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Biomedical subjects

H Kikuchi

Publications and source records attributed to H Kikuchi.

At least 55 records · Page 3Linked to original sources
PubMed2001

Improved outcome of adult T cell leukemia/lymphoma with allogeneic hematopoietic stem cell transplantation.

Adult T cell leukemia/lymphoma (ATL) is a poor prognosis T cell malignancy. In order to improve the outcome, we employed allogeneic stem cell transplantation (allo-SCT) for ATL in 10 patients, nine of whom were from HLA-identical siblings and one from an unrelated donor. Conditioning regimens varied among the patients except that all received total body irradiation. The patients tolerated the regimens well with mild, if any toxicity, and engraftment occurred in all cases. Median leukemia-free survival after allo-SCT was 17.5+ months (range 3.7-34.4+). Six of the 10 patients developed acute GVHD (one case each with grade I, III or IV, and three cases with grade II) and three patients developed extensive chronic GVHD. Four patients died after allo-SCT during the study period from either acute GVHD (grade IV), pneumonitis, gastrointestinal bleeding or renal insufficiency. Two of the 10 cases with no symptoms of GVHD relapsed with clinical ATL. These results strongly suggest that allo-SCT may improve the survival in ATL if a controlled degree of GVHD develops.

Adult↗
PubMed2001

Long-term production of erythropoietin after electroporation-mediated transfer of plasmid DNA into the muscles of normal and uremic rats.

The anemia associated with chronic renal failure is one of the best target diseases for erythropoietin (Epo) gene transfer. We previously reported a short-term (1 month) study of continuous rat Epo delivery by muscle-targeted gene transfer of plasmid DNA expressing rat Epo (pCAGGS-Epo) using in vivo electroporation in normal rats. Here, we performed a long-term pharmacokinetic study of continuous Epo delivery by this method in normal rats and uremic five-sixths nephrectomized rats. In normal rats, Epo gene expression and sufficient erythropoiesis occurred with Epo gene transfer in a dose-dependent manner, and persisted for at least 11 weeks. Repeated administration of the plasmid DNA effectively produced erythropoiesis. Similar erythropoiesis was observed in the uremic rats, and persisted for more than 15 weeks. Both normal and uremic rats showed a significant decrease in platelet count. Moreover, the uremic rats showed Epo-induced hypertension, which is the major side-effect of recombinant human Epo. These results demonstrate that muscle-targeted pCAGGS-Epo transfer by in vivo electroporation is a useful procedure for the long-term continuous delivery of Epo in both normal and uremic rats.

Animals↗
PubMed2001

Antibody elimination by apheresis in living donor liver transplant recipients.

In the present study, we investigated retrospectively the indications and the efficacy of the elimination of preexisting antiallogeneic antibodies in liver transplant recipients. Three patients who were ABO blood type incompatible were subjected to plasmapheresis and double filtration plasmapheresis before the living donor liver transplantation (LDLTx), and the titers decreased to less than 8. After transplantation, plasmapheresis was also performed in 3 cases, and continuous hemodiafiltration in 1 case, and in 2 out of these 3 patients acute rejection was recognized. Two patients who were crossmatch positive were subjected to plasmapheresis before transplantation, and the T warm titers were reduced to less than Score 2. These 2 patients had no acute rejections after transplantation. We conclude that in liver transplant patients apheresis is effective to prevent acute rejection induced by preexisting anti-A and/or anti-B antibodies and anti-donor specific antibodies before transplantation, but it is not effective in a patient with accelerated humoral rejection occurring after transplantation.

ABO Blood-Group System↗
PubMed2001

Experience with artificial liver support in 16 living related liver transplant recipients.

This study was a retrospective investigation about the indication and efficacy of artifical liver support for liver transplant recipients. Apheresis was performed in 16 of 41 patients subjected to living related liver transplantation (LRLTx) as articial liver support, including plasmapheresis (PP) in 13 cases, continuous hemodiafiltration (CHDF) in 7 cases, and plasma adsorption (PA) in 2 cases. One patient with cryptogenic liver cirrhosis was subjected to PP before the LRLTx, and the result was satisfactory. On the contrary, the results of PP and CHDF for graft, respiratory, or cardiac failure were not acceptable. Only 1 patient survived despite multiple organ failure. Both PP and PA for patients with hyperbilirubinemia were effective and improved their critical conditions. We conclude that apheresis for liver transplant patients is effective to treat hyperbilirubinemia, but it is not indicated for respiratory and cardiac failure nor for hepatic failure.

