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Biomedical subjects

D N Danforth

Publications and source records attributed to D N Danforth.

At least 55 records · Page 3Linked to original sources

The morphology of the human cervix.

The normal human cervix is a collagenous structure that undergoes a dramatic and probably unique metamorphosis in late pregnancy and labor, effacing and dilating without injury to permit the baby to pass through and, thereafter, returning in the course of a few weeks to its former state. In addition to collagen, the cervix contains small amounts of smooth muscle and elastic tissue, and it is unreasonable to presume they would be found here if they were not to have some function. Whatever this function may be, it appears to be secondary, and possibly supportive, to the role of the collagenous system. Coordinated uterine contractions are involved in the processes of effacement and dilatation of the cervix. However, they appear to be incidental rather than causative, being initiated by the same factors that are also responsible for the cervical changes. When these influences are withdrawn after delivery, remodeling processes begin and the cervix returns to its nonpregnant morphologic and functional state.

Abortion, Spontaneous↗

Melatonin-induced increase in cytoplasmic estrogen receptor activity in hamster uteri.

The pineal gland hormone, melatonin, has been shown to influence the growth and metabolism of uterine tissue in the Syrian hamster. Because the uterus is an estrogen-responsive target tissue, we studied the effect of melatonin on the unoccupied estrogen receptor (ER) activity of immature hamster uteri in vivo and in vitro. A single sc injection of 2.5 micrograms melatonin increased the ER activity of uterine cytosol (Rc) 30% within 60 min [from 147.4 +/- 14.1 (SE), to 191.8 +/- 18.5 fmol/mg protein]. Scatchard analysis showed the induced population of receptor to be homogeneous and of high affinity, with an equilibrium dissociation constant (Kd = 0.08 nM) similar to that for uteri for vehicle-treated animals. The induction of Rc by melatonin persisted for 90 min, but Rc returned to control levels by 2 h after injection. Scatchard analysis of unoccupied nuclear receptor showed no significant differences either in the quantity of receptor (vehicle = 379.7 +/- 46.7, melatonin = 396.9 +/- 76.7 fmol/mg protein) or in the Kd (vehicle = 0.75 nM, melatonin = 0.60 nM) between these two groups. In vitro incubation of fresh whole uteri for 60 min in media containing 10(-5) M melatonin increased Rc by 83% (from 41.3 +/- 10.7 to 75.4 +/- 11.0 fmol/mg protein), supporting a direct effect of melatonin on uterine tissue. The Rc induced by melatonin both in vivo and in vitro was sensitive to the degree of homogenization used in preparation of the cytosol. Whereas conservative homogenization (two 10-sec bursts with an intermittent 40-sec cooling period) of uteri from melatonin-treated animals was associated with a significant increase in Rc, homogenization for 60 sec without intermittent cooling showed a significant decrease (from 251.1 +/- 17.4 to 182.7 +/- 5.8 fmol/mg protein) as compared with uteri from vehicle-treated animals. Whole organ analysis of uteri from animals injected with melatonin followed by [3H]estradiol, in which no homogenization was used, demonstrated a 26% increase in Rc specific binding, confirming induction as the primary response to melatonin. These findings demonstrate the ability of melatonin to modulate ER activity in hamster uteri, and may help explain the effects of melatonin on uterine growth and metabolism.

Animals↗

Hormonal status of patients with primary malignant melanoma: a review of 313 cases.

We studied 313 patients with a confirmed diagnosis of primary malignant melanoma who presented to The University of Texas System Cancer Center between 1976 and 1980, to determine the relationship of endocrine status to the presentation of this tumor. There were 171 women and 142 men, a ratio of 1.20:1. Age, age range, race, and residence distribution were comparable for both sexes. The women married and had their first pregnancy at ages at least comparable to the population in general. They tended to have multiple pregnancies (average, 2.64), to nurse their children, to have an aggregate 32 years of menstrual activity, and to use exogenous hormones (73%). The female patients in this study had more favorable lesions than their male counterparts in all five microstaging categories: type of melanoma, location, level of invasion, thickness, and stage. Analysis of the hormonal subgroups among the women revealed the morphology of the primary tumor to be independent of menopausal status, parity, or the use of exogenous hormones. These findings suggest that hormonal background does not effect the acquisition of malignant melanoma, but may influence its subsequent spread.

