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Biomedical subjects

T Nakane

Publications and source records attributed to T Nakane.

At least 91 records · Page 5Linked to original sources
PubMed1986

Regional differences of responses to adrenoceptor agonists in isolated and perfused canine coronary arteries.

Regional differences of the responses to adrenoceptor agonists were investigated in isolated canine coronary arteries by use of a cannula inserting method. Acetylcholine induced a dose-dependent vasodilation. Norepinephrine and epinephrine produced a vasoconstriction followed by a strong vasodilation in large coronary arteries and only a weak vasodilation in small coronary arteries. Phenylephrine (a selective alpha-1 agonist) induced a strong vasoconstriction in both arteries. The threshold dose and ED50 value for phenylephrine in small coronary arteries were much larger than those in large coronary arteries, although the vasoconstrictions by KCl and prostaglandin F2 alpha were not different between in large and small coronary arteries. Clonidine and xylazine (selective alpha-2 agonists) produced a slight vasoconstriction but not dose-dependently and a vasodilation with extremely large doses. ED50 value of vasodilation for salbutamol (a selective beta-2 agonist) was approximately 80 times greater than that for isoproterenol (a non-selective beta-agonist) in large coronary arteries, but was approximately 20 times in small coronary arteries. The maximal dilator response to salbutamol was about the same as that to isoproterenol in small coronary arteries, whereas it was much smaller than that to isoproterenol in large coronary arteries. These results suggest that adrenoceptors are heterogeneous according to the distance from the coronary orifice in canine epicardial coronary arteries.

Acetylcholine↗
PubMed1986

Corticotrophin-releasing factor in extra-hypothalamic brain of the mouse: demonstration by immunoassay and immunoneutralization of bioassayable activity.

Corticotrophin-releasing factor (CRF) bioactivity has been described in the extra-hypothalamic brain, but its relationship to hypothalamic CRF has remained questionable. Of the seven regions of the mouse brain examined, highest concentrations of CRF-like immunoreactivity (CRF-LI) and bioassayable CRF activity were present in the median eminence and hypothalamus. However, substantial CRF-LI and bioassayable CRF activity were also seen in brain extracts from the amygdala, thalamus, frontal cortex, pons medulla and cerebellum. Bioactivity was largely neutralized by prior incubation with heat-inactivated antiserum to ovine CRF. These findings, in conjunction with previous immunocytochemical evidence, strongly suggest that a substance closely resembling hypothalamic CRF is present in the extrahypothalamic brain of the mouse.

Amygdala↗
PubMed1985

The effects of centrally administered neuropeptides on the development of gastric lesions in the rat.

Centrally administered neuropeptides were investigated for their effects on the development of gastric lesions in rats. Thyrotropin releasing hormone (TRH), vasoactive intestinal peptide (VIP) and gonadotropin releasing hormone (LHRH) produced gastric lesions acutely, with TRH demonstrating the most pronounced effect in terms of incidence and severity. Ten-fold higher doses of the same peptides administered intravenously produced none or very few gastric lesions. Moreover, pretreatment with atropine partially inhibited their production. Corticotropin releasing factor (CRF) exhibited only mild ulcerogenic effects, and the gastric lesions induced with this peptide developed more slowly than with TRH, VIP and LHRH. Although ulcerogenic in their own right, none of these four neuropeptides significantly potentiated the potent ulcerogenic effects of cold-restraint stress. Since other neuropeptides, including somatostatin, human pancreatic growth hormone releasing factor (hpGRF), substance P, bombesin, and neurotensin, had no demonstrable effects on gastric mucosa, we can conclude that the lesions were not a general effect of intracisternal administration of neuropeptides. The results suggest that within the central nervous system, there are several neuropeptides that play a significant role in the development of gastric lesions via, at least in part, vagal-dependent mechanisms.

Animals↗
PubMed1985

Long-term growth hormone responses to nonspecific hypothalamic hormones in acromegalic patients.

