Biomedical subjects

K Yoshimoto

Publications and source records attributed to K Yoshimoto.

At least 163 records · Page 9Linked to original sources

PubMed1993

Relatively good prognosis of multiple endocrine neoplasia type 2B in Japanese: review of cases in Japan and analysis of genetic changes in tumors.

Since 1968, a total of 23 patients with multiple endocrine neoplasia type 2B (MEN 2B) have been identified in Japan. The mean age at diagnosis was 20.3 years (range, 6 to 39 years). All patients had neuromas and bumpy lips. All patients underwent thyroidectomy for medullary thyroid carcinoma (MTC). Ten of 23 patients had pheochromocytomas. One patient died of cerebral bleeding at the age of 43, 2 patients died of MTC at the age of 35 and 12. Five-, 10-, and 15-year survival rates were 100%, 92%, and 88%, respectively. The clinical course of MTC in MEN 2B in Japanese is not so aggressive when compared with about a 50% 10-year survival reported for Caucasians. Genetic analysis of 4 MTC and 1 pheochromocytoma from 4 patients with MEN 2B revealed no common changes in regard to loss of heterozygosity on 21 chromosomes or point mutations of the ras, Gs alpha, or p53 genes.

Adolescent↗

PubMed1993

Chronic tonsillitis and IgA nephropathy. Clinical study of patients with and without tonsillectomy.

To determine whether tonsillectomy is a significantly effective treatment in the clinical course of IgA nephropathy, we did a comparative study on 50 patients with IgA nephropathy and chronic tonsillitis. We divided the patients into two groups: 35 patients with and 15 without tonsillectomy (control group). With or without tonsillectomy, renal function became progressively worse during the follow-up period in most patients with a serum creatinine level of > 1.4 mg/dl at the time of renal biopsy. In patients with a serum creatinine level of < or = 1.4 mg/dl, renal function remained normal in all subjects with tonsillectomy, but worsened in 3 patients out of 13 without tonsillectomy. Improvement in proteinuria/hematuria was found more frequently in the tonsillectomized group than in the controls. Furthermore, the serum IgA level was significantly reduced after tonsillectomy, especially in patients showing improvement. From these results we conclude that tonsillectomy was effective for patients with IgA nephropathy complicated by tonsillitis when the operation was performed before deterioration of renal function.

Adult↗

PubMed1993

CNS mechanisms of alcohol self-administration.

Neurochemical and neuropharmacological studies were undertaken to examine the possible involvement of the ventral tegmental area (VTA) dopamine (DA) system and the dorsal raphe nucleus (DRN) serotonin (5-HT) system in regulating oral alcohol self-administration. In vivo microdialysis studies demonstrated that either i.p. ethanol administration (1.0-2.0 g/kg) or local perfusion with ethanol (100 mM) could enhance the extracellular concentrations of both DA and 5-HT in the nucleus accumbens (ACB). Furthermore, the effects of local perfusion with ethanol on DA release in the ACB could be blocked by co-perfusion with a 5-HT3 antagonist. In the selectively-bred alcohol preferring P line of rats, there appears to be abnormal 5-HT and/or DA systems in certain limbic structures, i.e., ACB, olfactory tubercles (OTU) and medial prefrontal cortex (MPF). This is indicated by (a) lower contents of DA and 5-HT; (b) fewer 5-HT immunostained fibers; (c) lower densities of 5-HT1B, 5-HT2 and D2 receptors; and (d) higher densities of 5-HT1A receptors in the CNS of P rats compared to the alcohol-nonpreferring NP line of rats. Neuropharmacological studies demonstrated that local microinfusion of the D2 antagonist, sulpiride, or, at low doses, the DA releaser, d-amphetamine, could increase alcohol drinking by P rats. Intracranial self-administration (ICSA) studies showed that the P line of rats, but not the NP line, will self-administer 50-150 mg% ethanol directly into the VTA. Overall, these results suggest an innate abnormal functioning of the VTA DA and DRN 5-HT systems may be key factors facilitating the rewarding actions of ethanol in the CNS of P rats.

Alcohol Drinking↗

PubMed1993

A drug-induced turbid peritoneal dialysate in five patients treated with continuous ambulatory peritoneal dialysis.

