RNA:DNA ratios in a developing fibrosarcoma and its lung metastases in C3H mice.

The quantitative ratios of RNA:DNA were followed in a developing transplanted fibrosarcoma in C3H mice and in its lung metastases. There was a significant increase in these ratios in developing tumors originating from cell suspensions (P smaller than 0.001) and a single implanted piece (P smaller than 0.05). No significant change was demonstrated in developing fibrosarcoma originating from two pieces of this tumor (P greater than 0.05) which were implanted simultaneously. When comparing the ratios of RNA and DNA of developing lung metastases to the primary tumors, we found a significantly higher ratio in the metastases (P smaller than 0.001). No significant changes in RNA:DNA ratios were demonstrated in normal proliferating tissues either in physiologic hyperplasia or embryo tissue culture (P greater than 0.05).

RNA:DNA ratios in human tumors.

A study has been made of the quantitative relation existing between the RNA:DNA ratios in benign and in malignant human tumors. It has been demonstrated that a significant difference (Student's t-test) existed between malignant and benign human tumors within the different groups studied: a) malignant and benign breast tumors (t=2.22, P less than 0.05); b) Hodgkin's disease in spleen and its controls (t=2.39, P less than 0.02); and c) malignant and benign thyroid tumors (t=4.23, P less than 0.01). The diagnostic value of this finding is discussed.

Hypothyroidism secondary to biologically inactive thyroid-stimulating hormone secretion by a pituitary chromophobe adenoma: recovery after removal of the tumor.

A 50-year-old man, suffering from a large pituitary adenoma and panhypopituitarism, was found to have severely elevated thyrotrophin (thyroid-stimulating hormone [TSH]) levels (greater than 20.2 microunits/mL). The thyroxine (T4) level was low (less than 3.0 micrograms/dL). Thyroid sodium iodide I 131 uptake was low (5% at 24 hours). A TSH test result was normal, with a 24-hour 131I uptake of 52% and a normal-looking thyroid gland on scintiscan. After surgical removal of the pituitary chromphobe adenoma, T4 levels returned to normal (6.8 micrograms/dL) and TSH levels improved substantially (9.0 microunits/mL). Findings from repeated 131I uptake tests were normal (22% at 24 hours). Other pituitary functions improved also. These results suggest that the patient had biologically inactive TSH produced by the tumor. Removal of the tumor probably enabled recovery of the active TSH with the return of normal thyroid uptake and T4 production. Whenever hypothyroidism and high levels of TSH coexist with pituitary dysfunction, a TSH test is needed to distinguish between primary hypothyroidism and hypothyroidism secondary to biologic inactive TSH.

Monoarthritis with heterophil-negative infectious mononucleosis. Case of an older patient.

A patient aged 57 years with infectious mononucleosis and monoarthritis of the knee joint is described. To our knowledge, this association in elderly patients has not been reported heretofore, nor has the pathogenesis of arthritis in infectious mononucleosis been established. Because of the clinical picture and the synovial fluid findings, we suggest that the main mechanism of this arthritis is viral replication in the synovia.

Complete remission of Cushing's disease by total bilateral adrenalectomy and adrenal autotransplantation.

A 15-yr-old girl was diagnosed as suffering from Cushing's disease. She was treated by bilateral adrenalectomy and autotransplantation of one third of each adrenal to the corresponding thigh. The adrenal that was embedded in the right satorius muscle started functioning after about 1 yr, as proven by significant differences in cortisol levels in both femoral veins (82.5 and 17.5 micrograms/100 ml). 19-[131I]Cholesterol scanning showed adrenal tissue in the right thigh, while no adrenal remnant was demonstrated. Eleven years after surgery, the patient is symptom free and does not require replacement therapy. We find that adrenal autotransplantation, which is a simple and nonrisky procedure, should be considered whenever bilateral adrenalectomy is chosen as a treatment for Cushing's disease.

Digoxin-like immunoreactive factor(s) in human gonadotropin stimulated follicular fluid.

