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Biomedical subjects

J Mitchell

Publications and source records attributed to J Mitchell.

At least 343 records · Page 19Linked to original sources
PubMed1985

Secretion of a cysteine proteinase from a hormone-independent cell population of cultured explants of murine mammary gland.

Cultured explants of mouse mammary gland were investigated for their capacity to secrete a cathepsin B-like cysteine proteinase. This enzyme had been shown previously to be secreted excessively from cultured explants of human breast tumors and spontaneous mouse mammary carcinomas. We now show that secretion is also observed from cultured explants of mammary gland. Lactating tissue and tissues obtained from mid- and late-pregnant mice were found to secrete the cysteine proteinase at very high rates, but secretion was also detectable from explants of virgin mammary glands and from tissues obtained from retired breeders. However, in all cases, it was found that secretion was greatest from explants maintained in hormone-free medium and did not depend on the maintenance of normal mammary gland function. Secretion was greatly reduced in the presence of the lactogenic hormone combination of insulin, prolactin, and hydrocortisone, and this suppression was found to be due to hydrocortisone. Insulin and prolactin, while resulting in better tissue maintenance in culture, had no effect on the secretion. Enzyme release was reversibly inhibited by cycloheximide and required the presence of viable tissue, ruling out the possibility that the accumulation of enzyme activity in the culture medium is due to dying cells. The presence of metabolically active cells in explants cultured in the absence of hormones was also demonstrated by the incorporation of radiolabeled precursors into protein and DNA. DNA synthesis in cultured explants of lactating tissue was not stimulated by the addition of hormones. Histological studies revealed that, while large areas of the explants showed severe degeneration after culture without added hormones, clusters of cells persisted which displayed a relatively high mitotic activity and which showed a lack of normal epithelial organization. These observations suggest the presence of a hormone-independent cell population in the mammary gland, which secretes the stable cysteine proteinase. The secretion process itself, however, is inhibited by corticosteroids.

Animals↗
PubMed1985

Meconium aspiration and fetal acidosis.

Meconium in labor is associated with increased perinatal morbidity and mortality. To identify the infants at risk, 53 women with moderate-to-thick meconium were followed in labor after obtaining baseline fetal scalp blood pH levels. Although 28 of the newborns (53%) exhibited an arterial cord pH of less than 7.25 at delivery, there were no significant predictive variables found in the electronic fetal monitoring score, Apgar score, or mode of delivery. Nine of the infants with a pH value of less than 7.25 had meconium below the vocal cords at delivery, but none in the infants with pH levels greater than or equal to 7.25. The P50 value for cumulative acidosis is 55 minutes, indicating a more rapid deterioration than an average-for-gestational-age fetus without meconium. Therefore, the presence of thick meconium implies that fetal stress must be avoided during labor, and early intervention is warranted when there is deviation from normal labor progress or fetal heart rate pattern.

Acidosis↗
PubMed1984

Tissue phospholipid fatty acid composition in the diabetic rat.

Tissue phospholipid fatty acid compositions in streptozotocin-induced diabetic rats were studied. The major changes in liver, plasma, erythrocyte and heart were increased proportions of linoleic and dihomo-gamma-linolenic acids and a decreased proportion of arachidonic acid. The latter was not significantly changed in phospholipids of kidney, adrenal gland and testis. Skin fatty acids in diabetic rats showed an increase in the proportion of arachidonic acid and a reduction in the proportion of linoleic acid. The fatty acid desaturating activity in diabetes may be regulated differently in different tissues.

Adrenal Glands↗
PubMed1984

An empirical study of the structure of the patrol/marking motivational system in the rat.

