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Biomedical subjects

K Hashizume

Publications and source records attributed to K Hashizume.

At least 127 records · Page 7Linked to original sources

The p73 gene is less involved in the development but involved in the progression of neuroblastoma.

We performed expression, mutation, loss of heterozygosity (LOH) and fluorescence in situ hybridization (FISH) analyses of the p73 gene in neuroblastomas (NBs). Reverse transcription-polymerase chain reaction (RT-PCR) using primers which can detect both the p73alpha and p73beta transcripts was performed on 30 fresh NBs and 22 NB cell lines. Aberrant expression of the p73 gene was found in 4 (25%) of 16 primary tumors found by mass screening and in 10 (71.4%) of 14 primary tumors found clinically. The rates of expression in these two types of tumors were significantly different (p=0.026, Fisher's exact test). The incidence of aberrant expression of the p73 gene was significantly higher in stage IV patients than in stages I, II, III plus IVS patients (p=0.0236, Fisher's exact test). No homozygous deletions or rearrangements of the p73 gene were found in any samples examined. In addition to the polymorphism in exon 2, a silent mutation (codon 336 GCC/GCT) was found in one primary tumor. LOH of the p73 gene was detected in 5 (15%) of 33 primary NBs using PCR-LOH analysis. FISH analysis showed that all 17 NB cell lines used in this study revealed allelic loss of the p73 gene, while most of them expressed the p73 gene. These results suggest that the p73 gene is not monoallelically expressed in NB. We conclude that the p73 gene is less involved in the development but involved in the progression of neuroblastoma.

DNA Primers↗

[A case of the syndrome of the sinking skin flap: case report].

A case of "the syndrome of the sinking skin flap" was presented. A 40-year-old-man had suffered from severe SAH 9 months before. An aneurysm of the anterior communicating artery was successfully clipped and the bone flap was removed for the purpose of the external decompression. Cranioplasty and V-P shunt were performed 1 month after SAH, but both were removed because of postoperative wound infection, viz. epidural and subdural abscess 4 months after SAH. Following this, L-P shunt was performed, and the patient was discharged with mild dementia. A concave deformity of the skin flap developed about 4 months after the L-P shunt. Neurological examination showed progressive left hemiparesis and akinetic mutism. A low CSF pressure was demonstrated, but RI cisternography revealed normal CSF circulation. Intrathecal infusion of the artificial CSF was carried out via lumbar puncture and concavity of the skin flap gradually improved. This procedure resulted in improvement of the neurological deficits. Cranioplasty with artificial bone was performed under continuous intrathecal infusion of the artificial CSF. Postoperative course was satisfactory and neurological examination revealed only mild dementia. The pathological mechanism in our case was probably due to the compression of the brain by the atmospheric pressure following the external decompression. Moreover, L-P shunt exaggerated this pathology by the overdrainage of CSF.

Adult↗

[Surgical treatments for 7 pituitary adenomas in multiple endocrine neoplasia type 1].

We analyzed 7 pituitary adenomas in patients with multiple endocrine neoplasia type 1 (MEN1). Their incidence was 1.6% among 450 patients with pituitary adenomas which had been treated surgically in our department between 1978 and 1999. The age, gender, symptoms, type of hormone secretion, pathological and operative findings in the MEN1 patients were not apparently different from those in the non-MEN1 patients. Incidence of non-functioning pituitary adenomas, however, was more frequently encountered in our series than that in previous reports among Caucasian people. One patient who had 5 previous operations for the MEN tumors died following postoperative subarachnoid hemorrhage. Four of the seven patients presented initial symptoms related to pituitary adenomas and increased serum Ca level was retrospectively recognized in three of the four at the time of treatment for the pituitary adenomas.

Adenoma↗

Portal venoplasty for recipients in living-related liver transplantation.