Adolescent↗
PubMed2001

Isolated diffuse mesangial sclerosis and Wilms tumor suppressor gene.

Diffuse mesangial sclerosis is a rare renal disease, occurring either in isolation or as part of Denys-Drash syndrome. Denys-Drash syndrome originates from mutations of the Wilms tumor suppressor gene (WT1 ). We describe the presence of WT1 mutations in 7 Japanese children with isolated diffuse mesangial sclerosis.

Female↗
PubMed2001

Subclinical hepatic dysfunction in laparoscopic cholecystectomy and laparoscopic colectomy.

Laparoscopic surgery causes a reduction in hepatic blood flow due to a number of factors, including raised intra-abdominal pressure, the neurohumoral response to surgical stress and the effect of patient position. The clinical significance of the phenomenon is not fully understood. Plasma concentrations of alcohol dehydrogenase (AD) and glutathione S-transferase (GST), which are concentrated in the centrilobular acinus of the liver, sensitively reflect hepatic hypoperfusion, and can be used to monitor reductions in hepatic blood flow. We compared perioperative AD, GST, aspartate aminotransferase (AST, normal range 14-32 IU litre(-1)) and alanine aminotransferase (ALT, normal range 8-41 U litre(-1)) concentrations in patients undergoing laparoscopic cholecystectomy or laparoscopic colectomy to study how patient position and surgical manipulation of the liver affect hepatocellular integrity during laparoscopy. There were significant postoperative increases in AD and GST in the cholecystectomy group [mean (SD) peak concentration 10.8 (4.7) U litre(-1) and 113 (55) microg litre(-1) respectively]. Although the duration of pneumoperitoneum was longer in the colectomy group, there were no comparable perioperative increases in AD and GST in this group [peak concentration 4.0 (4.0) U litre(-1) and 33 (35) microg litre(-1) respectively]. AST and ALT on the first postoperative day were significantly higher in the laparoscopic cholecystectomy group (41 and 34 U litre(-1) respectively) than in the laparoscopic colectomy group (24 and 18 U litre(-1); P<0.05 for each). These results indicate that patient position and the effects of surgical manipulation of the liver affect perioperative hepatic perfusion significantly.

Adult↗
PubMed2001

Various indigestible saccharides enhance net calcium transport from the epithelium of the small and large intestine of rats in vitro.

An Ussing chamber technique was used to determine the effects of six indigestible saccharides on net Ca absorption from the luminal side to the basolateral side of isolated preparations of rat jejunal, ileal, cecal and colonic epithelium in vitro. The concentrations of Ca in the Tris buffer solution on the serosal side and on the mucosal side were 1.25 and 10 mmol/L, respectively. After a 30-min incubation, the Ca concentration in the serosal medium was determined and the net transepithelial Ca transport was calculated. The addition of 0.1-200 mmol/L maltitol, difructose anhydride (DFA)III, DFAIV, raffinose, fructooligosaccharide (FOS) or polydextrose (PD) to the mucosal medium increased the net Ca absorption dose-dependently in the jejunum, ileum, cecum and colon preparations. The threshold concentration required to enhance Ca transport and the extent of enhancement of Ca transport differed among the saccharides tested and among the portions of the intestine examined. Among the saccharides tested, DFA IV had the strongest effect on Ca absorption in the jejunum and cecum. We conclude that indigestible carbohydrates directly affect the epithelial tissue and promote Ca absorption in both the small and large intestine in vitro.

Animals↗
PubMed2001

Novel bifunctional hyperthermostable carboxypeptidase/aminoacylase from Pyrococcus horikoshii OT3.

