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Biomedical subjects

T Kakegawa

Publications and source records attributed to T Kakegawa.

At least 271 records · Page 15Linked to original sources

Electrical stimulation of several limbic areas suppressed the growth hormone (GH) release induced by human pancreatic GH-releasing factor in pentobarbital-anesthetized rats.

The present study was designed to clarify the topography in the limbic system related to the suppression of GH release induced by iv injected human pancreatic GH-releasing factor (hpGRF) in pentobarbital-anesthetized rats. Bipolar concentric stimulating electrodes were implanted in certain limbic areas 1 week before the stimulation. Under pentobarbital anesthesia, 10 micrograms hpGRF dissolved in 0.3 ml saline were injected iv, which increased the plasma GH level from 19.8 +/- 3.6 (mean +/- SE) to 846.0 +/- 40.5 ng/ml in 10 min. After the plasma GH level showed its highest value (at 10 min), it gradually decreased to 30.5 +/- 3.0 ng/ml by 60 min. This hpGRF-induced response was suppressed by the electrical stimulation (for the first 10 min) of the medial amygdaloid nucleus (Me), the lateral septum, or the bed nucleus of the stria terminalis. The inhibition rate ranged between 31.9-42.4% of control at 10 min. This inhibition was abolished by prior lesion of the periventricular nucleus of the hypothalamus, where the somatostatinergic nerve terminals in the median eminence originate. Sectioning the stria terminalis also abolished the inhibitory effect of GH release due to Me stimulation. The electrical stimulation of other amygdaloid nuclei or of the medial septum exerted no inhibitory effect on hpGRF-induced GH release. These results indicate that stimulation of the Me, the lateral septum, or the bed nucleus of the stria terminalis exerts an inhibitory effect on GH release, and the periventricular nucleus of the hypothalamus and the stria terminalis (in the case of Me stimulation) are important for this inhibitory effect.

Amygdala↗

Thyroid hormone response to thyrotrophin releasing hormone (TRH) in the sex-linked dwarf chicken.

The effect of an injection of thyrotrophin releasing hormone (TRH) on plasma levels of thyroid hormones was studied in dwarf and normal Rhode Island Red chickens with similar genotypes other than for the sex-linked dwarf gene dw. The sex-linked dwarf chickens had different plasma iodothyronine levels from control normal chickens: high thyroxine (T4), low triiodothyronine (T3) and similar reverse T3 (rT3) levels. The injection of TRH (10 micrograms/kg) in 5-day- and 5-week-old normal chickens increased the plasma T4 within 30 min without a significant increase in T3, whereas the injection of TRH in 11-and 26-week-old normal chickens increased plasma T3 60 min later. In dwarfs the response of T4 to TRH was the same as that in normals but no increased T3 response was observed. The plasma level of rT3 was not influenced by the TRH injection in either strain. These results suggest that although in the sex-linked dwarfs thyroidal response to exogenous TRH is similar to that of normals, the dwarf gene dw inhibits the conversion of T4 to T3 in peripheral tissues without any inhibitory effect on rT3 production.

Aging↗

Stimulation of growth hormone release in dwarf and normal chickens by thyrotrophin releasing hormone (TRH) or human pancreatic growth hormone releasing factor (hpGRF).

The effect of thyrotrophin releasing hormone (TRH) or human pancreatic growth hormone releasing factor (hpGRF) on growth hormone (GH) release was studied in both dwarf and normal Rhode Island Red chickens with a similar genotype except for a sex-linked dw gene. Both TRH (10 micrograms/kg) and hpGRF (20 micrograms/kg) injections stimulated plasma GH release within 15 min in young and adult chickens. The increase in GH release was higher in young cockerels than that in adult chickens. The age-related decline in the response to TRH stimulation was observed in both strains, while hpGRF was a still potent GH-releaser in adult chickens. The maximal and long acting response was observed in young dwarf chickens, suggesting differences in GH pools releasable by TRH and GRF in the anterior pituitary gland. The pituitary gland was stimulated directly by perifusion with hpGRF (1 microgram/ml and 10 micrograms/ml) or TRH (1 microgram/ml). Repeated perifusion of GRF at 40 min intervals blunted further increase in GH release, but successive perifusion with TRH stimulated GH release. The results suggest the possibility that desensitization to the effects of hpGRF occurs in vitro and that the extent of response depends on the number of receptors for hpGRF or TRH and/or the amount of GH stored in the pituitary gland.

