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Biomedical subjects

Hiroyuki Kobayashi

Publications and source records attributed to Hiroyuki Kobayashi.

At least 37 records · Page 2Linked to original sources

The role of monocyte chemoattractant protein-1 in biliary atresia.

BACKGROUND: The aim of this study was to explain the role of monocyte chemoattractant protein-1 (MCP-1) in biliary atresia (BA). METHODS: Concentrations of serum MCP-1 and collagen type IV were measured in 38 patients with BA by using commercially available kits. MCP-1 was also assessed in liver biopsy specimens by using immunohistochemistry. Subjects were classified into groups. Group 1 comprised BA patients with normal liver function (n = 13), group II comprised BA patients with moderate liver dysfunction (n = 18), group III comprised BA patients older than 20 years awaiting liver transplantation (n = 7), and the control group comprised age-matched patients without evidence of liver disease (n = 23). RESULTS: Serum MCP-1 levels were significantly increased in group II compared with group I (P < .0001) and the control group (P < .0001). Serum MCP-1 levels in group III were lower than in the control group (P < .0001). There was a significant linear correlation between serum MCP-1 levels and type IV collagen levels in group II. Group II subjects with portal hypertension (PH) had higher MCP-1 levels than those without PH (P = .0009). Biopsy specimens showed MCP-1 was expressed mainly on biliary epithelial cells, vascular endothelial cells, and hepatocytes in group II. CONCLUSIONS: These findings suggest that MCP-1 probably plays a significant role in the development of progressive liver fibrosis in BA.

Adolescent↗

Laparoscopy-assisted transanal pull-through at the time of suction rectal biopsy: a new approach to treating selected cases of Hirschsprung disease.

AIM: We present a new approach to treating selected cases of Hirschsprung disease (HD) where suction rectal biopsy (SRBx) is performed in an operating room, and rapid acetylcholinesterase staining (RAST) is used to identify histopathology within 20 minutes, allowing primary laparoscopy-assisted transanal pull-through (PLTPT) to be commenced "immediately" (n = 7). MATERIALS AND METHODS: All subjects had an obvious caliber change in the rectum/sigmoid colon on barium enema and were strongly suspected of having HD. RESULTS: Rapid acetylcholinesterase staining clearly demonstrated acetylcholinesterase-positive hypertrophic nerve trunks and absence of ganglion cells in all SRBx specimens, indicating that all 7 patients had HD. All 7 proceeded to uneventful PLTPT. By taking this approach, SRBx results were available extremely quickly, and hospital stay was reduced by 2 to 4 days. DISCUSSION: Our approach enhanced the treatment of selected cases of HD by proceeding immediately to PLTPT after SRBx specimens were examined using RAST.

Acetylcholinesterase↗

DNA-binding properties of the antibody specific for the Dewar photoproduct of thymidylyl-(3-5')-thymidine.

A monoclonal antibody (DEM-1) specific for the Dewar photoproduct is used for detection and quantification of photolesions in DNA. To help understand the molecular recognition of damaged DNA by the antibody protein, we have cloned and sequenced the variable region genes of DEM-1. We have also prepared Fab fragments of DEM-1 (DEM1Fab), and synthesized two kinds of 3'-biotinylated oligonucleotides of different lengths containing a central Dewar photoproduct of TpT to analyze the effects of the antigen size on the binding rates by means of surface plasmon resonance (SPR). Results obtained from SPR analyses suggest that DEM1Fab may recognize tetranucleotide unit as the epitope.

Amino Acid Sequence↗

Obstruction due to rectal cuff after laparoscopy-assisted transanal endorectal pull-through for Hirschsprung's disease.

We report a case of persistent obstruction after laparoscopy-assisted transanal endorectal pullthrough for Hirschsprung's disease in a 4-week-old boy with biopsy-proven HD. Before pull-through, the posterior rectal cuff was split along its entire length cranially, starting from the dentate line. Initial recovery was uneventful; however, signs of obstruction developed 3 weeks postoperatively. Reoperation through a posterior sagittal approach confirmed a residual rectal cuff surrounding the neo-rectum circumferentially. The dorsal side of the residual rectal cuff was removed completely. At follow-up 5 years later, he defecates 2 to 4 times a day with occasional staining. We hypothesize that the persistent postoperative obstruction was caused by a long residual rectal cuff that spontaneously reapproximated and/or became folded during pull-through. Therefore, a shorter cuff with near-total posterior excision should be strongly considered during laparoscopy-assisted transanal endorectal pull-through for Hirschsprung's disease.

