Search PubMed⌕ Search

Biomedical subjects

K Yoshimoto

Publications and source records attributed to K Yoshimoto.

At least 217 records · Page 12Linked to original sources
PubMed1988

Ectopic growth hormone-releasing hormone (GHRH) syndrome in a case with multiple endocrine neoplasia type I.

A 36-yr-old man with multiple endocrine neoplasia (MEN) type I had an ectopic growth hormone-releasing hormone (GHRH) syndrome due to a GHRH-secreting pancreatic tumor. The immunoreactive (IR)-GHRH concentration in his plasma ranged from 161 to 400 pg/ml (299 +/- 61 pg/ml, mean +/- SD; normal, 10.4 +/- 4.1 pg/ml), and a significant correlation was found between his plasma IR-GHRH and GH (r = 0.622, p less than 0.02). After removal of the pancreatic tumor, the high plasma GH concentration returned to nearly the normal range (42.2 +/- 31.3 to 9.6 +/- 3.8 ng/ml). These changes paralleled the normalization of his plasma IR-GHRH (16.1 +/- 3.8 pg/ml) and some of his symptoms related to acromegaly improved. However, plasma GH (7.7 +/- 1.3 ng/ml) and IGF-I (591 +/- 22 ng/ml) concentrations were high at 12 months after surgery, suggesting adenomatous changes in the pituitary somatotrophs. Before surgery, exogenous GHRH induced a marked increase in plasma GH, and somatostatin and its agonist (SMS201-995) completely suppressed GH secretion, but not IR-GHRH release. No pulsatile secretion of either IR-GHRH or GH was observed during sleep. An apparent increase in the plasma GH concentration was observed in response to administration of TRH, glucose, arginine or insulin, while plasma IR-GHRH did not show any fluctuation. However, these responses of plasma GH were reduced or no longer observed one month and one year after surgery. These results indicate that 1) a moderate increase in circulating GHRH due to ectopic secretion from a pancreatic tumor stimulated GH secretion resulting in acromegaly, and evoked GH responses to various provocative tests indistinguishable from those in patients with classical acromegaly, and 2) the ectopic secretion of GHRH may play an etiological role in the pituitary lesion of this patient with MEN type I.

Acromegaly↗
PubMed1988

[A nationwide study of the antimicrobial susceptibility of clinical isolates of Staphylococcus aureus in Japan].

We described antimicrobial susceptibilities of clinical isolates of Staphylococcus aureus in 1985 and also a 6-year survey of changing patterns of their susceptibilities to ampicillin (ABPC), cefazolin (CEZ), cefmetazole (CMZ) and gentamicin (GM) from 1980 to 1985 in 103 hospitals. The MICs were determined by the standard method of the Japan Society of Chemotherapy. Among 2,891 isolates in 1985, ratios of resistant strains to ABPC and GM were 24% and 29%, respectively, and those to CEZ and CMZ were 8% and 3%, respectively. Gradual increases in numbers of resistant strains to ABPC, CEZ and CMZ were observed until 1984 but a trend for decreases in numbers of resistant strains to the above 3 antibiotics was observed in 1985. A continuous rise in numbers of resistant strains to GM until 1985 was noted. Isolates from clinical materials such as pus, bile, and urine showed higher incidences of resistance to ABPC and GM than those from sputum, secreta and throat swab. Rates of resistant strains to CEZ were the highest in isolates from bile, pus, sputum and urine. Rates of resistant strains to CMZ were the highest in isolates from bile, and decreased in isolates from sputum, urine and pus in this order. Rates of resistant isolates from inpatients to the 4 antibiotics tested were greater than those from outpatients.

Anti-Bacterial Agents↗
PubMed1987

Reexamination of the relationship between alcohol preference and brain monoamines in inbred strains of mice including senescence-accelerated mice.

The relationship between voluntary alcohol consumption and brain monoamine levels was studied in the inbred strains of C57BL/6N, C57BL/6J, A/J, BALB/cA, CBA/N, C3H/He and DBA/2cr mice; the congeneric mouse strain, B10.Br/Sg, and the senescence accelerated mouse (SAM P1, SAM P2). The C57BL strains exhibited a high alcohol preference whereas the other strains exhibited a low alcohol preference. A clear positive relationship was found between alcohol intake (g/kg/day) and brain norepinephrine level (r = 0.683, p less than 0.05), and a clear negative relationship between alcohol intake and brain serotonin level (r = -0.628, p less than 0.05). The content of brain dopamine was not clearly correlated with alcohol intake (r = -0.206, p greater than 0.05). These findings suggest that in mice voluntary alcohol preference is influenced by brain norepinephrine and serotonin levels genetically.

