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Biomedical subjects

T Ikegami

Publications and source records attributed to T Ikegami.

At least 91 records · Page 5Linked to original sources

Prediction of effectiveness of shunting in patients with normal pressure hydrocephalus by cerebral blood flow measurement and computed tomography cisternography.

Measurement of cerebral blood flow (CBF) and computed tomography (CT) cisternography were performed in 37 patients with a tentative diagnosis of normal pressure hydrocephalus (NPH) to predict their surgical outcome. The mean CBF of the whole brain was measured quantitatively by single photon emission computed tomography with technetium-99m-hexamethylpropylene amine oxime before surgery. The results of CT cisternography were classified into four patterns: type I, no ventricular stasis at 24 hours; type II, no ventricular stasis with delayed clearance of cerebral blush; type III, persistent ventricular stasis with prominent cerebral blush; type IV, persistent ventricular stasis with diminished cerebral blush and/or asymmetrical filling of the sylvian fissures. The mean CBF was significantly lower than that of age-matched controls (p < 0.005). Patients with a favorable outcome had a significantly higher mean CBF than patients with an unfavorable outcome (p < 0.005). Patients with the type I pattern did not respond to shunting. Some patients with type II and III patterns responded to shunting but improvement was unsatisfactory. Patients with type IV pattern responded well to shunting, and those with a mean CBF of 35 ml/100 g/min or over achieved a favorable outcome. The combination of CBF measurement and CT cisternography can improve the prediction of surgical outcome in patients with suspected NPH.

Adult↗

Deletion variant of hepatocyte growth factor prolongs allograft survival after liver transplantation in rats.

BACKGROUND: Despite continued progress in the development of immunosuppressive agents, allograft rejection remains an important cause of morbidity and mortality after liver transplantation. We examined the effect of the deletion variant of hepatocyte growth factor (dHGF) on allograft rejection after liver transplantation. METHODS: Male Dark Agouti rats (RT1a) were selected as donors and male Lewis rats (RT1l) as recipients for a rejection model. The recipients were divided into 2 groups after orthotopic liver transplantation (OLTx): in the dHGF group dHGF was given intravenously twice a day (1 mg/kg/day) after OLTx, whereas in the control group vehicle buffer was given intravenously daily twice after OLTx. The survival period, serum chemistry studies, and histopathologic findings were then compared between the 2 groups. RESULTS: The mean survival period after OLTx in the dHGF group was significantly longer than that in the control group (21.4 +/- 1.3 days vs 11.8 +/- 0.4 days, P < .001). On the 10th posttransplant day the serum albumin level significantly improved in the dHGF group (P < .01), and the serum total bilirubin and aspartate aminotransferase levels were significantly lower in the dHGF group (P < .01 and P < .05, respectively). On the 10th posttransplant day a histologic examination revealed no apparent difference in the severity of rejection between the 2 groups. The number of proliferating cell nuclear antigen-positive hepatocytes in the dHGF group significantly increased (P < .01), whereas the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling-positive hepatocytes were significantly reduced in the dHGF group (P < .01) in comparison with those in the control group. CONCLUSION: dHGF has an antiapoptotic property as well as a proliferative and protective effect on hepatocytes under allograft rejection. dHGF might serve as a novel agent for reducing the harmful effects of hepatic allograft rejection in rats.

Amino Acid Sequence↗

The chemopreventive role of ursodeoxycholic acid in azoxymethane-treated rats: suppressive effects on enhanced group II phospholipase A2 expression in colonic tissue.

Great interest has been focused on the chemoprevention of colonic carcinogenesis by oral administration of ursodeoxycholic acid (UDCA) because its administration reportedly reduces the incidence of colon cancer in animal experiments. To elucidate the precise role of UDCA in the chemoprevention of azoxymethane-induced colon carcinogenesis, we examined the expression levels of group II phospholipase A2 in the colonic tissue of UDCA-treated and untreated rats and correlated the levels with the findings of aberrant crypt foci, putative preneoplastic lesions. Twelve weeks after azoxymethane exposure, the total number of aberrant crypt foci in 0.4% UDCA-fed rats and 1% UDCA-fed rats was significantly decreased compared to the untreated animals. The mucosal concentrations of PGE2 and 6-keto PGF1alpha were significantly lower in the UDCA-treated rats than in untreated rats. In correlation with lowering, the enhanced activity, protein mass and mRNA levels of group II phospholipase A2 were significantly attenuated in the UDCA-treated animals. The chemopreventive role of UDCA in colon carcinogenesis may lie in its modulation of the arachidonate metabolism in colonic mucosa.