BACKGROUND: In living-related liver transplantation (LRLT) in small children, standard end-to-end portal vein (PV) anastomosis is usually difficult because of a inadequate total PV length, or because of a size mismatch between the graft and the recipient PV. In this report, we present our new portal venoplasty technique for the recipient PV. METHODS: After dissection of the recipient PV, the wall between the right and left branches of the PV is severed longitudinally as in the branch patch technique. The anterior and posterior edges of both branches are joined using running sutures, to form a longer and wider PV for anastomosis. RESULTS: This new portal venoplasty technique was used in 7 of 28 child cases, and gave good results without thrombosis or other complications. CONCLUSIONS: Our new portal venoplasty technique is useful in LRLT in small children when the recipient or graft PV is not long enough.

Adult↗

Functional interaction between Oct-1 and retinoid X receptor.

The retinoid X receptor (RXR) is a member of the nuclear hormone receptor superfamily and heterodimerizes with a variety of other family members such as the thyroid hormone receptor (TR),1 retinoic acid receptor, vitamin D receptor, and peroxisome proliferator-activated receptor. Therefore, RXR is supposed to play a key role in a ligand-dependent regulation of gene transcription by nuclear receptors. In this study, we have identified the octamer-binding transcription factor-1 (Oct-1) as a novel interaction factor of RXR. In vitro pull-down assays using RXR deletion mutants showed that the interaction surfaces were located in the region encompassing the DNA binding domain (C domain) and the hinge domain (D domain) of RXR. We also showed that RXR interacted with the POU homeodomain but not with the POU-specific domain of Oct-1. Gel shift analysis revealed that Oct-1 reduced the binding of TR/RXR heterodimers to the thyroid hormone response element (TRE). In transient transfection assays using COS1 cells, Oct-1 repressed the T3-dependent transcriptional activity of TR/RXR heterodimers, consistent with in vitro DNA binding data; however, transcriptional activation by Gal4-TR(LBD) (LBD, ligand binding domain), which lacks its own DNA binding domain but retains responsiveness to T3, was not influenced by Oct-1. These results suggest that Oct-1 functionally interacts with RXR and negatively regulates the nuclear receptor signaling pathway by altering the DNA binding ability of the receptors.

Animals↗

Versatility of the inferior epigastric artery as an interpositional vascular graft in living-related liver transplantation.

We have used the recipient inferior epigastric artery as an interpositional vascular graft in living-related liver transplantation cases with hepatic artery obstruction, enabling us to restore the arterial inflow sufficiently to the transplanted liver. The inferior epigastric artery is easy to access during abdominal surgery. Easy to harvest, it is anatomically constant and has a caliber equivalent to that of the hepatic artery. Donor site morbidity is negligible. There is no risk of rejection because of the autograft. There has been no report on the availability of the inferior epigastric artery for hepatic artery reconstruction. We consider this vessel as a good option for an arterial conduit in case of the inadequacy or thrombosis of the hepatic artery in living-related liver transplantation.

Adolescent↗

Pattern of FHIT gene expression in normal and leukaemic cells.

Chromosomal aberrations and inactivation of tumour suppressor genes are frequent in acute leukaemia. To determine whether the FHIT gene is involved in the development of leukaemia, we examined the FHIT transcript in 65 leukaemia cell lines, 5 fresh acute leukaemia patients at diagnosis and in complete remission, normal peripheral blood lymphocytes obtained from 14 healthy volunteers and Epstein-Barr (EB) virus transformed 5 B-cell lines (EB-lines), using nested reverse transcription-polymerase chain reaction and direct sequencing. The transcripts were classified into 4 patterns: pattern I revealed the normal transcripts only, pattern II the altered transcripts in addition to the normal transcripts, pattern III the altered transcripts without the normal transcripts and pattern IV an absence of normal and altered FHIT transcripts. Nineteen cell lines were classified as pattern I, 32 as pattern II, 2 as pattern III and 12 as pattern IV. The frequency of loss of FHIT expression (pattern III or IV) varied in each type of leukaemia cell line; the order ranked from the highest incidence was acute myeloid leukaemia (AML), T-cell acute lymphoblastic leukaemia (T-ALL), B-precursor ALL, B-ALL, and chronic myeloid leukaemia (CML). No genomic rearrangement was found in any samples examined. All of 5 patients showed same pattern II FHIT transcripts at 2 different stages of the disease. All normal peripheral blood lymphocytes and EB-lines were classified as pattern I or II. Our results suggested that patterns III and IV of FHIT transcripts might be associated with the development of a subset of leukaemia, while pattern II which has so far been reported as an aberrant transcript in varieties of malignant tumours might not be associated with leukaemogenesis.

