Search PubMed⌕ Search

Biomedical subjects

K Hashizume

Publications and source records attributed to K Hashizume.

At least 109 records · Page 6Linked to original sources
PubMed2000

Novel deletional mutation of the MEN 1 gene in a kindred with multiple endocrine neoplasia type 1.

MEN1 gene mutation in a Japanese kindred with multiple endocrine neoplasia type 1 was examined. A heterozygous deletion involving 29 base pairs in exon 10 (1606del29) was identified in the proband, and the same deletion was found in the affected family members. Most previously reported germline MEN1 gene mutations are nucleotide substitutions and small insertions/deletions, and a large deletion is rare. The hairpin structure mediated by an incomplete palindromic sequence at deletion termini is the most likely mechanism to be associated with the deletion in the present family.

Adult↗
PubMed2000

Proliferation-associated expression of the MEN1 gene as revealed by in situ hybridization: possible role of the menin as a negative regulator of cell proliferation under DNA damage.

The gene responsible for multiple endocrine neoplasia type 1 (MEN1) has recently been identified. Wide expression of the MEN1 gene in endocrine and non-endocrine organs examined by northern blotting has been reported, but the detailed cellular distribution of the MEN1 transcript in each tissue has not yet been examined in any species. In this report, expression of the MEN1 gene in adult human tissues was studied by in situ hybridization. The MEN1 transcript was widely observed in all tissues examined, and an enhanced expression in relation to cell proliferation was seen in some organs. Cell cycle arrest at the G1-S border reduced the MEN1 mRNA level to less than 50% of that in exponentially growing asynchronous cells. The expression increased as cells entered into S phase, indicating cell cycle-associated transcriptional regulation of the MEN1 gene. Increase or decrease of the amount of menin did not affect proliferation of CHO cells under normal conditions. However, when cells were exposed to the DNA-cross-linking agent, diepoxybutane, overexpression of wild-type menin inhibited DNA synthesis. This effect was not observed when cells were exposed to ultraviolet light. These results suggest that menin may negatively regulate cell cycle under certain DNA damage.

Adult↗
PubMed2000

Effect of high-frequency oscillatory ventilation on the upper airways of kittens.

BACKGROUND: High-frequency oscillatory ventilation (HFOV) has become the preferred method of ventilation for the fragile lungs of neonates and infants because its beneficial effects on lungs are well known; however, its benefits on upper airways are not yet known. We investigated the effects of HFOV and conventional mechanical ventilation (CMV) on the airways of kittens with normal lungs. METHODS: Ten healthy cross-bred kittens, 2-3-months-old, with a mean bodyweight of 0.98 kg, were randomly divided into two groups: HFOV and CMV. Kittens were intubated and ventilated for 24 h. A semiquantitative scoring system was used to grade histopathological tissue changes in the cricoid, mid-trachea, carina and left bonchus. The injury scores of the two groups were ranked and compared using a two-tailed Mann-Whitney rank test. RESULTS: Histopathologic changes were similar and mild in both groups under light microscopic examination. There was no significant difference in airway injury between the two groups. CONCLUSIONS: We conclude that, in this animal model, HFOV results in minimal airway damage when properly managed and causes no greater tracheobronchial injury than CMV.

Animals↗
PubMed2000

Thyroid hormone regulation of apoptosis induced by retinoic acid in promyeloleukemic HL-60 cells: studies with retinoic acid receptor-specific and retinoid x receptor-specific ligands.