Animals↗

Four novel mutations of the connexin 32 gene in four Japanese families with Charcot-Marie-Tooth disease type 1.

DNA-based mutation analysis on the connexin 32 gene was performed in 49 families with Charcot-Marie-Tooth disease (CMT) type 1 but without duplication involving the chromosomal region, 17p12-p11.2. Mutations were identified in five of the 49 families, and four of the five mutations were hitherto undescribed: Va137Met, Glu57His, Arg142Glu, Val177Ala. X-linked CMT sometimes lacks evidence for X-linked transmission and cannot be differentiated from CMT type 2, especially in females with mildly decreased nerve conduction velocity. Therefore, molecular analysis is useful for molecular pathology of their disease.

Adolescent↗

Novel mutations of the glutaryl-CoA dehydrogenase gene in two Japanese patients with glutaric aciduria type I.

We identified three different point mutations in the glutaryl-CoA dehydrogenase (GCDH) gene in two unrelated Japanese patients with glutaric aciduria type I (GA-I). One patient was a homozygote for Arg355His and the other a compound heterozygote for Ser305Leu and Met339Val. Arg355His and Met339Val are mutations hitherto undescribed, and all three mutations are predicted to alter the secondary structure of GCDH. Molecular analysis is useful for definite diagnosis and/or prenatal diagnosis of GA-I.

Amino Acid Metabolism, Inborn Errors↗

Evolution of strategies in the three-person iterated prisoner's dilemma game.

A three-person iterated prisoner's dilemma (3p-IPD) game is studied. The present simulation uses a lattice model of finite state automata. In particular, the similarity between a noisy 2p- and a noiseless 3p-IPD game is discussed. It is known that, due to the noise, Tit for Tat loses its robustness and is taken over by more complex strategies in a noiseless IPD game. But in the 3p-IPD game, even without noise, Tit for Tat loses its robustness and is also taken over by more complex strategies. It is found that similar strategies take over Tit for Tat in both situations. We thus remark that the role of noise in the two person game is replaced by the third player in the three-person game. As a result, the strategies diversify in both the noisy 2p- and the quiet 3p- IPD game. It is also found that game strategies in an automaton form can be understood as a combination of defensive and offensive substructures. A recognition of these substructures enables us to study the mechanism of robustness in the strategies of the 3p-IPD game.

Animals↗

Relationship between in vivo FK506 clearance and in vitro 13-demethylation activity in living-related liver transplantation.

BACKGROUND: Although it is important to maintain an appropriate blood concentration of FK506 after liver transplantation, significant interindividual variability in the actual FK506 dosage has been observed, presumably due to the wide variability of cytochrome P450 3A4 activity in liver microsomes. METHODS: A study was conducted in patients undergoing living-related liver transplantation and their donors to investigate the relationship between the in vitro FK506 demethylation activity in graft liver microsomes and the in vivo blood clearance of FK506. Liver biopsy tissue was obtained from 17 living donors to measure the in vitro formation rate of 13-demethyl derivative (M-I: the major metabolite of FK506). Erythromycin N-demethylation activity in vitro was also assessed in 11 cases. The FK506 blood clearance (CLss) was calculated from its constant infusion rate and steady-state blood concentration on day 4 after transplantation in 17 recipients. RESULTS: The FK506 infusion rate varied 4.6-fold from 8.3 to 38.4 ng/min/kg. The mean CLss of FK506 was 22.1+/-10.8 ml/min (10.1-45.2 ml/min). The M-I formation rate showed a wide variability, ranging from 0.098 to 0.571 nmol/min/mg protein. A significant correlation was observed between the in vitro estimated total metabolic ability of the graft for FK506 (M-I formation rate x graft weight) and the in vivo CLss of FK506 (r=0.770, P<0.001). Erythromycin N-demethylation (0.066-0.443 nmol/min/mg protein) showed a strong correlation with the M-I formation rate (r=0.891, P<0.01). CONCLUSIONS: The in vivo FK506 clearance can mainly reflect in vitro FK506 demethylation activity.

Adolescent↗

Novel breakpoints of the EWS gene and the WT1 gene in a desmoplastic small round cell tumor.

