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Biomedical subjects

L Wide

Publications and source records attributed to L Wide.

At least 19 recordsLinked to original sources

Isolation of human pituitary prolactin.

A process developed earlier for the extraction of human follitropin, lutropin, thyrotropin and growth hormone from homogenized frozen pituitaries provided a residue utilized for the isolation of prolactin. The isolation procedure involved extraction at pH 9.8, molecular sieve chromatography on Sepharose CL-6B, hydrophobic interaction chromatography on phenyl-Sepharose CL-4B, molecular sieve chromatography on Sephadex G-100 Superfine, and ion-exchange chromatography on DEAE-Sepharose CL-6B using a convex gradient. The progressive purification was guided by radioimmunoassays. The final product was obtained in yields of 31 microgram/gland, and was equipotent with a pituitary preparation (VLS-3) supplied by the National Pituitary Agency (NIH, Bethesda, U.S.A.). Contamination hormones negligible (less than 0.05%). No heterogeneity of the isolated prolactin was observed by sedimentation-equilibrium analysis in the ultracentrifuge, by SDS electrophoresis in polyacrylamide gel or by molecular sieve chromatography in 6 M guanidine hydrochloride. These different techniques gave values in the range of 21 000-23 000 for the molecular weight of prolactin. In free zone electrophoresis, and also in polyacrylamide gel electrophoresis the prolactin preparation was, however, heterogeneous and resolved at alkaline pH into three distinct components. The former technique permitted isolation and assay of the components, indicating that they were all fully active.

Chromatography, Agarose

Intranasal gonadotropin-releasing hormone agonist as a contraceptive agent.

The stimulatory luteinising hormone-releasing hormone (LRH) analogue D-Ser(TBU)6-EA10-LRH was administered intranasally once daily to twenty-seven regularly menstruating women to determine its efficacy as a contraceptive agent. Ovulation was inhibited during all but 2 of the 89 treatment months. The failures were due to initial technical problems with the nasal spray. Twenty-one of the twenty-seven women had slight menstrual-like anovulatory bleeds during the 3--6 month trial. The remaining six women were amenorrhoeic. Ovulatory menstrual cycles rapidly returned after discontinuation of treatment. There were no serious side-effects.

Administration, Intranasal

The effect of splanchnic block on renin production and renal haemodynamics in hypertensive patients.

In eighteen patients with hypertension the effect of a splanchnic block was studied with respect to the plasma renin activity (PRA) in the renal vein and to the renal haemodynamics. A significant reduction of the PRA was noted during splanchnic block, both in kidneys with arterial stenosis, and in those without. The decrease in renin activity took place despite a simultaneous decrease in renal vascular resistance, which in itself should increase the secretion of renin. This supports the view that the sympathetic nervous system dominates over the baroreceptors in patients with hypertension at the pressure levels investigated and if the sodium intake is restricted.

Adult

Serum ferritin during inflammation. A study on myocardial infarction.

The ferritin level in serum was investigated in 9 patients with myocardial infarction, all with a history of chest pain of less than 4 hours before admission. A significant rise in serum ferritin level was found in 8 patients. The rise was generally smaller than that seen in acute infection and not significantly correlated to the size of infarction, as estimated from changes in serum levels of myoglobin, ASAT and LDH. The rise started after a mean of 30 hours, the peak being reached within a week (M 4.3 days). Serum ferritin then fell to 120--300% (M 190) of the initial level, where it remained. An initial rise in serum iron levels was unexpectedly seen within 12 hours in 7 patients.

Aged

Clinical correlations between long-term (IgE) and short-term (IgG S-TS) anaphylactic antibodies in atopic and 'non-atopic' subjects with respiratory allergic disease.

