Search PubMed⌕ Search

Biomedical subjects

Y Kohno

Publications and source records attributed to Y Kohno.

At least 19 recordsLinked to original sources
PubMed2006

Expression of Y-box-binding protein dbpC/contrin, a potentially new cancer/testis antigen.

Y-box-binding proteins are members of the human cold-shock domain protein superfamily, which includes dbpA, dbpB/YB-1, and dbpC/contrin. dbpC/contrin is a germ cell-specific Y-box-binding protein and is suggested to function as a nuclear transcription factor and RNA-binding protein in the cytoplasm. Whereas ubiquitous dbpB/YB-1 expression has been well studied in various types of human carcinomas as a prognostic or predictive marker, the dbpC/contrin expression in human tumour cells has not been reported. In this report, we provide the first evidence showing that dbpC was highly expressed in human testicular seminoma and ovarian dysgerminomas, and in carcinomas in other tissues and that its expression in normal tissues is nearly restricted to germ cells and placental trophoblasts. These results indicate that dbpC/contrin would be a potentially novel cancer/testis antigen.

Adult↗
PubMed2006

Significant correlations between the flow volume of patent ductus venosus and early neonatal liver function: possible involvement of patent ductus venosus in postnatal liver function.

BACKGROUND: The biochemical features of portosystemic venous shunt with high flow volume are hypergalactosaemia, hyperammonaemia, prolonged blood coagulation time, and raised serum bile acid concentration. The ductus venosus remains open with shunt flow in most neonates for a certain period after birth. However, the effects of blood flow through the ductus venosus on neonatal liver function remain unclear. OBJECTIVE: To elucidate the effect of patency of the ductus venosus on liver function in early neonates. METHODS: Subjects were divided into three groups by gestational age (group I, 29-32 weeks; group II, 33-36 weeks; group III, 37-41 weeks). The shunt flow volume through the ductus venosus was examined serially using ultrasonography, and correlations between flow volume and liver function in the respective groups were calculated during the first week after birth. RESULTS: Group I had a higher flow volume and later functional closure than the other two groups. Plasma ammonia and serum total bile acid concentrations correlated with flow volume in groups I and II, and blood galactose and galactose 1-phosphate concentrations correlated significantly with flow volume in group III. Percentage hepaplastin also correlated significantly with flow volume in all groups, but plasma vitamin K concentration did not in any group. CONCLUSIONS: Patent ductus venosus has a considerable effect on crucial liver functions such as ammonia detoxification, blood coagulation, and regulation of serum total bile acid concentration in early neonates.

Ammonia↗
PubMed2006

Adenosine A1 receptor antagonist improves intradialytic hypotension.

Intradialytic hypotension is a most frequent complication of hemodialysis and may contribute to cardiovascular events and high mortality. There is a hypothesis that an increase in adenosine generation during hemodialysis may cause vasodilation and a decrease in cardiac output, which results in systemic hypotension. We studied whether this can be blocked by an adenosine A1 receptor antagonist. We investigated the effects of an A1 antagonist, FK352, injection in 30 chronic hemodialysis patients with frequent intradialytic hypotension by a prospective, multicenter, double-blind placebo-controlled study for 4 weeks after 4 weeks of the observation period. Intradialytic hypotension was defined as systolic blood pressure (SBP) less than 110 mmHg, with SBP drop of more than 30 mmHg from the predialysis level. The efficacy of FK352 was primarily assessed by the reduction rate of dialysis hypotension between the FK352 and placebo groups. Incidence of emergency treatments caused by hypotension was evaluated. FK352 (50 mg, intravenous) or an equivalent placebo was injected into the dialysis circuit 1 h after starting dialysis. Blood pressure and heart rate were monitored every 30 min during dialysis. FK352 significantly improved intradialytic hypotension (P=0.046), in that the reduction rates of intradialytic hypotension in the FK352 and placebo groups were -12.8% (Q1 (first quantile), Q3 (third quantile): -27.5, -1.7), and +8.3% (Q1, Q3: -16.6, +16.7), respectively. The frequency of discontinuation of dialysis was significantly reduced by FK352. No apparent side effects were observed from treatment with FK352. In conclusion, the A1 antagonist FK352 may offer a novel therapeutic option for chronic dialysis patients associated with intradialytic hypotension.

Adenosine↗
PubMed2006

Central tegmental tract involvement in an infant with 6-pyruvoyltetrahydropterin synthetase deficiency.

