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Biomedical subjects

W D Odell

Publications and source records attributed to W D Odell.

At least 19 recordsLinked to original sources

ACTH immunoactivity in normal rat tissues: modulation by hypophysectomy and adrenalectomy.

This study investigates the effect of pertubation of the normal pituitary-adrenal axis on concentrations of adrenocorticotropin (ACTH)-like immunoactivity in peripheral tissues. We used a polyclonal antibody (West antibody) to measure ACTH-like immunoactivity in glacial acetic acid extracts of five tissues in adult male rats at increasing times (1, 7, 14, and 28 days) after hypophysectomy or adrenalectomy, and in normal control rats. Concentrations of ACTH-like immunoactivity were similar to those previously reported in liver, colon, heart, and small intestine and were not significantly affected by either hypophysectomy or adrenalectomy. While hypophysectomy also had no effect in the kidney, adrenalectomy resulted in a four-fold increase in extractable immunoactivity, first noticeable at seven days (p less than 0.005), but increasing progressively to 28 days (p less than 0.0005). Gel filtration showed that most of the increase in activity in kidneys of adrenalectomized rats corresponded to the 4.5 kD form comprising most of the serum ACTH immunoactivity and suggesting that the activity increase in kidney was largely due to ACTH derived from blood.

Adrenalectomy

Human chorionic gonadotropin--like material: presence in normal human tissues.

With the use of radioreceptor assay for gonadotropin and a beta-chain radioimmunoassay for human chorionic gonadotropin (hCG), we have been able to demonstrate the presence of hCG-like material in all normal human tissues tested. This activity was completely absorbed by a hCHG-antibody affinity column and was demonstrated to have altered carbohydrate content by studies showing this material did not bind to concanavalin A (con A)-Sepharose affinity columns. In identical studies greater than 90% of placental hCG was bound to con A. However, if placental hCG is rendered carbohydrate free it also does not bind to con A. It is known that carbohydrate-free hCG is cleared rapidly from the circulation and thus possesses little or no biological potency in vivo. Accordingly, we hypothesize: (1) that this hCG-like material in normal tissues has the protein structure of hCG but does not possess the carbohydrate moieties of placental hCG and probably has little or no bioactivity in vivo and (2) that the trophoblastic cell is not unique in its ability to synthesize hCG but has developed the ability to glycosylate hCG, transforming a ubiquitous cellular protein into a hormone, hCG might better be called human cellular gonadotropin.

Chorionic Gonadotropin

ProACTH: use for early detection of lung cancer.

ProACTH was identified by radioimmunoassay and column chromatography in extracts of 38 lung carcinomas. One hundred patients were evaluated because of abnormalities on chest roentgenograms; 53 (72 per cent) of 74 with lung cancers had increased plasma ACTH immunoreactivity; all 26 with benign abnormalities had normal ACTH. Of 101 patients with obstructive lung disease, five of 20 with elevated plasma ACTH levels and two of 81 with normal plasma ACTH levels had lung cancer within two years. In three of 31 patients with granulomatous lung disease plasma ACTH levels were elevated during acute exacerbation of the disease, but they returned to normal after recovery. We conclude that plasma ACTH immunoreactivity is frequently increased early in the course of lung carcinoma.

Adrenocorticotropic Hormone

Ectopic production of lipotropin by cancer.

Lipotropin (LPH) has been evaluated as a potential tumor marker using a sensitive beta melanocyte-stimulating hormone (beta MSH) radioimmunoassay. All 79 acetic acid extracts of carcinomas of lung, colon, stomach, esophagus and breast contained LPH in concentrations greater than blood; 61 of 79 extracts contained LPH in larger amounts than control tissues from patients without cancer. In a blind prospective study, plasma LPH was quantified in 107 patients admitted for work-up because of an abnormality on a chest roentgenogram. Thirty-one of 33 patients subsequently diagnosed as having benign lesions had plasma LPH within the 95 per cent confidence limits of normal subjects whereas 28 (36 per cent) of the 74 patients subsequently diagnosed histologically as having primary lung carcinoma had elevated levels. In control studies, 13 of 100 patients with chronic obstructive pulmonary disease had elevated plasma LPH levels; three of the 13 with elevated levels and four with normal levels have been diagnosed, during the two years of follow-up, as having lung carcinoma. In control studies of 23 patients with granulomatous lung disease, 22 had normal levels of LPH. In those with carcinoma of the colon elevated plasma LPH levels were observed in two of 21 untreated patients and in 11 of 61 patients receiving noncurative chemotherapy. Elevated plasma LPH levels were also observed in 10 of 59 patients with breast cancer, eight of 28 with pancreatic cancer, eight of 22 with gastric or esophageal cancer, six of 16 with renal cancer, four of eight with prostatic cancer, one of seven with cervical cancer and one of six with ovarian cancer. We conclude, an elevated LPH level is frequently observed in blood and tumor tissue from patients with various types of carcinoma.

