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Biomedical subjects

K Takebe

Publications and source records attributed to K Takebe.

At least 37 records · Page 2Linked to original sources
PubMed1991

Neonatal androgenization increases vasoactive intestinal peptide levels in rat anterior pituitary: possible involvement of vasoactive intestinal peptide in the neonatal androgenization-induced hyperprolactinemia.

Accumulating evidence suggests that vasoactive intestinal peptide (VIP) may be a physiological PRL-releasing factor. In the present study, we examined a possible involvement of VIP in the neonatal androgenization (NA)-induced hyperprolactinemia. Twenty-four hours after birth, newborn female rats were injected sc with 1,000 micrograms of testosterone (NA) or with oil vehicle only (control). Both groups were sacrificed at 8 weeks of age. Compared to controls, NA rats showed significantly higher plasma PRL levels (7.3 fold), anterior pituitary (AP) PRL content (2.1 fold) and plasma estradiol levels (2.1 fold). AP VIP content was extremely higher (61 fold) in NA rats than in controls. However, NA did not affect VIP content in the suprachiasmatic nucleus, paraventricular nucleus or median eminence. These results suggest that the NA-induced hyperprolactinemia may be mediated, at least in part, by paracrine and/or autocrine effects of the increased AP VIP on PRL secretion. However, since the potentiation by NA of the AP VIP content was extremely marked compared to those of the other parameters, the possibility was also raised that the increased AP VIP may be involved in other endocrine and/or nonendocrine events occurring in the AP.

Androgens↗
PubMed1991

Corticotropin response to combined administration of human corticotropin-releasing hormone and small-dose arginine vasopressin in normal subjects.

Arginine vasopressin (AVP) is known to potentiate corticotropin (ACTH) secretion by human corticotropin-releasing hormone (hCRH), and a combined administration of hCRH and AVP appears useful as a pituitary ACTH reserve test. This study was designed to evaluate the appropriate dose of AVP and its route of administration, for better estimation of pituitary ACTH reserve in humans, when used in combination with a conventional hCRH stimulation test. First, intravenous (IV) doses of hCRH (100 micrograms) and AVP (0, 0.1, and 0.3 U) were administered simultaneously in six normal subjects. Second, IV hCRH was administered with intramuscular (IM) AVP (0, 1.0, 3.0, and 5.0 U) in 10 normal subjects. Blood samples for measurement of plasma ACTH were obtained at 0, 15, 30, 45, 60, 90, and 120 minutes after the hCRH with and without AVP administration. The order of AVP doses was randomly chosen in each subject. The peak plasma ACTH level was 65.0 +/- 16.0 pg/mL (30 minutes) with hCRH alone and 139.5 +/- 35.6 pg/mL (15 minutes) with hCRH plus 0.3 U IV AVP in six normal subjects. Similarly, the peak plasma ACTH level was 43.5 +/- 5.6 pg/mL (30 minutes) with hCRH alone and 116.0 +/- 19.6 (15 minutes) and 96.6 +/- 24.0 pg/mL (15 minutes) with hCRH plus 3.0 and 5.0 U IM AVP in 10 normal subjects, respectively. The hCRH-induced ACTH responses (delta ACTH) with both IV and IM AVP were significantly (P less than .05) greater than the respective control values with hCRH alone. The responses (delta ACTH) were comparable between the two phases of 3.0 and 5.0 U IM AVP.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1991

Vasoactive intestinal peptide levels in the hypothalamus and anterior pituitary do not change in association with the pre-ovulatory prolactin surge in the rat.

We examined whether vasoactive intestinal peptide (VIP) is involved in the preovulatory prolactin (PRL) surge in the rat. Ovariectomized adult rats implanted sc with an estradiol capsule 2 days previously were decapitated at hourly intervals between 1100-1800 h. The plasma PRL and luteinizing hormone showed an evident surge at 1700 h and 1800 h, respectively. The anterior pituitary PRL content was significantly lower at and after 1600 h than at 1100 h. However, there was no significant change in the VIP content in the suprachiasmatic nucleus, paraventricular nucleus, median eminence or anterior pituitary throughout the entire period of observation. Since all of these regions are known to be involved in the VIP synthesis and/or release, the present results appear to cast some doubt on previous studies reporting a significant role for VIP in the generation of the pre-ovulatory PRL surge.

Animals↗
PubMed1991

A pilot clinical trial of a new oral hypoglycemic agent, CS-045, in patients with non-insulin dependent diabetes mellitus.