Age Factors↗

Plasma thyrotrophin (TSH) response to intrahypothalamic injection of an alpha 2-adrenergic receptor agonist (clonidine).

To delineate the site at which the central noradrenergic (NE) system may exert its stimulatory influence on the thyrotrophin (TSH) secretion, plasma TSH concentrations were measured before and after clonidine (an alpha 2-agonist) administration to the hypothalamus of unanaesthetized, unrestrained rats. When the animals received a simultaneous injection of clonidine (0.2 microgram) and phenoxybenzamine (2.0 micrograms) into the dorsomedial nucleus (DMN)/the paraventricular nucleus (PVN), a significant rise in TSH levels was observed. Injection of the mixture into the anterior hypothalamus, posterior hypothalamus, ventromedial hypothalamus, and arcuate nucleus had no influence on the plasma TSH concentration. Clonidine (10.0 micrograms/100 g body weight) and phenoxybenzamine (100 micrograms/100 g body weight) injected into the jugular vein also caused a prompt increase in the plasma TSH concentration. In rats with an intact small hypothalamic island, the TSH response to the iv injection of the drugs was considerably diminished. These data support the view that NE receptors in the DMN/PVN are of importance in exerting an NE-stimulatory influence on the TSH secretion, probably through the TRH neurons.

Adrenergic alpha-Agonists↗

[Studies on hemorrhagic gastritis after extended gastric devascularization using portal hypertensive dogs].

We studied a cause of postoperative hemorrhagic gastritis in the disease of portal hypertension experimentally. Five portal hypertensive dogs, produced by our whole liver compression procedure, underwent transabdominal devascularization on one-third upper gastric portion. In the gastric cardia, mucosal blood flow and tissue oxygen tension (PTO2) were measured by Hydrogen gas clearance method and PTO2 sensor for 14 days after surgery. Moreover P50, 2,3-DPG, pH, Hb, and blood temperature were also monitored for 14 days. In gastric hemodynamic changes, mucosal blood flow showed a moderate reduction immediately after surgery and returned to the previous value on the 14th postoperative day, although the value of PTO2 was dropped gradually for 14 days. Especially, postoperative changes in PTO2 showed significant correlation with P50 and 2,3-DPG. On the other hand, slight atrophic gastritis was recognized microscopically in devascularized gastric cardia. From these results, mucosal hypoxia of the upper gastric portion may be influenced by a remarkable reduction of P50 and 2,3-DPG, and it seems to easily lead to the state of hemorrhagic gastritis.

Animals↗

[Phase II study of cisplatin in esophageal carcinoma].

A multi-institutional cooperative phase II study of Cisplatin for esophageal carcinoma was conducted. Cisplatin was administered by i.v. infusion at 10-20 mg/m2 body surface area daily for 5 days and repeated every 3-4 weeks (method A) or at 50-100 mg/m2 body surface area once every 3-4 weeks (method B). Out of 78 cases entered, 47 were evaluable. No complete response (CR) was obtained and partial responses (PR) were observed in 10 cases, the overall response rate being 21.3%. Response rates by administration methods A and B were 12.5% and 25.8%, respectively. Responders to treatment exhibited significantly longer survival periods compared to non-responders (p less than 0.05, generalized Wilcoxon test). Major adverse reactions were gastrointestinal symptoms, generalized malaise, bone marrow suppression and renal disorders. One case of leukopenia leading to eventual death from pneumonia was observed.

Adult↗

[Growth hormone-producing pituitary adenoma in an 8-year-old girl: case report].