Plasma digoxin-like immunoreactive factor(s) (DLIF) have been reported in various pathophysiological conditions associated with volume expansion and linked to the regulation of blood volume and pressure. We hypothesized that DLIF might be present in rapidly expanding gonadotropin-stimulated ovarian follicles. The mean total and free DLIF concentrations in the follicles (n = 9) studied were 4925 nmol/L and 1885 nmol/L, respectively. These concentrations were substantially higher than the plasma total and free DLIF levels in these women: 1216 nmol/L and 158 nmol/L, respectively (p less than 0.0001). The plasma DLIF levels in the gonadotropin-treated women were comparable to those in term pregnant women, which are known to be higher than those in non-pregnant women. The ovary thus may be a source of DLIF in the plasma of gonadotropin-treated women, and DLIF may have a role in ovarian follicular fluid homeostasis.

Bone turnover in cortical and trabecular bone in normal women and in women with osteoporosis.

UNLABELLED: This study is based on the assumption that is bone turnover, shown by the uptake of 99mTc-MDP, indicates a high rate of bone loss in patients with osteoporosis, it could potentially predict bone loss in patients at risk before significant bone loss has occurred. METHODS: Quantitative bone SPECT (QBS) using 99mTc-MDP, expressed as the %ID/cc x 10(-3), was performed in 71 women who had osteoporosis in the lumbar vertebrae, the femoral neck or both, and in 54 age-matched normal female controls. Of the women with osteoporosis, 42 had postmenopausal osteoporosis and 29 had primary hyperparathyroidism (HPT) and osteoporosis. RESULTS: QBS increased with age in the cortical bone and decreased in the trabecular bone of the normal women. Quantitative bone SPECT in the femoral neck was 3.18 +/- 1.20 and was 2.73 +/- 1.06 in the femoral shaft in 20 women with postmenopausal osteoporosis of the femoral neck. In 19 women with HPT and osteoporosis of the femoral neck, the QBS value in the femoral neck was 3.57 +/- 0.92 and in the femoral shaft 3.38 +/- 1.12. These values were also significantly higher for the femoral neck and for the femoral shaft than those of normals. Although QBS values were higher in the lumbar region in 39 women with postmenopausal osteoporosis (4.59 +/- 1.45) and in 27 women with HPT (4.30 +/- 1.52), as compared with the normal group (4.28 +/- 1.61), the difference was not statistically significant. CONCLUSION: This study shows that bone turnover is significantly higher in the cortical bone of women with osteoporosis than in normal women.

Natural killer cell activity in post-necrotic cirrhotic patients as related to hepatitis-B virus infection and plasma zinc levels.

In view of the suggested physiological role of natural killer (NK) cells in immunosurveillance and defence against viral infections, we have investigated the relationship between hepatitis B virus (HBV) infection and NK activity against K-562 cells in patients with post-necrotic cirrhosis. Overall, the NK activity in cirrhotic patients did not differ from age- and sex-matched controls. However, cirrhotic males with evidence of HBV infection with or without HBs antigenemia tend to have lower NK activity than controls. Cirrhotic males without evidence of HBV infection do not differ from controls. Such a trend was not observed in the female cirrhotic patients examined. In addition significantly reduced NK activity was observed in cirrhotic patients with low plasma zinc levels. This relationship is of interest because of the known association between zinc deficiency and various immunodeficiencies.

Calmodulin inhibitors and 8-(N,N-diethylamino)-octyl-3,4,5-trimethoxybenzoate do not prevent the inhibitory effect of prostaglandin F2 alpha on cyclic AMP production in isolated rat corpora lutea.