CS-045, (+/-)-5-[4-(6-hydroxy-2,5,7,8-tetramkethylchroman-2- ylmethoxy)benzyl]-2,4-thiazolidinedione, lowers plasma glucose in several animal models of non-insulin dependent diabetes mellitus (NIDDM) presumably by increasing insulin sensitivity. Little adverse effect was found in a phase 1 study on healthy male subjects. In order to test its efficacy in lowering plasma glucose in NIDDM in man, a pilot multi-center clinical trial of CS-045 was carried out in 146 patients with NIDDM whose glycemic control was inadequate (FPG greater than 140 mg/dl) on diet and/or other oral hypoglycemic agents. CS-045 was given orally in a daily dose of 200 mg or 400 mg for 12 weeks in addition to the previous treatment. The mean fasting plasma glucose (FPG) and fructosamine began to decrease within 2 weeks and the mean HbA1c within 8 weeks. After 12 weeks, the FPG fell from 192 +/- 41 to 155 +/- 45 mg/dl (P less than 0.01), fructosamine from 3.7 +/- 0.6 to 3.3 +/- 0.6 (P less than 0.01), and HbA1c from 8.9 +/- 1.5 to 8.1 +/- 1.5% (P less than 0.01). The drug was effective in 39% of patients in that FPG fell by more than 20% of the initial value. This rate of efficacy was the same when CS-045 was given alone or together with other oral hypoglycemic agents. The drug was more effective in a dosage of 400 mg than with 200 mg (the rate of efficacy 46% vs 25%) and more effective in obese patients than in lean patients (46% vs 25%).(ABSTRACT TRUNCATED AT 250 WORDS)

Biomarkers↗
PubMed1991

[Clinical evaluation of cefuzonam (CZON) for bacterial pneumonia and lung abscess: comparative study with cefotiam (CTM)].

A double blind study was conducted to objectively evaluate the usefulness of Cefuzonam (CZON) in the treatment of bacterial pneumonia and lung abscess. Cefotiam (CTM) was used as a control drug. Each drug was administered by intravenous drip infusion at 1 g at a time, twice daily, for 14 days as a rule. The results are as follows: 1. Enrolled in this study were 145 cases in total, comprising 72 of CZON group and 73 of CTM group. Of the total cases, 109 (53 of CZON group and 56 CTM group) were evaluated for clinical efficacy by the evaluation committee. Exclusion rate and background of patients were not significantly different between the two groups. 2. Clinical effectiveness assessed by the committee showed the efficacy rates of 84.9% (45 cases out of 53) for the CZON group and 83.3% (47 cases out of 56) for the CTM group, with no significant difference between the two groups. 3. The bacteriological eradication rates were 89.5% (17 strains out of 19) for the CZON group and 78.3% (18 strains out of 23) for the CTM group, with no significant difference between the two groups. 4. The incidence of side effects was 5 cases (7.5%) for the CZON group and 3 cases (4.2%) for the CTM group. The incidence rate of laboratory test abnormality was 28.4% (19 cases out of 67) for the CZON group and 31.3% (12 cases out of 67) for the CTM group. There was no significant difference between the two groups. 5. Usefulness rates calculated by the committee were 79.2% (42 cases out of 53) for the CZON group and 76.8% (43 cases out of 56) for the CTM group. There was no significant difference between the two groups. These results show that CZON is a useful drug in the treatment of bacterial pneumonia and lung abscess.

Adolescent↗
PubMed1991

[Superoxide anion (O2-) production by polymorphonuclear leukocytes in insulin dependent diabetes mellitus (IDDM)].

The superoxide anion (O2-) production in polymorphonuclear leukocytes stimulated by phorbol myristate acetate in IDDM and non-insulin dependent diabetes mellitus (NIDDM) was determined by the method of Johnston et al, compared with that of each age matched controls. And the correlation between O2- production and hemoglobin (Hb) A1 and A1c value was investigated. The O2- production in IDDM was 24.4 +/- 7.4 (mean +/- SD, n mol per 4 X 10(5) cells) at 10 min. and 51.4 +/- 8.7 at 30 min., in NIDDM each 31.6 +/- 9.3, 60.2 +/- 14.4, and in controls each 40.5 +/- 4.2, 72.4 +/- 3.1. O2- production in IDDM was significantly lower than that in NIDDM (p less than 0.001 at 10 min. and p less than 0.01 30 min.) and controls (p less than 0.001 at 10 and 30 min.). O2- production at 10 and 30 min. possessed a negative correlation with Hba1 and A1c value (HbA1: p less than 0.01 at 10 min. p less than 0.05 at 30 min., HbA1c: p less than 0.01 at 10 and 30 min.). These findings suggest that impaired O2- production might be one of the factors accounting for depressed bactericidal activity of polymorphonuclear leukocytes in IDDM, and that a protracted hyperglycemia might shed some effect on O2- production.

Adult↗
PubMed1991

In vivo and in vitro studies in a patient with cyclical Cushing's disease showing some responsiveness to bromocriptine.

