Biomedical subjects

L Wide

Publications and source records attributed to L Wide.

At least 145 records · Page 8Linked to original sources

PubMed1986

Influence of the assay method used on the selection of the most active forms of FSH from the human pituitary.

The biological properties of different forms of human pituitary FSH, varying in their molecular charge, were investigated. FSH in two individual human pituitaries and a pool of 30 human pituitaries was extracted and subjected to electrophoresis. From each electrophoresis 14 consecutive fractions with the highest RIA activity were examined with in vitro and in vivo bioassays. The in vitro assay was based upon the estimation of oestradiol produced by cultured Sertoli cells from 10 day old rats. The in vivo bioassay was an hCG augmented test using immature female mice injected on 3 consecutive days. The increase in ovarian weight was the index of response. Both in the individual and in the pooled pituitary material the less negatively charged forms had the highest activity in the in vitro bioassay. In contrast, the more negatively charged forms had the highest activity in the in vivo bioassay. Forms of FSH from each of the two individual pituitary extracts were pooled according to their migration rate and injected iv into mice. The amount of FSH remaining in the circulation of the mouse after 1 h was related to the molecular charge. The highest value was obtained with the pool containing the more negatively charged forms of the hormone. The results indicate that the disappearance rate of the FSH molecule is a dominant factor in the in vivo bioassay. A consequence of these observations will be that the assay method chosen to monitor the purification of FSH will have a major influence on the biological properties of the final preparation.

Adolescent↗

PubMed1986

Thyroid function in a cassava-eating population affected by epidemic spastic paraparesis.

Thyroid function was studied in a rural population in Mozambique that had been affected by an epidemic of spastic paraparesis attributed to dietary cyanide exposure from cassava. Laboratory investigation on a sample of this population demonstrated very high levels of serum and urinary thiocyanate, indicating a heavy exposure to cyanide. The urinary excretion of iodine was within normal limits, indicating an adequate intake of iodine. The serum levels of FT4I were somewhat decreased and serum FT3I, T3/T4 ratio and TSH were somewhat raised. This hormone pattern suggests an adaptation to the antithyroid effect of thiocyanate, but not overt hypothyroidism. A follow-up study on school children was performed, and it also demonstrated high thiocyanate exposure, adequate intake of iodine, and absence of endemic goitre. The results show that if iodine supply is adequate, the thyroid gland is capable of adaptation to a heavy body burden of thiocyanate without development of overt hypothyroidism or goitre.

Adolescent↗

PubMed1986

Gonadotrophin in the term placenta of the dolphin (Tursiops truncatus), the Californian sea lion (Zalophus californianus), the grey seal (Halichoerus grypus) and man.

Chorionic gonadotrophin activity in extracts of the term placenta of a dolphin, a sea lion and a grey seal was measured by its effectiveness in increasing uterine weight in the mouse and by solid-phase RIA using hCG as immunogen and labelled antigen. Bioreactive (B) gonadotrophin was found in these placentae and, compared to the human term placenta, the concentration of CG in the dolphin was higher, in the sea lion similar and in the grey seal lower. The biological activity in each species was neutralized with a rabbit anti-hCG serum. All placental extracts contained material active in the hCG immunoassay (I). The ratio B/I was significantly higher for the CG in the placental extracts of the marine mammals compared with that of the human term placenta. Results of in-vivo bioassay, RIA, electrophoretic and gel-chromatographic studies indicate structural similarities between CG in the placentae of the marine mammals and human CG.

Animals↗

PubMed1986

Treatment of malignant carcinoid tumors with human leukocyte interferon: long-term results.