We report here a 15-year-old boy with an intraabdominal desmoplastic small round cell tumor (DSRCT). Cytogenetic analysis of the tumor cells showed the chromosomal translocation (11;22). Reverse-transcriptase polymerase chain reaction and sequencing analysis revealed a chimeric transcriptional message of the EWS gene exon 10 fused to the WT1 gene exon 8. The typical chimeric transcript seen in DSRCT is an in-frame fusion of EWS exon 7 to WT1 exon 8. The tumor in this case had a novel and longer chimeric transcript, which should be a potent transcription factor. Genetic analysis is a very powerful and specific aid in the differential diagnosis of small round cell tumors.

Abdominal Neoplasms↗

Concomitant caudate lobe resection as an option for donor hepatectomy in adult living related liver transplantation.

In this article, we describe a successful adult living related partial liver transplantation (LRLT) using the left lobe with the left-side caudate lobe (the Spiegel lobe and the left side of the paracaval portion). The size of the donor's left lobe was 29% of the recipient's standard liver volume and did not seem to meet our criteria for adult-to-adult LRLT. However, the donor had a thick left-side caudate lobe. The estimated volume of the left lobe with the left-side caudate lobe was 32%, which met our criteria for the adult recipient. The recipient's CT scan on day 87 after transplantation showed the preserved blood flow and no biliary congestion in the left-side caudate lobe, which suggests maintenance of lobe function. This procedure may be an option for adult-to-adult LRLT in which the donor has a thick left-side caudate lobe.

Adult↗

Cerebral blood flow measurement in patients with impaired consciousness: usefulness of 99mTc-HMPAO single-photon emission tomography in clinical practice.

The relationship between impairment of consciousness and quantitative cerebral blood flow (CBF) was investigated. The mean CBF of the whole brain was measured by the Patlak-plot method using technetium-99m hexamethylpropylene amine oxime single-photon emission tomography (99mTc-HMPAO SPET) in patients with the following diseases: cerebral infarction, intraparenchymal haemorrhage, subarachnoid haemorrhage, brain tumour and cerebral contusion. The clinical symptoms were evaluated according to the severity of impaired consciousness, aphasia and dementia. Four hundred and eighty-five CBF measurements were performed. Patients with alert consciousness showed an age-related decline in mean CBF. Patients with aphasia showed a significant reduction in mean CBF compared with those without aphasia. Impaired consciousness was proportional to reduction in mean CBF regardless of types of pathology, and the size of lesion did not influence the mean CBF. Patients with dementia showed a significant reduction in mean CBF proportional to the severity of dementia. The quantitative measurement of CBF using 99mTc-HMPAO SPET is reliable in clinical evaluations.

Adolescent↗

Novel mutations of the peripheral myelin protein 22 gene in two pedigrees with Dejerine-Sottas disease.

Peripheral myelin protein 22 (PMP22), a membrane glycoprotein, plays a significant role in the formation and/or maintenance of compact myelin in the peripheral nervous system. We studied two pedigrees with Dejerine-Sottas disease and identified two novel mutations in the PMP22 gene: one a 2-bp deletional mutation at nucleotide positions 426 and 427 of exon 4 (this is predicted to alter the reading frame at leucine 80 and thus to lead to frame-shifted translation), and the other a guanine to thymine substitution at nucleotide position 636 leading to a cysteine substitution for glycine 150. Both mutations were located in the putative transmembrane domains reported in many cases of Charcot-Marie-Tooth neuropathy, Dejerine-Sottas disease, and hereditary neuropathy with liability to pressure palsies. The results suggest an important role for the putative transmembrane domains of PMP22 in its function.

Adult↗

Survival of patient with late onset hepatic failure by living-related liver transplantation from maternal donor with incompatible blood type.

A 14-year-old girl with blood type B with late onset hepatic failure (LOHF) of unknown cause has survived through living-related liver transplantation (LRLT). No hepatitis virus, including HAV, HBV, HCV, and HGV, was positive at the onset of LOHF. Autoimmune hepatitis was thought to be the cause because of positive results for serum anti-nuclear antibody at 80 times dilution and elevated gamma-globulin, but treatment with glucocorticoid did not suppress the progressive hepatic failure. Supportive therapy, including pulse therapy with 1g methylprednisolone for 3 days, ursodesoxycholic acid, branched-chain amino acid, and azathioprine did not resolve the hepatic failure. She was treated by repeated plasmapheresis and plasma absorption for 10 months, and then received the left lobe of her mother's liver. (Her mother's blood type was AB). The patient had been well, being treated with tacrolimus and prednisolone, although the serum titer of anti-blood type B antibody was high just after LRLT and mild liver dysfunction continued for more than 3 years after LRLT. Follow-up biopsy 3 years after LRLT revealed chronic hepatitis and progression to liver cirrhosis. Re-transplantation is now under consideration; the patient is now aged 19 years.

