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Biomedical subjects

K Hashizume

Publications and source records attributed to K Hashizume.

At least 19 recordsLinked to original sources
PubMed1996

Analysis of the pancreatic beta cell in the mouse with targeted disruption of the pancreatic beta cell-specific glucokinase gene.

This is the first systematic study on the pancreatic beta cell function in the heterozygous mouse with targeted disruption of the beta cell glucokinase gene. The heterozygotes' beta cell displayed the following characteristics: (1) impaired glucose sensitivity with normal glucose responsiveness, (2) poor discrimination of alpha and beta glucose anomers, and (3) normal response to glucose in the presence of 25 mM K+ and 150 microM diazoxide. Both the first and the second phases of glucose-stimulated insulin release were depressed. Although the heterozygotes were mildly hyperglycemic, insulin treatment further suppressed beta cell function, implying the beta cell glucose toxicity is not the cause of impaired glucose sensitivity. The data are compatible with the glucokinase glucose sensor concept inasmuch as glucose sensitivity is reduced in the heterozygotes' beta cell. The anomeric malaise and preservation of the ATP-sensitive K+ channel-independent glucose action were considered due to chronic hyperglycemia.

Animals↗
PubMed1996

The time course of glucose metabolism in rat cerebral ischemia with middle cerebral artery occlusion-reperfusion model and the effect of MK-801.

Following cerebral ischemia, the extracellular concentration of excitatory amino acids increases, and the excitatory cell death may play an important role contributing to ischemic neuronal damage. Although sequential metabolic changes in permanent local cerebral ischemia have been reported, the effect of reperfusion in local cerebral ischemia on glucose metabolism is less clear. In order to investigate the time course change of glucose metabolism in a middle cerebral artery occlusion-reperfusion model and the effect of dizocilpin (MK-801) on glucose metabolism, the 14C-Deoxyglucose method was used. Hypermetabolism occurred at 30 min after the middle cerebral artery (MCA) occlusion, and reached a peak at 60 min after ischemia in both ischemic core and penumbra. The shift from hyper- to hypometabolism was observed after the ischemia. The reperfusion facilitated the decrease of cerebral glucose metabolism in the ischemic region following 2 h of MCA occlusion. The pretreatment of MK-801 (0.4 mg kg-1) inhibited both increased glucose metabolism during ischemia and decreased glucose metabolism during reperfusion. These findings support the hypothesis that excitation-induced hyper-metabolism plays a major role in the ischemic insult following focal cerebral vascular occlusion.

Animals↗
PubMed1996

Genetic screening in hereditary multiple endocrine neoplasia type 1: absence of a founder effect among Japanese families.

Ten Japanese families with hereditary multiple endocrine neoplasia type 1 (MEN1) were examined. Five DNA polymorphic markers on the long arm of chromosome 11 were analyzed for genetic screening of MEN1 in members of affected families, and disease carriers were identified before clinical manifestations. Unlike MEN1 families in Newfoundland or in Tasmania, no consistent haplotypes were segregated with the disease in the Japanese families when defined by 5 nearby markers. The identification of asymptomatic disease carriers is of substantial clinical importance for early management, genetic counseling and to avoid unnecessary screening for non-disease carriers. However, genetic screening of family members by polymorphic markers could be useful only to each family, and no generally applicable markers were found for Japanese subjects with MEN1.

Adult↗
PubMed1996

A new HLA-DQB1*0306 allele sharing motifs from DQB1*03032 and DQB1*04 sequences.

We have discovered a new HLA-DQB1 allele in a Japanese family, MAT. In the family the new allele segregates in three generations and demonstrates the positive association with DRB1*0901. We observed a novel RFLP pattern in the course of examining the modified PCR-RFLP method for HLA-DQB1 genotyping. The PCR-SSOP analysis also showed a new hybridized pattern. Sequence analysis of the allele indicates that it was generated by a gene conversion-like event between the HLADQB1*03032 and one of DQB1*04 contemporary alleles. This new allelic product did not react with all of allosera and monoclonal antibodies against DQ1, DQ2, DQ3, DQ4 and DQ7. The HLA molecule encoded by the allele is not defined by serology. This new allele was officially recognized and named DQB1*0306 by the WHO Nomenclature Committee in November 1995.