Thirty-six patients with malignant carcinoid tumors were treated with human leukocyte interferon (IFN) im at doses of 3-6 megaunits/day. The origins of the primary tumors were as follows: mid-gut (29 patients); pulmonary (four); rectal (one); ovarian (one); and unknown (one). Nineteen of the 36 patients had previously been treated with cytotoxic agents, streptozocin plus 5-fluorouracil or doxorubicin, but showed progressive disease. With IFN objective tumor responses were seen in 17 of the 36 patients (47%): in 14 of the 29 patients with mid-gut carcinoids (48%) and in three of the four patients with lung carcinoids (75%). The median duration of response was 34 months. Stable disease was noted in 14 of 36 patients (39%), all presenting mid-gut carcinoids. The median duration of stable disease was 25 months. Progressive disease from the start of IFN therapy was seen in five patients (14%). All responders except one had a greater than 50% reduction of urinary 5-hydroxyindoleacetic acid or alpha-human chorionic gonadotropin, whereas four patients also had a significant reduction of tumor size on computerized tomographic scan or at laparotomy. Two patients achieved complete remission. Improvement of clinical manifestations of the carcinoid syndrome was seen in all patients with objective response. Adverse effects including influenza-like syndrome, reduction of blood cells, chemical signs of liver dysfunction, and disturbed lipid metabolism occurred but were reversible or could be circumvented by dose reduction. Autoimmune phenomena were also noted such as development of thyroid autoantibodies with thyroiditis, SLE syndrome with antinuclear factors, and parietal cell antibodies with pernicious anemia. IFN therapy seems to be very effective in controlling tumor-secreted substances and thus giving relief of clinical symptoms. It also arrests tumor growth for extended time periods (median, 2 years). The adverse effects are surmountable and less severe than with cytotoxic therapy.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1985

Return of menstruation and normalization of prolactin in hyperprolactinemic women with bromocriptine-induced pregnancy.

Fifty-eight hyperprolactinemic women were followed up for 13 to 108 months after at least one bromocriptine-induced pregnancy for investigation of whether the pregnancy had any adverse long-term effects on the hyperprolactinemic state. Fifteen women had two term pregnancies. The prolactin (PRL) level decreased greater than 50% in 20 women after the pregnancy. Only two women showed a PRL level increase. Spontaneous uterine bleedings returned in 16 women, whereas 42 remained amenorrheic. Thus, bromocriptine-induced pregnancy in women with hyperprolactinemia has no negative long-term effect on PRL secretion.

Adult↗

PubMed1985

Acute effects of ethanol intake on the serum concentrations of parathyroid hormone, calcium and phosphate.

Several previous observations from animal and in-vitro studies indicate that both the acute and chronic ingestion of ethanol could affect calcium regulation but little data is available concerning the effects of ethanol in man. Twelve healthy male subjects drank 0.8 g ethanol/kg body weight in the form of whisky so that the serum ethanol concentrations reached an average of 17.4 +/- 2.5 (SD) mmol/l. At this time there were no significant differences for the serum concentrations of parathyroid hormone, calcium or phosphate. Thus, it appears that there is little acute effect on calcium homeostasis in man of a moderate rise of serum ethanol levels.

Adult↗

PubMed1985

Effects of secretin on parathyroid hormone and calcium in normal subjects, patients with hyperparathyroidism and patients with gastrinoma.

In vitro studies have demonstrated that secretin can stimulate the release of parathyroid hormone (PTH), but reports concerning its effects on PTH and calcium in vivo are contradictory. To examine this question further, a bolus injection of secretin (75 IU) was given to 12 normal subjects and 10 patients with primary hyperparathyroidism (HPT). Six of the patients had multiple endocrine neoplasia and five had endocrine pancreatic tumours (EPT). Three normocalcaemic patients with EPT were also included in the study. The mean serum gastrin level rose significantly (from 19 to 40 pmol/l, p less than 0.01) within 15 min of secretin injection in the normal subjects. HPT patients without EPT had a somewhat higher mean basal level of gastrin (39 pmol/l, p less than 0.05 compared with controls), but it did not increase significantly after the secretin bolus. In six EPT patients the gastrin concentrations rose by more than 300 pmol/l. Although secretin had a biological capacity to release gastrin, it had no discernible effects on either serum PTH or serum calcium in any of the groups studied. Nor were any changes in PTH or calcium observed when secretin was given as a continuous infusion (3 IU/kg/h) over 90 min. Thus, our data do not support the concept that secretin, in vivo, is a secretagogue of PTH.

Adult↗

PubMed1985

Regional and systemic effects of short-term intense muscular work on plasma concentration and content of total and ionized calcium.