A rare case of pituitary adenoma in childhood presenting as giantism is reported. A 6-year-old girl came to our attention in 1982 because of excessive growth noted since the age of 3 yr. Her appearance revealed giantism. She also had a 4 year history of genital bleeding, but no development of external genitalia nor mammary gland. Endocrinological studies revealed markedly elevated serum basal levels of both growth hormone (GH) and prolactin (PRL). She had a bromocriptine therapy for 1 year and 8 months, but it was difficult to suppress her excessive growth rate. So she was admitted at the age of 8 years to undergo the operation. Visual fields were intact. X-ray examination of the skull demonstrated a slightly enlarged sella turcica. Computerized tomography revealed an isodense mass at the pituitary fossa without extrasellar extention. Repeated endocrinological studies were carried out. Basal levels of GH and PRL were 43.8 ng/ml and 67 ng/ml. All other pituitary function were normal, except for puberal responses of luteinizing hormone (LH) and follicle stimulating hormone in LH-RH loading test. 50 g oral glucose tolerance test was normal. Transsphenoidal microsurgery was performed in August 1984. The tumor filled up the pituitary fossa with fibrous element. Histological examination disclosed a mixed adenoma, predominantly chromophobe, with a few granulated eosinophils. Immunoperoxidase staining was also performed on the adenoma. Most of the tumor cells stained for GH, and a few of them stained for PRL. Postoperatively hypopituitalism was not complicated. Surgery produced a decrease in serum PRL level under 20 ng/ml, but serum GH level was not enough reduced under 10 ng/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma↗

Small-cell carcinoma of the rectum. Clinicopathologic study.

Three cases of small-cell carcinoma of the rectum are presented. Our conclusions are as follows: small-cell carcinoma and carcinoid tumor of the rectum might have a common origin; indications for surgical intervention for small-cell carcinoma of the rectum should be considered seriously; small-cell carcinoma of the rectum should be classified as an aggressive type of rectal tumor that metastasizes easily to distant organs.

Adult↗

Inhibitory effect of hypothalamic stimulation on growth hormone (GH) release induced by GH-releasing factor in the rat.

The object of the present experiments was to clarify the topography of hypothalamic areas related to the suppression of GH release induced by human pancreatic GH-releasing factor (hpGRF). One week before the experiments, bipolar concentric stimulating electrodes were implanted in the organum vasculosum of the lamina terminalis (OVLT), the periventricular nucleus of the hypothalamus (Pe), the ventromedial nucleus of the hypothalamus (VMH), the lateral hypothalamic area (LHA), or the ventral premammillary nucleus (PMV). At the same time, the jugular vein was cannulated for blood sampling, and lesion of the anterior Pe was performed with a cathodal current. One and one half hours before the first blood sampling the rats were anesthetized with pentobarbital to prevent spontaneous GH bursts. One minute after the first blood sampling, 10 micrograms hpGRF dissolved in 0.3 ml saline was injected iv through the cannula. The blood samples were collected at 10, 20, 30, and 60 min after the zero-time sample. The above mentioned hypothalamic nuclei were electrically stimulated for the first 10 min. Injection of hpGRF increased the plasma GH level from 44.2 +/- 7.3 ng/ml (mean +/- SE) to 981.4 +/- 59.8 ng/ml in 10 min, and the plasma GH level gradually decreased to 50.8 +/- 8.8 ng/ml by 60 min. The hpGRF-induced GH release was most effectively suppressed by the stimulation of the Pe. After the stimulation of the OVLT, the VMH, the LHA, or the PMV, the suppression of hpGRF-induced GH release was weaker than that of the Pe. This stimulation-induced suppression was fully or partly prevented in Pe-lesioned animals. These results indicate that the stimulation of the Pe, the OVLT, the VMH, the LHA, or the PMV exerts an inhibitory effect on GH release. For this inhibitory effect, the Pe was essential. The results are discussed with regard to the topography of immunoreactive SRIF neuronal cell bodies and processes in the hypothalamus.