Alleles↗
PubMed1996

Decidual prolactin-related protein: heterologous expression and characterization.

As a first step in understanding the role of decidual PRL-related protein (dPRP) during pregnancy, we have generated recombinant dPRP protein. In this report, we present data on the generation, purification, and characterization of recombinant dPRP protein. The dPRP complementary DNA was subcloned into the pMSXND vector, and the vector was transfected into Chinese hamster ovary (CHO) cells by electroporation. After appropriate selection, amplification, and induction procedures, recombinant dPRP was purified from conditioned medium of the CHO-dPRP cells using ultrafiltration, size-exclusion chromatography, and reverse phase HPLC. Recombinant dPRP was found to possess electrophoretic mobility, immunoreactivity, and N-terminal amino acid sequence identical to those of dPRP isolated from decidual tissue. Polyclonal antibodies were generated to the recombinant dPRP and used for Western blot analysis. dPRP is capable of binding heparin, and a significant fraction of synthesized dPRP resides within the decidual extracellular matrix. Recombinant dPRP failed to bind to PRL receptors and showed no stimulatory activity in the PRL-dependent rat Nb2 lymphoma cell proliferation assay. Additional studies have shown that heterologous expression of dPRP in CHO cells significantly increased the ability of CHO cells to form tumors in athymic mice. In conclusion, recombinant dPRP possesses characteristics similar to those of dPRP of decidual origin and is a heparin-binding protein that may facilitate the establishment of pregnancy.

Animals↗
PubMed1996

Gs alpha mutation may be uncommon in patients with multiple endocrine neoplasia type 1.

Activating mutations of the Gs alpha gene, termed gsp, have been identified in various endocrine tumors. Recently, a high frequency of gsp mutation in patients with multiple endocrinopathies was reported, and a family with both McCune-Albright syndrome and multiple endocrine neoplasia type 1 was described. Each suggests that the oncogenic mutations of Gs alpha may play an important role in tumorigenesis in patients with multiple neoplastic endocrinopathies, and a search for the gsp mutation in multiple endocrine neoplasia type 1 (MEN1) should be undertaken. We, therefore, reevaluated the frequency of gsp mutations in endocrine tumors of patients with MEN1. Of 18 tumors from 13 patients with MEN1, we found no gsp mutations regardless of heredity. We conclude that the gsp mutation may be uncommon in endocrine tumors of MEN1 patients, and thus, this mutation plays little, if any, role in their tumorigenesis.

Adult↗
PubMed1996

Acromegaly associated with Chiari-I malformation and polycystic ovary syndrome.

We report a 19-year-old female case of acromegaly associated with Chiari-I malformation and polycystic ovary syndrome. She also had syringomyelia and thoracic scoliosis. Although the association of acromegaly and Chiari-I malformation was by chance, exaggerated secretion of growth hormone may have aggravated the scoliosis. The incidence of polycystic ovary in acromegalic patients remains to be elucidated. However, elevation of plasma insulin and insulin-like growth factor, that is usually observed in patients with acromegaly, could stimulate androgen production in the ovaries. The patient was successfully treated with transsphenoidal adenomectomy for pituitary tumor and correction surgery for thoracic scoliosis.

Acromegaly↗
PubMed1996

Intraoperative electrocorticography in children with medically intractable epilepsy.

Intraoperative electrocorticography (ECoG) was performed to localize epileptic foci in 20 children undergoing temporal and extratemporal surgery for intractable epilepsy under modified neuroleptanalgesia. Nitrous oxide gas was discontinued at least 15 minutes before and during preresection ECoG recording, which lasted for 30 minutes. Seventeen patients showed epileptiform discharges on preresection ECoG. Hyperventilation loading, monitored by electroencephalography or ECoG in all patients, induced enhanced or induced epileptiform activities in 17 patients and provoked electroencephalographic seizures in 10 patients. All foci in non-eloquent areas were resected. Fifteen patients have been seizure-free with reduced medication, and two patients have achieved worthwhile improvement. Habitual seizures have remained in three patients. Two of these patients had foci in eloquent areas which could not be resected. Intraoperative ECoG can improve the outcome of surgery for intractable epilepsy by localizing epileptic foci for resection.

Adolescent↗
PubMed1996

Walking patterns and finger rhythm of older adults.

