in spite of the relatively small population size. Inbreeding and preservation of genetic variation should be minor concerns in selecting sires.

Animals↗
PubMed1984

Quercetin, an inhibitor of lactate transport and a hyperthermic sensitizer of HeLa cells.

Since cancer cells produce large amounts of lactate via aerobic glycolysis and since an acidic pH has been shown to selectively enhance the cytotoxic effects of hyperthermia, we are examining the influence of cell exposure to drugs which inhibit lactate transport and lower intracellular pH upon cytotoxic effects of hyperthermia. Quercetin, a bioflavonoid that produces lactate transport inhibition, was not cytotoxic up to 4 hr at 37 degrees (0.1 mM). When HeLa cells were exposed to quercetin at 41 and 42 degrees, significant potentiation of hyperthermia-induced cytotoxicity was observed. The magnitude of the potentiation was dependent on the drug concentration, pH of the culture medium, temperature, and duration of treatment. In contrast, treatment of cells with rutin, a structurally related bioflavonoid that lacks the property of lactate transport inhibition, showed no hyperthermic potentiation.

Biological Transport↗
PubMed1984

Thymidine as a kinetic and biochemical modulator of 1-beta-D-arabinofuranosylcytosine in human acute nonlymphocytic leukemia.

We have carried out a clinical trial in which patients with relapsed leukemia were treated with thymidine (dThd) prior to and concomitantly with the administration of 1-beta-D-arabinofuranosylcytosine (ara-C) in an effort to kinetically and biochemically modulate the leukemic cells with two objectives: (a) to increase the S-phase fraction before giving ara-C; and (b) to increase the uptake and phosphorylation of ara-C. Six patients with acute nonlymphocytic leukemia who had relapsed after conventional or experimental therapy were given continuous i.v. infusions of dThd in conjunction with ara-C. dThd was started at 75 g/sq m/day (producing 1 mM plasma levels) and was given for 5 to 8 days until the proportion of bone marrow cells in S-phase (measured by autoradiography and flow cytometry) had increased and/or stabilized; then ara-C at 200 mg/sq m/day was begun. Twenty-four hr after initiation of ara-C therapy, the dThd dose was reduced to 30 g/sq m/day (plasma dThd, 0.1 to 0.6 mM). Both drugs were continued for 6 to 12 days until marrow aplasia or unacceptable toxicity occurred. Four patients with a base-line labeling index lower than 30% experienced a sustained increase in the S-phase fraction; two patients with a base-line labeling index higher than 30% experienced a reduction in the S-phase compartment during dThd infusion, in one case followed by an increase. The degree of S-phase arrest did not correlate with remission induction. In 5 patients, the flash incorporation of labeled ara-C into nucleoside triphosphate and deoxycytidine into DNA of bone marrow cells was measured. Three patients had a significant increase in the incorporation of deoxycytidine into DNA. Two of them achieved a complete remission. Increases in ara-C uptake were less impressive. A new technique was used to measure the absolute number of blasts present in the bone marrow. A decrease in leukemic cells between 0.9 and 2.6 logs10/mm was found at the end of the infusions. Three patients experienced greater than 2-log reduction. Two of them entered complete remission that lasted 6 weeks and 3 months, respectively. These correlations should be interpreted with caution because of the small number of patients treated. This study suggests that dThd, although of very limited therapeutic value by itself, may have potentiated the antitumor activity of ara-C to some extent. Whether this effect is of significance can only be determined by further studies.

Acute Disease↗
PubMed1984

Phase I evaluation of a biochemically designed combination: PALA, thymidine, and 5-FU.

Fifteen patients with advanced solid tumors participated in a phase I study of a biochemically designed combination chemotherapy program which employed PALA and thymidine (TdR) with 5-FU. PALA (250-2000 mg/m2) was given 24 hours before a 90-minute iv infusion of TdR (45 g). 5-FU (100-150 mg/m2) was given as a rapid iv injection 30 minutes after beginning the TdR infusion. This three-drug treatment was repeated once weekly for 3 weeks. Neurotoxicity, manifested as dizziness, lethargy, and confusion, was dose-limiting. Myelosuppression was noted at all dose levels, as was mild to moderate mucositis and diarrhea. Further clinical evaluation of this combination does not appear to be warranted.

Antineoplastic Combined Chemotherapy Protocols↗