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Biomedical subjects

J Young

Publications and source records attributed to J Young.

At least 451 records · Page 25Linked to original sources
PubMed1985

An inhibitor of ornithine decarboxylase in the thymus and spleen of dexamethasone-treated rats.

A marked decrease in activity of ornithine decarboxylase in thymus and spleen occurs soon after treatment of rats with a glucocorticoid. In the present study, evidence was obtained that extracts of these tissues prepared 5 h after administration of dexamethasone, when the enzyme activity is very low, contain an inhibitor of ornithine decarboxylase. The inhibitor is also present at 12 h after treatment and, in lesser amount, at 2.5 h, but was not evident at 24 h. The inhibitory activity was destroyed by treatment with heat or with trypsin, and was not lost on dialysis of the extract. Preliminary experiments indicate that the Mr of the inhibitor is greater than 50 000, which differentiates it from antizyme, an inhibitor of ornithine decarboxylase found in several other cell types. The inhibitor seems to act by a non-catalytic and non-competitive mechanism. The inhibition is dependent on the amount of inhibitor and does not change with time. Since inhibition is not changed by dialysis of the inhibitory extract, its activity apparently does not require small-Mr substances. This differentiates it from inhibitors which inactivate ornithine decarboxylase by covalent modification, such as the polyamine-dependent protein kinase or transglutaminase. The formation of this inhibitor is an early event in lymphoid tissues in response to dexamethasone and may be important in causing the inhibition of cell division which precedes the destruction of lymphocytes.

Animals↗
PubMed1985

Squamous carcinoma of the vagina: treatment, complications, and long-term follow-up.

Seventy-five cases of primary squamous cell carcinoma of the vagina treated at the University of Pennsylvania are reviewed with long-term follow-up presented. These comprised 2.5% of all female genital malignancies treated during 1958 to 1980 inclusive. Patients treated during that time with non-squamous cell cancers have been excluded. Patients are analyzed with regard to stage, therapy, complications, and survival. Sixty-five percent of patients were stage I or II. Five-year survival for the entire group was 45%. Patients treated with radical surgery other than exenteration did well, with 7 of 8 surviving 5 years. Serious treatment complications were mostly related to radiation therapy and primarily involved the bowel and bladder. Three patients died of complications. Recurrence carried a grave prognosis as 30 of 33 patients with recurrence died of disease. Most recurrences were diagnosed within the first year following treatment. Patients with advanced disease were more likely to have distant recurrences. Although radiation therapy is generally the treatment of choice, radical surgery can yield excellent results when used in carefully selected patients. With meticulous attention to radiation dosage and technique it is hoped that treatment morbidity can be reduced. Optimal treatment of advanced disease may require some form of adjuvant systemic therapy.

Adult↗
PubMed1985

The significance of gastric emptying in children with intestinal malrotation.

Persistent gastrointestinal symptoms are common postoperatively in children with intestinal malrotation. We investigated this problem in 14 children with intestinal malrotation who had a Ladd procedure (3 patients), gastroschisis repaired (6 patients), or omphalocele repaired (5 patients) between one month and 15 years prior to study. In 13 patients, gastric emptying was measured at 30 minutes (%GE30) and at 60 minutes (%GE60) following ingestion of 99m-Tc sulfur colloid in apple juice. We estimated the degree of gastric peristalsis using the %GE corrected for immediate postcibal gastroesophageal reflux (corrected %GE). Patients with vomiting exhibited slow gastric emptying compared to patients without vomiting (%GE30: 14.0 +/- 5.5 v 32.5 +/- 4.2, P less than .005). The slow gastric emptying was related to slow gastric peristalsis (corrected %GE30: 20.3 +/- 5.0 v 47.1 +/- 6.0, P less than .005). In all 5 patients with persistent bloating and diarrhea, gastric peristalsis was rapid at 30 minutes (corrected %GE30 = 56.7 +/- 4.2) and at 60 minutes (corrected %GE60 = 69.5 +/- 5.3). To assess the role of gastroesophageal reflux (GER) in persisting symptoms, all children had extended (18 to 24 hours) esophageal pH monitoring. Eleven (79%) of the 14 patients demonstrated GER by esophageal pH monitoring, including four of six patients without reflux symptoms. All ten children under two years of age demonstrated GER regardless of symptoms or congenital anatomic abnormality. In conclusion, GER is common in patients under two years of age with intestinal malrotation, but clinical symptoms seem related more to extreme variations in gastric peristalsis than to GER.