The existence and structure of an hypothesized motivational system of patrol/marking was supported and elucidated by a behavioral study on untrained highly inbred laboratory rats. One rat (the "runner") was placed into a test chamber containing a wire-mesh running wheel flanked by two chambers, one of which contained another rat (the "target"). Four conditions of runners (socially-isolated males, socially-housed males, non-estrous females, and estrous females) were exposed to four types of targets (socially-housed males, non-estrous females, estrous females, and blank targets consisting of any empty target chamber). Also placed in the chamber was a Petri dish containing scent-markings of the target rat. The experiment was designed in a counterbalanced way with 10 replications and repeated two times in two separate years. As predicted from the hypothesis, scent-marking, sniffing the dish, locomotion (number of wheel revolutions), and approach (differential running towards the target) were all correlated with each other and varied in the same way as a function of the hormonal and experiential condition of the runner and the type of target. They were interpreted to reflect motor patterns of a single unitary patrol/marking motivational system. Grooming, on the other hand, did not correlate with the other behaviors and facial gland secretion was, therefore, rejected as a motor pattern of patrol/marking.

Animals↗
PubMed1984

Effect of dietary depletion and repletion of linoleic acid on renal fatty acid composition and urinary prostaglandin excretion.

To study the effect of dietary modification on urinary prostaglandin E (UPGE) excretion and on renal fatty acid compositions, weanling male rats were raised on a fat-free diet for 6 weeks and were switched to a diet containing 2 energy % of linoleic acid (LA) for 8 days. During fat deprivation, UPGE excretion increased in the first week (6.9 ng/24 hours urine), fell to a minimum of 1.1 ng/24 hours at 3rd week and thereafter remained at a level lower than that in the controls (3.1 ng/24 hours). UPGE excretion returned rapidly to normal (2.7 ng/hr) only 24 hours after LA supplementation. During LA treatment, arachidonic acid (AA) concentrations in renal cholesteryl esters rapidly increased from 19% to 27% (33% in the controls), while concentrations in renal phospholipids (PL) and renal free fatty acids (FFA) did not change during the first four days but reached the normal range at the 8th day. The present studies demonstrate that chronically fat deficient animals excreted significantly less UPGE than that in the controls. However, this deficiency could be rapidly reversed by LA supplementation despite the fact that AA levels in renal lipid fractions remained well below normal. This suggests that dietary LA may be rapidly converted to AA and subsequently to PGE without AA levels rising in the lipid fractions usually thought of as being PG precursors.

Animals↗
PubMed1984

131-iodine conjugated antibody cell kill enhanced by bromodeoxyuridine.

131I-conjugated monoclonal and polyclonal antibodies are being administered in vivo to kill human tumor cells. Although these conjugates deliver relatively large doses of radiation to tumors (10 to 50 Gy), the rate of dose delivery is low (0.05 to 0.2 Gy/hour). Radiation delivered at low dose rates kills fewer cells that exhibit large shoulders on radiation survival curves than radiation delivered at high dose rates. To determine whether the cell kill produced by low dose rate radiation is enhanced by a radiation sensitizer (bromodeoxyuridine, BUdR) we studied the cell kill produced by an 131I-conjugated polyclonal antibody against Chinese hamster V79 cells. V79 cells were labeled with 131I-conjugated antibody (10-20 microCi/micrograms) and unconjugated antibody, and frozen for up to 30 days in liquid nitrogen. The surviving fraction of cells was measured at intervals of 5 to 10 days. Cells not containing BUdR were also studied. The 131I-conjugated antibody produced up to 40% cell kill and BUdR increased the fraction of cells killed to 75%. Our studies demonstrate that cells frozen at -196 degrees C are useful for the investigation of the cell kill produced by isotopes that deliver radiation at low dose rates and that the cell kill caused by 131I-conjugated antibodies can be enhanced by BUdR.

Animals↗
PubMed1984

Identification of bromodeoxyuridine in malignant and normal cells following therapy: relationship to complications.