3,5,3'-Triiodo-L-thyronine (T3) potentiates apoptosis during the all-trans-retinoic acid-induced differentiation of promyeloleukemic HL-60 cells. We examined whether the retinoid receptor-specific thyroid hormone action is present during differentiation of HL-60 cells in this study. We used two distinct retinoid receptor agonists. T3 potentiates G1 arrest induced by Am80, a retinoic acid receptor (RAR)-specific agonist, but had no effect on G1 arrest induced by HX600, a retinoid x receptor (RXR)-specific agonist. Am80 alone induces the apoptosis, and T3 enhances it. Although HX600 alone fails to increase the apoptotic fraction, T3 enables the compounds to induce apoptosis. Am80-induced expression of CD11b, a marker for the differentiation, is enhanced by T3. However, T3 or HX600 or both do not affect the expression of CD11b. T3 does not alter the amount of mRNAs of various members of the bcl-2 family. T3, however, enhances the Am80-induced expression of bfl-1 and suppression of bcl-2. In contrast, T3 does not alter either bfl-1 and bcl-2 expression in the presence of HX600. Our observations suggest that cooperative action of T3 with an RXR-specific ligand is different from that with an RAR ligand in cellular apoptotic regulation and that thyroid hormone may be available as a chemotherapeutic agent in acute leukemia.

Apoptosis↗
PubMed2000

Quantitative analysis of DNA binding affinity and dimerization properties of wild-type and mutant thyroid hormone receptor beta1.

Thyroid hormone (triiodothyronine [T3]) actions are mediated through binding of thyroid hormone receptors (TRs) to specific DNA sequences (thyroid hormone response elements [TREs]) as monomers, homodimers, and heterodimers with thyroid hormone receptor auxiliary proteins (TRAPs). We quantitatively characterized dimerization of wild-type (WT) and mutant TRbetas by coimmunoprecipitation, and binding to DNA by electrophoretic gel mobility shift assays (EMSA). Binding affinities of TR retinoid X receptor-alpha (RXRalpha) heterodimers to DNA were determined by competing with excess nonradiolabeled TREs in EMSA. TRs in vitro synthesized in reticulocyte lysates (RL), and human RXRalpha expressed in a Sf9 cell-baculovirus system (BAC), were coincubated with 32P-labeled rat malic enzyme (ME), palindromic (PAL), or chicken lysozyme F2 (F2) TREs. The mutant TRbetas tested were R316H and G345R, which have nondetectable T3 binding and have previously been reported to show weak and potent dominant negative effect, respectively. Scatchard analysis showed no significant differences in Kas between WT and mutant TR-RXRalpha heterodimers binding to DNA. We measured affinity of heterodimerization between TRs and RXRalpha in solution in the absence of DNA, and by coimmunoprecipitation using anti-TRbeta1WT specific antibodies. 35S-labeled RL-RXRalpha was incubated with BAC-WT or TRbeta or R316H in the absence or presence of increasing amounts of nonlabeled BAC-RXRalpha. Displacement curves were obtained by counting radioactivity of precipitated 35S-RXRalpha, that was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and autoradiography. Kds of WT and TRbeta R316H heterodimerizing with RXRalpha were approximately the same. Binding affinity of TR homodimers for F2-TRE was studied because this TRE binds homodimers strongly. Scatchard analysis clearly showed that DNA binding affinity of BAC-WT homodimers did not differ with or without 100 nM T3, but maximal binding capacity (MBC) was reduced three-fold to fourfold in the presence of 100 nM T3. In contrast, BACTRbeta-R316H homodimers showed a fivefold reduction in DNA binding affinity for F2, both in the presence and absence of T3, and approximately the same MBC as WT in the absence of T3. Mutant RL-G345R homodimers showed approximately the same Ka as RL-WT homodimers for binding to F2 and the same MBC in the presence and absence of T3. These results indicate that (1) T3 reduced TRbeta homodimerization in solution but does not effect DNA binding of formed homodimers; (2) T3 does not influence DNA binding affinity of TR/RxR heterodimers; and (3) TRbeta mutant R316H homodimers have reduced DNA binding affinity but homodimerization and heterodimerization in solution does not differ from WT TRbeta.

Animals↗
PubMed2000

Humoral immunity against the proline-rich peptide epitope of the IgA1 hinge region in IgA nephropathy.