Turbid peritoneal dialysate is one of the heralding signs for infective peritonitis in patients treated with continuous ambulatory peritoneal dialysis (CAPD). Peritoneal dialysate drained from 5 out of 8 patients undergoing CAPD became turbid within 24 h after the administration of a new dihydropyridine type of calcium channel blocker, manidipine hydrochloride (10 or 20 mg/day). Although the dialysate was visually indistinguishable from that observed during infective peritonitis, no clinical manifestations being suggestive of infective peritonitis were observed. The turbid dialysate contained normal leukocyte counts (< 10 mm-3), and the bacterial (aerobic and anaerobic) and fungal cultures of the dialysate failed to produce organisms. Cytology of the dialysate showed no malignant cells. Biochemical analysis of the dialysate revealed that the fluid contained an elevated triglyceride concentration [range: 12 to 32 mg/100 ml (0.14 to 0.37 mmol/l], while the clear dialysate obtained from 9 uncomplicated CAPD-patients contained less than the detection limit of the assay for triglyceride [< 5 mg/100 ml (0.06 mmol/l)]. All patients were found to consume a nutritionally balanced diet consisting of 1800 to 2400 Kcal/day during the manidipine therapy. No appreciable change was observed in the mean (+/- SD) fasting serum triglyceride concentrations determined before and 24 h after the withdrawal of the manidipine therapy (194 +/- 84 and 186 +/- 106 mg/100 ml, respectively) in the 5 CAPD-patients with turbid peritoneal dialysate. Within 24 h after the withdrawal of the manidipine therapy the peritoneal dialysate became clear spontaneously and the triglyceride concentration in the dialysate was normalized in all of them.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

[Nephrotic syndrome with microcellular projections into the thickened basement membrane].

A 47 year-old patient with an 8-year history of proteinuria was admitted to our hospital in 1989. His laboratory data were compatible with nephrotic syndrome: total serum protein 5.9g/dl (albumin 3.0g/dl), total serum cholesterol 280mg/dl and total urinary protein excretion 5.0g/day. Renal biopsy specimens contained 27 glomeruli associated with sclerosis and collapse of loops under light microscopical examination. In addition, mesangial proliferation and thickening of the basement membrane were visualized. With immunofluorescent study granular IgG deposits were detected in the peripheral region of the glomeruli. Staining for IgA, IgM, C3, Clq, light chain and Congo-red were all negative. On electron microscopy, microtubules apparently resembling cellular projections appeared to thicken the basement membrane. We are tempted to conclude that the current case is an atypical glomerulopathy accompanied by a glomerular microtubular-like structure.

Basement Membrane↗

PubMed1993

[Two case reports of refractory heart failure treated by continuous ambulatory peritoneal dialysis].

In this report, we present 2 cases of severe congestive heart failure and mild renal insufficiency in patients who underwent continuous ambulatory peritoneal dialysis (CAPD) after stabilization using the extracorporeal ultrafiltration method (ECUM). Long-term good control of congestive heart failure was achieved following the institution of CAPD. Case 1, a 58-year-old woman with rheumatic arthritis and diabetes mellitus had anteroseptal myocardial infarction at the age of 52. And case 2, a 68-year-old man, who underwent coronary artery bypass surgery at the age of 66 and had extensive anterior infarction after the operation. They were admitted to the hospital with dyspnea due to congestive heart failure. In both cases, systolic cardiac function was severely impaired and mild renal insufficiency was present at the time of hospitalization. After admission, symptomatic relief was not obtained by conventional therapies and symptoms of congestive heart failure worsened until the patients suffered from severe respiratory distress even at rest. ECUM was then instituted to remove excess fluid and clinical improvement was achieved. After the initiation of ECUM, responsiveness to diuretics was not restored, and the procedure was necessary every day or every other day for the prevention of symptoms due to fluid overload. About 20 days after the initiation of ECUM, CAPD was begun for the long-term control of congestive heart failure and renal failure, and for the purpose of hospital discharge. Good control of heart failure was achieved after the initiation of CAPD.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1993

[Antimicrobial susceptibility patterns of the Proteeae in Japan, 1989].