Walking patterns and rhythmic movement of the fingers were examined in a total of 1,134 male and female community residents 65 years of age and over. Walking patterns were characterized according to the ratio of step length divided by step rate (cadence), called the Walk Ratio, during level walking at preferred and maximum speeds. The walking pattern tended to change according to age; older subjects walked with shorter steps (smaller Walk Ratio). Rhythmic movement was examined using the finger-tapping test in time to the sound of a 4-Hz metronome. Hastened tapping or finger festination, in which the subject tapped faster than requested (constant error of 3 msec. and over in the intertap interval), was characteristic of aging; 16.8% of the subjects exhibited finger festination and the occurrence increased with age, especially among those in their eighties (29.3%). Finger festination was accompanied by walking patterns with an increased step rate, or a smaller Walk Ratio. These characteristics of aging were discussed as similar to extrapyramidal symptoms of walking and rhythm production in patients with Parkinson's disease.

Acceleration↗
PubMed1996

[Reconstruction procedure for full-thickness chest wall defects].

Reconstruction of full-thickness chest wall defects after the total layer resection of the chest wall has been performed on 6 cases. Five of 6 cases had local recurrent of breast carcinoma, one case had a recurrent liposarcoma in the chest wall. The reconstruction procedure of skeletal chest wall used to double soft Marlex mesh. The soft tissue layer of the chest wall was reconstructed with myocutaneous flaps in five cases (four cases using latissimus dorsi, one case using rectus abdominis), with omental pedicle graft and free skin flap in one case. Minor wound complications occurred in 2 in the 6 cases, one case had myocutaneous flap using rectus abdominis, the other case using omental pedicle flap, but any postoperative complications including respiratory insufficiency was not seen with myocutaneous flap using latissimus dorsi. The latissimus dorsi myocutaneous flap was most suitable to cover the soft tissue layer of the chest. We confirmed that Marlex mesh and latissimus dorsi myocutaneous flap were able to reconstructed for large defects of full-thickness chest wall involving the sternum, there were best approach to reconstruction full-thickness chest wall defects after total layer chest wall resection.

Aged↗
PubMed1996

[Familial multiple cavernous angioma in the brain and spinal cord].

We reported two patients from the same family underwent operation for neurological symptoms due to vascular lesions that were proved on pathological examination to be cavernous angiomas. Case 1, a 64-year-old woman was admitted to our hospital because of paraparesis. MRI revealed a mass lesion with high signal intensity in T1 and T2 weighted images at T3-4 level. Complete excision was carried out and diagnosis of cavernous angioma was made. Three years later, she experienced a mild headache and dizziness. CT scan demonstrated a subcortical hematoma in the right frontal lobe. Postoperative pathological diagnosis was cavernous angioma. Case 2, a 65-year-old woman (younger sister of case 1) was operated for the tumor of spinal cord, and diagnosed as a cavernous angioma. Two years later, she developed diplopia and ataxic gait. MRI showed multiple cavernous angioma in the brain including pons. Pontine lesion which was responsible for this episode was removed, and diagnosis was a cavernous angioma histopathologically.

Aged↗
PubMed1995

Transcriptional regulation of human thyroid hormone receptor beta 1 gene expression: effect of human retinoid X receptor and identification of a transcriptional silencer region.

Effects of human retinoid X receptor alpha (hRXR alpha) and its ligand, 9-cis-retinoic acid, on T3-mediated auto-regulation of hTR beta 1 gene expression were examined using a chloramphenicol acetyltransferase (CAT) reporter system, and a deletional analysis of the promoter. hRXR alpha enhanced T3-dependent CAT induction mediated through the proximal (p) TRE in a ligand (9-cis-retinoic acid) independent manner. In a gel mobility shift assay, hRXR alpha enhanced the binding of hTR beta 1 to the pTRE by the formation of hRXR alpha-hTR beta 1 heterodimers. On the other hand, hRXR alpha and 9-cis-retinoic acid did not show any effects on T3-dependent CAT induction mediated through the distal (d) TRE or the binding of hTR beta 1 to the dTRE. A four hundred-base pair (bp) fragment adjacent upstream of the dTRE showed a T3 independent suppressor effect on the function of the pTRE and dTRE. Thus, this region may be an important regulator of the T3 dependent up-regulation of the TR beta 1 gene expression which is observed only under specific conditions.