Genome sequencing of the thermophilic archaeon Pyrococcus horikoshii OT3 revealed a gene which had high sequence similarity to the gene encoding the carboxypeptidase of Sulfolobus solfataricus and also to that encoding the aminoacylase from Bacillus stearothermophilus. The gene from P. horikoshii comprises an open reading frame of 1,164 bp with an ATG initiation codon and a TGA termination codon, encoding a 43,058-Da protein of 387 amino acid residues. However, some of the proposed active-site residues for carboxypeptidase were not found in this gene. The gene was overexpressed in Escherichia coli with the pET vector system, and the expressed enzyme had high hydrolytic activity for both carboxypeptidase and aminoacylase at high temperatures. The enzyme was stable at 90 degrees C, with the highest activity above 95 degrees C. The enzyme contained one bound zinc ion per one molecule that was essential for the activity. The results of site-directed mutagenesis of Glu367, which corresponds to the essential Glu270 in bovine carboxypeptidase A and the essential Glu in other known carboxypeptidases, revealed that Glu367 was not essential for this enzyme. The results of chemical modification of the SH group and site-directed mutagenesis of Cys102 indicated that Cys102 was located at the active site and was related to the activity. From these findings, it was proven that this enzyme is a hyperthermostable, bifunctional, new zinc-dependent metalloenzyme which is structurally similar to carboxypeptidase but whose hydrolytic mechanism is similar to that of aminoacylase. Some characteristics of this enzyme suggested that carboxypeptidase and aminoacylase might have evolved from a common origin.

Amidohydrolases↗
PubMed2001

Prolonged mild hypothermia therapy protects the brain against permanent focal ischemia.

BACKGROUND AND PURPOSE: The efficacy of hypothermic intervention for permanent focal ischemia has yet to be clarified. This study investigated the effect of a prolonged moderate or mild hypothermia on permanent focal ischemia in rats. METHODS: Two permanent focal ischemia models in male Sprague-Dawley rats were used. Moderate (30 degrees C, in experiment 1) or mild (33 degrees C, in experiment 2) hypothermia was achieved at the time of the induction of focal ischemia and was maintained for 2 hours under general anesthesia. Thereafter, the hypothermic condition was maintained by means of a cold room for a total of 24 hours. The infarct volume and neurological function were analyzed for a maximum of 21 days and compared with that of the normothermia group. Regional cerebral blood flow was monitored for 6 hours in the ischemic core and penumbra region. RESULTS: In experiment 1, the total infarct volume in the normothermic group was 368+/-59 mm(3); in contrast, it was significantly smaller in the hypothermia group: 169+/-33 mm(3) at 48 hours (mean+/-SEM, P:<0.05). In experiment 2, the infarct volume was 211+/-19 mm(3) in the normothermia group and 88+/-15 mm(3) in the hypothermia group at 21 days (P:<0.05). There were significant differences in neurological function from days 2 through 21 between the two groups. Mean regional cerebral blood flow in the penumbra region increased to a level >50% of baseline. CONCLUSIONS: Prolonged mild hypothermia suppressed the development of cerebral infarct and neurological deficit chronically after the induction of permanent focal ischemia.

Animals↗
PubMed2001

Broad-spectrum and selective serine protease inhibitors prevent expression of platelet-derived growth factor-BB and cerebral vasospasm after subarachnoid hemorrhage: vasospasm caused by cisternal injection of recombinant platelet-derived growth factor-BB.

BACKGROUND AND PURPOSE: Plasma serine protease cascade, including the complement system and thrombin, is activated in the subarachnoid space during the acute phase after subarachnoid hemorrhage (SAH). To examine the effect of protease cascade-based inflammation and subsequent vascular repair in the development of cerebral vasospasm, we examined the effect of 2 synthetic serine protease inhibitors-FUT-175, an inhibitor of thrombin and the complement system, and argatroban, a selective inhibitor of thrombin-on the development of cerebral vasospasm in a rabbit SAH model. METHODS: One hundred Japanese White male rabbits were used in the study. The SAH was simulated by a single injection of autologous arterial blood into the cisterna magna. To evaluate the development of cerebral vasospasm, the caliber of the basilar artery was measured on x-ray film before and at 2 days after SAH. Nine groups of rabbits (n=6 each) were treated with continuous intravenous injection of FUT-175 (2.5, 5, 10, or 20 mg/d), argatroban (1.25, 2.5, or 5 mg/d), or the same amount of saline (vehicle) for 48 hours, starting 40 minutes after SAH. Two days after SAH, the expression of homodimer of platelet-derived growth factor-BB (PDGF-BB) in the basilar artery was examined with immunohistochemical techniques. In 20 normal rabbits, 5 microg of recombinant PDGF-BB or vehicle was injected into the cisterna magna, and the basilar arteries were examined on angiograms for 48 hours. RESULTS: Significant differences were observed in the caliber of the basilar arteries between the vehicle group and the groups with the 3 larger doses of FUT-175 (vehicle, 52+/-5.0%; 5 mg, 79+/-5.7%; 10 mg, 80+/-2.5%; 20 mg, 80+/-3.7%) and between the vehicle group and the groups with the 2 larger doses of argatroban (vehicle, 52+/-6.4%; 2.5 mg, 81+/-9.0%; 5 mg, 85+/-4.1%) (P<0.05). In the histological examination, administration of effective doses of FUT-175 or argatroban suppressed the expression of PDGF-BB in the endothelial and medial smooth muscle cell layers. Exogenous PDGF-BB caused delayed and prolonged vasoconstriction on normal basilar arteries. CONCLUSIONS: Activation of the serine protease cascade and/or thrombin after SAH was demonstrated to play an essential role in the development of cerebral vasospasm. The expression of PDGF-BB-like protein in the arterial walls correlated with the development of cerebral vasospasm. Elevated PDGF-BB level in the subarachnoid space was found to induce delayed and chronic vasoconstriction.