Hirschsprung Disease↗

Edaravone reduces myocardial infarct size and improves cardiac function and remodelling in rabbits.

1. In the present study, we investigated the effect of 3-methyl-1-phenyl-2-pyrazolin-5-one (edaravone), a free radical scavenger, on myocardial infarct (MI) size and cardiac function in an in vivo model of MI in rabbits. We further investigated the contribution of hydroxyl radicals, superoxide and nitric oxide (NO) to its effects. 2. Anaesthetized open-chest Japanese white male rabbits were subjected to 30 min coronary occlusion and 48 h reperfusion. The control group (n = 10) was injected with saline 10 min before reperfusion. The edaravone group (n = 10) was injected with a bolus of 3 mg/kg edaravone 10 min before reperfusion. The edaravone + N(G)-nitro-L-arginine methyl ester (L-NAME) group (n = 5) was given 10 mg/kg, i.v., L-NAME 10 min before the administration of 3 mg/kg edaravone. The L-NAME group (n = 5) was given 10 mg/kg, i.v., L-NAME 20 min before reperfusion. Infarct size was measured using the triphenyl tetrazolium chloride method and is expressed as a percentage of area at risk. Cardiac function was assessed by echocardiography 14 days after infarction. 3. In another series of experiments, rabbits were subjected to 30 min coronary occlusion and 30 min reperfusion and myocardial interstitial 2,3-dihydroxybenzoic acid (DHBA) and 2,5-DHBA levels, indicators of hydroxyl radical, were measured using a microdialysis technique. 4. Infarct size in the edaravone group was significantly reduced compared with that in the control group (27.4 +/- 6.8 vs 43.4 +/- 6.8%, respectively; P < 0.05). The edaravone-induced reduction of infarct size was abolished by pretreatment with L-NAME. Myocardial interstitial levels of 2,3-DHBA and 2,5-DHBA increased 20 and 30 min after ischaemia and peaked at 10 min reperfusion in the control group. Edaravone significantly inhibited the increase in 2,3-DHBA and 2,5-DHBA levels seen during reperfusion. Dihydroethidium staining showing in situ detection of superoxide was less intense in ischaemic myocardium in the edaravone-treated group compared with the control group. Edaravone improved cardiac function and left ventricular remodelling 14 days after infarction. 5. In conclusion, edaravone significantly reduces MI size and improves cardiac function and LV remodelling by decreasing hydroxyl radicals and superoxide in the myocardium and increasing the production of NO during reperfusion in rabbits.

Animals↗

Cystic meningioangiomatosis.

A case of cerebral meningioangiomatosis with rare cyst formation is reported. A 14-year-old boy without any stigmata of neurofibromatosis type 2 presented intractable complex partial and generalized seizures since the age of 12 years. Neuroradiological studies showed an abnormal cystic mass with calcification in the left frontal lobe of the cerebrum. The tumor was located in the leptomeninges and cerebral cortex. The patient underwent surgical treatment because medical treatment with phenytoin and sodium valproate was not sufficient to control the seizures. An intraoperative electrocorticogram revealed that epileptic foci were recorded from the cortex, which was adjacent to the lesion. Histopathology showed specific features of meningioangiomatosis with meningioma-like nodules. The patient did not have any seizures with anticonvulsants after surgery. It is important to distinguish meningioangiomatosis from other possible cortical lesions and epileptic foci should be carefully considered before resection, because it is a benign and surgically manageable cause of seizures.

Adolescent↗

Combined effects of benidipine and diltiazem on cardiohemodynamics in anesthetized dogs.

