Biomedical subjects

Y Miyoshi

Publications and source records attributed to Y Miyoshi.

At least 163 records · Page 9Linked to original sources

PubMed1994

Combination therapy with transcatheter arterial embolization and percutaneous ethanol injection for advanced hepatocellular carcinoma.

The effectiveness of transcatheter arterial embolization (TAE) combined with percutaneous ethanol injection (PEI) was investigated in 18 patients with advanced hepatocellular carcinoma (HCC), and compared with 18 patients with HCC treated by TAE therapy alone. In both groups, patients had multiple lesions or a single lesion larger than 3 cm. The pretreatment characteristics of the patients in the two groups showed that serum bilirubin in the TAE-PEI group was significantly higher than that in the TAE-only group, but that the patients in the two groups were comparable in all other respects. The cumulative survival rate of the TAE-PEI group estimated by the Kaplan-Meier method was 100% for 10 months, 82% for 20 months, 53% for 30 months and 18% for 40 months, whereas that of the TAE-only group was 75% for 10 months, 50% for 20 months, 30% for 30 months and 30% for 40 months. The survival rate in the TAE-PEI group was significantly higher than that in the TAE group. Moreover, the survival rate of patients whose main tumor was 4 cm or larger, was significantly higher in the TAE-PEI group than that in the TAE-only group. The average survival period of these patients in the TAE-PEI group was five times as long as that in the TAE-only group. The survival rate of Child's B and C patients in the TAE-PEI group was significantly higher than that in the TAE-only group.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1993

The influence of donor age on cografting of adrenal medulla with pretransected peripheral nerve.

Pretransected peripheral nerve has been demonstrated to enhance the survival of cografted adrenal medullary chromaffin cells and the recovery of host dopaminergic (DA) systems in animal models of Parkinson's disease. In the present study, we examined the effect of donor age on survival of cografted chromaffin cells. Adrenal medulla and pretransected peripheral nerve from young (1-month-old) or aging (12-month-old) donors were cografted into the striatum of MPTP-treated young (2-month-old) C57/BL mice. Although chromaffin cell survivability was increased by cografting with pretransected peripheral nerve despite donor age, survivability of chromaffin cells from aging donors was less than that using young donors. Image analysis of striatal DA fibers and chemical analysis of striatal DA showed that cografting with pretransected peripheral nerve enhanced the recovery of striatal DA systems more prominently than adrenal grafting alone. However, this effect was less in mice receiving aging donor tissues compared with mice receiving young donor tissues.

Adrenal Medulla↗

PubMed1993

Enhanced recovery of the nigrostriatal dopaminergic system in MPTP-treated mice following intrastriatal injection of basic fibroblast growth factor in relation to aging.

Studies have suggested that the restorative effects of adrenal medullary chromaffin cell grafts in animal models of Parkinson's disease may be related to trophic factors contained within the chromaffin cells. Basic fibroblast growth factor (bFGF) is present in chromaffin cells and has been shown to exert trophic effects on dopaminergic neurons in vitro. Basic FGF was stereotaxically injected into the striatum of young (2-month-old) and aging (12-month-old) C57BL/6 mice which had been treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) 1 week earlier. MPTP treatment reduced tyrosine hydroxylase (TH)-immunoreactive (IR) fibers in the striatum and striatal dopamine (DA) concentration in both the young and older mice 5 weeks later. Computerized image analysis of striatal DA fibers in young mice treated with bFGF showed significant recovery of DA fibers up to 600 microns from the injection site 5 weeks after MPTP administration. Striatal DA fibers in older mice treated with bFGF showed significant recovery only up to 300 microns from the injection site, and the degree of recovery was very limited compared with young mice. HPLC analysis of DA concentration revealed that striatal DA in young mice recovered significantly when treated with bFGF, but no significant recovery was observed in older mice. It is concluded that bFGF enhances the recovery of striatal DA systems from MPTP toxicity both in young and in older mice, but that such benefits are very limited in older mice.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed1993

Detection of 12 germ-line mutations in the adenomatous polyposis coli gene by polymerase chain reaction.