BACKGROUND: The human IgA1 hinge region is a unique mucin-like O-linked proline-rich glycopeptide, and its core peptide was found to be exposed aberrantly by the underglycosylation in IgA nephropathy (IgAN). We describe here the presence of humoral immunity against the IgA1 hinge peptide epitope in IgAN and evaluate the relationship between the underglycosylation of the IgA1 hinge region and humoral immunity. METHOD: The serum anti-IgA1 hinge peptide antibody (anti-alpha1HP ab) titre was measured and compared between the IgAN (n=37) and control groups (n=34) by enzyme-linked immunosorbent assay (ELISA) using a synthetic peptide corresponding to the human IgA1 hinge region, PVPSTPPTPSPSTPPTPSPS, as an antigen. Next, to evaluate the relationship between the underglycosylation of the IgA1 hinge region and the humoral immunity, the reactivity of the serum IgG from the patients with IgAN against monoclonal IgA1 which had been digested enzymatically to remove the carbohydrates from the IgA1 hinge region was measured by ELISA. RESULTS: The anti-alpha1HP ab titre was significantly higher in the IgAN group than in the control group (OD value: IgG class, 0.564+/-0.344 vs 0. 331+/-0.154, P=0.0014; IgM class, 0.272+/-0.148 vs 0.141+/-0.072, P<0.0001) and it was positive in approximately 40% of the patients with IgAN. In addition, the reactivity of the serum IgG from the IgAN patients against the monoclonal IgA1 was found to be increased as the carbohydrates were enzymatically removed from the IgA1 hinge region (when native=100; asialo, 122+/-9.5; agalacto, 167+/-11.5; naked, 188+/-3.9). CONCLUSION: These results suggested that the peptide epitope of the IgA1 hinge region which was aberrantly exposed by underglycosylation could induce the humoral immune response in IgAN.

Adolescent↗
PubMed2000

Effects of abstinence from cigarette smoking on the cardiorespiratory capacity.

PURPOSE: The purpose of this study was to determine the effect of 6 or 7 d of abstinence from cigarette smoking on the cardiorespiratory capacity of young men. METHODS: The subjects were 11 male volunteers, mean age 20.5 yr. Their mean smoking duration and cigarettes smoked per day were about 3.5 yr and 20.5 cigarettes, respectively. On the first day of the study, the subjects' physical characteristics, pulmonary functions, and maximal oxygen debt predicted by bicycle ergometer exercise were measured. The subjects' heart rate at rest (HRrest), blood pressure, venous blood analysis and maximal oxygen intake (VO2max) in a treadmill exercise test were measured on the second day. From the time of the second-day measurements, the subjects abstained from cigarette smoking. On the eighth and ninth days of the study, the same measurements were taken as the measurements of the first and second days, respectively. RESULTS: The changes between before and after abstinence from smoking were as follows. The plasma cotinine had almost disappeared after the 7 d of abstinence from smoking. Pulmonary functions did not show a significant improvement. Although there were no significant changes in the HRrest or systolic or diastolic blood pressure, the pulse pressure was significantly increased (P < 0.05). Although the blood components were not changed significantly, the PO2, O2 saturation, HCO3, and CO2 concentration were significantly increased. The predicted maximal oxygen debt was not significantly decreased. Although the VO2max and maximal ventilation volume were not changed, the exercise time was significantly prolonged (P < 0.001). The heart rate during the treadmill exercise at almost all stages decreased significantly; however, the maximal heart rate did not change. CONCLUSION: In conclusion, exercise performance was improved by the 7 d of abstinence from smoking.

Adult↗
PubMed2000

An experimental animal model of split cord malformation.