Base Sequence↗
PubMed1995

Effects of thapsigargin, an intracellular CA2+ pump inhibitor, on insulin release by rat pancreatic B-cell.

This is the first report as to the effects of thapsigargin (Tg), an inhibitor of intracellular Ca2+ pumps, on insulin release by pancreatic B-cells. Tg does not alter basal insulin release by the isolated islets, with 3 mM glucose. However, it potentiates high glucose-induced insulin release: potentiation of the first phase response is dose-related in a concentration range of 1.3-40 microM. In isolated B-cells, Tg causes a minimal rise in basal cytosolic free calcium concentration ([Ca2+]i) and eliminates high glucose-induced initial lowering of [Ca2+]i. Tg does not alter glucose oxidation by the islets and the islet insulin content. An elimination of glucose-induced sequestration of Ca2+ into Tg-sensitive intracellular pool(s) is considered to be the cause of Tg potentiation of glucose effect on insulin release.

Animals↗
PubMed1995

Differential effects of aging on motoneurons and peripheral nerves innervating the hindlimb and forelimb muscles of rats.

We examined the number and size of ulnar (forelimb) and medial gastrocnemius (MG, hindlimb) motoneurons in middle-aged (9 months of age) and aged (27 months of age) male Fischer 344 rats. Morphological properties of the ulnar and the MG nerves were also studied. No significant difference was found in the mean number of the ulnar motoneurons between the two age groups, while that of MG motoneurons was significantly less in aged animals. A decrease in the number of myelinated fibers (including both afferent and efferent fibers) in the ulnar nerves was less than that in the MG nerves, although the age difference was not significant in either of the nerves. Soma atrophy of aged motoneurons was found in both MG and ulnar motor nuclei. The mean fascicular areas and myelinated fiber diameters were significantly increased in both the MG and the ulnar nerves in aged rats, but these were less pronounced for the ulnar nerve. The results indicate that most ulnar motoneurons, unlike MG motoneurons, survive at least to the age of 27 months. Morphological changes in the peripheral nerves were also less for the ulnar nerve than for the MG nerve. Thus, we conclude that the effects of aging on motoneurons and peripheral nerves innervating MG muscle of the hindlimb are greater than those innervating forelimb muscles.

Aging↗
PubMed1995

A novel point mutation (R243Q) in exon 7 of the c-erbA beta thyroid hormone receptor gene in a family with resistance to thyroid hormone.

Resistance to thyroid hormone (RTH) is characterized by variable tissue hyporesponsiveness to thyroid hormones. Recently, a large number of different point mutations have been identified in the c-erbA beta thyroid hormone receptor (TR beta) in subjects with RTH. We describe a Japanese family with RTH with a novel point mutation in exon 7 of the TR beta gene. A single nucleotide substitution, guanine for adenine, was identified at the second position of codon 243 located in the hinge domain between the ligand binding and DNA binding domains in one of the two alleles of the proband and his mother, resulting in the substitution of the normal arginine (CGG) with a glutamine (CAG). Except for one family, point mutations so far described in RTH are clustered at exons 8-10 of the TR beta gene. This report presents a novel mutation in the characteristic portion in exon 7 of the TR beta.

Amino Acid Sequence↗
PubMed1995

Ketoacidosis-onset noninsulin dependent diabetes in Japanese subjects.

In 5 patients (2 women and 3 men, aged 16-36 years), diabetic ketoacidosis developed without precipitating illness. Pancreatic islet cell antibody was negative, and the duration of insulin dependency was shorter than 4 weeks. Hemoglobin A1c was < or = 6.3% for the mean period of 2.8 years thereafter, with diet therapy alone in 4 and with 5 mg glyburide in 1. Four were overweight before the development of diabetes, and 3 of them positive for family history of adult-onset, non-ketotic diabetes. Frequency of human leukocyte antigen B61 was increased significantly in the patients. In a patient not previously overweight, family history of diabetes was negative, and human leukocyte antigen haplotypes common in insulin-dependent diabetes mellitus were accumulated. Serum immunoreactive insulin was within normal range or supranormal with normal glucose tolerance after recovery. The patients closely resemble black Americans with ketoacidosis-onset non-insulin dependent diabetes.

Adolescent↗