Isokinetic work with one leg was carried out with maximal force for 2 min by five healthy subjects. The concentrations of plasma total calcium and of ionized calcium in the effluent from the leg increased by a mean of 13.6 +/- 1.8% (SD) and 16.2 +/- 2.0%, respectively. The corresponding rises in the resting arm were 7.7 +/- 4.3% and 8.1 +/- 3.0%. There was a close correlation (r = 0.86; P less than 0.001) between the degree of exercise-induced acidosis and the rise in plasma ionized calcium. However, the calcium values normalized both in the leg and in the arm within 5 min after the exercise and were similar at the two measuring sites despite a lower pH in the leg sample. During work there was a reduction of the plasma volume of 11.2 +/- 6.0% in the regional (femoral) and 12.4 +/- 4.2% in the systemic (antecubital) sample (P less than 0.001 compared to baseline values for both measurements). When adjustments were made for the reduction in plasma volume as well as for acidosis it was evident that, despite the apparent increases in the calcium concentrations, there was a net reduction of the plasma ionized calcium content (the total amount of plasma ionized calcium). This decrease was significantly (P less than 0.05) more pronounced in the exercising leg than in the systemic circulation but the difference could largely be explained by higher calcium-lactate complex formation in the leg.

Adult↗

PubMed1985

Thyrotropin-releasing hormone testing during antithyroid drug treatment of Graves' disease as an indicator of remission.

In 74 patients with hyperthyroid Graves' disease, TRH tests were undertaken every third month during the course of a standardized antithyroid drug and T4 treatment program. The antithyroid drug dose was reduced gradually and finally withdrawn when persistently normal TSH responses were obtained. In 46 patients (62%), such normal responses occurred and therapy was discontinued after a mean treatment period of 13 months (range, 5-24 months). In the remaining unresponsive 28 patients (38%), therapy was gradually withdrawn after 2 yr of treatment (mean treatment period, 27 months; range, 25-36 months; P = 0.0001 vs. the other group). The mean overall follow-up period after cessation of treatment was 65 months (range, 32-100 months) and did not differ between the TRH-responsive and TRH-unresponsive group. In the TRH-responsive group, 12 relapses (26%) occurred 23 months (range, 6-45 months) after discontinuation of therapy, in contrast to 20 relapses (71%) after 6 months (range, 0-12 months) in the TRH-unresponsive group. The differences in relapse rates and time duration until relapse are highly significant (P = 0.0003 and P = 0.0001, respectively). Small but significant differences in serum T3 and T4 levels were found between the groups throughout the treatment periods, emphasizing the importance of thyroid hormone levels in regulating the pituitary responsiveness to TRH. It is concluded that regular TRH tests during antithyroid drug treatment are useful in deciding the dose and duration of therapy and in predicting the likelihood of remission.

Adult↗

PubMed1985

Serum growth hormone in patients with carcinoid tumours; basal levels and response to glucose and thyrotrophin releasing hormone.

The regulation of serum growth hormone was studied in 33 consecutive patients with carcinoid tumours; both diurnal serum GH and GH responses to an i.v. glucose load and TRH were assessed. Seventeen of the patients (52%) showed disturbed regulation of serum GH and 10 had at least two abnormal tests. Four patients had clinically overt acromegaly. The diurnal mean serum GH levels were higher (P less than 0.001) in patients with carcinoid tumours than in control subjects and more than one third (41%) had levels in a range similar to that of acromegalic patients without carcinoid tumours. The disturbance in serum GH regulation might have been caused in some patient by tumour secreted growth hormone releasing factor(s) which act directly on pituitary somatotrophs, but other tumour-related non-specific stimulation must be considered. Carcinoid tumours should be considered in the aetiology of acromegaly.

Acromegaly↗

PubMed1985

Median charge and charge heterogeneity of human pituitary FSH, LH and TSH. I. Zone electrophoresis in agarose suspension.

The charge and charge heterogeneity of FSH, LH and TSH in 63 extracts of individual human pituitaries were investigated by use of zone electrophoresis in 0.17% agarose suspension in veronal buffer at pH 8.6 followed by hormone analyses by radioimmunoassay. The migration velocities are similar to those in free solution and directly proportional to differences in charge in the buffer. The technique gave highly reproducible results and the recovery of hormone activity after electrophoresis was about 100%. Methods for estimation of median charge, expressed as median migration rate, and of degree of charge heterogeneity are described. Each pituitary contained a sequence of different forms, estimated at 20 or more, of each of the three hormones, with minor differences in charge. The degree of charge heterogeneity within the pituitary was similar for FSH, LH and TSH. The distribution curves of radioimmunological activity in relation to migration rate were close to normality for the three glycoprotein hormones. This was in contrast to that found for Prl and GH. The merits of the electrophoretic technique are discussed.