Alcohol Drinking↗
PubMed1987

Pharmacological effects of nicergoline and its metabolites, decomposition products and impurities in animals.

The main pharmacological effects and acute toxicity of nicergoline (NCG, ester type), its 5 metabolites [1-DN (ester type), 1-MMDL, 1-OHMMDL, MDL (ergoline-alcohol type) and 5-BNA (bromonicotinic acid)], 2 decomposition products (1-MMDL and 5-BNA) and 2 impurities [1-DN and 5-CN (ester type)] were studied in animals. In mice, the acute intraperitoneal toxicity of 1-MMDL, 1-OHMMDL and 5-CN was similar to that of NCG (LD50 197.6 mg/kg). The toxicity of 1-DN, MDL and 5-BNA was approximately 2-fold, 2- fold and one half of NCG, respectively. These substances caused no delayed death. In protective effects against KCN- and adrenaline-induced death in mice when given i.p., 1-DN and 1-MMDL were less potent than NCG, and 1-CN was similar in potency to NCG. In competitive inhibitory effects on phenylephrine-induced contraction of isolated guinea pig vas deferens, 1-DN was less potent, 1-MMDL was much less potent and 5-CN was more potent than NCG. In an inhibitory effect on collagen-induced platelet aggregation in vitro using rat platelet-rich plasma, 1-DN and 5-CN were similar in activity to NCG and 1-MMDL was less active than NCG. On the other hand, 1-OHMMDL, MDL and 5-BNA were inactive in these experiments. In experiments on gross behavior, motor function and barbital anesthesia using mice, when given i.p., 5-CN as well as NCG moderately induced depressive effects on the central nervous systems. 1-DN and 1-MMDL were less potent in the effects than NCG. In anesthetized rats, when given i.v., 1-DN and 5-CN dose-dependently caused lowering effects on blood pressure similar to NCG. 1-MMDL and 1-OHMMDL were less potent than NCG in the lowering effect. 1-DN and 5-CN moderately decreased the contractile force in the isolated guinea pig heart when given i.a. 5-CN alone decreased urine volume in rats when given i.p. and all the substances had no effect on the intestinal transit ability in mice when given i.p. These results suggest that the pharmacological effects of NCG are due to NCG per se and in part to its metabolites. As regards structure-activity relationships, NCG, 1-DN and 5-CN with an ester linkage were found to be more potent in pharmacological activities than ergoline-alcohol compounds.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1986

[Pharmacological study of nicergoline. (II). Protective effect on ischemic brain damages in animals].

Effects of nicergoline on ischemic brain damages induced by bilateral carotid arterial ligation (BCAL) in ICR-strain mice and mongolian gerbils and lipid peroxide formation (LPOF) in normal brain homogenate of rats were compared with those of dihydroergotoxine (DHE). In mice, nicergoline (16 mg/kg, i.p.) significantly reduced the cumulative mortality rate after BCAL (from 80-83% in the control to 50-55%). In gerbils, nicergoline (32 mg/kg, i.p.) significantly prolonged the mean onset time of ischemic seizure following recirculation after the 30-min BCAL (from 45.8 min in the control to 94.9 min). DHE also showed protective effects in these animals. In the ischemic brain of mice, marked decreases of creatine-P, ATP, glucose and glycogen; a remarkable increase of lactate; and elevation of L/P ratio were observed 1 to 10 min after BCAL. Nicergoline (16 mg/kg, i.p.) slightly prevented these decreases and significantly suppressed the increase of lactate and the elevation of L/P ratio 2 min after BCAL. The inhibitory action of nicergoline (20-100 microM) on LPOF is more potent than those of alpha-tocopherol and DHE. These results suggest that nicergoline may have protective effects against ischemic brain damages due to its ameliorating action on cerebral energy metabolism and partially due to its inhibitory action of LPOF.

Animals↗
PubMed1986

[Pharmacological study of nicergoline. (I): Protective effect against anoxic brain damages in animals].