We examined the combined effects of the calcium channel blockers 1,4-dihydropyridine (benidipine) and benzothiazepine (diltiazem) on cardiohemodynamics in anesthetized dogs. Benidipine (3 microg/kg) lowered blood pressure (BP) slightly and continuously increased coronary flow (CF). Diltiazem (300, 1000 microg/kg) decreased BP, heart rate (HR), and the maximum rate of rise of left ventricular pressure (LV dP/dt max) with the increase of doses. Diltiazem increased CF, though it was transient when compared to benidipine. A combination of benidipine (3 microg/kg) and diltiazem (300 microg/kg) showed continuous decreases in BP, HR, and LV dP/dt max, and an increase in CF that was similar to that recorded for the benidipine group. The level of double product (DP: systolic BPxHR, an index of myocardium energy consumption) in the combination group was significantly lower than that of the benidipine group. The plasma concentrations of benidipine and diltiazem in the combination group were similar to those of the groups receiving either drug. These results demonstrate that the combination of benidipine and diltiazem increases CF more continuously than diltiazem alone, and decreases DP more potently than benidipine alone, indicating that the combination therapy possesses favorable properties as a treatment for angina pectoris. Therefore, the combination of benidipine and diltiazem is suggested as a useful treatment for improving the clinical benefits of monotherapy for angina, compared with the use of diltiazem alone at higher doses.

Anesthesia↗

Nicorandil improves post-ischemic myocardial dysfunction in association with opening the mitochondrial K(ATP) channels and decreasing hydroxyl radicals in isolated rat hearts.

BACKGROUND: Nicorandil has been reported to induce cardioprotection by opening the mitochondrial K(ATP) channels. However, whether nicorandil affects reactive oxygen species is unclear. METHODS AND RESULTS: The hearts of male Sprague-Dawley rats were excised and perfused on a Langendorff apparatus with Krebs-Henseleit solution with a gas mixture of 95% O(2) and 5% CO(2). 1 mmol/L of nicorandil was given 10 min before ischemia. Left ventricular developed pressure (LVDP, mmHg), +/-dP/dt (mmHg/s) and coronary flow (ml/min) were continuously monitored. All hearts were perfused for a total of 120 min consisting of a 30 min pre-ischemic period, followed by a 30 min global ischemia and 60 min reperfusion with and without 5-hydroxydecanoic acid sodium salt (5-HD), a mitochondrial K(ATP) channel blocker. The concentrations of 2,3-dihydroxybenzoic acid (2,3-DHBA), an indicator of hydroxyl radicals, in the perfusate during reperfusion period were also measured. Nicorandil significantly improved LVDP and +/-dP/dt, and increased coronary flow during reperfusion. Pretreatment with 5-HD abolished the improvement of LVDP and +/-dP/dt, and the increase in coronary flow induced by nicorandil. Nicorandil significantly attenuated the concentrations of 2,3-DHBA during reperfusion, which were restored by 5-HD. CONCLUSION: Nicorandil is protective against post-ischemic left ventricular dysfunction in association with opening the mitochondrial K(ATP) channels, decreasing hydroxyl radicals and increasing coronary flow in the isolated rat heart.

Animals↗

Schedule-dependent interactions between pemetrexed and cisplatin in human carcinoma cell lines in vitro.

The combination of pemetrexed and cisplatin shows good clinical activity against mesothelioma and lung cancer. In order to study the potential cellular basis for this, and provide leads as to how to optimize the combination, we studied the schedule-dependent cytotoxic effects of pemetrexed and cisplatin against four human cancer cell lines in vitro. Tumor cells were incubated with pemetrexed and cisplatin for 24 h at various schedules. The combination effects after 5 days were analyzed by the isobologram method. Both simultaneous exposure to pemetrexed and cisplatin for 24 h and sequential exposure to cisplatin for 24 h followed by pemetrexed for 24 h produced antagonistic effects in human lung cancer A549, breast cancer MCF7, and ovarian cancer PA1 cells and additive effects in colon cancer WiDr cells. Pemetrexed for 24 h followed by cisplatin for 24 h produced synergistic effects in MCF7 cells, additive/synergistic effects in A549 and PA1 cells, and additive effects in WiDr cells. Cell cycle analysis of MCF7 and PA1 cells supported these findings. Our results suggest that the simultaneous clinical administration of pemetrexed and cisplatin may be suboptimal. The optimal schedule of pemetrexed in combination with cisplatin at the cellular level is the sequential administration of pemetrexed followed by cisplatin and this schedule is worthy of clinical investigations.

