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Biomedical subjects

D W Morrish

Publications and source records attributed to D W Morrish.

At least 37 records · Page 2Linked to original sources

131I treatment of thyroid papillary carcinoma in a patient with renal failure.

Procedures for 131I ablation in renal failure are not known. In one patient receiving dialysis, detailed dosimetry and health safety aspects were obtained. The results showed insignificant contamination of equipment, but a surprisingly significant reduction in biologic half-life of 131I due to efficient dialysis extraction. The data indicate that 131I ablation can be done safely and easily during dialysis but that much higher 131I doses must be used to achieve equivalent results to those obtained in patients with normal renal function.

Adult↗

Mechanisms of endocrine dysfunction in patients with testicular cancer.

To determine mechanisms of endocrine dysfunction in patients with testicular cancer, we performed static and dynamic testing of the hypothalamic-pituitary-testicular axis and testicular exocrine function in 13 patients and 11 normal control subjects, as well as in vitro studies of tumor tissue and remaining adjacent "normal" testicular tissue in the 13 patients. In tumor tissue, we demonstrated (a) elevated concentrations of total serum estradiol and serum estradiol not bound to sex hormone-binding globulin, (b) impaired spermatogenesis and sperm motility, and (c) blocking of multiple enzymes necessary for steroidogenesis. The data were consistent with a paracrine-endocrine mechanism in which tumor-produced human chorionic gonadotropin stimulates production of estradiol by "normal" testicular tissue but not tumor tissue, and the high estradiol levels then result in impaired spermatogenesis.

Adult↗

The dual effect of epidermal growth factor upon human chorionic gonadotropin secretion by the first trimester placenta in vitro.

Epidermal growth factor (EGF) is believed to play an important role in the regulation of placental function. We have examined the effect of EGF upon first trimester (7-10 gestational weeks) placental hCG secretion and cellular differentiation using both static (explants and isolated cells) and kinetic (superfusion of explants) culture methods. In superfused explants, short (1-4 min) pulses of EGF increased both the rate and amplitude of spontaneous pulsatility of hCG. The frequency increased from 3/h to 5/h, and the amplitude increased compared to the control channels as calculated by the area under the curve. This effect was dose dependent and the concentration of 50 ng/ml, which was the lowest dose tested, was the most effective. In explants cultured for 24 h, EGF caused a 2-fold increase in hCG secretion, compared to control, P less than 0.05. In two different dispersed trophoblastic cell cultures, EGF added daily for the first week caused a 180% increase in hCG secretion, P less than 0.05. However, according to morphological criteria, i.e. light microscopy and vital staining, no significant effect upon the rate of differentiation to syncytiotrophoblast was observed in long-term cultures of one of these preparations. In conclusion, EGF plays a dual trophic role in stimulating hCG secretion in the first trimester. However, this effect is not dependent on cellular differentiation.

Cell Differentiation↗

Absence of feedback inhibition of prolactin secretion by the prostate.

Previous observations in rodents and man have suggested the existence of feedback inhibition of pituitary prolactin secretion by the prostate. Thyrotrophin releasing hormone (TRH) tests performed in males before and after prostatectomy demonstrated no difference in prolactin or thyrotrophin (TSH) secretion. These data do not support the hypothesis of a prostate-pituitary feedback loop in the control of prolactin secretion. The results also imply that prostatic TRH acts in a paracrine manner.

Aged↗

Ultrastructural localization of human placental lactogen in distinctive granules in human term placenta: comparison with granules containing human chorionic gonadotropin.

Human placental lactogen (hPL) is known to originate in the syncytiotrophoblast, as demonstrated by light microscopic peroxidase and immunofluorescent staining. However, ultrastructural localization of hPL has not previously been performed. In these experiments, immunostaining of electron microscopic sections using protein A-gold and avidin-biotin complex techniques was used to study hPL and human chorionic gonadotropin (beta hCG) localization in first trimester and term placentae. HPL was localized in many small (0.12-0.25 micron) granules. In contrast, beta hCG was found in large (0.40-1.2 micron) granule complexes. The results therefore demonstrate that these two hormones are stored in two morphologically distinct types of cytoplasmic granules. Since hPL and hCG have different secretory mechanisms, this methodology will be useful in studying these differing mechanisms in human placenta.