The sera of atopic and non-atopic persons with allergic pulmonary disorders were examined for long-term sensitizing, IgE and short-term sensitizing heat-stable (S-TS) antibodies which were present separately or together in the sera of some patients sensitive to antigens such as budgerigar serum proteins and Aspergillus funigatus. In fourteen atopic patients with extrinsic asthma, six had both types of antibody to common allergens, and of nine non-atopic patients with crytogenic (intrinsic) asthma, four had only heat-stable short-term sensitizing antibodies. The sera of atopic subjects with type I prick test reactions and positive RAST's, showed specific IgE antibody by baboon PCA tests to budgerigar serum proteins, A. funigatus, Timothy grass pollen extract and hen egg extract, and not to Dermatophagoides farinae, possibly because of naturally occurring mite antibodies in the baboon. The sera of non-atopic asthmatics, who had given negative prick test but positive immediate, dual or late intracutaneous tests, and only late asthmatic reactions, contained precipitins in most cases and gave little or no RAST reaction. On baboon PCA these sera contained either, S-TS antibody alone, or S-TS plus long-term sensitizing antibody, or long-term sensitizing antibody alone. Some of the sera with long-term sensitizing antibody contained blocking antibody which could diffuse away in the 24 hr delay for the baboon PCA test and could also be responsible for the negative RAST. Tests with insoluble anti-IgE immuno-adsorbents on two sera from persons sensitive to aspergillus confirmed that the S-TS activity was not due to IgE, and on two sera with negative RAST and negative prick tests to budgerigar serum antigens confirmed that the 24 hr monkey PCA responses were due to IgE.

Allergens

Bromocriptine treatment of seven women with primary amenorrhoea and prolactin-secreting pituitary tumours.

Seven women with primary amenorrhoea and hyperprolactinaemia were treated with bromocriptine. All the women had started to develop secondary sex characteristics at normal age but pubertal development stopped and menarche did not occur. Radiological signs of a pituitary tumour were found in all the women. Before the pituitary tumour was diagnosed, four women had been given longterm cyclical oestrogen replacement therapy. Three women had received primary tumour therapy with surgery and/or irradiation but had persistent hyperprolactinaemia. The basal luteinizing hormone (LH) levels were low in four of the women while all the women had normal basal levels of follicle-stimulating hormone (FSH) and normal or exaggerated gonadotrophin responses to luteinizing hormone-releasing hormone (LHRH). None of the women had evidence of endogenous oestrogen production before treatment. Bromocriptine treatment normalized the raised serum prolactin levels (46-2900 microgram/l) in all but one woman, in whom the prolactin level decreased from 160 to 38 microgram/l. Regular ovulatory menstrual cycles appeared in four women, one of whom had previously been treated by transsphenoidal adenomectomy followed by external irradiation. Two other women with persistent hyperprolactinaemia after previous surgical and/or irradiation treatment of large pituitary tumours did not menstruate after more than one year of treatment with bromocriptine. One infertile patient with a microadenoma conceived at the first ovulation on therapy and developed symptoms and signs of tumour growth during pregnancy.

Adenoma, Chromophobe

Reduced gonadotropin secretion in postmenopausal women during treatment with a stimulatory LRH analogue.

The potent and long-acting LRH agonist D-Ser(TBU)6-EA10-LRH was administered in a daily subcutaneous dose of 5 microgram to 5 postmenopausal women for a period of 10 days. The LRH analogue produced a significant decrease in both the basal FSH and LH levels and the gonadotropin responses to the agonist. The estrogen levels in serum remained unchanged during the study period. The results suggest that D-Ser(TBU)6-EA10-LRH has a direct inhibitory effect at the pituitary level.

Aged

Inhibitory effects on gonadotrophin secretion and gonadal function in men during chronic treatment with a potent stimulatory luteinizing hormone-releasing hormone analogue.

Long-term treatment with the potent and long-acting stimulatory luteinizing hormone-releasing hormone (LRH) analogue D-Ser(TBU)6-EA10-LRH was given to 4 healthy men to study its effects on pituitary gonadotropin secretion and gonadal function. Five micrograms of the LRH agonist was self-administered sc once daily over 17 weeks. Weekly basal blood samples were obtained for determination of follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolacting (PRL) and testosterone. The gonadotrophin responses to the LRH analogue were also determined during the treatment period. LRH tests were performed after treatment. Seminal fluid specimens were collected during and after treatment. A reduction of the basal serum gonadotrophin and testosterone levels were observed during the treatment period. The FSH and LH responses to the analogue were also diminished. After discontinuation of treatment the gonadotrophin and testosterone concentrations returned to pre-treatment levels within a week. The PRL levels and the seminal fluid specimens did not show any significant changes during the study period. The results suggest that chronic treatment with D-Ser(TBU)6-EA10-LRH has an inhibitory effect on the pituitary gonadotrophin secretion in healthy men. It seems likely that the reduced testosterone level is secondary to the diminished gonadotrophin secretion.