Abdominal Muscles↗
PubMed1985

Noncardiogenic pulmonary edema after charcoal hemoperfusion.

Hemoperfusion over cellulose-coated activated charcoal was used to treat a patient with severe doxepin overdose. Noncardiogenic pulmonary edema (NCPE) developed temporally in relation to the procedure. In this case, NCPE may have been from complement activation by the cellulose-coated charcoal column.

Charcoal↗
PubMed1985

Potassium fluxes in bovine adrenal cells during adrenocorticotropin stimulation.

Active (ouabain-sensitive) and passive (ouabain-insensitive) fluxes of 43K were measured in isolated bovine zona fasciculata/reticularis cells. ACTH inhibited passive influx in a dose-dependent manner and, at a concentration that maximally stimulated steroidogenesis (10(-8) M), also inhibited passive efflux. ACTH did not affect active potassium transport. Angiotensin II (10(-6) M) and cAMP (10(-2) M) inhibited passive influx to the same extent as did 10(-8) M ACTH. Angiotensin II (10(-6) M) also reduced active potassium uptake, although this did not appear to be related to changes in cortisol biosynthesis. Increases in cortisol synthesis by ouabain-treated cells in response to angiotensin II and ACTH were proportional to decreases in potassium influx. The addition of cortisol (1 microgram/ml) to cells slightly reduced passive potassium uptake, but not to the same extent as did 10(-8) M ACTH. Frusemide, an inhibitor of passive sodium/potassium cotransport, did not wholly abolish the effects of ACTH on potassium influx. These changes in flux are probably related to electrophysiological changes in membrane potential. Their significance in the regulation of ACTH actions has yet to be determined.

Adrenal Glands↗
PubMed1984

Pharmacokinetics and tolerance of intravenous and intramuscular recombinant alpha 2 interferon in patients with malignancies.

Fifteen patients with advanced hematopoietic and other malignancies were treated with recombinant DNA produced Alpha 2 Interferon (IFN) (Schering) by intravenous (IV) and intramuscular (IM) routes at weekly intervals in escalating doses from 1 X 10(6) IU to 100 X 10(6) IU in order to determine the tolerance and pharmacokinetics. The most common side effects included fever, chills, myalgia, and arthralgia. At doses of 60 X 10(6) or above, severe but reversible hypotension was observed in five patients receiving interferon by intravenous route. Patients receiving interferon by intramuscular route had fever, chills, and myalgias but did not develop hypotension at the same dosage. Two patients with non-Hodgkin lymphoma showed objective evidence of regression. Our data suggest a biphasic pattern of elimination with terminal half-life ranging from 1.9 to 2.9 hours and peak titer of 16,000 units and under for IV interferon, and terminal half-life of 6 hours with peak titers of 600 units for intramuscular interferon. However, interpatient variability precludes a definite conclusion. Although the areas under the serum concentration vs time curves were similar, the intravenous route provided higher but unsustained levels of interferon than the intramuscular route.

Adolescent↗
PubMed1984

Splenectomy after angiographic embolization of the splenic artery in patients with massive splenomegaly and severe thrombocytopenia, in juvenile subacute myelomonocytic leukemia.

Splenectomy for massive splenomegaly in thrombocytopenic patients refractory to platelet transfusions carries increased surgical risks. Blocking of the splenic artery may reduce the size of the organ, prolong the survival of transfused platelets, and reduce the surgical complications. We describe four cases of extreme splenomegaly and thrombocytopenia where successful splenectomy was carried out after angiographic embolization of the splenic artery in children with juvenile chronic myelogenous leukemia. Significant improvement was observed in platelet counts and in the survival of platelets after transfusions in three of the patients. There was a concomitant decrease in transfusion requirements. Isoimmunization prevented prolonged platelet survival in the fourth case. We recommend earlier splenectomy in these patients to reduce transfusion requirements and delay the onset of poor platelet survival after transfusions.