ABO Blood-Group System↗

Solution structure of the DNA- and RPA-binding domain of the human repair factor XPA.

The solution structure of the central domain of the human nucleotide excision repair protein XPA, which binds to damaged DNA and replication protein A (RPA), was determined by nuclear magnetic resonance (NMR) spectroscopy. The central domain consists of a zinc-containing subdomain and a C-terminal subdomain. The zinc-containing subdomain has a compact globular structure and is distinct from the zinc-fingers found in transcription factors. The C-terminal subdomain folds into a novel alpha/beta structure with a positively charged superficial cleft. From the NMR spectra of the complexes, DNA and RPA binding surfaces are suggested.

Amino Acid Sequence↗

Neonatal hyperbilirubinemia and mutation of the bilirubin uridine diphosphate-glucuronosyltransferase gene: a common missense mutation among Japanese, Koreans and Chinese.

We analyzed the bilirubin uridine diphosphate-glucuronosyltransferase (B-UGT) gene in 42 Japanese newborns with hyperbilirubinemia and determined that 21 infants were heterozygous while 3 was homozygous for Gly71Arg. Allele frequency of Gly71Arg was 0.32 in newborns with hyperbilirubinemia, which was significantly higher than 0.13 in healthy Japanese controls. This mutant allele is also prevalent among Korean and Chinese healthy controls with a frequency of 0.23 in both populations. However, this mutation was not detected in 50 healthy German controls. These data suggest that the high frequency of the Gly71Arg mutation of the B-UGT gene is associated with high incidence of neonatal hyperbilirubinemia in Japanese, Korean and Chinese populations.

Alleles↗

Living related liver transplantation in adults.

OBJECTIVE: To evaluate the outcome of living related liver transplantation (LRLT) in adult patients and to assess graft size disparity and graft regeneration. SUMMARY BACKGROUND DATA: Although LRLT has been accepted as an optional life-saving procedure for pediatric patients with end-stage liver disease, the feasibility of LRLT for adult patients has not been reported with reference to a clinical series. METHODS: Adult-to-adult LRLT was performed using whole left lobar grafts in 13 patients (5 with primary biliary cirrhosis, 6 with familial amyloid polyneuropathy, 1 with biliary atresia, and 1 with citrullinemia). The 13 donors comprised 5 husbands, 3 sons, 2 sisters, 2 fathers, and 1 mother. The ratio of the graft volume to standard liver volume (GV/SV ratio) was calculated for use as a parameter of graft size disparity. RESULTS: Although the liver graft was markedly small for size (GV/SV ratio 32%-59% at the time of LRLT), none of the 13 patients developed postoperative liver failure. Eleven of the patients are still alive and well with satisfactory graft function 2 to 35 months after LRLT. Graft liver volume increased rapidly after LRLT and approximated the standard liver volume with time. CONCLUSIONS: Our LRLT program for adult patients has produced good results. LRLT in adults can be indicated for selected donor-recipient combinations.

Adult↗

Chitosanase activity of the enzyme previously reported as beta-1,3-1,4-glucanase from Bacillus circulans WL-12.

Chitosanases 33 kDa and 40 kDa in size were detected in the culture supernatant of Bacillus circulans WL-12. One of the two chitosanases, chitosanse 40 (40-kDa chitosanase) has been shown to be identical to the enzyme which has been reported previously as a beta-1,3-1,4-glucanase by Bueno et al. The enzyme has been classified into family 8 glycosyl hydrolases together with the enzymes formally known as cellulase family D. This enzyme named chitosanase 40/beta-1,3-1,4-glucanase hydrolyzed both chitosan and beta-1,3-1,4-glucan with similar efficiency. However, the production of the enzyme was induced with chitosan but not by beta-1,3-1,4-glucan. Therefore, it seems possible that the major substrate of this enzyme is chitosan rather than beta-1,3-1,4-glucan. Analysis of degradation products generated from partially N-acetylated chitosan showed that chitosanase 40/beta-1,3-1,4-glucanse hydrolyzes GlcN-GlcN and GlcN-GlcNAc linkages but not GlcNAc-GlcNAc nor GlcNAc-GlcN. The specificity for hydrolyzing linkages of this enzyme is similar to that of the chitosanase from S. griseus HUT6037.

Bacillus↗