In the rat corpus luteum, prostaglandin F2 alpha (PGF2 alpha) rapidly inhibits LH-induced cyclic AMP (cAMP) production when given in vivo or to isolated corpora lutea, but not to broken-cell preparations. The suggestion that increased cytosolic calcium concentration mediates PGF2 alpha action was investigated in corpora lutea of pseudopregnancy induced in immature rats by administration of pregnant mare serum gonadotrophin (15 i.u.). Isolated 10-day-old corpora lutea were incubated for 90 min with LH (5 micrograms/ml), PGF2 alpha (10 mumol/l) and other additions, and cAMP concentration in the tissue was estimated. The putative inhibitor of intracellular calcium release or action, 8-(n,N-diethylamino)-octyl-3,4,5-trimethoxybenzoate (TMB-8; 30 or 150 mumol/l), did not abolish the effect of PGF2 alpha. Similarly ineffective was the combination of TMB-8 (150 mumol/l) and calcium-depleted medium (free ionized calcium concentration, 30 nmol/l). Calmodulin inhibitors of three different chemical structures were then tested. The phenothiazine trifluoperazine, at 300 as well as 30 mumol/l, did not interfere with the inhibitory effect of PGF2 alpha on cAMP, while suppressing (at 300 mumol/l) progesterone secretion in LH-treated tissue. Furthermore, inhibition by PGF2 alpha was not impaired by pimozide, a diphenylbutylpiperidine (25 and 50 mumol/l) nor by N-(6-aminohexyl)-5-chloro-1-naphthalene sulphonamide (W-7; 15 and 45 mumol/l). In the presence of LH alone, W-7 (45 mumol/l) inhibited and TMB-8 (30 mumol/l augmented cAMP accumulation, indicating that the luteal tissue was effectively exposed to these compounds. Thus, drugs known to inhibit calcium- and calmodulin-dependent processes in a variety of tissues did not abolish the inhibitory action of PGF2 alpha on luteal cAMP production.

Characterization of the specific binding of prolactin to binding sites in the seminal vesicle of the rat.

The binding of ovine prolactin to the seminal vesicles of the rat has been characterized and found to be a saturable process, dependent upon time, temperature, protein concentration of the seminal vesicle and divalent ions. Its specificity was similar to that reported for prolactin binding to other organ preparations. Time and temperature studies of the specific binding revealed that equilibrium was reached after 16 h at 5 degrees C or 4 h at 19 degrees C. Nonspecific binding was also dependent on time and temperature. This parameter has been reported to comprise up to 70% of the total binding to various organ-binding sites, but it fell to below 20% after 48 h at 19 degrees C, thus demonstrating the high degree of specificity required of target organ receptors. From degradation studies it was evident that no damage occurred to the free hormone during incubation for up to 70 h at 5 degrees C or 16 h at 19 degrees C. However, there seems to be a difference in the susceptibility of bound and free ovine prolactin to damage during incubation: after 40 h at 19 degrees C the hormone in the supernatant fraction had lost 85% of its binding ability, whereas a high level of specific binding was evident in the pellet. A Scatchard plot of competitive binding studies revealed two classes of binding sites, of which the high-affinity, low-capacity site was similar to that reported previously and consistent with a physiological receptor for prolactin in the seminal vesicle of the rat.

Specific binding of prolactin to seminal vesicle, prostate and testicular homogenates of immature, mature and aged rats.

Ovine prolactin was iodinated by the lactoperoxidase method and purified by gel filtration on Sephadex G-100. The binding ability of the labelled hormone was determined, by incubation with liver homogenate from rabbits in late pregnancy, to be 8-8% total binding/mg protein, of which 86% was specific. The fraction of 125I-labelled ovine prolactin which bound most strongly was subsequently used to study its binding to rat seminal vesicle, prostate and testicular homogenates. The total binding to the seminal vesicle homogenate taken from mature (80-day-old) rats was the highest (11-69%/mg protein), but the greatest degree of binding specificity (82-6%) was to immature (30-day-old) rat prostate. Both total and specific binding to rat testicular homogenate were consistently very low. The binding specificity was demonstrated by displacement studies: while ovine prolactin caused displacement of specific binding, human chorionic gonadotropin, rat thyrotropin and human follicle-stimulating hormone did not cause any significant displacement of bound 125I-labelled ovine prolactin. Affinity constants (Ka) and binding capacities for the seminal vesicle and prostate homogenates were determined by Scatchard analysis and the effect of age on these parameters was studied. There was no difference in Ka between the aged (220-day-old), immature and mature rat tissue homogenates; however, a significant fall in binding capacity was observed in the mature rat prostate, and a further fall in the aged rat prostate. No such change was observed in the binding capacity of the seminal vesicle, as estimated by Scatchard analysis, although total and specific binding to the mature homogenates was higher than that of the other age groups.

The effect of inhibitors on insulin regulation of hormone secretion by cultured human trophoblast.