In this study, we examined an experimental animal model of split cord malformation (SCM) produced by the surgical induction of a fistula. In Cynopus pyrrhogaster neurulae (stage 18.5 +/- 0.5), the neural plate was incised and divided to construct a fistula that mimicked a neurenteric canal. After the procedure, the development of these embryos was examined morphologically and histologically. Following incubation, hemicords, hemicords with their own heminotochords, and dermal sinus were observed in histological sections of embryos with an induced fistula. These abnormalities varied with the length and duration of the fistula, and the induction of this fistula apparently caused the development of this anomaly. The histological findings resembled the findings in human cases. The results of this study support the hypothesis that SCM may originate from an accessory neurenteric canal.

Amphibians↗
PubMed2000

Generalized seizures induced by an epileptic focus in the mesencephalic reticular formation: impact on the understanding of the generalizing mechanism.

The mode of seizure propagation was studied using a generalized seizure model induced by microinjection of kainic acid (KA) into a unilateral mesencephalic reticular formation (MRF) in cats and rats. Stereotactic surgery was performed under pentobarbital anesthesia; an injection cannula was placed into a unilateral MRF, and bipolar electrodes were implanted into the MRF and the thalamus. Microinjection of KA induced generalized seizures. Focal electrical seizures were elicited in the injected site of the MRF starting 30 min after the injection. The initial clinical change during each seizure was behavioral arrest. These seizures immediately developed to generalized seizures, which were characterized by generalized tonic convulsions with short-term clonic convulsions. On EEG, each generalized seizure started at the same time in all the sites of the brain recorded. Autoradiographic study using a rat model demonstrated high glucose utilization in the MRF, bilateral thalamus, forebrain and bilateral cerebral cortices. The results demonstrated an active participation of MRF in the mechanism of generalized seizures.

Animals↗
PubMed2000

[Effect of thiabendazole (TBZ) on glutathione (GSH) and GSH related enzymes in mice liver].

The present study examines the effects of thiabendazole (TBZ), its metabolites, 5-hydroxythiabendazole (5-OH TBZ) and 2-acetylbenzimidazole (ABI), and structural related compounds, thiazoles and thioamides on glutathione (GSH) concentration and GSH-related enzymes in the livers of ICR 11 week-old female mice. GSH concentration in liver and kidney of mice given orally TBZ 0.65 mol/kg (TBZ group) increased significantly compared with control mice from 24 h to 48 h after administration of TBZ. Even in mice to which TBZ at 0.175 mol/kg was administered in combination with L-buthionine sulfoximine (BSO) 4 mmol/kg (i.p.) (BSO-TBZ group), kidney GSH showed significant increase compared with BSO-control mice 48 h after the administration of TBZ. gamma-Glutamylcysteine synthetase (gamma-GCS) activity in the livers of the TBZ group markedly increased at 48 h and that of BSO-TBZ group increased from 24 h to 48 h. gamma-GCS in mice liver is thus enhanced by TBZ regardless of BSO administration. Hepatic glutathione peroxidase activity of the TBZ group did not change in response to cumene hydroperoxide assubstrate. That of BSO-treated mice decreased by TBZ-coadministration and significant differences was noted between BSO-control and BSO-TBZ group from 1 h to 48 h later. Hepatic glutathione S-transferase (GST) activity toward 1,2-dichloro-4-nitrobenzene (DCNB) was significantly elevated 24 h after administrations of TBZ in TBZ and BSO-TBZ groups. GST activity toward 1,2-epoxy-3-(p-nitrophenoxy) propane of TBZ group increased from 0.5 h to 24 h. Hepatic GST activity toward DCNB and 1-chloro-2,4-dinitrobenzene did not change by administration of 0.65 mol/kg 5-OH TBZ or ABI but increased by administrations of 0.33 mol/kg of thiazole, 4-methylthiazole, 4,5-dimethylthiazole or 2,4-dimethylthiazole. Increase in GSH concentration and GST activity in mice liver by TBZ administration may be considered to provide protection from TBZ or its active metabolites.

Animals↗
PubMed2000

Frequency of facial angiofibromas in Japanese patients with multiple endocrine neoplasia type 1.