Adolescent↗

PubMed1985

Median charge and charge heterogeneity of human pituitary FSH, LH and TSH. II. Relationship to sex and age.

The median charge and the degree of charge heterogeneity of FSH, LH and TSH in extracts from pituitaries of 63 individuals were determined by electrophoresis in 0.17% agarose suspension at pH 8.6 followed by hormone analyses by radioimmunoassay. Charge was expressed as migration rate in relation to that of human serum albumin. FSH, LH and TSH showed similar degrees of charge heterogeneity within the pituitary, and this degree of heterogeneity was not related to sex or age. There was a sex- and age-related variation in median charge of FSH and LH but not of TSH. The forms of FSH and LH were more acidic at higher ages and the most acidic forms were found in elderly women. Women 32 to 47 years old had more acidic forms of FSH than those 14 to 20 years of age. The median charge of LH was similar in young men and women, while that of FSH was more basic in young women than in young men. These results indicate that the effect of gonadal feedback on the molecular charge is different for FSH and LH. Studies with neuraminidase-treated pituitary extracts indicated that the sex- and age-dependent variations of the charge on FSH were due to differences in the sialic acid content. The amount of FSH in the pituitary was significantly smaller in men than in women. The contents of TSH and LH in the pituitary were lower in the higher age groups. No such decrease with age was found for FSH.

Adolescent↗

PubMed1985

Pulsatile GnRH therapy--an alternative successful therapy for induction of ovulation in infertile normo- and hyperprolactinaemic amenorrhoeic women with pituitary tumours.

Pulsatile treatment with gonadotrophin-releasing hormone (GnRH) was given to induce ovulation in 3 infertile, amenorrhoeic women with pituitary tumours not suitable for conventional therapy with human gonadotrophins or dopamine agonists. Two of the women had prolactinomas and the third a non-secreting adenoma. The GnRH therapy resulted in ovulations in all the 3 women, in 2 of them despite marked hyperprolactinaemia. Two women conceived and had term pregnancies. One pregnancy was uneventful while the woman with the non-secreting tumour developed symptoms of raised intracranial pressure. These symptoms rapidly disappeared when bromocriptine therapy was instituted. Chronic pulsatile GnRH administration is an effective alternative treatment for induction of ovulation in some amenorrhoeic women with pituitary tumours.

Adenoma↗

PubMed1985

Relationship between corpora lutea or fetal number and plasma concentrations of progesterone and testosterone in mice.

Blastocysts (1-14) were transferred unilaterally into 63 pseudopregnant mice which were killed on Day 17. Plasma progesterone concentrations were significantly (P less than 0.05) lower in animals with one fetus than in those with 2-5 or 9-14 fetuses. Plasma testosterone concentrations were correlated with fetal number in mice with 1-13 fetuses (P less than 0.001). The total placental content of chorionic gonadotrophin in 13 litters varied directly with the number in the litter (1-6), and was 1.67 +/- 0.15 ng/placenta. The number of corpora lutea per mouse was negatively correlated with mean CL volume per mouse (P less than 0.001), and the number of conceptuses was positively correlated with mean CL volume per mouse (P less than 0.001). The effect of conceptuses on the ovary was systemic. The relationship between plasma testosterone concentration and conceptus number may be due to gonadotrophins acting on the ovary, or androgens produced by the placenta or fetus.

Animals↗

PubMed1985

Concentration of unconjugated estriol in capillary whole blood from pregnant women.

A radio-immunological method applied to the estimation of unconjugated estriol in capillary whole blood is described. The concentration of unconjugated estriol in capillary whole blood and venous serum from 35 pregnant women was measured. Close relation was found between values in venous serum and capillary whole blood. The intra-assay variation was 4.9% for venous and 7.8% for capillary whole blood samples when analysed in duplicate. The day-to-day variability was of the same order for venous (10.0%) as for capillary (8.4%) samples. It is concluded that unconjugated estriol can be measured in small amounts (25 microliter) of capillary whole blood and that this method offers practical advantages over methods using venous serum or plasma.