Nonspecific hypothalamic hormones such as thyrotropin-releasing hormone or luteinizing hormone-releasing hormone, or both, elicited abnormal growth hormone responses in 73 of 108 (67.6%) acromegalic patients. After transsphenoidal adenomectomy, the provocative tests using these hormones were repeated in 26 patients with abnormal preoperative growth hormone responses to study variations in these responses during a 1-8-year observation period (average duration, 4 years). After surgery, 7 of the 26 patients regained normal basal growth hormone levels (less than 5 ng/mL) and manifested normal responses to the hypothalamic hormones. During the postoperative observation period, their basal growth hormone levels remained normal as did their responses to provocation with hypothalamic hormones, confirming that the adenoma had been completely resected. Eight other patients demonstrated normal growth hormone levels after surgery; however, they continued to have abnormal responses to provocation with hypothalamic hormones, suggesting the presence of residual adenomatous tissue in the gland. These patients manifested no marked increase in basal or peak growth hormone levels during the follow-up period (from less than 1 to less than 7.5 years) and they were all in clinical remission without any other treatment. Only one incompletely adenomectomized patient who had received no additional treatment experienced regrowth of the tumor. The main factor affecting the surgical results appears to be the preoperative basal growth hormone level, because abnormal growth hormone secretion ceased in all patients who had manifested preoperative levels below 45 ng/mL. Technical refinements of the operative procedure are another important factor in the postoperative outcome. Peritumoral tissue resection after simple selective adenomectomy is mandatory for better surgical results. Our studies indicate that fairly good results can be obtained without risk of the recurrence of the tumor or regrowth, when postoperative growth hormone levels are below 5 ng/mL and that the results are not affected by the postoperative growth hormone responses to provocation with hypothalamic hormones.

Acromegaly↗
PubMed1985

Evidence for a role of endogenous corticotropin-releasing factor in cold, ether, immobilization, and traumatic stress.

The role of corticotropin-releasing factor (CRF) in four model stresses (cold, ether, immobilization, and trauma) was examined in the guinea pig by using passive immunoneutralization with anti-CRF antiserum. Plasma corticotropin levels were measured at various times after exposure to stress, and groups treated with CRF antiserum were compared with those treated with normal rabbit serum. Of the four stresses tested, ether had the most pronounced effect on corticotropin secretion. Treatment with anti-CRF inhibited most of the ether-induced corticotropin secretory response, the difference between the normal serum- and the anti-CRF antiserum-treated groups being significant at 5 and 10 min (P less than 0.01). Corticotropin responses to cold stress in the two groups differed at the 0.05 level of significance at 10 and 20 min. After administration of trauma (leg fracture), a statistically significant difference (P less than 0.01) between the two groups also was evident, albeit only at 20 min. During immobilization, corticotropin levels differed significantly from control only in the normal serum-treated group but not in the anti-CRF-treated group. These findings show that CRF antiserum was effective in reducing corticotropin levels, indicating that CRF has an important role in mediating corticotropin response to stress. The fact that neutralization was incomplete might be due to an inability of the antiserum to sufficiently neutralize the endogenous CRF or, more likely, reflects the contribution of additional mediators, notably catecholamines and vasopressin, of corticotropin release upon stress.

Adrenocorticotropic Hormone↗
PubMed1985

Levels of human and rat hypothalamic growth hormone-releasing factor as determined by specific radioimmunoassay systems.