During a clinical Phase I study of bromodeoxyuridine (BUdR) as a radiation sensitizer we identified the normal and malignant cells that incorporated the BUdR. BUdR was infused for up to 14 days and the in vivo incorporation of BUdR into DNA was assessed using an immunohistochemical technique and a monoclonal antibody directed against BUdR. BUdR was identified in 50% of breast cancer cells and 10% of cells in a malignant melanoma. BUdR was also found in the basal layer of the normal epidermis and in 50% of cells in the marrow. The incorporation of BUdR into cells in the epidermis and marrow may produce the phototoxicity and myelosuppression observed in patients treated with BUdR. Sequential biopsies from a breast cancer taken prior to and following radiotherapy suggested that cells that incorporated BUdR may have been selectively killed by the radiation. The immunohistochemical technique used to identify BUdR appeared to be useful for studies of in vivo and in vitro cell proliferation.

Bone Marrow↗
PubMed1984

Dual regulation of intermediate filament phosphorylation.

Intermediate filament proteins have been isolated from ME-180, cells of a human cervical carcinoma. Eight of these proteins have been identified as keratins by immunologic cross-reactivity to antibodies raised against authentic human epidermal keratins. The ME-180 keratin proteins consist of two major subunits designated MEK-1 and MEK-2 with approximate molecular weights of 58,000 and 53,000, respectively, and six minor subunits of 59, 57, 52.5, 50.5, 45, and 40 kilodaltons. When ME-180 cells were incubated for 2-24 h in the presence of [32P]orthophosphate, MEK-1 and MEK-2 as well as the 52.5- and 40-kilodalton keratins were phosphorylated at their serine residues. V8 protease digests revealed that phosphorylation of MEK-2 is restricted to one peptide representing approximately half the molecule. Regulation of MEK-1 and MEK-2 phosphorylation has been studied by prelabeling the cells for 2 h in 32P-labeled medium. This was followed by up to 2 h of continued incubation in the same medium after the addition of a variety of perturbing agents. The phosphorylation of MEK-2 increased in the presence of 10(-4) M dibutyryl cyclic AMP (twofold), 1 mM methylisobutylxanthine (2.5-fold), 10(-5) M isoproterenol (fivefold), and 10(-9) M cholera toxin (sevenfold). In contrast, MEK-1 phosphorylation was unaffected by these agents. Neither cyclic GMP, Ca++, hydrocortisone, nor epidermal growth factor had any effect on the phosphorylation of MEK-1 or MEK-2. The results indicate that the phosphorylation of these two keratins is independently controlled by cyclic AMP-dependent kinase for MEK-2 and by cyclic nucleotide-independent kinase for MEK-1. The observed differences in control suggest distinct functions for MEK-1 and MEK-2 within the cytoskeletal network.

Cells, Cultured↗
PubMed1984

Deoxycorticosterone acetate hypertension in the sheep.

A model of hypertension induced by mineralocoriticoid-excess in the sheep is described. Deoxycorticosterone acetate (DOCA), 100 mg/kg was implanted subcutaneously in adult sheep (n = 13). Before DOCA administration, and for 30 days thereafter, mean arterial blood pressure (MAP), plasma electrolyte levels, plasma renin activities, water and electrolyte intakes and urinary outputs were monitored. Within 72 h after DOCA implantation MAP had risen from a control value of 83.0 +/- 2.0 to 93.0 to 3.0 mmHg, MAP stabilized at 114.0 +/- 3.0 mmHg three weeks later. Water intake had increased significantly by the 4th post-implant day and reached a maximum of 10.0 +/- 1.2 l/day by the third week. The following biochemical changes were significant within 24 h after DOCA implantation; (1) plasma potassium fell from 4.4 +/- 0.1 to 3.42 +/- 0.13 mEq/l; (2) plasma sodium rose from 144.4 +/- 0.6 to 147.0 +/- 0.4 mEq/l; (3) plasma renin activity fell from 1.29 +/- 0.42 to 0.13 +/- 0.08 ng ANG l/ml/h. The rapidity of onset and reversal of arterial pressure elevation in this model render it a useful tool in providing insight into the mechanism responsible for this form of hypertension.

Animals↗
PubMed1984

Electrical stimulation of the salivatory nucleus in the rat.