The high frequency of cutaneous manifestations in patients with multiple endocrine neoplasia type 1 (MEN 1) has recently been reported. Since prevalence of some cutaneous diseases varies among different ethnic groups, we examined the frequency of facial angiofibromas in Japanese patients with familial MEN 1. Among 27 patients with germline MEN1 gene mutation and one asymptomatic gene carrier, angiofibromas were identified in 43% (12/28) of the subjects. This frequency was significantly lower than that of Caucasian patients, but nonetheless almost equaled those of pituitary tumors and pancreas endocrine tumors. Angiofibromas should be considered as one of major manifestations in MEN 1 regardless of patients' ethnic origin, and clinicians should pay careful attention to the cutaneous lesions in patients with endocrine tumors.

Adult↗
PubMed2000

Mechanism of liver-selective thyromimetic activity of SK&F L-94901: evidence for the presence of a cell-type-specific nuclear iodothyronine transport process.

The thyromimetic compound SK&F L-94901 shows more potent thyromimetic activity in the liver than in the pituitary gland or heart when administered to rats. The mechanisms of liver-selectivity of SK&F L-94901 were examined using cultured rat hepatoma cells (dRLH-84) and rat pituitary tumor cells (GH3), both of which showed saturable cellular uptake of tri-iodothyronine (T(3)). When isolated nuclei with partial disruption of the outer nuclear membrane were used, SK&F L-94901 competed for [(125)I]T(3) binding to nuclear receptors almost equally in dRLH-84 and GH3 cells. SK&F L-94901 also did not discriminate thyroid hormone receptors (TR) alpha1 and beta1 in terms of binding affinity and activation of the thyroid hormone responsive element. In intact cells, however, SK&F L-94901 was a more potent inhibitor of nuclear [(125)I]T(3) binding in dRLH-84 cells than in GH3 cells at an early phase of the nuclear uptake process and after binding equilibrium. These data suggest that SK&F L-94901 is more effectively transported to nuclear TRs in hepatic cells than in pituitary cells and therefore shows liver-selective thyromimetic activity. In conclusion, SK&F L-94901 discriminates hepatic cells and pituitary cells at the nuclear transport process. The cellular transporters responsible for this discrimination were not evident.

Animals↗
PubMed2000

Rapid oscillation of insulin release by the rat pancreatic islets under stringent Ca2+-free conditions.

Oscillation of insulin release by the pancreatic islets was evaluated under stringent Ca(2+)-free conditions for the first time. Isolated single rat islets were exposed to 16.7 mM glucose in the presence of 1.9 mM Ca(2+), or under the stringent Ca(2+)-free conditions (Ca(2+) omission with 1 mM EGTA, 6 microM forskolin and 100 nM phorbol 12-myristate 13-acetate). Fifteen minutes after the initiation of glucose stimulation, effluent was collected at a 6-s interval, insulin was determined in duplicate by a highly sensitive insulin radioimmunoassay, and oscillation and pulsatility of release statistically analyzed. Significant oscillation of insulin release was observed in all islets irrespective of presence and absence of Ca(2+). Significant pulsatility of release was detected in 7 of 11 islets in the presence of Ca(2+) and three of six isl! ets in the absence of Ca(2+). In conclusion, high glucose elicits oscillatory insulin release both in the presence and absence of extracellular Ca(2+).

Animals↗
PubMed2000

Chromogranin A expression in hepatocellular carcinoma in a patient with germline MEN1 gene mutation.

Hepatocellular carcinoma (HCC) was found in a patient with multiple endocrine neoplasia type 1 (MEN 1). The intriguing finding was that the HCC in the patient was positively stained for chromogranin A (CgA), a cellular marker for endocrine and neuroendocrine tumors. The patient had a pancreas endocrine tumor and type C hepatitis, that made pathological diagnosis of the origin of the tumor complicated.