Blood Transfusion↗
PubMed1984

Metabolic, endocrine, and reproductive changes of a woman channel swimmer.

We report the coordinated metabolic, hormonal, and reproductive data of a female channel swimmer during the pre-swim training period, immediately post-swim, and in the post-swim untrained state. Urine and blood samples collected at these times were assayed for diurnal urinary catecholamines, urinary C-peptide and 3-methylhistidine, total blood ketone bodies, glycerol, the reproductive hormones, adrenal androgens, and thyroid hormones. Subcutaneous fat was measured by ultrasonography. All of the metabolic and hormonal data post-swim except cortisol reflected the severe physiological stress. Urinary catecholamines returned to near-normal levels by 12 hours post-swim. The metabolic changes were associated with reproductive changes, including a shortened luteal phase, absence of ovulation, and increased LH secretion relative to FSH. The swimmer maintained high levels of body fat; she did not become amenorrheic. Metabolic and reproductive hormone levels returned to normal by 2 months post-swim.

Adipose Tissue↗
PubMed1984

Reversal of histamine-mediated immunosuppression by structurally diverse histamine type II (H2) receptor antagonists.

The effect of a series of structurally-diverse histamine type II (H2)-receptor antagonists on histamine-mediated immunosuppression of human peripheral blood lymphocytes (HPBL) has been examined. This analysis of structure--activity relationships was undertaken to examine the validity of the recent proposal arising from clinical studies that H2-receptor antagonists containing a furan ring were devoid of the effects on lymphocyte function reported previously in studies using cimetidine and other H2-receptor antagonists containing an imidazole nucleus. Cimetidine and two furan-containing antagonists, ranitidine and SKF 93479, were found to be devoid of any effect on PHA-induced proliferation of human peripheral blood lymphocytes over a wide concentration range (10(-4) to 10(-10)M). At high drug concentrations (10(-3)M) significant suppression of mitogen stimulation was observed but this was accompanied by significant cytotoxicity. All three antagonists were effective in reversing the suppression of PHA-stimulation of HPBL induced by exogenous histamine. Reversal of histamine-induced immunosuppression was obtained at drug concentrations (2.0 X 10(-4) to 1.0 X 10(-6)M) which were non-toxic and did not affect PHA-induced proliferation in the absence of histamine. Ranitidine was the most potent antagonist in reversing histamine-mediated immunosuppression. The ability of structurally-diverse H2-receptor antagonists to modify the action of histamine on lymphocyte function lends support to the view that histamine exerts its effects via classical H2-receptors. The ability of ranitidine to alter lymphocyte responsiveness in analogous fashion to cimetidine indicates that the possibility of alterations in immune function should be considered in clinical studies using ranitidine and other furan-containing H2-receptor antagonists.

Animals↗
PubMed1984

Appetite and weight change in patients presenting with depressive illness.

Appetite and weight in 193 moderately depressed outpatients who satisfied Feighner's criteria for a primary depressive episode were found to be strongly associated with previous appetite and weight history. There was no overall association between weight change and severity of depression, nor with the classical features of endogenous depression, such as early morning waking and morning worsening of mood. Appetite change in either direction was, however, associated with a more severe degree of depression on the Hamilton and Beck scales. Normal appetite changes in response to stress occur in an exaggerated way in this depressive illness.

Adult↗
PubMed1984

Physiologic and anthropometric factors underlying endurance performance in children.