Unilateral electrical stimulation of the salivatory nucleus evoked a secretion from the ipsilateral parotid gland which was well maintained. Flow rate was not affected by sympathetic decentralization or by adrenoceptor antagonists but was abolished by atropine. Protein secretion was reduced by beta-adrenoceptor antagonists but not by sympathetic decentralization or adrenalectomy. In support of previous histochemical findings it is concluded that the cells of the reticular formation are the origin of the preganglionic parasympathetic fibres to the salivary glands but that a beta-adrenoceptor mechanism as yet unidentified is also involved in the protein secretion.

Adrenalectomy↗
PubMed1984

Aortic stiffness in the DOCA-hypertensive pig.

Pulsatile changes in aortic diameter and pressure were monitored in order to obtain an index of aortic stiffness in the conscious pig during the development of mineralocorticoid hypertension. The aortic stiffness index increased but to a much lesser extent than it did in response to a similar pressure elevation produced by phenylephrine infusion. This observation suggests that chronic exposure to an elevated pulsatile pressure reduces the stiffness index at the elevated pressure.

Animals↗
PubMed1984

Role of prostaglandin-induced cervical changes in labor induction.

The role of the cervix in labor induction has been studied in a previous report. Cervical preparation by mechanical methods did not alter the course of induced labor. The same hypothesis is further elucidated in the present study using prostaglandin E2 vaginal suppositories for cervical preparation. Forty-seven pregnant women near term with Bishop scores of 4 or less were divided into three study groups: control subjects, oxytocin-treated patients, and prostaglandin group. A 12-hour preparation phase procedure was carried out to produce cervical and/or myometrial changes. All women had continuous measurement of uterine activity by an extraovular catheter. At the end of the preparation phase, the Bishop score was reevaluated, amniotomy carried out in all patients, and oxytocin infusion either started or continued. Although prostaglandin and oxytocin both significantly changed the cervix, oxytocin had the shortest induction-to-delivery interval, though the prostaglandin-treated group required lower concentrations of oxytocin. The authors conclude that with rigid control of Bishop score and timing of amniotomy and oxytocin infusion rates, prostaglandin-induced cervical changes alone did not uniquely benefit labor induction in the doses used, or within the time frame of the study.

Adult↗
PubMed1984

Effects of propranolol on thyroid function in the dog.

The effect of propranolol on thyroid function was evaluated in 6 mature euthyroid Beagles. Propranolol was administered orally in doses of 20 mg given 3 times daily for 2 weeks and then increased to 40 mg given 3 times daily for an additional 2 weeks. Six age- and sex-matched, euthyroid Beagles served as controls. Serum base-line concentrations of tetraiodothyronine (T4), triiodothyronine (T3), and reverse triiodothyronine (rT3) were measured before propranolol administration and at weekly intervals thereafter. Thyroid response to 5 IU of aqueous thyroid stimulating hormone administered IV was monitored before propranolol administration and at the 2- and 4-week treatment intervals. The T4, T3, and rT3 concentrations were measured by radioimmunoassay. There were no significant differences in base-line or postthyroid stimulating hormone serum concentrations of T4, T3, or rT3 in any individual or between the treatment or control groups at any treatment interval (P greater than 0.05). Seemingly, the therapeutic use of propranolol in euthyroid dogs should not alter thyroid hormone metabolism.

Animals↗
PubMed1984

Health care experience among employees prior to and after enrollment in a prepaid health insurance plan (HMO).

Company medical and benefit records of employees who were enrolled in prepaid health insurance plans (HMOs) in Minneapolis, Washington, D.C., and Seattle were reviewed for hospital and surgical utilization prior to as well as after their enrollment. Comparisons were made for the same calendar periods with closely matched employees who were covered by Blue Cross/Blue Shield (BC/BS). The results indicate that after enrollment the HMO subjects at each location had lower rates for hospital and surgical utilization than the BC/BS controls. For the period prior to enrollment, during which time coverage was through BC/BS, the prospective HMO subjects at two locations had lower hospital and surgical utilization than the controls. Possible explanations of this potential self-selection bias are discussed.

Adult↗