We report the case of an asymptomatic 2-month-old infant with 6-pyruvoyltetrahydropterin synthetase deficiency detected through a neonatal phenylketonuria screening program. MR imaging revealed symmetrical lesions in the central tegmental tract with reduced diffusion, which resolved after treatment. A possible explanation for these lesions is intramyelinic edema resulting from brain insults in utero.

Brain↗
PubMed2005

Prediction of oral clearance from in vitro metabolic data using recombinant CYPs: comparison among well-stirred, parallel-tube, distributed and dispersion models.

Intrinsic clearances (CLint-HLM-total) for the metabolism of NE-100, metoprolol, clarithromycin (CAM), lornoxicam and tenoxicam were predicted from in vitro data with recombinant cytochorme P450s (CYPs) using relative activity factor (RAF) and then compared with CLint-HLM observed in human liver microsomes (HLM). The predicted CLint-HLM-total correlated well with the observed CLint-HLM in HLM. When oral clearances (CLoral) of low-clearance drugs such as metoprolol, CAM, lornoxicam and tenoxicam were predicted from the in vitro data using four physiological models (well-stirred, parallel tube, distributed and dispersion models), the predicted CLoral corresponded well with the observed CLoralin vivo and were similar among the four models. For a high-clearance drug, the predicted CLoral of NE-100 in extensive CYP2D6 metabolizers (EMs) was substantially different between individual models, although the predicted CLoral in a poor metabolizer of CYP2D6 (PMs) was similar. The CLoral ratio of NE-100 between the EMs and the PMs predicted from the dispersion model, which leads to a reliable prediction for the high-clearance drug, was 48.4, but the ratio decreased depending on the increase of the NE-100 plasma concentration. The results suggest that the CLoral decrease in the EMs is caused by saturation of NE-100 metabolism mediated by CYP2D6 and is based on increases in plasma NE-100 concentrations dependent on the dose of NE-100. The study suggests that the RAF and the in vitro-in vivo scaling approaches are useful for predicting CLoral from in vitro data with recombinant CYPs without using HLM and hepatocytes.

Administration, Oral↗
PubMed2005

Continuous hydrogen production from organic waste.

The antibiotic effects of lactic acid bacteria, Lactobacillus paracasei, on hydrogen production were investigated using glucose as the substrate for the batch experiments. The effects of lactic acid bacteria on hydrogen fermentation depended on pH and the inhibition of hydrogen-producing bacteria was prevented by keeping the pH over 5.0. Then, a continuous hydrogen production experiment was conducted by using bean curd manufacturing waste as an actual organic waste at pH 5.5 at 35 degrees C. The increase of the substrate concentration and the addition of nitrogen gave precedence to acetic and butyric acids production in the metabolic pathway and suppressed propionic acid production. As the result, continuous hydrogen production from municipal organic waste was enabled.

Ammonium Chloride↗
PubMed2004

Clinically mild encephalitis/encephalopathy with a reversible splenial lesion.

OBJECTIVE: To clarify whether patients with clinical diagnoses of encephalitis/encephalopathy with a reversible lesion in the splenium of the corpus callosum (SCC) share common clinical features. METHODS: Possible encephalitis/encephalopathy patients with a reversible isolated SCC lesion on MRI were collected retrospectively. Their clinical, laboratory, and radiologic data were reviewed. RESULTS: Fifteen encephalitis/encephalopathy patients with a reversible isolated SCC lesion were identified among 22 patients referred for this study. All 15 patients had relatively mild clinical courses. Twelve of the 15 patients had disorders of consciousness. Eight patients had seizures, and three of them received antiepileptic drugs. All 15 patients clinically recovered completely within 1 month (8 patients within a week) after the onset of neurologic symptoms. The SCC lesion was ovoid in six patients; it extended irregularly from the center to the lateral portion of SCC in the other eight patients. Homogeneously reduced diffusion was seen in all seven patients who underwent diffusion-weighted imaging. There was no enhancement in the five patients so examined. The SCC lesion had completely disappeared in all patients at follow-up MRI exams between 3 days and 2 months after the initial MRI (within 1 week in eight patients). CONCLUSION: The clinical features among the affected patients were nearly identical, consisting of relatively mild CNS manifestations and complete recovery within 1 month.

Adolescent↗
PubMed2004

Historical trends of PCDD/Fs and CO-PCBs in a sediment core collected in Sendai Bay, Japan.