Animals↗

Acute changes of iodothyronine excretion by bile after a single and repeated administration of dexamethasone in rats.

Bile was collected from cannulated bile duct under pentobarbiturate anesthesia and the excretion of several iodothyronines was estimated with the aid of radioimmunoassay as described previously. The excretion of triiodothyronine (T3) was significantly decreased between 4 and 6 h after a single injection of 20 and 40 mg kg-1 dexamethasone (DEX), while no changes in the excretion of thyroxine (T4) and reverse triiodothyronine (rT3) were found. In another experiment a decrease of T3 excretion was observed together with an increase of rT3 excretion and of T4/T3 and rT3/T3 ratio between 9 and 11 h after a single injection of 0.75, 1.5 and 3.0 mg kg-1 DEX, the differences being in most cases significant as compared to controls. In the same experiments a dose related increase of excretion of 3,3'-diiodothyronine (3,3'-T2) and 3,5-diiodothyronine (3,5-T2) was found, while the excretion of 3',5'-diiodothyronine (3',5'-T2) decreased with dose of DEX. Similar results were observed even after the administration of 1.5 and 3.0 mg kg-1 DEX for 5 days. In addition, the level of rT3 in serum was significantly increased at 9 h after a single dose of 3.0 mg kg-1 DEX and after 5 days administration of 1.5 and 3.0 mg kg-1 DEX. The data support a previous view that the changes in biliary excretion of iodothyronines are closely related to deiodinating metabolism of T4 in the liver and are expressed earlier and more remarkably than these in their plasma level.

Animals↗

Analysis of surgical treatment for carcinoma situated in the cervical esophagus.

Between 1960 and 1982, 64 operations were performed for carcinoma of the cervical esophagus including the cervicothoracic segment. Of these 64 patients, 12 underwent cervical esophagectomy and 52 had total esophagectomy. Visceral replacements were employed in 61 patients by the skin flap (3 cases), the intestine pedicle graft (10 cases), and the stomach tube (48 cases). The operative mortality rate associated with cervical esophagectomy was 33.3% and that with total esophagectomy was 5.8%. The 5-year survival rate for patients who had cervical esophagectomy was 16.7% and that for patients with total esophagectomy was 30.0%. A direct comparison of the surgical results of cervical and total esophagectomy should not be discussed at the same level, because the cervical esophagectomy operations were performed before 1967. However, the discussion of histologic examinations for removed lymph nodes and resected esophagus will be of value. Analysis of these histologic findings was performed aggressively and we obtained the following results. Total esophagectomy completely removes the intramural invasive cancer cells in the anal stump of resected esophagus, and then dissection of the intrathoracic, including cervical, lymph nodes is possible. In addition to these merits, stomach replacement for esophageal reconstruction has the advantage of the only anastomosis (pharyngogastrostomy) as compared with the other visceral replacements. For these reasons it may be recommended that total esophagectomy with stomach replacement is adequate for the treatment of the advanced carcinoma situated in the cervical esophagus.

Adult↗

[Quantitative and qualitative analysis on the lymph node metastasis of carcinoma of the esophagus].

The results of quantitative and qualitative analysis of lymph nodes dissected during resection of the esophageal carcinoma are as follows. The rate of positive lymph nodes per number of cases was 51.3% (120/234 patients). The rate of positive lymph nodes per number of nodes examined was 15.9% (406/2548 nodes). The correlation between the n-number and the average number of positive lymph nodes for a patient is shown. In the cases in which tumors disappeared from the adventitia of the esophagus by pre-operative radiation, the rate of positive lymph nodes per number of cases and of nodes examined were less than other cases. The metastases in the distant lymph nodes were much less. In the cases in which tumors reached the surgical margin on the adventitia side of the esophagus, the rate of positive lymph nodes per number of cases and of nodes examined were more than others. The metastases in the distant lymph nodes were much more. The pre-operative radiation had no influence on the spreading of the lymph node metastasis. The n-number, the number of positive lymph nodes and of dissected nodes, and the rate of them for each patient had great influence on long-term results.