Acid Anhydride Hydrolases↗

Chronopharmacology for deoxyspergualin: toxicity and efficacy in the rat.

BACKGROUND: Deoxyspergualin (DSG), a potent immunosuppressive drug, has been clinically used as a rescue therapy for acute graft rejection. However, DSG has severe adverse effects that limits its use. Here, we examined the optimized therapeutic protocol for DSG using chronopharmacological profiles of it. METHODS: First, a dosing time-dependent difference in the toxicity and efficacy of DSG was determined using a heterotopic heart transplantation model. Second, chronokinetics of DSG were examined to reveal the mechanism for dosing time-dependent differences in the effect. RESULTS: In rats treated with DSG at the active period, bone marrow suppression and damage of small intestine were significantly severe. However, no significant difference was found in cardiac allograft survival and pharmacokinetics according to the timing of drug administration. CONCLUSIONS: The toxicity of DSG varied with the dosing time, whereas its efficacy did not. The chronopharmacological approach may provide merits for immunosuppressive therapy with DSG in clinical organ transplantation.

Animals↗

1,25-Dihydroxyvitamin D3 suppresses the expression of the VCAM-1 receptor, VLA-4 in human leukemic HL-60 cells.

Very late antigen-4 (VLA-4) is the complex with alpha4 and beta1 integrins, which is the receptors to fibronectin and VCAM-1. We evaluate the effect of 1,25(OH)2D3 on the expression of VLA-4 in human leukemic HL-60, U937 cells and human melanoma A375 cells. Flow cytometric analysis demonstrate that the expression of alpha4 integrin is negatively regulated in the cell lines we studied. The expression of beta1 integrin is also decreased in HL-60 and U937 cells. The mRNA expression of alpha4 integrin is significantly decreased by the treatment with 1,25(OH)2D3, whereas 1,25(OH)2D3 does not alter the expression of beta1 mRNA. The adhesion assay demonstrate that the number of adherent cells treated with 1, 25(OH)2D3 is significantly lower than that untreated on VCAM-1-coated wells. Because VCAM-1 is highly expressed in the endothelial cells, it is possible that 1,25(OH)2D3 prevents the attachment of the cells from the endothelial cells in vivo.

Antigens, CD↗

Effect of hypothermia on kainic acid-induced limbic seizures: an electroencephalographic and 14C-deoxyglucose autoradiographic study.

The effect of body temperature on kainic acid (KA)-induced limbic seizures was examined in Wistar rats. In rats undergoing limbic seizure induced by 1 microgram intra-amygdaloid injection of KA, the post-injection latency of initial ictal discharges in the left amygdala was significantly longer in rats whose body temperature was lowered to 30 degrees C (2.55+/-0.94 min at 37 degrees C, 13.19+/-5. 70 min at 30 degrees C; p=0.0017). The post-injection latency of initial ictal discharges in the left hippocampus was also significantly longer under the same conditions (23.68+/-9.96 min at 37 degrees C, 43.85+/-17.98 min at 30 degrees C; p=0.0253). The number of limbic seizures occurring in the first 2 h post-injection was significantly lower in hypothermic rats (30.0+/-10.7 at 37 degrees C, 8.71+/-2.69 at 30 degrees C; p=0.0017), as was the total duration of limbic seizures over the same period (23.61+/-8.45 min at 37 degrees C, 10.30+/-4.48 min at 30 degrees C; p=0.0060). Local cerebral glucose utilization (LCGU), measured 2 h post-injection, was significantly lower in hypothermic rats, mainly in the limbic structures. 14C-deoxyglucose autoradiograms showed decreased radiation density not only in the left amygdala and bilateral hippocampus, but also in the cerebral cortex of hypothermic rats. The results of the present experiment demonstrate that the use of hypothermia, which has been shown to be effective in the treatment of acute cerebral ischemia and brain injury, may also be effective in the treatment of status epileptics.