Carcinoma↗

[CNS sarcoidosis presenting with intracerebral hemorrhage: case report].

Sarcoidosis is a systemic, chronic inflammatory disease characterized by non-caseating epithelioid granuloma. It is well known that the central nervous system (CNS) is also involved in about 5% of patients with systemic sarcoidosis. Although CNS sarcoidosis presents with various neurological manifestations, intracerebral bleeding is quite rare. In this report, we describe a case in which a patient suffered from intracerebral hemorrhagic due to CNS sarcoidosis. A 57-year-old male who had been diagnosed as having systemic sarcoidosis was admitted to our hospital due to status epilepticus. Plain CT scan showed a subcortical hematoma in the left marginal gyrus. Serial MR imaging revealed that an enhanced mass in the overlying cortex had gradually increased its size. Subsequently, the enhanced mass and hematoma were totally removed, using a navigation system. Pathological examination revealed typical findings of sarcoidosis. We discuss the mechanism of intracerebral bleeding due to CNS sarcoidosis in this report.

Brain↗

[Temozolomide in the treatment of recurrent malignant glioma].

Temozolomide (TMZ) has demonstrated activity and acceptable toxicity for the treatment of recurrent malignant gliomas in carious prospective phase II studies. No information is, however, available on TMZ treatment for recurrent malignant glioma in Japanese patients. We report Hokkaido University Hospital experience on 35 adult patients with a recurrent malignant glioma, including 13 glioblastomas, 9 anaplastic astrocytomas, and 13 anaplastic oligondendroglial tumors. The median age was 52 years. The starting dose of TMZ was 150 mg/m2/day for 5 days. When no remarkable toxicity was observed, the dose was increased to 200 mg/m2 for subsequent cycles, every 4 week. In the 35 patients, the overall objective response rate (partial response) was 12% and 74% of the patients achieved disease stabilization. The median progression-free survival was 28 weeks and the median overall survival was 43 weeks. Although hematological toxicity was the most frequent adverse event (CTC grade 3 or 4 in 6 patients), overall toxicity was generally mild. Four patients required hospitalization due to the toxicity, but 28 patients had been treated with TMZ at our outpatient clinic. These results suggested that the reported efficacy and toxicity profile of TMZ for the treatment of Japanese patients with recurrent malignant glioma is reproducible from the setting of clinical trials in the western countries.

Administration, Oral↗

Diagnostic laparoscopy-assisted cholangiography in infants with prolonged jaundice.

Cholangiography is often crucial for establishing the definitive cause of neonatal jaundice. We present our protocol for using laparoscopy-assisted cholangiography in infants with prolonged jaundice and discuss its benefits. Firstly, a 5 mm supra-umbilical trocar is introduced to create a port for a 0 degrees laparoscope. A 5 mm trocar is then inserted through a right subcostal incision to allow the liver and gallbladder to be visualized. If the gallbladder is of good size, the fundus is exteriorized through the right subcostal trocar site and a catheter is inserted into the gallbladder for cholangiography. If the gallbladder is atretic, the fundus is not exteriorized and a laparotomy is performed for open intraoperative cholangiography because the lumen of an atretic gallbladder is usually not fully patent and cholangiography through its exteriorized fundus often fails. We reviewed 18 jaundiced infants thought to have biliary atresia (BA) who had laparoscopy-assisted cholangiography. At laparoscopy, four patients had good sized gallbladders and minimal to mild liver fibrosis. They underwent cholangiography via the exteriorized fundus, and BA in two cases and biliary hypoplasia in two cases were identified. The remaining 14 had atretic gallbladders and varying degrees of liver fibrosis. Cholangiography via the exteriorized fundus was performed in one patient, but failed and converted to open cholangiography. Open intraoperative cholangiography identified BA in all 14 cases. All BA cases progressed to Kasai portoenterostomy directly after diagnosis. Laparoscopy is used to determine the type of cholangiography to be performed based on the appearance of the gallbladder and this simple, accurate, and safe protocol allows the anatomical structure of the biliary tree to be obtained accurately with minimal surgical intervention.

Bile Ducts↗