Chorionic Gonadotropin↗

Immunolocalization of alpha and beta chains of human chorionic gonadotropin, placental lactogen and pregnancy-specific beta-glycoprotein in term placenta by a touch preparation method.

Touch preparations of human placenta yield cells retaining antigenic reactivity to immunoperoxidase stains for alpha and beta chains of human chorionic gonadotropin, placental lactogen, and pregnancy-specific beta glycoprotein. This method is a rapid and simple alternative to conventional frozen and paraffin-embedded sections for detection of placental peptides.

Chorionic Gonadotropin↗

Demonstration of specific secretory granules for human chorionic gonadotropin in placenta.

Existence of secretory granules and exocytosis during secretion of human chorionic gonadotropin (hCG) in human placenta has been a point of controversy. Using two methods, the highly sensitive avidin-biotin complex (ABC) method and the protein A-gold technique, for immunochemical identification of beta-hCG on electron microscopic sections, we have examined placentas at 8-10 weeks gestation and at term for the presence of secretory granules. First-trimester placentas demonstrated plentiful syncytiotrophoblast cytoplasmic granules, some undergoing exocytosis, when stained using specific beta-hCG antiserum in the ABC and protein A-gold methods. Term placentas did not show positive reaction product. The data demonstrate that the classic secretory granule-exocytosis pathway mediates placental hCG secretion. However, clear morphological differences exist between placenta granules and hormone secretory granules observed in pituitary, consistent with known functional differences between these organs. This methodology will be useful for further studies of the secretory pathways for placental peptides.

Chorionic Gonadotropin↗

Epidermal growth factor induces differentiation and secretion of human chorionic gonadotropin and placental lactogen in normal human placenta.

Human trophoblast differentiates by the fusion of cytotrophoblasts to form syncytiotrophoblast. To determine factors controlling this process, the effects of epidermal growth factor (EGF) on trophoblast differentiation were studied using long term serum-free culture of isolated trophoblast. Only trophoblast was present in the cultures, as demonstrated by positive immunoperoxidase staining with beta hCG, cytokeratin, and trophoblast-specific H315 monoclonal antisera and by the absence of contaminating endothelial cells, fibroblasts, and macrophages, as shown by negative staining with vimentin and OKM1 monoclonal antisera. EGF induced large sustained increases in hCG and human placental lactogen (hPL) secretion in a dose-dependent manner. The minimum effective dose was 0.1 ng/mL, and the maximum effective dose was 1 ng/mL. Light and electron microscopic studies showed EGF-induced differentiation of cytotrophoblast to form syncytiotrophoblast. DNA content and cell number did not change during the process. The formation of syncytia thus probably accounted for the increase in hCG and hPL secretion. We conclude that EGF causes morphological differentiation, but not cell proliferation, of trophoblasts, and the differentiation results in increased hCG and hPL secretion from the syncytia.

Cell Differentiation↗

Critical factors in establishing monolayer cultures of normal human placental cells in serum-free medium.

Comparative studies have been performed to determine the best method for preparing monolayer cultures of normal human term trophoblast cells. The use of 0.25% trypsin-10 U/ml DNAse I provided the highest cell viability and greatest hormone production, but was critically dependent on the trypsin lot used. Cell function in culture was not improved with various substrata, nor did other factors (medium type, pH, red blood cell removal) affect the results. Optimization of dispersal and culture conditions permitted the trophoblast cells to survive with intact hormone secretion and response to secretagogues under serum-free conditions. These studies thus define the best methodology for establishing trophoblast cells in monolayer cultures.

Cell Separation↗

Preservation of human chorionic gonadotropin and placental lactogen secretion and normal morphology following long-term culture of normal human placental cells.

In order to study the regulation of hCG and hPL secretion during gestation, a system for the preservation of the functional integrity of normal placental cells in long-term culture was established. Normal term placental cells were dispersed with 0.25% trypsin-500 units DNAse I and cultured in a monolayer in Dulbecco's modified Eagle medium with 10% fetal bovine serum. Normal cell morphology, basal hCG and hPL production and hCG responses to dibutyryl cAMP were preserved till 54 days of culture. This model may be useful for the study of long-term regulation of normal placental hCG and hPL synthesis and secretion.

Bucladesine↗

Gynecomastia after cytotoxic therapy for metastatic testicular cancer.