Adult↗

Pressure effects of urinary reflux studied with renal autotransplantation and pyelocystostomy.

The pressure effects of urinary reflux on renal structure and function were studied using a canine model in which the kidney was autotransplanted to the iliac fossa and the urine drained through a pyelocystostomy. This provided grade III reflux of urine (distention of the renal pelvis and calyces). A control group of nonrefluxing animals with the ureter and ureterovesical valve intact was studied in an identical fashion, and all animals were observed for one year. The reflux of sterile urine was not associated with any impairment of the inulin clearance or transport maximum of para-aminohippuric acid. There were no histologic abnormalities of glomeruli, tubules, or interstitium noted in the animals exposed to sterile reflux, nor were any differences found between the study and control groups. The transmission of bladder pressures into the renal pelvis and calyces during reflux is considered an unimportant factor in explaining the renal damage noted from sterile reflux of short duration in adults. The pyelocystostomy provides a satisfactory means of urinary drainage, and may be used effectively to study the properties of urinary reflex.

Animals↗

Endodermal sinus tumor of the ovary. The orphan tumor.

The endodermal sinus tumor of the ovary is a rare and highly lethal germ cell tumor. At least 10 different names have been applied to it, and so long as its name remains unsettled the collection of information will continue to be greatly impeded. One of the patients who came under our observation died after 21 months despite surgical removal of all evident disease followed by radiation and chemotherapy; the other patient, whose tumor could be removed only partially, and who received intensive chemotherapy for 4 months but refused all treatment thereafter, is well without evidence of disease 3 years after the initial diagnosis was made. Despite the dismal outlook for patients with this tumor, a few encouraging features emphasize the need to report new cases as they appear, and to continue the search for agents that will control it.

Adolescent↗

Renal changes in primary aldosteronism.

The clinical presentations and renal biopsy specimens of 18 patients with primary aldosteronism were reviewed to determine the characteristic pathologic features of the kidney in this syndrome. All patients were hypertensive with a mean blood pressure of 192 nm. Hg systolic and 122 mm. Hg diastolic. The average duration of hypertension was 6.88 years. The mean serum potassium was 2.88 mEq. per l. and the mean plasma carbon dioxide was 31.4 mEq. per l. A significant history of urinary tract disease was noted in 8 patients. Laboratory and diagnostic studies evaluating renal structure and function were abnormal in 11 patients. Renal biopsies from all 18 individuals showed evidence of parenchymal damage. Hypertensive and hypokalemic changes were the most significant abnormalities and were considered moderate to severe in 78 and 89 per cent of the patients, respectively. Histologic evidence of pyelonephritis was noted in 2 patients only and no renal specimens contained characteristic changes of metabolic alkalosis. The preoperatively hypertensive and renal evaluations did not reflect the severity of the renal changes noted histologically. The extent of renal injury caused by hypertension and hypokalemia in these patients emphasizes the consequences of primary aldosteronism. Early diagnosis and treatment of this disorder are essential if these consequences are to be avoided.

Adult↗

Elevated plasma proglucagon-like component with a glucagon-secreting tumor. Effect of streptozotocin.

To determine the character of the glucagon secretion and its modification by streptozotocin, were studied the plasma of a patient with recurrent pancreatic alpha-cell carcinoma. The plasma immunoreactive glucagon level before treatment of 4.80 ng per milliliter. Biogel column separation of the plasma immunoreactive glucagon revealed four components; the predominant component had a molecular weight of 9000 daltons and was designated as proglucagon-like. This fraction constituted 60 to 90 per cent of the total circulating immunoreactive glucagon, and had a biologic activity of 32 percent of that of an immunoequivalent amount of normal (porcine) pancreatic glucagon. After treatment with streptozocin (1.5 g per square meter) the plasma immunoreactive glucagon level decreased to 0.24 ng per milliliter. Treatment was accompanied by a marked reduction in the proglucagon-like component and the appearance of pancreatic glucagon (molecular weight of 3500 daltons) as the major post-therapy fraction. These findings support the use of streptozotocin in the management of unresectable glucagon-secreting tumors.

Adenoma, Islet Cell↗

Plasma immunoreactive glucagon fractions in four cases of glucagonoma: increased "large glucagon-immunoreactivity".