BACKGROUND: The adenomatous polyposis coli (APC) gene at chromosome 5q21 that is responsible for familial adenomatous polyposis (FAP) was recently isolated, and germ-line mutations in a substantial number of FAP families were characterized. Based on this information, the authors attempted to develop a presymptomatic diagnosis test for members of families that carry FAP. METHODS: A rapid screening procedure using a polymerase chain reaction (PCR) method without radioisotopes, if necessary, coupled with digestion of restriction enzymes has been performed by detection of germ-line mutations that alter the size of DNA fragments or affect the recognition site of restriction enzymes in the APC locus. RESULTS: A rapid screening procedure to detect germ-line mutations at 12 loci that cause adenomatous polyposis was established. CONCLUSIONS: Using these 12 systems, presymptomatic diagnoses can be made with 100% accuracy within 24 hours. The procedures will be useful for counselling of members in some FAP families, which accounted for nearly 40% of the 95 FAP kindreds that have been detected by the germ-line mutations so far.

Adenomatous Polyposis Coli↗

PubMed1993

Parkinson-like symptoms as a manifestation of systemic lupus erythematosus.

A 42-year-old Japanese woman with systemic lupus erythematosus (SLE) developed Parkinsonian-like movements. Steroid pulse therapy was most effective and additional anti-Parkinsonian drugs were not required. Although psychosis, seizures and meningitis are common central nervous system (CNS) manifestations in SLE patients, Parkinsonian-like symptoms are extremely rare. The putative genesis and treatment of CNS lupus are discussed.

Adult↗

PubMed1993

Estimation of the protein content of thyroid hormone receptor alpha 1 and beta 1 in rat tissues by western blotting.

Recent studies of the expression of c-erbA/thyroid hormone receptor (TR) mRNAs have revealed a dissociation between T3-binding activity and the behavior of the mRNAs that code the functional TRs in some tissues. Compared with T3-binding activity, TR(alpha 1 + beta 1) mRNA is disproportionally high in the brain and low in the liver. Using anti-TR antiserum, 4BII, which recognizes TR alpha 1 and beta 1, but not the alpha 2-variant, we measured TR protein content in rat tissues by Western blotting. Two protein bands of 47 and 55 kilodaltons (kDa) were specifically identified as TR proteins. The positions of the in vitro transcription/translation products of c-erbA/TR alpha 1 and beta 1 cDNA on the gel were consistent with those of the 47- and 55-kDa bands, respectively. The 47- and 55-kDa proteins in nuclear proteins extracted with 0.4 M KCl from rat tissues were analyzed by Western blotting, and the intensity of TR protein bands in each tissue was measured by a densitometer. The relative TR protein concentration was highest in liver, followed by brain, kidney, and testis. We compared the TR protein level measured by Western blotting with the maximal T3-binding capacity (Cmax) in the same aliquot of samples from liver and brain. Both the TR protein level and the Cmax in the brain were about 40% of those in the liver, suggesting that the Cmax per receptor molecule is constant in these two tissues, and an abundant amount of functional TR proteins exists in the liver, corresponding to the high level of T3-binding activity.

Animals↗

PubMed1993

Pituitary resistance to thyroid hormone associated with a base mutation in the hormone-binding domain of the human 3,5,3'-triiodothyronine receptor-beta.

Point mutations in the human T3 receptor-beta (TR beta) gene causing single amino acid substitutions have been identified in several different kindreds with generalized resistance to thyroid hormone. Until now, no study has been reported on the TR gene in cases of pituitary resistance (PRTH). In the present study, we analyzed the TR beta gene in a 30-yr-old Japanese female with PRTH. She exhibited clinical features of hyperthyroidism, elevated serum thyroid hormone levels accompanied by inappropriately increased secretion of TSH, mildly elevated basal metabolic rate, and increased urinary excretion of hydroxyproline. No pituitary tumor was detected. DNA fragments of exons 3-8 of the genomic TR beta gene were generated by the polymerase chain reaction and analyzed by a single stranded conformation polymorphism method. Exon 7 of the patient's TR beta gene showed an abnormal band, suggesting the existence of mutation(s). By subcloning and sequencing the DNA, a point mutation was identified in one allele at nucleotide 1297 (C to T), which altered the 333rd amino acid, arginine, to tryptophan. Neither of her apparently normal parents had any mutations of the TR beta gene. In vitro translation products of the mutant TR beta gene showed remarkably decreased T3-binding activity (Ka, 2.1 x 10(8) M-1; normal TR beta Ka, 1.1 x 10(10) M-1). Since the molecular defect detected in a patient with PRTH is similar to that seen in subjects with generalized resistance to thyroid hormone, both types of the syndrome may represent a continuous spectrum of the same etiological defect with variable tissue resistance to thyroid hormone.