Adenocarcinoma

Evidence for existence of cortical androgen-stimulating hormone.

An animal model using dexamethosone-suppressed, castrated dogs was developed to test the hypothesis that a pituitary hormone other than ACTH modulates adrenal androgen (AA) secretion. Plasma samples were obtained every 15 min during infusions of saline, synthetic alpha 1-24 corticotropin, porcine 1-39 corticotropin (ACTH), or bovine pituitary gland extract (PE) in a wide range of doses. Androstenedione (A), dehydroepiandrosterone (DHA), and cortisol (F) were quantified by radioimmunoassay. When the ratio of AA levels was related to those of F, in order to correct for ACTH content in the PE, the slopes of the dose-response curves for corticotropin and PE were different at the 0.01 level. For A the dose-response slope for the PE was 0.18 +/- 0.5 SE, whereas that of ACTH was 0.02 +/- 0.01. For the DHA response the slopes were 0.17 +/- 0.04 for the PE and 0.04 +/- 0.03 for ACTH. Related studies showed no increase in AA levels in response to luteinizing hormone-releasing hormone, bovine growth hormone (GH), bovine prolactin, ovine thyroid-stimulating hormone (TSH), or synthetic aqueous arginine vasopressin (AVP). We conclude that a pituitary factor other than ACTH, prolactin, GH, luteinizing hormone, follicle-stimulating hormone, TSH, or AVP may be responsible for the observed increase in AA concentrations.

Adrenal Cortex

Specificity of short-loop feedback of luteinizing hormone in the rabbit.

The specificity of the gonadotropin short-loop feedback mechanism was investigated in castrated rabbits by blood sampling from an indwelling jugular venous catheter for follicle-stimulating hormone (FSH) after the intravenous administration of purified human luteinizing hormone (hLH). Although we have previously shown that such hLH administration results in a decrease of rabbit LH, no decrease in rabbit FSH was seen in these experiments. This specificity of LH feedback is compatible with the site of feedback being at the (1) pituitary level or (2) at the hypothalamic level provided two separate LH and FSH releasing factors exist.

Animals

Pituitary gland: site of short-loop feedback for luteinizing hormone in the rabbit.

The development of a species specific radioimmunoassay for rabbit luteinizing hormone (LH) has permitted the direct demonstration of LH feedback control of LH secretion (short-loop feedback control). In previous studies we showed that small bolus injections of human LH (hLH) intravenously administered to castrate female rabbits suppressed rabbit LH for 20-30 min. Human LH had no effect on rabbit follicle-stimulating hormone secretion. This control system was responsive to amounts of hLH estimated to be present in blood of eugonadal men and women. These studies were designed to determine whether this feedback control was exerted at a pituitary or hypothalamic level. Two groups of studies were carried out: (a) in vivo studies: Rabbit LH was quantified in the blood of castrated female New Zealand White rabbits receiving either constant hLH perfusion (2.75 IU/min) or saline perfusion, plus a bolus injection of 0.5, 6, or 20 mug of gonadotropin-releasing hormone (GnRH). Human LH decreased the response to 6 and 20 mug of GnRH by 31 and 36%, respectively, and abolished the response to 0.5 mug, GnRH. (b) in vitro studies: Rabbit pituitary slices were incubated in the presence of medium alone, medium plus hLH (25 mIU/ml), medium plus GnRH (20 mug/ml), and medium plus both GnRH and hLH. hLH decreased basal rabbit LH release into the medium and abolished GnRH-stimulated rabbit LH release. hLH had no effect on rabbit follicle-stimulating hormone release. From these results we conclude that a direct and specific feedback control of LH on LH exists at a pituitary level.