We discussed the antimicrobial susceptibilities of Proteeae isolated in Japan, 1989. Eight hundred six clinical isolates were collected from 47 hospitals. These were comprised of 431 strains of Proteus mirabilis, 155 Proteus vulgaris, 154 Morganella morganii, 44 Providencia rettgeri and 22 Providencia stuartii. Antibiotics tested in this study were 2 penicillins, 5 cephems, 1 carbapenem and 2 aminoglycosides. The MIC's were determined using the standard method of the Japan Society of Chemotherapy. Susceptibilities of the above strains to these antibiotics are described below; 1. Latamoxef, ceftizoxime and imipenem had excellent activities with no evident differences among the species of Proteeae. 2. Ampicillin and cefazolin were less active against Indol-positive Proteeae. 3. Piperacillin and cefmetazole were also strongly active drugs against P. mirabilis, P. vulgaris and P. stuartii, and cefotiam against P. mirabilis and P. stuartii. 4. Gentamicin and netilmicin showed excellent activities against M. morganii.

Anti-Bacterial Agents↗

PubMed1993

Monitoring of ethanol levels in the rat nucleus accumbens by brain microdialysis.

Brain microdialysis was used to measure nucleus accumbens (NAC) ethanol (EtOH) over several hours after intraperitoneal (i.p.) injection of EtOH. Levels of EtOH in NAC perfusates were assayed by gas chromatography. Peak EtOH levels were observed 40 min after the injection and the three doses of EtOH, 0.5, 1.0, and 2.0 g/kg, resulted in peak perfusate levels of 5 mM, 18 mM, and 38 mM, respectively. Measurement of regional brain EtOH levels may prove useful for studying the relationship between patterns of alcohol consumption and the action of EtOH in the central nervous system.

Alcohol Drinking↗

PubMed1992

Two new nonsense mutations in type Ia antithrombin III deficiency at Leu 140 and Arg 197.

Using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and DNA sequencing, the molecular basis of hereditary type Ia antithrombin III (AT III) deficiency was disclosed in two families. One mutation was a change from T to A in the codon of TTA for Leu 140 forming a stop codon of TAA, which was confirmed by mutated primer-mediated PCR-HindIII digestion. The application of this method demonstrated that all four affected members had the mutant allele in a heterozygous state and that none of unaffected subjects had this mutation. Another mutation in the second family was a change from C to T in the codon of CGA for Arg 197 also forming a stop codon of TGA, which was confirmed by PCR-HaeIII digestion. Based on these, it was concluded that the two new nonsense mutations in the AT III gene in a heterozygous state are the molecular basis of hereditary type Ia AT III deficiency.

Antithrombin III↗

PubMed1992

Role of p53 mutations in endocrine tumorigenesis: mutation detection by polymerase chain reaction-single strand conformation polymorphism.

To elucidate the molecular basis for endocrine tumorigenesis, p53 mutations in human endocrine tumors were analyzed by using polymerase chain reaction-single strand conformation polymorphism. Exons 5 through 10 of the p53 gene were studied in genomic DNAs from 134 primary endocrine tumors and 6 human endocrine cancer-derived cell lines. Mutations were detected and identified in 4 endocrine tumors, including one parathyroid adenoma and three thyroid carcinoma cell lines. The sites of these mutations were in exons 5 (codon 151 and 152) and 7 (codon 248 and 255). In all of three tumor cell lines, but not in a parathyroid adenoma, the normal allele encoding the p53 gene was lost. However, p53 mutations were not found in any other endocrine tumors or cell lines. Based upon these results, we concluded that the p53 gene may play a role in the tumorigenesis of a limited number of parathyroid adenoma and thyroid cancers, and that the p53 mutation with an allelic loss of the p53 gene is an important factor in malignant tumorigenesis of the thyroid gland.

Base Sequence↗

PubMed1992

Highly polymorphic region of the human prothrombin (F2) gene.

We have found a highly polymorphic region in the human prothrombin gene. Our sequence differed from that previously reported at as many as 6 positions in a 225-bp stretch spanning exon 6 and its flanking regions; four of these positions were related to endonuclease restriction sites for AluI, HpaII(MspI), MboII, and NcoI. AluI and HpaII digested all alleles of the Japanese tested. MboII and NcoI restriction fragment length polymorphisms are highly heterozygous and not in linkage disequilibrium; they thus serve as good human DNA markers.