Adult↗

PubMed1993

Simultaneous determination of methamphetamine and its metabolites in the urine samples of abusers by high performance liquid chromatography with chemiluminescence detection.

A HPLC determination method for methamphetamine (MA) and its metabolites in the urine samples of abusers has been developed. MA, amphetamine (AP), norephedrine (NE), p-hydroxymethamphetamine (pOHMA), p-hydroxyamphetamine (pOHAP) and an internal standard, namely beta-phenylethylamine (PEA) were derivatized with dansyl chloride. They were separated on a reversed phase column with gradient elution using an acetonitrile/tetrahydrofuran/imidazole buffer mobile phase and chemilumigenically determined using bis(2,4,6-trichlorophenyl)-oxalate/hydrogen peroxide as post column reagents. The lower determination limits were as low as 1 x 10(-14)-3 x 10(-14) mol. AP, NE, pOHAP and PEA were derivatized with naphthalene-2,3-dicarboxaldehyde, and were separated on a reversed phase column using an acetonitrile/imidazole buffer mobile phase and chemilumigenically determined. The lower determination limits were 3 x 10(-16)-1.5 x 10(-15) mol. Enzymatic hydrolysis of glucuronides of pOHMA (pOHMAG) and pOHAP (pOHAPG) allowed them to be determined as pOHMA and pOHAP, respectively. After adjusting the pH of the urine samples to 10.5 and adding PEA, all metabolites except glucuronides were extracted quantitatively into chloroform-isopropanol (3:1). Utilizing the two methods, MA and all metabolites were determined in urine samples of MA abusers. The tendency, in order of decreasing concentration was: [MA] > [A] > [pOHMAG] > [pOHMA] > [NE] > [pOHAPG] > [pOHAP]. Although ephedrine (EP) was was detected in several samples, it was not considered to be a metabolite of MA but rather a component derived from cough medicine.

Adolescent↗

PubMed1993

Neuropsychological outcome and social recovery of head-injured patients.

The Wechsler Adult Intelligence Scale and Yatabe-Guilford personality test were administered to 123 patients hospitalized for head injury who had made a relatively good recovery. Intelligence quotient (IQ) was correlated with clinical condition based on the Glasgow Coma Scale and duration of coma. More severely injured patients tended to show a greater decline in IQ. The type of lesion, as described by computed tomography, was also an important factor in predicting the outcome of intellectual function. The mean IQ of patients with diffuse injury, such as diffuse axonal injury and diffuse brain swelling, and intracerebral hematoma, was significantly lower than that of the control subjects, especially performance IQ (PIQ). Several patients demonstrated improved IQ level during the initial year. In particular, PIQ improved more than verbal IQ. The difference between the IQ of patients achieving social recovery and not was significant (p < 0.001). Causes of difficulty in returning to previous work were decreased IQ and personality change, such as lack of cooperativeness. Neuropsychological evaluation is important in predicting social recovery and selecting necessary neuropsychological rehabilitation.

Adolescent↗

PubMed1993

[RAEB transformed into AML (M0) showing Ph1 chromosome and rearrangement of major cluster region].

A 78 year old female was found to have pancytopenia in February 1991. Bone marrow was normocellular with 11.7% blasts and showed dysmegakaryopoietic changes. A diagnosis of MDS (RAEB) was made and she was treated with transfusions and ubenimex. Leukemic transformation was noted in July. On Admission in October 1991, her laboratory examinations revealed the following: WBC 38,900/microliters with 93% blast, Hb 8.0 g/dl, Plt 2.1 x 10(4)/microliters, a hypercellular bone marrow with 74% blasts which were negative for myeloperoxidase (MPO) by light microscopy, but were positive by electron microscopy. Surface marker for CD13 was positive. These findings corresponded to M0 of the FAB subtype. Chromosome analysis revealed Ph1 chromosome with 46XX, t (9;22) (q34;q11) in 3 of 3 cells examined, Southern analysis showed the rearrangement of the break point cluster region (bcr). Reverse transcriptase polymerase chain reaction technique demonstrated the presence of major bcr/abl mRNA. She was treated with transfusions and methyl-prednisolone. Her blast counts declined and Ph1 chromosome was only positive in 1 of 12 metaphases examined. She died of pneumonia in December 1991. Eleven cases with MDS showing Ph1 chromosome have previously been reported. The observations indicate that Ph1 chromosome positive acute leukemias were heterogenous in nature.