Animals

Parathormone and perinatal calcium homeostasis.

Plasma parathormone (PTH) and calcium concentrations were measured in 309 specimens collected from 190 newborns during the first 7 days of life. The patient material consisted of 51 preterm, 130 term, and 9 postterm infants, including 22 infants of diabetic mothers (IDM), 38 infants with hypocalcemia, and 25 asphyxiated infants. PTH was detectable, although in low concentrations, in cord blood samples despite the presence of elevated calcium concentrations. Postpartum, PTH concentrations in term, appropriate for gestational age (AGA) infants remained low during the first 2 days of life; a significant (P less than 0.05) and sustained increase in plasma hormone levels was noted starting on day 3. PTH concentrations in IDM and preterm infants remained low for 3 days and a significant hormone increase did not occur until day 4. Hypocalcemia was common in IDM and asphyxiated infants; these infants accounted for two-thirds of all hypocalcemic infants. The profile of plasma calcium in IDM during the first week of life was different than that of any other group of infants. Plasma calcium concentrations remained depressed over this period of time and exhibited a temporary drop on day 4 accompanied by an increase in plasma PTH levels. Asphyxiated infants exhibited low plasma calcium concentrations, despite PTH levels that were significantly (P less than 0.007) higher than those of age-matched term AGA newborns.

Asphyxia Neonatorum

Calcitonin in nonthyroidal cancer.

A blind prospective study was undertaken to determine the use of calcitonin (CT) as a tumor marker. After final diagnosis, results revealed elevated plasma CT (greater than 150 pg/ml) in common cancers as follows: lung, 38%; colon, 24%; breast, 38%; pancreas, 42%; and gastric, 30%. Fifty-eight percent of oat cell carcinomas were associated with elevated plasma CT. CT immunoreactivity was detected in 14% of tumor extracts and was not detectable in normal tissue other than thyroid. Hypercalcemia was not the cause of hypercalcitonemia. Incubation studies of [125I]human CT in cancer plasma and tumor extracts demonstrated that measurements were not an artifact of label degradation. In a survey of control patients with nonneoplastic disease, elevated CT was noted in renal failure, acute gastrointestinal bleeding, and in some patients with chronic obstructive lung disease. In conclusion, plasma CT is elevated in a substantial proportion of common neoplasms and is useful as a tumor marker.

Breast Neoplasms

Prolactin-secreting tumors in men: surgical cure.

Two men presented with decreasing libido and impotence. Endocrine evaluation showed that they both had low levels of serum testosterone and a prolactin-secreting adenoma. Transsphenoidal removal of their tumors resulted in normalization of serum prolactin and testosterone concentrations and normalization of sexual function. These patients represent the first two nonacromegalic men with prolactin-secreting tumors and hypogonadism in whom surgical resection of their tumors resulted in a complete clinical and biochemical remission. We discuss the effects of elevated prolactin on male sexual function.

Adenoma

Improved method of purifying some radiolabeled glycopeptide hormones.

We describe a simplified method for purifying radiolabeled glycopeptide hormones (thyrotropin, lutropin, follitropin, and human choriogonadotropin), which results in preparations of over 95% immunoreactivity. This method is based on competitive elution from columns of the plant lectin, concanavalin A, and is applicable to glycopeptide hormones derived from several species.

Chorionic Gonadotropin

Adrenal androgens in patients with chronic marked elevation of prolactin.

It has been postulated, based on data in animals and the fact that the cortisol-adrenal androgen ratio is different before and after adrenarche, that prolactin (Prl) may modulate adrenal androgen secretion. As one way of testing this hypothesis, cortisol, androstenedione (A), dehydroepiandrosterone (DHA), and dehydroepiandrosterone sulphate (DHAS) were measured by radioimmunoassay in the sera of thirteen patients with suspected or proven pituitary tumours and marked chronic elevations of serum Prl (range 68-990 ng/ml, mean 198.9 ng/ml). Values for cortisol, A, DHA, and DHAS were not significantly different between the groups of normal controls and patients with elevated Prl concentrations. This is interpreted as negative evidence for the theoretical connection between Prl and adrenal androgen secretion.

Androstenedione