This study investigated the relationship between endurance performance and several measures of aerobic, anaerobic, and morphological fitness in 30 girls and 28 boys, 10 to 14 years of age. A multistage treadmill test was used for assessment of VO2 max (ml X kg-1 X min-1) and anaerobic threshold (AT) expressed both in absolute (AT-VO2) and relative (% VO2 max) terms. Anaerobic capacity (AC) was measured in a 30-s cycling task and expressed as kpm . kg of body weight-1 X min-1. Percent fat was estimated from skinfolds. The correlations between these measures and 2-km run time were: -0.73, -0.73, -0.50, -0.77, and 0.55 for VO2 max, AT-VO2, AT-%VO2 max, AC, and percent fat, respectively. When entered into a forward selection multiple regression with run time as the dependent variable, AC accounted for 59.5% of the variance and VO2 max accounted for an additional 6.9%, with AT and percent fat making no significant additional contribution. When the girls and boys were compared, no reliable differences were found for run time and AC. The boys exhibited reliably higher values for VO2 max and AT-VO2. No reliable difference in percent fat was found for the younger boys and girls, but the older girls were significantly fatter than the older boys. Thus, in children 10 to 14 there is a substantial relation between measures of anaerobic and aerobic function, although to some extent they provide independent information about endurance performance.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed1984

Cellular localization of the transforming protein of wild-type and temperature-sensitive Fujinami sarcoma virus.

Fujinami sarcoma virus (FSV) encodes a 140,000-dalton transforming protein, P140, which contains gag- and fps-specific sequences. The cellular localization of this protein was examined by fractionation of [35S]methionine-labeled, FSV-infected chicken embryo fibroblasts. In homogenates of cells infected by wild-type, temperature-resistant FSV prepared in either hypotonic or isotonic buffer, 60 to 80% of the P140 was particulate. Isopycnic separation on discontinuous sucrose gradients indicated that the majority of the particulate P140 was present in a light membrane fraction enriched for plasma membranes. Much of the particulate P140 could be solubilized by the addition of 0.6 M salt to a postnuclear supernatant, suggesting that P140 is not an integral membrane protein. Particulate P140 may be associated with membranes either directly as a peripheral membrane protein or indirectly via cytoskeletal elements. In cells infected by mutants of FSV temperature sensitive for cellular transformation, most of the P140 is particulate at the permissive temperature, whereas most is soluble at the nonpermissive temperature; this change in distribution is not a secondary consequence of the change in cellular phenotype, since it also occurs in nonconditionally transformed cells doubly infected with temperature-sensitive FSV and wild-type Rous sarcoma virus. The movement of P140 from the particulate to the soluble fraction occurs rapidly when cells infected by temperature-sensitive FSV are shifted from the permissive to the nonpermissive temperature. Furthermore, P140 moves from the soluble to the particulate fraction, although somewhat more slowly, when cells are shifted from the nonpermissive to the permissive temperature. These observations suggest that the association of P140 with plasma membranes or the cytoskeleton may play a role in transformation by FSV.

Animals↗
PubMed1984

Changes occurring in appetite and weight during short-term antidepressant treatment.

Changes in appetite and weight were recorded in mild to moderately depressed out-patients during the course of clinical trials of various antidepressant drugs. After six weeks, differences due to treatment regimes were minimal. Patients who on becoming depressed experienced severe changes in appetite and weight in either direction, tended to return to normal. The significant associations of appetite and weight change during treatment were with weight, appetite, and carbohydrate preference at presentation, and also with the 'appetite history' and 'weight history'. The associations with the degree of depression were relatively minor.

Antidepressive Agents↗
PubMed1984

Inhibition by etomidate of steroidogenesis in isolated bovine adrenal cells.

Adverse side effects of the anaesthetic etomidate have been indirectly linked with inhibition of adrenocorticoid synthesis. The present in vitro study has shown that this is a direct effect and indicated which biosynthetic reactions are affected by etomidate. Isolated bovine adrenocortical cells were incubated with and without 10(-8)M ACTH and with increasing doses of etomidate (0-625 ng/ml). ACTH-stimulated cortisol synthesis was significantly inhibited by a concentration of etomidate (25 ng/ml), which is much less than therapeutic plasma levels (100-500 ng/ml). Both basal and ACTH stimulated synthesis of cortisol, progesterone, 17 alpha hydroxyprogesterone and corticosterone were inhibited by 625 ng etomidate/ml whereas deoxycorticosterone output was more than doubled with this dose of anaesthetic. These observations suggest that etomidate inhibits mitochondrial cytochrome P450-dependent hydroxylation reactions in the adrenal steroidogenic pathway.

Adrenal Cortex↗