The vertical distribution of dioxins in a sediment core was investigated to elucidate historical trends of dioxins discharged into Sendai Bay, Japan. The dioxin concentration was 410 pg/g dry weight (dw) in sediments deposited in the mid-1930s and 3870 pg/g dw in those deposited in the mid-1980s. Dioxin fluxes increased from the mid-1930s and then reached a maximum in the mid-1980s. 1,3,6,8-TeCDD+1,3,7,9-TeCDD, OCDD, and Co-PCB concentrations were 110, 140, and 26 pg/g dw, respectively, in mid-1930s sediments, and reached maximums of 1800, 1100, and 200 pg/g dw, respectively, in mid-1980s sediments. Shipments to Miyagi Prefecture of CNP and PCP products, the major sources of 1,3,6,8-TeCDD+1,3,7,9-TeCDD and OCDD, were highest in 1975 (4700t) and 1970 (3100t), respectively; and in Japan, the amount of PCBs, the major source of Co-PCB congeners, used was highest (11,100t) in 1970. Thus, the period for which the maximum concentrations of 1,3,6,8+1,3,7,9-TeCDD, OCDD, and Co-PCBs were measured in the sediment core (mid-1980s) did not correspond to the time of maximum use of CNP, PCP, or PCB products, but lagged behind by more than 10 years. We attributed this time lag to the time required for the movement of dioxins from Miyagi Prefecture to Sendai Bay.

Benzofurans↗
PubMed2004

Living-donor liver transplantation for propionic acidaemia.

Three patients with the severe form of propionic acidaemia were treated with living-donor liver transplantation (LDLT). The procedure was successful for all patients and the incidence of metabolic decompensation was reduced dramatically even without protein restriction. Biochemically, however, the improvement was not significant and the patients continued to excrete large amounts of propionic acid metabolites. One of the patients experienced a severe acidaemic episode 3 years after transplantation. LDLT has a beneficial effect on the care of severely affected patients since it reduces the risk of metabolic decompensation and improves the quality of life with less strict dietary control. Adequate protein restriction and medication need to be maintained even after successful transplantation.

Amino Acid Metabolism, Inborn Errors↗
PubMed2004

High-throughput screening for the assessment of time-dependent inhibitions of new drug candidates on recombinant CYP2D6 and CYP3A4 using a single concentration method.

1. The inhibitory effects of various test compounds on recombinant human CYP3A4 activity assayed by fluorescent metabolite formation from 7-benzyloxyquinoline (7-BQ) and the effect of pre-incubation on inhibition were evaluated using the microtitre plate assay with multiple concentrations of test compounds (multiple concentration method). 2. Among the test compounds studied, ketoconazole inhibited CYP3A4 activity most extensively, followed by miconazole, troleandomycin, terfenazine and midazolam. The IC(50) values of other compounds exceeded 10 microM, but those of many compounds decreased after pre-incubation. The inhibitory effects of verapamil, amiodarone and diltiazem after pre-incubation were 205, 154 and 833 times greater than those in the case of co-incubation, respectively. 3. To assess the inhibitory effects more readily, the validity of the microtitre plate assay with a single concentration of the test compound (single concentration method) was studied. The accuracy of the automated dispensation and the coefficient of variation on enzyme activity were approximately 3%. 4. The IC(50) values estimated using the per cent of residual activity from the single concentration method matched closely those from the multiple concentration method. When the IC(50) value as inhibitor concentration was used for a single concentration method, the method enabled easy estimation of inhibitory patterns (such as competitive or time-dependent inhibition) on cytochromes P450. Therefore, from the ease of the technique, automation of the microtitre plate assay and application of the single concentration method might be useful for inhibitory assessment of cytochromes P450 more than that of current conventional methods.

Amiodarone↗
PubMed2004

Prediction of differences in in vivo oral clearance of N,N-dipropyl-2-[4-methoxy-3-(2-phenylethoxy)phenyl] ethylamine monohydrochloride (NE-100) between extensive and poor metabolizers from in vitro metabolic data in human liver microsomes lacking CYP2D6 activity and recombinant CYPs.