The effect of insulin in physiological concentrations on hormone secretion by human term trophoblast cell culture was studied in relation to insulin control of glucose transport and utilization. Specific inhibitors to these 2 functions were added to the culture, either alone to test for a dose response or with insulin. 2-Deoxy-D-glucose, which inhibits glycolysis, did not change the pattern of response of estradiol and placental lactogen (hPL) secretion to insulin. Phloridzin, an inhibitor of glucose transport, interfered with the stimulatory effect of insulin on hPL secretion, but stimulated insulin inhibition of estradiol secretion when added by itself. The results indicate that hPL response to insulin is dependent on glucose transport, but is independent of glycolysis. Estradiol response is dependent on glucose transport, but is independent of glycolysis.

Binding of iodinated rat and ovine prolactins to prolactin receptors and to its antibodies.

Most studies of prolactin receptors in rat tissues have not used the homologous 125I-labeled rat prolactin as tracers, but rather 125I-labeled ovine or human prolactin. We have compared the effect of different methods of iodination on the specific binding of rat and ovine prolactin to sites in the seminal vesicle of rats and the liver of mice post-partum. Ovine prolactin, either iodinated with lactoperoxidase or with mild chloramine-T (10 micrograms), showed 3 times the specific binding of correspondingly-iodinated rat prolactin. This greater sensitivity of rat prolactin to oxidative damage during iodination, as compared with ovine prolactin is further shown by the difference in Sephadex G-100 elution constant of unlabeled and labeled rat prolactin. . This difference was absent in the case of ovine prolactin. Parallel studies of the binding of the labeled hormone to homologous antibody revealed that immunoreactivity of labeled ovine prolactin was not affected by any of the iodination methods. Rat-prolactin immunoreactivity was depressed by lactoperoxidase iodination as compared with chloramine-T iodination. Rat prolactin was also less potent than ovine prolactin in inhibiting the binding of homologous and heterologous labeled hormone to its receptors, to a larger degree than could be expected from the bioassay potency of the various hormone preparations. These results reflect the greater sensitivity to damage of the biologically active site of rat prolactin, as compared with the ovine hormone.

The modulation of placental lactogen secretion by calcium: studies with cultured human term trophoblast.

Previous reports have documented the negative regulatory effect of calcium ion on the secretion of human placental lactogen by the placenta. Human term trophoblasts were dispersed from term placenta and maintained in monolayer cell culture. Incubation of the cultured trophoblast with EGTA produced a dose-dependent stimulation of placental lactogen secretion. The calcium ionophore A23187 inhibited hormone secretion. This inhibitory effect was eliminated by the addition of the calcium-calmodulin complex inhibitor trifluoperazine. It is concluded that calcium exerts a negative regulatory effect on the secretion of placental lactogen by a mechanism which requires the action of the calcium-calmodulin complex.

Electrocardiographic voltage changes during hyperthyroidism.

Electrocardiograms of 67 thyrotoxic patients were studied. Subsequent electrocardiograms during euthyroidism in 16 patients permitted an analysis of voltage changes. Decreases in voltages after radioiodine therapy were significant (P less than 0.01) for the P wave in lead, V1, R wave in leads II, AVF, V4, V5, and V6, maximal RS wave, and maximal R wave and were present in all but one patient. Criteria for left ventricular hypertrophy (sum of S wave in V1 plus R wave in V5 or V6 greater than 35 mm), present in 21% of patients, regressed in all five patients who had later electrocardiograms during euthyroidism. Left ventricular hypertrophy or high-voltage R waves in the absence of usual causes may suggest the presence of hyperthyroidism. The concept that cardiac voltage is determined in part by thyroid hormone is reviewed; this relationship may be the basis for increased voltage in hyperthyroidism as well as decreased voltage in hypothyroidism.

Splenic echinococcal cyst burrowing into left pleural space.

We describe a rare case of hydatid cyst in the spleen which communicated to the left pleural cavity. The patient presented with respiratory distress, characterized by nonproductive cough and dyspnea. The difficulties in diagnosis, using standard laboratory and radiologic techniques, were overcome by the use of ultrasound examination diagnosing both the cysts and the supra-diaphragmatic extension.

Talcosis presenting as pulmonary infiltrates in an HIV-positive heroin addict.