Animals↗
PubMed2001

Ebselen reduces cytochrome c release from mitochondria and subsequent DNA fragmentation after transient focal cerebral ischemia in mice.

BACKGROUND AND PURPOSE: The seleno-organic compound ebselen has both antioxidant and anti-inflammatory properties. Although ebselen has been shown to protect the brain against stroke, it is unclear how ebselen provides neuroprotection. In the present study the authors examined whether ebselen inhibits neuronal apoptosis resulting from transient focal cerebral ischemia in mice. The cytochrome c release and DNA fragmentation, both of which are biochemical markers of apoptosis, were compared between vehicle- and ebselen-treated mice. METHODS: Cerebral ischemia was induced by transient middle cerebral artery occlusion for 30 minutes in ICR mice under halothane anesthesia. Ebselen (10 mg/kg) was given orally twice, 30 minutes before ischemia and 12 hours after reperfusion. By Western blot analysis, we examined release of mitochondrial cytochrome c. To evaluate brain damage, the brain sections were treated for terminal deoxynucleotidyl transferase-mediated DNA nick-end labeling (TUNEL) and Nissl staining. Prolonged neuroprotective efficacy of ebselen was determined by counting neuronal nuclei (NeuN) immunopositive cells at 21 days after ischemia. RESULTS: - Cytochrome c release was detected in the ischemic hemisphere at 3 to 24 hours after ischemia. Ebselen treatment diminished the cytochrome c release at 12 and 24 hours. In addition, ebselen decreased both DNA fragmentation determined by TUNEL and brain damage volume at 3 days after ischemia. Furthermore, ebselen increased the number of NeuN immunopositive cells at 21 days after ischemia. CONCLUSIONS: These results indicate that ebselen attenuates ischemic neuronal apoptosis by inhibiting cytochrome c release. Ebselen may be a potential compound in stroke therapy.

Animals↗
PubMed2001

A novel WT1 gene mutation associated with wilms' tumor and congenital male genitourinary malformation.

WT1 is located on the short arm of human chromosome 11 and consists of 10 coding exons. Mutations of this gene have been reported to be the cause of Wilms' tumor, congenital male genitourinary malformations, and/or renal disorders. We describe here a novel WT1 gene mutation, i.e. a point mutation at intron 7 (+2) in both the tumor and the germline cells of a patient with Wilms' tumor and congenital male genitourinary malformation, but without renal disorder. The position of the mutation is at a splice donor site of intron 7, which causes the splicing out of exon 7 and generates a truncated protein. This type of mutation in the WT1 zinc finger domain has not been reported before. The mutation is of paternal origin and is heterozygous in the germline cells. In the tumor cells, however, the maternal allele is largely lost, from 11p12 to 11p15, which results in maternal loss of heterozygosity. These results, together with the data from previous reports, suggest that WT1 may function in gonadogenesis, nephrogenesis, and Wilms' tumor tumorigenesis.

Chromosomes, Human, Pair 11↗
PubMed2001

The change in characteristics of microcrystalline cellulose during wet granulation using a high-shear mixer.