Capillaries↗

PubMed1985

Secondary hyperparathyroidism in diabetic and nondiabetic patients on long-term continuous ambulatory peritoneal dialysis (CAPD).

Serum values of calcium, phosphate, alkaline phosphatases and parathyroid hormone (PTH) are reported for 24 diabetic and 26 nondiabetic patients treated with continuous ambulatory peritoneal dialysis (CAPD) for a total of 779 months, without the use of vitamin D or calcium supplements. Radiographic data are reported for 25 patients followed on CAPD for at least 12 months. Serum calcium was well maintained and control of hyperphosphataemia acceptable, but phosphate-binding therapy had to be continued in the majority of patients. Diabetic patients had lower serum phosphate levels and higher serum calcium than nondiabetic patients during the first year of CAPD. In nondiabetic patients the institution of CAPD was followed by a fall in PTH, possibly largely reflecting transperitoneal PTH elimination. No patient achieved normalization of serum PTH on CAPD. Although no symptomatic bone disease was observed, radiographic evidence of progressive hyperparathyroid bone disease developed in 3 of the 25 examined patients, all nondiabetic. In summary, long-term CAPD with a dialysate calcium concentration of 1.75 mmol/l seems to be compatible with normocalcaemia and a steady-state situation with regard to secondary hyperparathyroidism in the majority of patients. Despite transperitoneal elimination, serum PTH remains elevated, and definite progression of hyperparathyroidism is observed in some patients, however, probably making a case for vitamin D therapy and/or intraperitoneal or peroral calcium supplementation in these patients.

Adult↗

PubMed1985

Stability studies on human pituitary prolactin.

Differently charged isomers of human pituitary prolactin were subjected to stability studies under various conditions. The study was guided by analytical electrophoresis and radioimmunoassay. In alkaline medium (pH 10) it was found that each isohormone was converted into faster-migrating components, probably due to deamidation. A quantitative study of this alteration was made by measuring the rate constant for this conversion assuming first-order kinetics. The result indicated that the rate constant decreased with increased acidity of the examined prolactin components. Furthermore, this alteration was also found to be paralleled by a decreased immunoactivity of the components. At neutral pH the conversion reaction was studied both in 0.9% NaCl and in human serum. For the least acidic isohormone the rate constant in serum was calculated to be about four times higher than that in the saline solution which in turn was comparatively low. It was concluded that the alteration observed at pH 10 might be attributed to non-enzymic deamidation. The conversion of prolactin that occurred in human serum indicated that this reaction could be caused by enzymes. A study of the immunoactivity of human prolactin as a function of time at various storage conditions is also included in this work. The stability of the hormone was found to be strictly concentration dependent and also affected by buffer ionic strength. In the presence of ethylene glycol (50%, v/v) at -20 degrees C and at a protein concentration in the range of 0.1-2 mg/ml the hormone was found to be both immunologically and electrophoretically stable for several years.

Drug Stability↗

PubMed1985

The dual action of glucose on the cytosolic Ca2+ activity in pancreatic beta-cells. Demonstration of an inhibitory effect of glucose on insulin release in the mouse and man.

The cytosolic Ca2+ activity was measured with the fluorescent indicator quin-2 in pancreatic beta-cells obtained from obese-hyperglycemic mice. When present at a concentration of 20 mmol/l in a medium physiologically balanced in cations, glucose induced a rise of cytosolic Ca2+ after a delay of 1--3 min. At lower concentrations of extracellular Ca2+ this effect was not only prevented but the sugar promptly reduced the cytosolic Ca2+ activity. The dual effect of glucose on cytosolic Ca2+ had its counterpart in the release of insulin. Whereas 20 mmol/l of glucose stimulated the release of insulin from mouse islets previously stored in a Ca2+-deficient medium, the sugar was clearly inhibitory when present at a concentration of 6 mmol/l. Intravenous glucose tolerance tests revealed a temporary glucose depression of the serum concentrations of insulin and C-peptide in several patients with diabetes. In a mentally retarded girl with hyperinsulinemia associated with acanthosis nigricans the glucose suppression of circulating insulin was prolonged and sufficiently pronounced to suggest an almost complete inhibition of the secretory activity of the pancreatic B-cells.

Aminoquinolines↗