Aged↗

PubMed1993

Detailed analysis of genetic alterations in colorectal tumors from patients with and without familial adenomatous polyposis (FAP).

To examine early genetic events during colorectal carcinogenesis, we searched for genetic alterations in 75 adenomas from seven patients with familial polyposis coli (FAP) and in 64 sporadic colorectal tumors (63 carcinomas and one adenoma). We investigated germ-line and somatic mutations in the APC gene, somatic mutations in the K-ras and p53 genes, and loss of heterozygosity (LOH) on chromosome 8p21-22. Thirty-two FAP adenomas carried detectable somatic mutations in the APC gene. The frequency of somatic APC mutations among adenomas was the same regardless of differences in size or histopathological classification. On the other hand, K-ras mutation was very rare in small adenomas where dysplasia was mild or moderate but frequent in large adenomas with severe dysplasia. Mutation of the p53 gene was observed in only two adenomas and LOH on 8p22 was detected in none. These results imply that a second 'hit' in the APC gene, but not necessarily mutation in K-ras or p53, is an important and critical event for formation of a colorectal adenoma.

Adenomatous Polyposis Coli↗

PubMed1993

[Neuropsychological outcome of head injury in children].

Wechsler Intelligence Scale for Children-Revised (WISC-R) and Yatabe-Guilford personality test were administered to 31 children who had been hospitalized for head injury and made a GR or MD by the Glasgow Outcome Scale (GOS). The type of lesion, as defined by CT scan categories, was an important factor to prognosticate the outcome of intellectual function. The IQ, especially performance IQ, of acute subdural hematoma (EDH) or severe diffuse brain injury (DBI) was lower than that caused by other types of lesion. Several children demonstrated improvement in IQ level during the initial year. The difference between the IQ of the children who could return to previous school life and that of the children who could not was significant. One of the causes of difficulty in returning to previous school life is decreasing IQ and personality change such as social disadaptability. Neuropsychological evaluation is important in predicting school recovery and deciding proper neuropsychological rehabilitation.

Child↗

PubMed1992

Frequent somatic mutations of the APC gene in human pancreatic cancer.

The APC (adenomatous polyposis coli) gene is responsible for familial adenomatous polyposis and is also associated with the development of sporadic tumors of the colon and stomach. To investigate whether or not mutations of APC play any role in tumors arising in other organs, we examined somatic mutations of this gene in sporadic (nonfamilial) renal cell carcinomas, hepatocellular carcinomas, and cancers of the lung and pancreas. DNAs isolated from tumors were examined by means of a RNase protection analysis, coupled with the polymerase chain reaction followed by DNA sequencing of the polymerase chain reaction products. By screening a part of the APC coding region, we detected somatic mutations in four of ten pancreatic cancers; each of these mutations would yield a truncated APC product due to a 1- or 5-base pair deletion. These results imply that mutations in APC contribute to carcinogenesis in the pancreas.

Base Sequence↗

PubMed1992

Correlation between the location of germ-line mutations in the APC gene and the number of colorectal polyps in familial adenomatous polyposis patients.

Recently we have isolated the adenomatous polyposis coli (APC) gene which causes familial adenomatous polyposis (FAP), and its germ-line mutations in a substantial number of FAP patients have been identified. On the basis of this information, we compared the location of germ-line mutations in the APC gene in 22 unrelated patients (12 of whom have been reported previously) with the number of colorectal polyps developed in FAP patients; 17 were sparse types and five were profuse types. All but one of the mutations were considered to cause truncation of the gene product by frame-shift due to deletion (14 cases) or nonsense mutation (seven cases). The location of the germ-line mutations seems to correlate with the two clinical types; germ-line mutations in five FAP patients with profuse polyps were observed between codon 1250 and codon 1464, whereas mutations in 17 FAP patients with fewer polyps were observed in the other regions of the APC gene. The result suggests that the number of colorectal polyps in FAP patients may be associated with a difference in the stability or biological function of the truncated APC protein.