Adult

Chorionic gonadotrophin in the mouse from implantation to term.

Chorionic gonadotrophin (CG) in implantation sites from Days 5 to 12 and placentae from Days 13 to 19 of pregnancy in the mouse was determined by utilizing a cross-reaction with human CG in a radioimmunoassay. Significant amounts of CG could be detected throughout the period of gestation investigated. The amount of CG per implantation site increased steadily from Day 5 to a peak on Day 11. In the second part of pregnancy a second peak was observed with the highest amount of CG per placenta found on Day 16. No gonadotrophic activity could be detected in blastocysts flushed from the uteri on Day 5 of pregnancy or in uteri of non-pregnant mice.

Animals

Pituitary responsiveness to luteinizing hormone-releasing hormone during treatment with subdermal D-norgestrel implants in women.

It has previously been reported that subdermal implants containing d-norgestrel inhibit ovulation through blockage of the positive feedback action of estrogen on luteinizing hormone (LH) release. In this study 100 micrograms of LH-releasing hormone (LRH) were injected intravenously to test the pituitary reserve capacity for gonadotrophin secretion in three women with three 40 mg d-norgestrel rods implanted subdermally for more than one year. The gonadotrophin release to LRH varied and seemed related to the ovarian steroid concentrations at the time of the LRH infusion in a manner similar to that seen during the normal menstrual cycle. It is concluded that low plasma levels of d-norgestreol do not inhibit the pituitary responsiveness to LRH. The results indicate that the blocking action of the gestagen on the positive feedback of estradiol on LH release occurs at the hypothalamus or higher CNS centers.

Adult

Effects of prolonged luteinizing hormone-releasing hormone therapy on follicular maturation, ovulation and corpus luteum function in amenorrhoeic women with anorexia nervosa.

Nine amenorrhoeic women with anorexia nervosa (AN) were given long-term treatment with 500 microgram of synthetic luteinizing hormone-releasing hormone (LRH) every 8 h. All the women had impaired luteinizing hormone (LH) secretion and no evidence of endogenous oestrogen production. Three of them also had deficient follicle-stimulating hormone (FSH) secretion. The pituitary reserve capacity for gonadotrophin secretion was normal but the response pattern to LRH was similar to that described in prepubertal girls. The constant administration of LRH normalized basal LH and FSH secretion and induced a cyclical gonadotrophin secretory pattern with differential changes of the LH and FSH responses to LRH during the treatment. LRH-induced gonadotrophin secretion produced follicular growth and maturation in all the women. Presumptive ovulation also occurred during the 8 treatment courses in which only LRH was administered. However, inadequate luteal phases were observed during 6 of these 8 cycles. Combined therapy with LRH and human chorionic gonadotrophin (HCG) during 5 treatment courses resulted in normal ovulatory cycles with adequate corpus luteum function.

Adult

Thyroid function in breast cancer patients before and up to two years after mastectomy.

In 41 women newly diagnosed as having breast cancer the thyroid function was assessed by determination of the serum TSH, tririodothyronine (T3), reverse triiodothyronine (rT3), thyroxine (T4), T3-resin uptake and free T4-index. Blood samples were drawn before the primary treatment and at follow-up after 7-28 months. There was no significant change in any of these variables during the period of observation. Nor was there any difference between the values of the patients who developed recurrent disease and of those who did not. These results contradict previously proposed hypotheses of a progressive decrease in thyroid function after primary treatment and of a relation between the clinical course and the thyroid function in breast cancer patients.

Adult

Serum ferritin during infection. A longitudinal study in renal transplant patients.

In order to follow the dynamics in the reaction of iron kinetic variables to acute infection, 8 renal transplantation patients were followed with test samples every second or third day for about two months. It was found that they just as previously shown in otherwise healthy subjects, responded to acute infection with a rise in serum ferritin levels, sometimes to very high values. In most cases the ferritin elevation started within two days after the onset of fever. The peak was reached within a week, except when very high values were obtained. The fall in serum ferritin after recovery from infection was much faster than in previously investigated groups of patients: the plasma half disappearance time for ferritin in one case was but 1.5 days. Transferrin did not change in response to infection. The expected fall in serum iron during infection was often absent and sometimes obscured by unexpected, sharp peaks in serum iron, which bore a temporal relationship to episodes of transplant rejection in 7 of 12 cases.

Acute Disease