Adult↗

[Lymph node involvement in carcinoma of the esophagus--re-evaluation for the grouping of lymph nodes].

Based on the analysis of the lymph nodes dissected during resection of 234 esophageal carcinomas and the long-term results of the patient, lymph nodes of the esophagus were grouped into 3 categories, n1, n2 and n3. The lymph nodes of n1 group were frequently involved in metastases and the long-term results of the patients with these lymph nodes metastases were excellent. The n2 lymph nodes were frequently involved in metastases but the survival rates of the patients were low. The n3 lymph nodes were rarely involved and the prognoses of the patients were poor. In comparison with the classification of lymph nodes for surgical dissection as described by the Japanese Society for Esophageal Disease, some problems in this category are discussed. However, this category was revealed to have close relation to the long-term results of the patients with carcinoma of the esophagus and was considered to be of clinical use.

Adult↗

Preferential stimulation of the in vivo synthesis of a protein by polyamines in Escherichia coli: purification and properties of the specific protein.

The possibility that polyamines can stimulate the synthesis of special kinds of proteins has been examined by using a polyamine-requiring mutant of Escherichia coli. It was found that the synthesis of some proteins, particularly one with a molecular weight (Mr) of 62K, was significantly stimulated following polyamine supplementation of polyamine-starved cells. The preferential stimulation of the synthesis of this polyamine-induced protein of Mr 62K (PI protein) was followed by the stimulation of overall protein synthesis by polyamines. PI protein was purified to homogeneity and some of its properties were examined. From studies on the effect of PI protein on MS2 RNA directed protein synthesis, it was shown that this protein stimulated the synthesis of RNA replicase by 2.2-fold in the presence of 1 mM spermidine.

Bacterial Proteins↗

Leiomyosarcoma of the breast--a case report and an electron microscopic study.

We treated a fifty six-year-old woman with leiomyosarcoma of the breast. Light microscopy showed typical findings of leiomyosarcoma and electron microscopy confirmed the smooth muscle origin of the tumor. The patient is well without evidence of metastases or local recurrence of the tumor fifty-five months after radical mastectomy.

Basement Membrane↗

Role of the hypothalamic paraventricular nucleus in the secretion of thyrotropin under adrenergic and cold-stimulated conditions in the rat.

To investigate the role of central noradrenergic systems in the regulation of TSH secretion, clonidine (an alpha 2-adrenergic agonist) and an electrolytic procedure were used. The administration of a small dose (50 micrograms/kg, iv) of clonidine induced a significant rise in immunoreactive TSH levels in the plasma with a short time lag in unanesthetized, unrestrained rats. The TSH-stimulating effect of clonidine was significantly reduced by passive immunization with rabbit antiserum to TRH. In rats with midbrain transection, the plasma TSH elevation in response to clonidine did not differ from that of sham-operated controls, whereas bilateral lesions in the paraventricular nucleus (PVN) markedly diminished the TSH secretory response. In contrast, the placement of electrolytic lesions in the dorsal raphe nucleus caused a significant increase in the basal TSH concentrations within 3 days, and magnified the TSH response to alpha 2-adrenergic stimulation. Acute exposure to cold (2-3 C) induced a prompt increase in the plasma TSH concentrations in normal rats. Bilateral lesions in the medial preoptic/anterior hypothalamus had no effect on the TSH response to cold exposure. In rats with the dorsal raphe nucleus lesions no significant effect was observed on the responsiveness to cold. In rats bearing PVN lesions, however, plasma TSH levels decreased significantly compared with sham-operated controls within 4 days, and also remained at basal levels during the whole period of cold exposure. The results of the present study provide evidence supporting the hypothesis that the PVN is essential for the process of TRH-TSH secretion, which is accelerated under cold-stimulated conditions, presumably via the central noradrenergic system(s).

Animals↗