Amygdala↗

An aberrant left subclavian artery aneurysm with right aortic arch: report of a case.

The case of a 41-year-old man who developed an aneurysm in his aberrant left subclavian artery is described. The patient had a right aortic arch. After a successful aortosubclavian artery bypass, symptoms due to brain ischemia disappeared. This is a very rare disease that is sometimes associated with an aortic anomaly, therefore the optimal therapeutic procedure need to be carefully selected, including the operative indications and approach.

Adult↗

Pericardio-peritoneal drainage using a subcostal approach.

A 56-year-old man admitted to our hospital for cardiac tamponade due to dilated cardiomyopathy did not respond to treatment by usual medical means or surgery. Pericardio-peritoneal drainage was conducted using a subcostal approach. Seven months later, the patient remains well and free of signs of pericardial tamponade. This method has proved to be safe and effective in patients with persistent massive pericardial effusion.

Cardiac Tamponade↗

Influence of tacrolimus on bile acid and lipid composition in continuously drained bile using a rat model. Comparative study with cyclosporine.

Cholestatic effects have been reported for cyclosporine (CsA), but information is still limited for tacrolimus (TCR). The purpose of this study was to investigate the influence of TCR on biliary bile acid and lipid composition as compared with CsA, using a continuously bile-drained rat model. Adult male Wistar rats received TCR (0.4 mg/kg, 1 mg/kg, and 4 mg/kg) or CsA (2.5 mg/kg, 10 mg/kg, and 25 mg/kg) by intramuscular injection (i.m.) daily for 10 days. On day 7, the common bile duct of all rats was cannulated, then bile was continuously collected for the following 3 days. Bile flow, bile acid secretion rate (BASR), and biliary lipids secretion were measured for each of the groups. TCR increased bile acid-dependent flow (BADF) but with no statistical significance. However, this agent did not influence total bile flow and biliary lipids secretion, while bile acid-independent flow (BAIF) was significantly reduced and bile acid synthesis (mainly cholic acid, CA, synthesis) was increased. In contrast, CsA was cholestatic, showing a tendency to reduce both BADF and BAIF. BASR was dose-dependently suppressed, especially in chenodeoxycholic acid (CDCA). Furthermore, biliary lipids secretions were also significantly decreased under a higher dose of CsA. TCR increased BADF with no influence on total bile flow, having a stimulating effect on CA production, although CsA dose-dependently diminishes CDCA production and consequently reduced bile secretion. Our results suggest that TCR is a less effective agent on cholestasis as compared to CsA.

Animals↗

Recurrence of medulloblastoma 19 years after the initial diagnosis.

A 25-year-old woman presented with recurrent medulloblastoma. She had been diagnosed with cerebellar medulloblastoma and treated for it at the age of 5 years. The new tumor was partially resected and chemotherapy was begun. However, a disseminated tumor of the spine was discovered and, despite radiotherapy, the patient became comatose and died. Histological examination of the tumor specimen showed characteristics similar to those of the first tumor. Late recurrence of medulloblastoma is rare, and a latency period of 19 years is the longest reported. This case violates Collins' rule and exceeds other proposed periods of risk. Extension of the period of follow-up in patients with medulloblastoma is advocated.

Adult↗

Different expression patterns of nitric oxide synthase isozymes in various gynecological cancers.