In vivo and in vitro studies were carried out in a 37-year old female with cyclical Cushing's disease. Preoperative studies revealed periodic secretions of urinary corticosteroids occurring with a cyclicity of 2-3 weeks. On transsphenoidal surgery, a microadenoma was visualized in the anteroinferior portion of the anterior pituitary. Gel filtration analyses of the adenoma and surrounding tissues revealed increased concentrations of beta-endorphin and an activated conversion of beta-lipotropin to beta-endorphin in the adenoma compared with the surrounding tissues. These findings were in agreement with the characteristics previously reported for corticotroph adenomas. However, unexpectedly, concentrations of ACTH and beta-lipotropin in the adenoma were only slightly higher than those in the surrounding tissues. Precise mechanisms underlying this unusual finding were elusive, but it may have been due to the periodic nature of her hypercortisolism. In addition, this patient was reproducibly responsive to bromocriptine (2.5 mg, per os) with a reduction of the plasma cortisol level. Although this may suggest an intermediate lobe subtype of Cushing's disease as proposed by Lamberts' group, our case did not have any other characteristic suggestive of this proposed variant. However, it is tempting to speculate that cyclical changes in the central dopaminergic tone may have been at least a partial trigger for the periodic hormonogenesis in this patient.

Adrenocorticotropic Hormone↗
PubMed1991

Paradoxical response of growth hormone to peptide histidine methionine in acromegaly: comparison with the effects of thyrotropin-releasing hormone and vasoactive intestinal peptide.

We examined whether peptide histidine methionine (PHM) induces a paradoxical rise in plasma GH in patients with acromegaly. PHM (100 micrograms) was given as an iv bolus to eight patients with active acromegaly, and plasma GH levels were measured before and at intervals up to 120 min after the injection. For comparison, the effects of TRH (500 micrograms) and vasoactive intestinal peptide (VIP, 100 micrograms), peptides known to paradoxically stimulate GH secretion in acromegalics, were assessed in all of the patients. A paradoxical rise (greater than 50% above the basal) in plasma GH was observed in five patients after both TRH and VIP administrations, although TRH responders were not always VIP responders, nor did VIP responders always respond to TRH. In two patients, the GH response to PHM fulfilled the criteria of a paradoxical increase. Both of these patients were also TRH and VIP responders. These results suggest that PHM may be another hypothalamic hormone capable of paradoxically stimulating GH secretion in at least some acromegalics, although PHM appears to be a less potent stimulator of GH release than TRH and VIP. The pathophysiological significance of this phenomenon is yet to be determined.

Acromegaly↗
PubMed1991

Failure to confirm a growth hormone-releasing activity of corticotropin-releasing hormone in acromegaly: comparison with the effects of other hypothalamic hormones.

We re-examined whether CRH stimulates GH secretion in acromegaly. Human CRH (100 micrograms) was given as an iv bolus to 15 patients with active acromegaly, and plasma GH levels were measured before and at intervals up to 120 min after the injection. For comparison, we assessed in all the patients the effects of TRH (500 micrograms), GnRH (100 micrograms), vasoactive intestinal peptide (100 micrograms) and peptide histidine methionine (100 micrograms), which are known paradoxically to stimulate GH secretion in acromegaly. A paradoxical GH response (greater than 50% above the basal) to TRH, GnRH, vasoactive intestinal peptide and peptide histidine methionine was observed in 12 (80%), 4 (27%), 5 (33%) and 2 (13%) patients, respectively. All the patients were responsive to at least one of these 4 peptides. However, none of the patients showed a positive GH response to hCRH. These results do not support a GH-releasing activity of CRH in acromegaly. Even if CRH has such an effect, it does not appear as potent as TRH, GnRH, vasoactive intestinal peptide and peptide histidine methionine. However, the possibility cannot be excluded that our negative data might have been due to the use of hCRH vs ovine CRH in earlier studies.

Acromegaly↗
PubMed1991

A null cell adenoma of the pituitary detected seven years after removal of a prolactinoma. Recurrence or de novo tumourigenesis?

We report an extremely unusual case of prolactinoma which emerged at recurrence as a null cell adenoma. A 53-year-old woman sought medical attention for progressive visual loss and headache. A pituitary tumour was detected by a computed tomographic scan, and hyperprolactinemia was noted. The tumour, removed by a transfrontal surgery, was a chromophobe adenoma, and immunohistochemically the adenoma cells were selectively positive for PRL, which indicated a prolactinoma. Postoperatively, her plasma PRL level was normalized. Seven years later, she noted blurred vision and again sought medical attention. A CT scan demonstrated recurrence of a pituitary tumour. On this occasion, however, she was not hyperprolactinemic. She underwent again a transfrontal resection of the pituitary tumour. Its histology was again a chromophobe adenoma, but the adenoma cells showed no positive immunostaining for any anterior pituitary hormone including PRL, which indicated a null cell adenoma. We have no clear explanation of the pathogenesis underlying her very unusual course. However, null cells (assuming that the original tumour was a mixed adenoma) left behind at the first surgery, or unidentified hypothalamic and/or pituitary derangements might possibly have been responsible for the recurrence. We learned from this patient that recurrent pituitary adenomas may not necessarily have the same endocrine features as did the original tumours. This information appears to make a valid clinical point, because if hormone levels alone are followed after pituitary surgery, recurrent pituitary tumours may be overlooked.