Polyclonal antibodies to synthetic human pancreatic growth hormone-releasing factor [hpGRF(1-44)NH2] and rat hypothalamic growth hormone-releasing factor [rhGRF(1-43)OH] were produced in rabbits by injecting these weak immunogens, coupled to thyroglobulin and emulsified with complete Freund's adjuvant in the presence of activated charcoal, directly into the spleen. A subsequent booster injection by the conventional intramuscular route resulted in high-titer antibodies, which at a 1:20,000 dilution were used to develop highly sensitive and specific radioimmunoassays for these peptides. By using antibodies with an apparent Ka of 3.3 X 10(-12) (human) and 7.7 X 10(-11) (rat), the sensitivity of these assays in both human and rat was found to be less than 1 fmol. The antibody to hpGRF(1-44)NH2 is directed against the COOH-terminal region of the molecule, as shown by its crossreactivity with various hpGRF analogues: 140% with hpGRF(30-44)NH2; 1%-2% with hpGRF(1-37)OH, hpGRF(1-40)OH, and hpGRF(1-40)NH2; and none with hpGRF(1-29)NH2. Serial dilutions of human and rat hypothalamic extracts demonstrated parallelism with the corresponding species-specific standard and 125I-labeled tracer. There was no crossreactivity with other neuropeptides, gastrointestinal peptides, or hypothalamic extracts of other species. The hypothalamic content in fmol/mg (wet weight) of tissue was 3.6 +/- 0.2 for the human and 11.1 +/- 5.5 for the rat. Age-related changes in hypothalamic GRF content were present in rats, with a gradual increase from 2 to 16 weeks and a correlation between increasing body weight and GRF content. These radioimmunoassays will serve as important tools for understanding the regulation of growth hormone secretion in both human and rat.

Age Factors↗
PubMed1985

[ACTH dependent Cushing's syndrome with an empty sella turcica: report of three cases with emphasis on diagnostic value of selective venous sampling].

Three cases of ACTH dependent Cushing's syndrome are reported with emphasis on diagnostic value of selective venous sampling. Case 1. A 44-year-old female was admitted to our hospital with clinical diagnosis of Cushing's disease. Endocrinological examination revealed typical data of Cushing's disease. High resolution CT scan showed an empty sella turcica, and a chest film showed multi-cystic lesion in the left lower lung field. In the first trial of selective venous sampling, central to peripheral ACTH ratio (C/P ratio) was high at the superior vena cava. So, an ectopic ACTH producing lung tumor was strongly suspected. Further examinations for lung tumor were performed, and finally showed lung cryptococcosis. Therefore, selective venous sampling was performed again, and pituitary ACTH dependency was diagnosed. An eccentric pituitary microadenoma was successfully removed by transsphenoidal surgery. Case 2. A 54-year-old female was admitted to our hospital with clinical diagnosis of Cushing's disease. In the endocrinological examinations plasma ACTH was not respond to provocation of LVP or CRF. In selective venous sampling, C/P ratios of ACTH were not greater than 2.0 at any sampling site. Further examinations showed lung tumor in the lower lobe of left lung. This tumor was surgically proved to be an ectopic ACTH producing lung carcinoid. Case 3. A 24-year-old female was admitted to our hospital for the purpose of further examination of Cushing's disease. Three years previously exploratory transsphenoidal surgery demonstrated an empty sella without adenoma. She received postoperative radiation therapy with a dose of 5000 rad. Endocrinological examination showed typical data due to Cushing's disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma↗
PubMed1983

Levels of corticotropin releasing factor-like immunoreactivity in mammalian hypothalamic and extrahypothalamic brain tissue as determined with a monoclonal antibody to the ovine material.

A monoclonal antibody to ovine corticotropin releasing factor (CRF) has been produced by fusion of a non-producing plasmacytoma cell line P3U1 with spleen cells of Balb/c mice immunized with the synthetic 41 amino acid peptide coupled covalently with rabbit myosin by a heterobifunctional reagent, N-succinimidyl 3-(2-pyridyldithio) propionate. A total immunizing dose of 500 micrograms resulted in a highly specific, high-affinity antibody with a Ka of 0.15 x 10(12) M-1, which was used to establish a specific RIA with a sensitivity of 10 pg/tube. Levels of corticotropin releasing factor-like immunoreactivity (CRF-LI) in a pg/mg of hypothalamic tissue ranged from 4-10 in ovine, 2.5-8 in bovine, 47.5-67.5 in mouse and 2.3-20 in human tissue. Moreover, CRF-LI was widely distributed in extrahypothalamic mouse brain at concentrations approximately one half those seen in hypothalamus.