The expression of nitric oxide synthase (NOS) in human gynecological cancers, including ovarian cancers, uterocervical cancers, and endometrial cancers for example, was examined by the reverse transcriptase/polymerase chain reaction, coupled with Southern hybridization and by immunohistochemistry. Nitric oxide synthase II (NOS II), an inducible form, was expressed in more than 90% of the cancers. Nitric oxide synthase I (NOS I), a neuronal form, was expressed in 58% of all the ovarian cancers, in which the serous type is found more frequently (5 out of 7) than the mucinous type (2 out of 6), and in all clear-cell cancers. The frequency of NOS I expression in uterocervical cancers and endometrial cancers was relatively low. Nitric oxide synthase III (NOS III), an endothelial form, was detected in 25% of ovarian and 33% of endometrial cancers, while no expression was detected in uterocervical cancers. In terms of cancer types, all clear-cell adenocarcinomas and most of the serous-type adenocarcinomas expressed both NOS I and NOS II, while most uterine squamous carcinomas and endometrial adenocarcinomas expressed only NOS II. However, there was no correlation between the frequency of NOS expression and patients' age or the clinical stage of the disease. Since NO increases vascular permeability and blood flow, the high frequency of NOS expression in gynecological cancers may serve to stimulate and promote tumor growth.

Blotting, Southern↗

Experimental small bowel transplantation using newborn intestine in rats: II. Revascularization of newborn intestine is independent of vascular endothelial growth factor.

BACKGROUND: Fetal and newborn intestine often are revascularized after subcutaneous transplantation without surgical vascular anastomosis. However, the mechanism of this ability remains unclear. METHODS: First, the ability of natural revascularization in newborn organs was tested. Newborn organs in whole (liver, kidney, heart, intestine, spleen, and pancreas) were grafted i nto the subcuta neous tissue of the adult rat and evaluated histopathologically 2 weeks after transplantation. Second, expression of vascular endothelial growth factor (VEGF) mRNA in the intestinal graft was determined before and after transplantation. Finally, we tested whether the free graft survival of newborn intestine was interrupted by TNP-470, an antiangiogenic agent. RESULTS: Spleen and intestine were revascularized at a higher rate (91.6%, 75%, respectively), and kidney and heart grafts survived at a lower rate (41.7%, 25%, respectively). But all of liver and pancreas grafts failed to be revascularized. VEGF mRNA was not induced in the course of revascularizing. Furthermore, TNP-470 did not interfere with neovascularization of the newborn intestinal graft in vivo. CONCLUSIONS: Each organ had an organ-specific angiogenic activity. Neovascularization of intestinal graft was not dependent on VEGF expression.

Angiogenesis Inhibitors↗

Experimental small bowel transplantation using newborn intestine in rats: I. Lipid absorption restored after transplantation of nonvascularized graft.

BACKGROUND/PURPOSE: Utilizing the characters of neovascularized activity of newborn organs, the authors developed a rat model of small bowel transplantation with a free graft of newborn intestine into the recipient's omentum. METHODS: Segmental intestine from newborn rats were grafted into the omentum without vascular anastomosis in a syngeneic combination (n = 19). The transplanted intestine was examined morphologically and electrophysiologically 4 weeks after grafting. Then, recipients' small intestine was totally substituted by the transplanted newborn intestine, and recipients' survival was recorded after orthotopical reconstruction. During the experimental periods, feces of these rats were collected, and total lipid excretion was measured. The short-gut rats, whose small bowel was totally resected, served as a control (n = 12). RESULTS: Thirteen of 19 grafts (68.4%) were judged as a histologically mature intestine. They showed typical slow waves that were identical to those of native small intestine. After all of the mature grafts were interposed, six recipients (46.2%) survived longer than 15 weeks. Control short gut animals severely lost weight and died except for one. CONCLUSION: Newborn intestinal transplantation could restore severe weight loss in the short-gut rats and save them.

Animals↗