Adenomatous Polyposis Coli↗

PubMed1992

The APC gene, responsible for familial adenomatous polyposis, is mutated in human gastric cancer.

Although gastric cancer is the most common cancer in the world, genetic changes during its carcinogenesis are not well understood. Since some gastric cancers are considered to originate from the intestinal metaplasia, it is likely that the adenomatous polyposis coli (APC) gene, the mutation of which causes adenomatous polyps in the colon, is associated with carcinogenesis of gastric cancer. Based on this idea, DNAs isolated from gastric cancers were examined by means of a RNase protection analysis coupled with polymerase chain reaction followed by sequencing of the polymerase chain reaction products. By screening nearly one-half of the coding region of the APC gene in 44 tumors, somatic mutations were detected in three tumors: a missense mutation, a nonsense mutation, and a 5-base pair deletion resulting in a frame shift which causes truncation of the gene product. These results suggest that the mutation of the APC gene also plays an important role during the carcinogenesis of at least some gastric cancers.

Adenocarcinoma↗

PubMed1992

Germ-line mutations of the APC gene in 53 familial adenomatous polyposis patients.

We searched for germ-line mutations of the APC gene in 79 unrelated patients with familial adenomatous polyposis using a ribonuclease protection analysis coupled with polymerase chain reaction amplifications of genomic DNA. Mutations were found in 53 patients (67%); 28 of the mutations were small deletions and 2 were 1- to 2-base-pair insertions; 19 were point mutations resulting in stop codons and only 4 were missense point mutations. Thus, 92% of the mutations were predicted to result in truncations of the APC protein. More than two-thirds (68%) of the mutations were clustered in the 5' half of the last exon, and nearly two-fifths of the total mutations occurred at one of five positions. This information has significant implications for understanding the role of APC mutation in inherited forms of colorectal neoplasia and for designing effective methods for genetic counseling and presymptomatic diagnosis.

Adenoma↗

PubMed1992

Disruption of the APC gene by a retrotransposal insertion of L1 sequence in a colon cancer.

The APC gene is responsible for familial adenomatous polyposis and is considered to be a tumor suppressor gene associated with development of sporadic colorectal tumors. Here we report the disruption of the APC gene caused by somatic insertion of a long interspersed repetitive element (LINE-1 sequence) into the last exon of the APC gene in a colon cancer. The inserted sequence was composed of a 3' portion of the LINE-1 consensus sequence and nearly 180 base pairs of polyadenylate tract. Furthermore, since an 8-base pair target site duplication was observed, retrotranscriptional insertion of an active LINE-1 sequence is suspected as the cause of this insertion event. This is the first report of the disruption of a tumor suppressor gene caused by somatic insertion of a mobile genetic element.

Adenomatous Polyposis Coli↗

PubMed1992

Single moving dipole obtained from magnetic field of the heart in patients with left ventricular hypertrophy.

Magnetocardiograms (MCGs) were recorded by means of a second-derivative SQUID (superconducting quantum interference device) magnetometer in 20 normal subjects and 28 patients with left ventricular overload to analyze the activation sequence of the heart and amplitude of estimated current source. In the normal subjects, the dipole was directed to the left and gradually superiorly 40 ms after the beginning of the QRS wave mainly due to the activation of the left ventricle. In the patients with hypertension, the direction and location of the dipoles were similar to those of the normal subjects, but their dipole moments were increased. In the patients with mitral regurgitation, the dipoles of late QRS were directed more inferiorly than in the normal subjects and their amplitude was increased. In the patients with aortic valve disease, the amplitude of the dipoles was increased markedly and their location was deviated more to the left than the dipoles of the normal subjects. We established the criterion for diagnosis of LVO from the dipole moment of 50 ms of 3.13 x 10(-3) A or more. The sensitivity of this criterion is significantly higher in the diagnosis of left ventricular overload than the electrocardiogram (ECG). The present study shows that the moving dipole method is useful to determine the increased electromotive force in patients with left ventricular overload and that sensitivity in diagnosis of left ventricular overload is increased.

Aortic Valve Insufficiency↗