Amino Acid Sequence↗

PubMed1992

Detection of a new polymorphism of the human prothrombin (F2) gene by combination of PASA and mutated primer-mediated PCR-RFLP.

A new polymorphism of the human prothrombin (F2) gene was detected by a combination of polymerase chain reaction (PCR) amplification of specific alleles (PASA) and mutated primer-mediated PCR restriction fragment length polymorphism (PCR-RFLP). The method is simple and useful for detecting polymorphisms and mutations. The new polymorphism of C1 and C2 examined by this method is highly heterozygous and serves as a good human DNA marker.

Base Sequence↗

PubMed1992

Regulation of nucleus accumbens dopamine release by the dorsal raphe nucleus in the rat.

The effects of microinfusing L-glutamate, serotonin (5-HT), (+-)-8-hydroxy-2-(di-N-propylamino) tetralin (8-OH DPAT; a 5-HT1A agonist), and muscimol (a GABAA agonist) into the dorsal raphe nucleus on the extracellular levels of 5-HT, dopamine (DA) and their metabolites in the nucleus accumbens were studied in unanesthetized, freely moving, adult male Wistar rats, using the technique of microdialysis coupled with small-bore HPLC. Administration of 0.75 micrograms L-glutamate produced a 25-50% increase (P less than 0.05) in the extracellular levels of both 5-HT and DA. On the other hand, infusion of 8-OH DPAT and, to a lesser extent, 5-HT produced a significant (P less than 0.05) decrease in the extracellular levels of both 5-HT and DA. Muscimol (0.25 or 0.50 microgram) had little effect on the extracellular concentrations of 5-HT or DA following its administration. In general, the extracellular levels of the major metabolites of 5-HT and DA in the nucleus accumbens were not altered by microinfusion of any of the agents. The data indicate that (a) the 5-HT neurons projecting to the nucleus accumbens from the dorsal raphe nucleus can be activated by excitatory amino acid receptors and inhibited by stimulation of 5-HT1A autoreceptors, and (b) the dorsal raphe nucleus 5-HT neuronal system may regulate the ventral tegmental area DA projection to the nucleus accumbens.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed1992

ras mutations in endocrine tumors: mutation detection by polymerase chain reaction-single strand conformation polymorphism.

To elucidate the molecular basis for endocrine tumorigenesis, ras mutations in human endocrine tumors were analyzed using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis. Mutations of the H-, K-, N-ras genes were examined in genomic DNAs from 169 successfully amplified primary endocrine tumors out of 189 samples. Four out of 24 thyroid follicular adenomas analyzed contained mutated N-ras codon 61, and one contained the mutated H-ras codon 61. One of the 19 pheochromocytomas revealed mutation of the H-ras codon 13. No mutations of the ras gene were detected in pituitary adenomas, parathyroid tumors, thyroid cancers, endocrine pancreatic tumors, and adrenocortical tumors. Based on these findings we conclude that activation of the ras gene may play a role in the tumorigenesis of a limited number of thyroid follicular adenomas and pheochromocytomas, and that mutation of the ras gene is not frequent in other human endocrine tumors.

Adult↗

PubMed1992

Ethanol enhances the release of dopamine and serotonin in the nucleus accumbens of HAD and LAD lines of rats.

The effects of intraperitoneal administration of ethanol, 0.5, 1.0, and 2.0 g/kg body weight, on the extracellular concentrations of dopamine (DA), serotonin (5-HT), and their major metabolites were studied in the nucleus accumbens (ACC) of alcohol-naive, selectively bred high-alcohol-drinking (HAD) and low-alcohol-drinking (LAD) lines of rats using the technique of microdialysis. In both lines, the extracellular levels of DA were increased following the injection of 1.0 and 2.0 g of ethanol/kg body weight while only the 2.0-g/kg dose elevated the concentration of 5-HT. None of the ethanol doses altered the extracellular levels of the major metabolites of DA and 5-HT. Dose-response curves for DA and 5-HT release indicated no marked difference in the sensitivity to ethanol between the lines. Local perfusion with 60 mM K+ through the microdialysis probe markedly enhanced the release of DA and 5-HT in the ACC of both lines; there was a small difference between the lines in the amounts of DA, but not 5-HT, released by K(+)-stimulation. Overall, the results indicate that (1) the ACC DA system is more sensitive than the ACC 5-HT system to intraperitoneal ethanol administration in both lines and (2) there is no evidence for a relationship between alcohol preference and sensitivity of the ACC DA and 5-HT systems to acute intraperitoneal ethanol administration.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1992