Immunoreactive glucagon (IRG) fractions from plasma of 8 normal subjects and 4 patients with glucagon secreting tumors were studied by gel filtration techniques on Bio Gel P--30 and Sephadex G--50 columns. The pancreatic glucagon specific anti serum (30K) of Unger was utilized to measure IRG. Columns were calibrated with labelled albumin, proinsulin, insulin and glucagon. Four peaks were defined in normal and tumor bearing patients: peak I (greater than 20 000 mol. wt.), peak II (primarily 9000 mol. wt.), peak III pancreatic glucagon (3500 mol. wt.) and peak IV small gucagon (less than 3500 mol. wt.). Glucagonoma patients differed from our normal and reported normal subjects in that peak II contained most of the circulating IRG. The percent of IRG associated with peak II was 9.5--31.5% in normals and 39.1--61.2% in glucagonomas. Glucagon-like biological activity in an isolated hepatocyte system was demonstrated for all peaks. However, relative to immunoreactivity, peak II showed reduced activity (25--33%). Immunoassay of dilutions of all peaks revealed the probability of immuno determinants identical with procine pancreatic glucagon. The presence of heterogenous IRG peaks with biological glucagon-like activity suggest that the larger molecules may be prohormones. Further, it is possible that specific elevation of peak II may be a diagnostic feature of glucagonomas.

Adenoma, Islet Cell↗

Incidental splenectomy: a review of the literature and the New York Hospital experience.

981 consecutive splenectomies at The New York Hospital were reviewed. 18.9% were removed incidental to some other procedure, either to facilitate exposure or because of uncontrolled bleeding from capsular tears. The primary operation with which this was most frequently associated was gastric resection for peptic ulcer disease, accounting for 20.5% of the spleens so removed. Conversely, the incidental splenectomy was noted in only 0.91% of all gastrectomies and 1.4% of all left colectomies designated as nonradical procedures. It is therefore seldom a necessary procedure. Incidental splenectomy is more frequent when midline abdoiminal incisions are employed, less frequent with paramedian or left rectus splitting incisions. 85% of the spleens removed incidentally were grossly and microscopically unremarkable; lacerations most probably result from excessive manipulation rather than pathological changes predisposing to rupture. The postoperative morbidity and mortality is discussed and is felt to be increased significantly by the incidental splenectomy.

Gastrectomy↗

Total unilateral renal destruction caused by irradiation for Hodgkin's disease.

Total unilateral renal destruction has been observed in a patient who previously received irradiation for Hodgkin's disease. The clinical features, after a six-year asymptomatic interval, included recurrent calculi and infection in what was subsequently demonstrated radiographically to be a nonfunctioning kidney. The gross and microscopic characteristics of the nephrectomy specimen have been described and correlated with the magnitude of irradiation and the clinical course.

Adult↗

Melatonin increases oestrogen receptor binding activity of human breast cancer cells.

Breast cancer is frequently a hormone-dependent tumour, and several studies have suggested that the pineal gland hormone melatonin may influence the growth and development of this malignancy. Subcutaneous injections of melatonin have been shown to inhibit, and pinealectomy to enhance, the development of dimethyl benz(a)anthracene (DMBA)-induced mammary tumours in rats. Use of the psychotropic drug thorazine, which increases plasma melatonin levels, has been associated with a decreased incidence of breast cancer in psychiatric patients. Calcification of the pineal gland has been correlated with an increased incidence of breast cancer in women. While the mechanism by which melatonin influences these tumours is unknown, both human breast cancer and DMBA-induced tumours contain oestrogen receptors (ER) and respond to changes in the oestrogen milieu. We therefore wondered whether melatonin might be altering ER binding activity of these tumours. We report here that in vitro incubation of MCF-7 human breast cancer cells with melatonin in physiological conditions increased the cytoplasmic and nuclear ER activity of these cells within 40 min, giving no change in the equilibrium dissociation constant (Kd) of the receptor. This induction was blocked by cycloheximide, and thus requires continuous protein synthesis. The modulation of ER binding activity of breast cancer by another endogenous hormone may be important for understanding the behaviour and treatment of this disease, and may provide insight into the factors regulating the synthesis and metabolism of steroid hormone receptors.

Breast Neoplasms↗