The objective of this study was to investigate the mechanism of hard granule formation and to demonstrate the applicability of X-ray diffraction methods for studying the polymeric pharmaceutical excipients. Using a high-shear mixer, microcrystalline cellulose (MCC) was granulated with water as the granulating liquid. The hardness of the MCC granules increased with granulation time and the amount of water added. The specific surface area measured by the N2 adsorption method was reduced during the process. Crystallite size of cellulose, calculated by Scherrer's equation adapted for wide angle X-ray diffraction method, decreased with granulation time and with increasing amounts of water added. Debye plots for X-ray small scattering patterns suggested that the average magnitude of the continuous solid region in MCC granules became significantly greater, whereas the specific surface area of the MCC granules, calculated from Debye plots, became smaller in comparison with that of intact MCC. These findings suggested that the long-chain structures in MCC were disrupted, resulting in smaller units with shorter chain lengths due to the strong shear force of the impeller. These smaller units then form a network within the granules. Thus, MCC granules are strengthened with longer granulation time and greater amounts of water, resulting in a more intricate network. The change in MCC chain length and physical structure can be experimentally detected using the small-angle X-ray scattering and wide-angle powder X-ray diffraction methods.

Cellulose↗
PubMed2001

Interaction of microcrystalline cellulose and water in granules prepared by a high-shear mixer.

Microcrystalline cellulose (MCC) granules were prepared by wet granulation using a high-shear mixer. Physical characteristics of the granules were investigated using near IR spectrometry, thermogravimetry and isothermal water vapor adsorption. Near IR spectra of dried MCC granules prepared for various granulation times exhibited different peak intensities at 1428, 1772, and 1920 nm, which were assigned to functional groups of cellulose or water. On isothermogravimetric analysis, the rate of dehydration of water was shown to decrease with granulation time. These results suggest that the physical structure of MCC could change during the granulation process, and the interaction between MCC and water was gradually strengthened. The isothermal water vapor adsorption curves suggested that the amorphous region of MCC would be divided by the strong shear force of the impeller, because the high adsorption ability of intact MCC in the low humidity region was diminished in granules collected following 5 and 10 min of granulation. It was suggested that MCC formed a network which caught water within its structure during the wet granulation process.

Cellulose↗
PubMed2001

Comparison of the upper gastrointestinal effects of etodolac and aspirin in healthy dogs.

Fifteen healthy castrated male dogs were separated into three treatment groups that were administered etodolac, aspirin and a placebo orally, respectively. All treatments were continued for 28 days. The animals were examined endoscopically on days 0, 3, 7, 10, 14, 17, 21, 24 and 28. There were no gastrointestinal mucosal lesions in either the etodolac or the placebo group, whereas some gastric lesions developed in the aspirin group after day 17. We considered that etodolac could be used for long-term treatments in dogs with fewer side-effects on the gastric mucosa than aspirin.

Animals↗
PubMed2001

Titanium casting: the surface reaction layer of castings obtained using ultra-low-temperature molds.

To examine whether the surface reaction layer of titanium castings can be reduced by lowering the mold temperature during casting, we cast titanium at three mold temperatures, including an ultra-low temperature produced by cooling the mold with liquid nitrogen, then measured the tensile strength and elongation of the castings. The titanium was cast using a centrifugal casting machine, and the molds were incinerated according to the manufacturers' instructions. Castings were then made with the molds at 200 degrees C, 600 degrees C, and an ultra-low temperature (-196 degrees C). The castability of titanium cast in the mold at the ultra-low temperature was good. The Vickers hardness near the surface layer of castings decreased as the mold temperature decreased.

Cold Temperature↗
PubMed2001

[A case of AFP-producing gastric cancer responding to low-dose CPT-11 and low-dose cisplatin combination chemotherapy].

UNLABELLED: Gastric cancers that produce alpha feto protein (AFP) usually have a poor prognosis. We report an AFP-producing gastric cancer that showed a partial response to low-dose CPT-11 and low-dose cisplatin combination chemotherapy. AFP-producing gastric cancers successfully treated with chemotherapy have been reported, but to our knowledge this is the first report of successful treatment with low-dose CPT-11 and low-dose cisplatin combination chemotherapy. CASE: A 49 year-old woman who had gastric cardiac cancer with esophageal invasion was admitted to our institution. Since AFP-positive cells were demonstrated immunohistochemically in biopsy specimens and levels of AFP in serum were high, AFP-producing cancer was diagnosed. Because of metastasis to Virchow's node and the paraaortic lymph nodes, the tumor was considered unresectable. The patient's poor general condition necessitated chemotherapy with low toxicity and high efficacy. She was treated with low-dose CPT-11 and low-dose cisplatin combination chemotherapy. After two cycles of this treatment, the tumor volume and the serum levels of AFP had decreased markedly. The only side effect of the treatment was leukopenia.

Antineoplastic Agents↗