The protective effects of nicergoline (NCG) against anoxic brain damages in animals were compared with those of dihydroergotoxine (DHE) and phentolamine (PTA). NCG (16 mg/kg, i.p.) prolonged the survival time of mice under hypobaric hypoxia, but DHE and PTA shortened the time. NCG (1-16 mg/kg, i.p. and 16-64 mg/kg, p.o.), like DHE, dose-dependently prolonged the survival time of mice after a lethal dose of KCN (3 mg/kg, i.v.), but PTA did not. NCG (8-128 micrograms/kg, i.v.), like DHE, dose-dependently protected against disappearance of EEG of rats in histotoxic anoxia induced by a sublethal dose of KCN (1.5 mg/kg, i.v.), but PTA did not. Its protective effect was 10 times or more stronger than that of DHE. NCG (1-16 mg/kg, i.p.) dose-dependently promoted recovery from behavioral disorders and disturbance of cerebral energy metabolism of mice in histotoxic anoxia induced by a sublethal dose of KCN (1.8 mg/kg, i.v.). NCG (100 microM), like DHE, showed antagonistic action against inhibition of cerebral cytochrome oxidase activity by KCN, but PTA did not. The ED50 values of NCG, DHE and PTA for the protective effect against adrenaline-induced death in mice were 1.18, 0.27 and 0.35 mg/kg (i.p.), respectively. 7) These results suggest that NCG may show protective effects against the anoxic brain damages due to its ameliorating action on cerebral energy metabolism, mainly contributed by an activation of cerebral cytochrome oxidase, without relation to its alpha-blocking action.

Animals↗
PubMed1986

[Pharmacological study of nicergoline. (III). Effects on cerebral and peripheral circulation in animals].

Effects of nicergoline on the cerebral and peripheral circulation were compared with those of dihydroergotoxine (DHE) and papaverine (PAP) in anesthetized and/or immobilized cats. The i.a. injection of nicergoline (0.032 approximately 32 micrograms/kg), similarly to PAP, caused dose-dependent increases in intramaxillary artery (as the human intracarotid artery) blood flow (IMBF) and femoral artery blood flow, but the injection of DHE had no effect on these blood flows. The i.v. injection of nicergoline (32 approximately 128 micrograms/kg) caused a dose-dependent fall in blood pressure (BP) and a transient slight decrease in cerebral vascular resistance, but did not affect IMBF, regional cerebral blood flow (r-CBF), intracranial pressure (ICP) and heart rate (HR). The i.v. injection of DHE produced a slight fall in BP and a marked long-lasting decrease in HR, without affecting other parameters. The i.v. injection of PAP (4 mg/kg) induced marked increases in IMBF, r-CBF, ICP and HR and caused a transient fall followed by a marked elevation in BP. The p.o. administration of nicergoline (0.06 approximately 4 mg/kg) caused a dose-dependent fall in BP and selective inhibition of pressure response to adrenaline (ID50: 0.25 mg/kg). The administration of DHE produced marked inhibition of pressure responses to both adrenaline and noradrenaline, accompanied with a slight fall in BP. Furthermore, the administration of nicergoline (3 approximately 100 mg/kg) induced a dose-dependent fall in BP in SHR. These results suggest that the cerebral and peripheral circulatory effects of nicergoline may be due to direct vasodilating action and alpha-blocking action in the animals.

Animals↗
PubMed1986

Increased expression of the c-myc gene without gene amplification in human lung cancer and colon cancer cell lines.

High levels of c-myc mRNA were observed in two human tumor cell lines, a giant cell carcinoma of the lung (C-Lu99) and a colon cancer (C1). The increased expression of c-myc in these cell lines, which was comparable with those in cell lines in which the c-myc gene is amplified, was not due to gene amplification. Run-on transcription revealed that the transcriptional rate of the c-myc gene was greatly increased in these cell lines.

Cell Line↗
PubMed1986

Rearrangement of the c-myc gene in two giant cell carcinomas of the lung.

The c-myc oncogene was found to be rearranged in a human cell line of giant cell carcinoma of the lung (C-Lu65) and in a human primary giant cell carcinoma of the lung (LuC38C). The rearrangements in C-Lu65 and LuC38C were in regions about 7.5 kb and 6 kb, respectively, upstream from the transcription initiation site. No rearrangement of the c-myc gene was observed in a non-cancerous portion (LuC38N) of the lung of the patient who carried LuC38C. These results suggest that rearrangement of the c-myc gene may play some role in tumorigenesis of giant cell carcinoma of the lung.

Carcinoma↗
PubMed1985

[Ectopic hormone production and gene expression in tumors].

Recent progress in research into ectopic hormone production and hormone gene expression in tumors is reviewed. Biochemical, immunochemical and morphological studies have shown that differentiation between "ectopic" and "eutopic" has become difficult and that the types of peptide hormones, neural peptides and growth factors produced, their molecular heterogeneities and ability of plural hormone production are greatly different in each tumor. Recently, the gene structures of many hormones and amino acid sequences of hormone precursors have been determined by genetic recombination techniques. However, the nature of hormone genes, the mechanism of gene expression and the processing mechanisms of hormone precursors in normal and tumor cells remain to be studied.

ACTH Syndrome, Ectopic↗