Amygdala↗
PubMed1983

Pituitary adenomas in acromegalic patients: an immunohistochemical and endocrinological study with special reference to prolactin-secreting adenoma.

To establish a functional classification of purification of pituitary adenomas in acromegalic patients, we used immunoperoxidase-staining techniques specific for GH and PRL. Surgical specimens from 55 acromegalic patients were studied. GH was demonstrated in all adenomas and PRL was found in 25 of them (45.5%). Immunohistologically, GH- and PRL-containing adenomas could be divided into 3 types. In type 1 (11 patients), immunoreactive PRL was present in single cells surrounded by immunoreactive GH cells. In type 2 (6 patients), immunoreactive PRL cells formed clusters. In Type 3 (8 patients), immunoreactive PRL and GH cells demonstrated a mosaic pattern, and it was difficult to determine which were in the majority. A double immunostaining method revealed 15 adenomas in which individual cells contained both GH and PRL. Hyperprolactinemia was present in 21 patients, 15 of these had immunoreactive PRL cells (type 1, 4 patients; type 2, 3 patients; type 3, 8 patients). There was no correlation between the size of the adenoma and its type. Endocrinologically, all patients with type 2 and 3 adenomas had an abnormal serum GH response to TRH administration; all type 3 patients had a substantial serum PRL response to TRH administration. Type 3 is considered to be an actively PRL-secreting adenoma, resulting in hyperprolactinemia.

Acromegaly↗
PubMed1983

Early operation for ruptured intracranial aneurysms: comparative study with computed tomography.

The relationship between the results of early operation for ruptured intracranial aneurysms (72 cases) and the preoperative computed tomographic (CT) findings was studied. There was a correlation among the surgical results, the development of symptomatic vasospasm, and high density on the preoperative CT scan, particularly the presence of a localized, thick layer in the subarachnoid space. However, no relationship was found between the occurrence of ventricular enlargement and the preoperative CT findings. Cisternal or ventricular drainage might contribute to an uncomplicated postoperative course for patients with severe subarachnoid clot shown on the preoperative CT scan.

Adult↗
PubMed1983

Distribution, biosynthesis, and physiological role of corticotropin-releasing factor in the human: an overview.

Our findings to date indicate that: A peptide resembling oCRF is present in human and mammalian hypothalamus. oCRF is present in human lumbar cerebrospinal fluid. oCRF concentrations do not differ in CSF from normal individuals and from patients with Cushing's syndrome. oCRF appears to be synthesized via a large oligopeptide precursor. An oCRF-like molecule (oCRF-LI) is present in hypothalamic brain tissue. We have also observed more tentative evidence of low levels of oCRF-LI outside of the brain. oCRF is likely to be a central mediator of stress in its multiple forms. We believe that oCRF is clearly of major physiological importance, but that many critical unanswered questions remain. Probably, the most fascinating of these, which we are only beginning to comprehend, concerns the functions of CRF in extrahypothalamic brain as well as the CRF which appears to be present outside the brain.

Animals↗
PubMed1982

[Computerized tomography of the traumatic hematoma in the corpus callosum. --Report of 2 cases].