Unique region of the minor capsid protein of human parvovirus B19 is exposed on the virion surface.

Capsids of the B19 parvovirus are composed of major (VP2; 58 kD) and minor (VP1; 83 kD) structural proteins. These proteins are identical except for a unique 226 amino acid region at the amino terminus of VP1. Previous immunization studies with recombinant empty capsids have demonstrated that the presence of VP1 was required to elicit virus-neutralizing antibody activity. However, to date, neutralizing epitopes have been identified only on VP2. Crystallographic studies of a related parvovirus (canine parvovirus) suggested the unique amino-terminal portion of VP1 assumed an internal position within the viral capsid. To determine the position of VP1 in both empty capsids and virions, we expressed a fusion protein containing the unique region of VP1. Antisera raised to this protein recognized recombinant empty capsids containing VP1 and VP2, but not those containing VP2 alone, in an enzyme-linked immunosorbent assay. The antisera immunoprecipitated both recombinant empty capsids and human plasma-derived virions, and agglutinated the latter as shown by immune electron microscopy. The sera contained potent neutralizing activity for virus infectivity in vitro. These data indicate that a portion of the amino terminus of VP1 is located on the virion surface, and that this region contains intrinsic neutralizing determinants. The external location of the VP1-specific tail may provide a site for engineered heterologous epitope presentation in novel recombinant vaccines.

Animals↗

PubMed1992

A kindred of multiple endocrine neoplasia type 2B.

We describe familial cases of multiple endocrine neoplasia (MEN) 2B: A 48-year-old man is the proband. He had pheochromocytoma, medullary thyroid carcinomas (MTCs), parathyroid hyperplasia, mucosal neuromas, eversion of eyelids and Marfanoid appearance, and then underwent adrenalectomy and total thyroidectomy. Family screening revealed that his two daughters (10 and 8 years old) had mucosal neuromas and increased serum calcitonin (CT). Both of them had MTCs but no pheochromocytoma, and their MTCs were surgically removed. The father and his children have been in favorable condition since the operations. Southern blot analysis with 33 polymorphic DNA probes was done in MTCs obtained from two daughters. An RBP3 (10q11.2) locus linked to a predisposing gene on chromosome 10 was uninformative in either patient because of constitutional homozygosity. Loss of heterozygosity at the MYCL1 locus on chromosome 1p32 was observed in MTC from the younger sister, but no loss of heterozygosity was recognized in other loci examined. Deletion of the 1p32 locus may play a role in the development of MEN 2B.

Adrenal Gland Neoplasms↗

PubMed1992

The level of serum granulocyte colony-stimulating factor in cancer patients with leukocytosis.

The level of serum granulocyte colony-stimulating factor (G-CSF) obtained from patients with leukocytosis (greater than 10,000/microliters) between May 1989 and April 1991 was measured by enzyme immunoassay. Studied were 18 patients with malignant neoplasms (median age, 64 years) and 14 patients with hematologic disease (median age, 59 years). Increased serum G-CSF values ranging from 70 to 374 pg/ml were noted in 7 of 15 lung cancer cases, a case of malignant thymoma and a blastic crisis of chronic myelogenous leukemia. The rest of the cases showed a normal value (less than 60 pg/ml). There was no correlation between the neutrophil count and G-CSF level. In lung cancer cases with high G-CSF values, neither a characteristic histologic type nor common elevation of tumor markers could be seen. The neutrophil alkaline phosphatase score was significantly increased and hypercalcemia was presented in high G-CSF cases. G-CSF may contribute at least in part to unknown leukocytosis observed in malignant neoplasms, especially in lung cancer.

Adult↗