Adenoma↗
PubMed1991

Hyperinsulinemia and blood pressure in non-obese middle-aged subjects with normal glucose tolerance.

A possible link between hyperinsulinemia and blood pressure was studied in non-obese subjects with normal glucose tolerance. First, the responses in plasma glucose and serum insulin to an oral glucose load (75-g oral glucose tolerance test) were compared between 42 patients with essential hypertension and 93 normotensive control subjects. Second, of the 93 normotensive subjects, the relations of serum insulin levels to blood pressure, serum cholesterol, and triglycerides concentrations were assessed in 8 hyperinsulinemic (serum insulin level [during fasting, or after glucose loading, or both] greater than 2 S.D. higher than the mean) and 8 pair-matched normoinsulinemic subjects (serum insulin level within 1 S.D. of the mean), individually matched for age, sex, and body mass index. Plasma glucose and serum insulin responses to the glucose load in hypertensive subjects were identical to the respective responses in normotensive subjects, while the mean total serum cholesterol level was slightly higher (p less than 0.05) in hypertensive subjects. The respective values for systolic and diastolic blood pressures, and total serum cholesterol and triglycerides concentrations were comparable in hyperinsulinemic and normoinsulinemic subjects. These results did not suggest a close association between hyperinsulinemia and elevated blood pressure in non-obese middle-aged Japanese subjects with normal glucose tolerance.

Blood Glucose↗
PubMed1991

Role of phospholipid in the formation of large aggregates and dissolution of insoluble calcium salts in mode bile solution.

The role of phospholipid in the formation of large aggregates and the dissolution of insoluble calcium salts in bile was studied in mode bile solutions of various lipid compositions. Calcium carbonate was added as an insoluble calcium salt. As the ratio of phospholipid concentration to bile acid increased, the rate of bile acid in the formation of large aggregates increased; total calcium concentration also increased but Ca2+ concentration did not change. Furthermore, a close relationship between the sum of the bile acid and phospholipid concentrations in the large aggregate fraction and the total calcium concentration in model bile solutions was observed. It could be concluded that phospholipid plays a role in dissolution of insoluble calcium salts by promoting the formation of large aggregates in bile.

Bile↗
PubMed1990

Effect of the glucocorticoid milieu on the immunostaining of peptide histidine isoleucine (PHI) in the rat hypothalamus.

Effects of adrenalectomy (ADX) or dexamethasone (DEX) treatment on the immunostaining of hypothalamic peptide histidine isoleucine (PHI) were examined in male rats. After colchicine treatment, PHI-containing cell bodies were observed in the suprachiasmatic nucleus (SCN) and the parvocellular division of the paraventricular nucleus (PVN). ADX increased and DEX dose-dependently decreased the number of PHI-immunopositive neurons in the PVN. The number of SCN-PHI neurons was not affected by any treatment employed in this study. These results suggest that PVN-PHI neurons are under the effects of the glucocorticoid milieu, and that the neurons may be involved in the glucocorticoid regulation of adrenocorticotropin and prolactin secretion.

Adrenalectomy↗
PubMed1990

Comparison of the renal effects of dilevalol and carteolol in patients with mild to moderate essential hypertension.

The effects of 6 weeks of treatment with dilevalol 100 mg once daily, or carteolol 10 mg once daily, on renal blood flow (RBF), glomerular filtration rate (GFR) and total renal vascular resistance (TRR) were studied in 10 patients with mild-to-moderate essential hypertension in a randomised cross-over experiment. Both drugs lowered the systolic and diastolic blood pressures to a similar extent without altering the heart rate. Carteolol non-significantly decreased RBF by 9.2% and GFR by 12.3% without altering. TRR, whereas dilevalol produced a significant reduction in TRR by 13.2% (p less than 0.05), a non-significant decrease in RBF by 4.6% and no change in GFR. Neither drug changed plasma osmotic pressure, serum total protein concentration, electrolytes or plasma aldosterone concentration. Plasma renin activity tended to be lower in the dilevalol phase as compared to the carteolol phase. The results suggest that dilevalol may cause a greater decrease in TRR and less reduction in GFR when compared to carteolol in patients with mild-to-moderate essential hypertension. The difference in the renal effects might be due to the difference in the potency of vasodilatory properties of both drugs at the doses applied.

Adult↗