A case of an HIV-positive young drug addict presenting with fever, respiratory distress, and pulmonary infiltrates is reported. Pulmonary talcosis was diagnosed by transbronchial biopsy. The differential diagnosis of pulmonary infiltrates in HIV-positive patients is reviewed and the predisposition of drug addicts to develop both HIV infection, as well as pulmonary talcosis, is discussed. Pulmonary talcosis must be considered in the differential diagnosis of pulmonary infiltrates of HIV-positive drug addicts.

Correlation between insulin clearance and insulin responsiveness: studies in normal, obese, hyperthyroid, and Cushing's syndrome patients.

Insulin clearance and secretion determine the plasma insulin concentration. To elucidate the significance of these parameters in man, we employed the euglycemic insulin clamp technique to measure insulin sensitivity, insulin responsiveness, and insulin clearance, and we calculated the basal insulin delivery rate. In 27 patients (six normal, six obese, ten hyperthyroid, and five with Cushing's syndrome), insulin was infused at rates of 0.3, 1, 3, or 10 mU/Kg/min, and insulin concentration and glucose utilization were measured. C-peptide concentrations were measured before and during insulin infusion and decreased significantly, indicating a reduction of endogenous insulin secretion to 62% of basal in normals and a similar reduction in the other groups. Maximal responsiveness to insulin was a glucose utilization rate of 450 +/- 20 mg/min/m2 in normals, unchanged in obese, 42% increased in hyperthyroid, and 34% decreased in Cushing's syndrome patients. Sensitivity to insulin was decreased in all three abnormal groups. Insulin clearance rates were 1,050 +/- 80 mL/min/m2 for normals, not significantly changed in obese, 45% increased in hyperthyroid, and 33% decreased in Cushing's syndrome patients. All three abnormal groups showed hyperinsulinemia compared to normal. The basal insulin delivery rates were calculated as 7.0 +/- 0.3 mU/min/m2, with a threefold increase in obese and in hyperthyroid and no significant change in Cushing's syndrome patients. Insulin clearance correlated well with insulin responsiveness (r = .65, P less than 0.001), but poorly with insulin sensitivity (r = .36).(ABSTRACT TRUNCATED AT 250 WORDS)

Diminished prolactin reserve in acromegaly.

Prolactin (PRL) secretion has been evaluated in twenty acromegalic patients. All had intact LH, FSH, and cortisol levels and normal thyroid function. Five patients had persistent hyperprolactinemia. The remainder had decreased basal PRL levels with impaired PRL responses to TRH and the dopaminergic antagonist metoclopramide (MET). Despite adequate hypoglycemia and an intact cortisol response, there was no PRL rise following insulin hypoglycemia. The imparied PRL response to TRH was evident in treated and untreated patients and was independent of GH levels. Basal hyperprolactinemia may be related to PRL secretion by the tumor cells or interference with the transport of PIF by the tumor. The decreased PRL reserve noted in the majority of the patients may be related to a decrease in lactotrope cell mass or, alternatively, to enhanced dopaminergic activity.

Placental concentrations of progesterone, estradiol-17 beta, and cyclic AMP at delivery.

In contrast to most mammals, human parturition is not preceded by a rise in the estradiol : progesterone ratio in peripheral plasma. Thus tissue concentrations of progesterone, estradiol-17 beta, and cyclic adenosine monophosphate (AMP) were measured in placentas obtained after spontaneous vaginal delivery (SVD, N = 11), after oxytocin-induced labor (OXIL, N = 5), and at elective cesarean section (ECS, N = 8). Both progesterone and estradiol were higher in placentas obtained from SVD compared with those from ECS (progesterone: 2.95 +/- 0.26 versus 1.96 +/- 0.29 ng/mg tissue, P < .025; estradiol: 33.6 +/- 5.2 versus 26.4 +/- 3.8 pg/mg). Placentas from OXIL had intermediate progesterone (2.50 +/- 0.47 ng/mg) but the highest estradiol concentration (41.4 +/- 3.2 pg/mg). Cyclic AMP was 29.8 +/- 1.5, 39.6 +/- 8.0, and 35.9 +/- 3.9 pmoles/100 mg tissue in SVD, OXIL, and ECS placentas, respectively. Thus no rise in the placental estradiol : progesterone ratio was found in association with spontaneous labor.