The value of the computerized tomography (CT) in the diagnosis of the intracerebral hematoma has been well documented. However, there is little report about the CT findings of the hematoma of the corpus callosum. This report presents two cases of the traumatic hematoma in the corpus callosum and is discussed about their CT findings. Two patients, 52 year-old male and 40 year-old male, respectively, are the cases of blunt mechanical head trauma which were accompanied neither by skull fracture nor by scalp injury. In all these cases, the findings that hematoma occupied from the genu to the body of the corpus callosum were verified by surgery and the axial CT revealed the following two similar findings. First; the hematoma in the genu of the corpus callosum was shown as a crescent-shaped high density mass. This finding seems to be due to the following anatomical structure, that is, the genu of the corpus callosum is located just in front of the anterior horn of the lateral ventricles in the shape of the convex towards posteriorly. Second; as the midportion of the body of the corpus callosum tends to be appeared narrow in width between both lateral ventricles, the hematoma which extended from the genu towards the body of the corpus callosum was shown as a dumbbell-shaped high density mass.

Cerebral Hemorrhage↗
PubMed1981

Concomitant secretion of adrenocorticotropin, beta-endorphin, and gamma-melanotropin from perfused pituitary tumor cells of Cushing's disease: effects of lysine vasopressin, rat median eminence extracts, thyrotropin-releasing hormone, and luteinizing hormone-releasing hormone.

Regulation of secretion of ACTH-, beta-endorphin-, and gamma-melanotropin-like immunoreactivities (ACTH-LI, beta-EP-LI, and gamma-MSH-LI, respectively) was studied by using a perfused Sephadex column containing dispersed pituitary tumor cells obtained from three patients with Cushing's disease. Serial dilution of the perfusion medium gave lines parallel to the standard curve in each RIA for ACTH, beta-EP and gamma-MSH, suggesting that immunoreactive materials in the medium are immunologically indistinguishable from the authentic peptides. Gel exclusion chromatography of the medium revealed the existence of ACTH, beta-lipotropin (beta-LPH), beta-EP, and their possible precursor protein. gamma-MSH-LI consists of a major peak of big gamma-MSH eluted near the elution position of beta-LPH, suggesting the entire or nearly entire N-terminal portion of the precursor molecule. The addition of lysine vasopressin and rat median eminence extracts (MEE) to the perfusion system concomitantly enhanced the release of ACTH-LI, beta-EP-LI, and gamma-MSH-LI, although the dose-response relationship was clear-cut only in the case of MEE. TRH and LRH also elicited the concomitant release of these peptides in one patient, in whom combined administration of TRH and LRH significantly augmented plasma cortisol levels when studied preoperatively. The molar ratio of ACTH-LI to beta-EP-LI was approximately 1.0, whereas gamma-MSH-LI was about one fourth of ACTH-LI when compared on a weight basis. These results indicate that 1) ACTH-producing human pituitary adenomas concomitantly secrete ACTH, beta-LPH, beta-EP, and big gamma-MSH, and 2) lysine vasopressin, MEE, TRH, and LRH act directly on pituitary cells to stimulate the release of these peptides.

Adenoma↗
PubMed1981

Anterior pituitary function after transsphenoidal selective adenomectomy in patients with Cushing's disease.

The anterior pituitary function in 25 patients with Cushing's disease was assessed before and after transsphenoidal adenomectomy. Pituitary adenoma was detected and removed in 24 cases, resulting in clinical remission in 22. Postoperative hypoadrenocorticism was observed in all of the cases with remission, necessitating substitution of glucocorticoid. One case had a recurrence after a year in remission. Plasma ACTH and cortisol rapidly decreased after surgery and remained at subnormal levels. However, diurnal rhythmicity of ACTH and cortisol appeared in 5 of 9 cases within 6 months after surgery and exhibited normal suppressibility in response to low dose dexamethasone. The impaired ACTH response to hypoglycemia was restored after surgery. The GH response to hypoglycemia and the TSH response to TRH were improved by correction of hypercorticism and became evident over time. These results suggest that preoperative impairment of anterior pituitary hormone secretion is secondary to hyperadrenocorticism and that ACTH hypersecretion by a primary pituitary adenoma is the primary etiology in Cushing's disease. We conclude that transphenoidal pituitary exploration should be considered as a first choice of treatment of Cushing's disease because of its high clinical remission rate in association with normalization of other endocrine functions.

Adenoma↗