1. It has previously been reported that N,N-dipropyl-2-[4-methoxy-3-(2-phenylethoxy)phenyl]-ethylamine monohydrochloride (NE-100) was predominantly metabolized by cytochrome P450 (CYP) 2D6 in human liver microsomes (HLM). In the present study, the contribution of CYP forms involved in the formation of the major metabolites of NE-100 in human liver lacking CYP2D6 activity (PM-HLM) has been predicted by use of in vitro kinetic data on recombinant CYPs microsomes (rCYPs). 2. In PM-HLM, NE-100 is predicted to be metabolized to N-despropyl-NE-100 (NE-098), p-hydroxy-NE-100 (NE-152) and m-hydroxyl-NE-100 (NE-163), but not to O-demethy-NE-100 (NE-125), which is a major metabolite in pooled human liver microsomes (EM-HLM). The relative activity factor approach assumed that NE-098 formation is predominantly catalysed by CYP3A4 and CYP2C9 and the NE-152+163mix (a mixture of two hydroxylated metabolites, NE-152 and NE-163) formation is only catalysed by CYP3A4. 3. The predicted contribution rates of CYP3A4 and CYP2C9 for NE-098 formation were 58.1 and 34.6%, respectively, in PM-HLM. These predicted results were strongly supported by kinetic and inhibition studies using PM-HLM. The intrinsic clearance of NE-100 predicted from rCYPs (the predicted CLint-HLM-total) corresponded to those observed from EM- and PM-HLM (the observed CLint-HLM). 4. The in vivo oral clearance (CLoral) of NE-100 in extensive metabolizers and poor metabolizers of CYP2D6 was predicted to be 50times higher in extensive metabolizers than poor metabolizers using in vitro-in vivo scaling method based on the dispersion model. These data suggest that polymorphism of CYP2D6 might greatly affect NE-100 metabolism in vivo.

Administration, Oral↗
PubMed2004

PCR-based capsular serotype determination of Haemophilus influenzae strains recovered from Japanese paediatric patients with invasive infection.

The serotypes of 53 isolates of Haemophilus influenzae from children with invasive infections were determined by a conventional slide agglutination test (SAT) and a recently proposed PCR-based method for serotyping H. influenzae. The PCR assay identified 47 (88.7%) type b isolates, one (1.9%) type e isolate and five (9.4%) non-typeable isolates. The only discrepancy between the methods was an isolate that was non-typeable by SAT, but was identified as serotype e by PCR. Of 41 isolates from patients with meningitis, 39 (95.1%) were type b. Of the five non-typeable isolates, three (60%) were from the blood of patients with septicaemic pneumonia and two (40%) were from the cerebrospinal fluid of patients with meningitis. None of the non-typeable isolates appeared to be a capsule-deficient mutant of an encapsulated H. influenzae strain. Overall, the study confirmed the usefulness of this PCR method for the serotyping of invasive H. influenzae isolates.

Bacterial Capsules↗
PubMed2003

Widening spectrum of congenital hemiplegia: Periventricular venous infarction in term neonates.

MRI in five term children with congenital hemiplegia without clinically apparent prenatal or perinatal difficulties showed a focal or porencephalic enlargement of the lateral ventricle and periventricular T2 prolongation, which were identical to findings of periventricular venous infarction seen in preterm children. Some cases of congenital hemiplegia in term neonates may be due to clinically silent periventricular venous infarction that occurred in utero.

Cerebral Hemorrhage↗
PubMed2003

The mitochondrial acetoacetyl-CoA thiolase (T2) deficiency in Japanese patients: urinary organic acid and blood acylcarnitine profiles under stable conditions have subtle abnormalities in T2-deficient patients with some residual T2 activity.

Mitochondrial acetoacetyl-CoA thiolase (T2) deficiency is an inborn error of metabolism affecting isoleucine and ketone bodies in the catabolic process. Mutation analysis and expression analysis of mutant cDNAs have facilitated the division of T2-deficient patients into two groups: those with null mutations in either allele (group 1) and those with mutation(s) retaining some residual T2 activity in at least one of two mutant alleles (group II). Among 5 Japanese T2-deficient patients, GK01 belonged to group I and the other patients (GK19, GK19B, GK30 and GK31) to group II. As we have suggested previously, the severity of ketoacidotic episodes in the group II patients was similar to that in the group I patient. However, the urinary organic acid and blood spot acylcarnitine profiles under stable conditions differed between the two groups. The group I patient had typical profiles for the T2 deficiency. In contrast, in all four patients in group II, tiglylglycine was not or was only faintly detected and the 2-methyl-3-hydroxybutyrate levels were less than the cutoff value. Their tiglylcarnitine levels were within the normal range and 2-methyl-3-hydroxy-, butyrylcarnitine was detected just around the cutoff value in our newborn screening pilot test. Hence, these analyses under stable conditions are not reliable for diagnosing the T2 deficiency in the group II patients. The T2 deficiency (group II) can be misdiagnosed as normal if these analyses are performed under nonepisodic conditions and possibly during the newborn screening for inborn errors of metabolism.

Acetoacetates↗