Carcinoma, Hepatocellular↗
PubMed2000

Primary malignant lymphoma of the cavernous sinus--case report.

A 59-year-old female presented with a very rare case of primary malignant lymphoma of the cavernous sinus manifesting as diplopia and right facial hypesthesia. Magnetic resonance (MR) imaging showed the tumor located in the right cavernous sinus as low intensity with marked enhancement by gadolinium. The tumor was partially removed by the transzygomatic extradural approach. The histological diagnosis was malignant lymphoma. Chest and abdominal computed tomography and gallium-67 scintigraphy revealed no other lesions in the body. The patient received conventional radiotherapy and her diplopia and right facial hypesthesia gradually improved. At 1 month after radiotherapy, MR imaging showed no evidence of residual tumor. Primary cavernous sinus malignant lymphoma is extremely rare, but should be considered in the differential diagnosis of cavernous sinus lesions. Histological confirmation of tumors in this region is essential for choosing the most appropriate treatment to achieve a better outcome.

Brain Neoplasms↗
PubMed2000

Cerulenin, an inhibitor of protein acylation, selectively attenuates nutrient stimulation of insulin release: a study in rat pancreatic islets.

Nutrients such as glucose stimulate insulin release from pancreatic beta-cells through both ATP-sensitive K+ channel-independent and -dependent mechanisms, which are most likely interrelated. Although little is known of the molecular basis of ATP-sensitive K+ channel-independent insulinotropic nutrient actions, mediation by cytosolic long-chain acyl-CoA has been implicated. Because protein acylation might be a sequel of cytosolic long-chain acyl-CoA accumulation, we examined if this reaction is engaged in nutrient stimulation of insulin release, using cerulenin, an inhibitor of protein acylation. In isolated rat pancreatic islets, cerulenin inhibited the glucose augmentation of Ca2+-stimulated insulin release evoked by a depolarizing concentration of K+ in the presence of diazoxide and Ca2+-independent insulin release triggered by a combination of forskolin and phorbol ester under stringent Ca2+-free conditions. Cerulenin inhibition of glucose effects was concentration dependent, with a 50% inhibitory concentration (IC50) of 5 microg/ml and complete inhibition at 100 microg/ml. Cerulenin also inhibited augmentation of insulin release by alpha-ketoisocaproate, a mitochondrial fuel. Furthermore, cerulenin abolished augmentation of both Ca2+-stimulated and Ca2+-independent insulin release by 10 micromol/l palmitate, which causes palmitoylation of cellular proteins. In contrast, cerulenin did not attenuate insulin release elicited by nonnutrient secretagogues, such as a depolarizing concentration of K+, activators of protein kinases A and C, and mastoparan. Glucose oxidation, ATP content in islets, and palmitate oxidation were not affected by cerulenin. In conclusion, cerulenin inhibits nutrient augmentation of insulin release with a high selectivity. The finding is consistent with a prominent role of protein acylation in the process of beta-cell nutrient sensing.

Acylation↗
PubMed2000

[Supplement with target hormone in aged patients with endocrine dysfunction: thyroid hormone replacement therapy].

Hypothyroidism is not rare in aged people. Hashimoto thyroiditis and radiation to the neck region are main causes of hypothyroidism in aged subjects. The symptoms are slowly progressing, and are similar to those of the aged subjects free from thyroid disease. Thus, it is difficult to make a diagnosis of hypo-thyroidism in the elderly. Administration of T4 (not T3) to patients with hypothyroidism completely releases them from symptoms, indicating that supplement with T4 is important in maintaining QOL. However, a risk of acute coronary syndrome is usually associated with the supplement. Rapid decrease in serum levels of TBG is frequently associated with acute coronary syndrome. Slowly increasing the dose of T4 and monitoring serum thyroxine-binding globulin (TBG) and electrocardiogram (ECG) are important during the period of increasing the dose of T4.

Aged↗