Four men with metastatic nonseminomatous testicular cancer, who had received combination chemotherapy, experienced transient gynecomastia. Serum hormone levels were measured during and after the resolution of the gynecomastia. These levels indicated toxic effects on Leydig's cells and germinal epithelium concurrent with raised serum estradiol levels in the absence of tumor. The gynecomastia may have been caused by Leydig's cell dysfunction or refeeding after substantial weight loss. This benign form of gynecomastia must be recognized to avoid unnecessary investigation and treatment.

Adult↗

Hypothalamic-pituitary-adrenal function in extrinsic asthma.

Hypothalamic-pituitary-adrenal function in a well-defined, carefully selected group of 25 patients with extrinsic asthma was assessed by measuring plasma levels of adrenocorticotropic hormone (ACTH) and of 11-deoxycorticol after administration of metyrapone and by measuring the level of cortisol following stimulation with cosyntropin. No difference was demonstrated between asthmatic subjects and 20 normal age-matched controls. In addition, neither the response of the level of ACTH nor of 11-deoxycortisol correlated with the duration of asthma or the severity as assessed in 23 patients by tests of pulmonary function. We conclude that there is no abnormality in hypothalamic-pituitary-adrenal function in patients with extrinsic asthma, and we suggest that previous data suggesting such an abnormality may reflect heterogeneous groups of patients, inaccurate methods, and the variability of normal responses to ACTH and stimulation with metyrapone.

17-Hydroxycorticosteroids↗

Carcinoembryonic antigen: 3 years' experience in a cancer clinic.

Long-term studies on multiple plasma samples of 988 patients with carcinoma of entodermal origin indicate that, especially for patients with colorectal cancer, repeatedly elevated or rising carcinoembryonic antigen (CEA) values are a sign of poor prognosis when found preoperatively, postoperatively or during chemotherapy. Persistently elevated CEA values in postoperative patients apparently free of disease are a useful marker for early detection of recurrence or metastases. Normal CEA values are of little or no prognostic value.

Antineoplastic Agents↗

Localization of human chorionic gonadoptropin and placental lactogen by immunogold labeling for electron microscopy: technique and limitations.

To demonstrate human chorionic gonadotropin (hCG) and human placental lactogen (hPL) secretory granules in placenta and to illustrate newer embedding techniques and specific immunospecificity problems in the placenta, labeling experiments using immunogold or peroxidase combined with avidin-biotin enhancement in epoxy LX-112-, Araldite-, or LR gold-embedded tissue fixed in 2.5% glutaraldehyde or 2.5% paraformaldehyde were carried out in term and first-trimester normal human placenta and in partial hydatidiform moles. Increased sensitivity of the low-temperature LR gold method was found for hPL-labeled granules. beta hCG-labeled granules were noted in syncytium of first-trimester placenta, and beta hCG-containing granules in hydatidiform moles were similar to those of normal placenta. Paraformaldehyde fixation and LR gold embedding permitted identification of endoplasmic reticulum-associated labeling not observed with other methods. A brief review and discussion of immunolabeling methods, controls, and embedding materials is presented. We conclude that further refinement of peptide localization methods in the placenta is possible but must take into account the abundant potentially cross-reacting peptides present in the placenta.

Chorionic Gonadotropin↗

Neonatal encephalopathy: an indicator of early sexual maturation in girls.

Of 161 girls with neonatal encephalopathy who were prospectively assessed until 8 years of age, 7 (4.3%) demonstrated variable degrees of early sexual maturation. This finding was significantly greater than the accepted 0.6%, estimated for the general population. Four of the 7 girls with early sexual maturation had physical disabilities (i.e., 3 with cerebral palsy, 1 neurosensory deafness) which indicated that 10% of the 40 physically disabled girls had early sexual maturation. Three (2.5%) of 121 girls without physical disabilities matured early. Sexual maturation began 5 years or longer after the diagnosis of neonatal encephalopathy. An increased incidence of early sexual maturation in girls with neonatal encephalopathy indicates the importance of long-term follow-up of this population. This study provides an indication of a link between newborn illnesses causing neonatal encephalopathy and early sexual maturation in girls without progressive, structural, intracranial pathology and suggests further study of some girls previously diagnosed as having idiopathic precocious puberty.

Asphyxia Neonatorum↗