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Biomedical subjects

H Nakai

Publications and source records attributed to H Nakai.

At least 163 records · Page 9Linked to original sources
PubMed1994

Enantiomeric separation of drugs by affinity electrokinetic chromatography using dextran sulfate.

Dextran sulfate (sodium salt), which is a mixture of a linear alpha-(1,6)-linked D-glucose polymer having a sulfate group in the molecule, has been employed as a chiral selector in affinity electrokinetic chromatography (EKC) for the separation of enantiomers of drugs. Enantiomers of trimetoquinol hydrochloride and its positional isomer have been successfully separated by the method using a 3-5% dextran sulfate buffer solution of pH 5.5 within 20 min. The effects of buffer pH, concentration of dextran sulfate, and additives (such as an organic solvent, urea and a surfactant) on the enantioselectivity were investigated. The choice of pH and the concentration of dextran sulfate has been important for the improvement in selectivity.

Buffers↗
PubMed1994

The fate of the adult exstrophy patient.

Between 1968 and 1993, 101 patients with bladder exstrophy or incontinent epispadias underwent surgery at our hospital. The standard procedure was ureterosigmoidostomy and additional genital reconstruction. Of the 56 patients who have reached adulthood 45 could be interviewed regarding social integration, sexuality and fertility. All patients have a functioning urinary diversion. Of the 45 patients questioned 41 have completed vocational training or are currently in training, 3 are unemployed and 1 lives at a therapeutic center. Among the patients 29 are married or have a steady partner. All women engage in sexual intercourse and 2 have delivered 3 children by cesarean section. All men achieve erection. Of the 28 men who underwent reconstruction of the external genitalia 11 have a penile deviation, which is distressing in only 2. Only 3 of the men are dissatisfied with the cosmetic result and 33% had epididymitis, necessitating 2 orchiectomies and 3 vasectomies. No patient with reconstruction of the external genitalia can ejaculate normally or has fathered children, whereas all 5 who did not undergo genital reconstruction had normal ejaculation and 2 have fathered children. Male patients with genital reconstruction and closure of the urethra have a high risk of infertility. Our patients demonstrate that the cosmetic results after genital reconstruction are satisfactory. However, in male patients, surgery is performed at the expense of fertility. Because this corrective procedure is usually performed during childhood, the parents must be informed of these consequences before surgical correction.

Adolescent↗
PubMed1994

Abnormal factor VIII Hiroshima: defect in crucial proteolytic cleavage by thrombin at Arg1689 detected by a novel ELISA.

We have established an ELISA for detecting thrombin cleavage of the FVIII light chain at Arg1689. The method used a coating alloantibody which recognized amino acid residues 2248-2312 in the C2 domain, together with a second monoclonal antibody, NMC-VIII/10, which recognized residues 1675-1684 in the amino-terminal region of the light chain. FVIII antigen (FVIII:Ag) was measured after treatment of plasma with various concentrations of thrombin. The FVIII:Ag of normal plasma was reduced in a dose-dependent manner by the thrombin, falling to 28% in the presence of 100 U/ml enzyme. The concentration of thrombin that achieved 50% reduction (IC50) was approximately 1.0 U/ml. The plasma of four haemophilia A positive (A+) and two haemophilia A reduced (AR) patients were analysed. The IC50 of all patients was more than 1.0 U/ml, indicating that thrombin cleavage of the FVIII light chain was defective. One haemophilia A+ plasma did not respond to thrombin in this ELISA system. The patient (TI) was a haemophiliac with FVIII coagulant activity of 0.04 U/ml and FVIII:Ag of 1.78 U/ml. In addition, immunoblotting of the purified FVIII from TI showed that thrombin cleavage of the 80 kilodalton (kD) light chain was impaired. The patient's DNA was amplified using the polymerase chain reaction with a set of synthetic oligonucleotide primers spanning amino acid residues 1646-1714. Sequence analysis of the amplified DNA fragments revealed a cytosine to thymine transition, converting an arginine 1689 to cysteine. This abnormal FVIII was designated as FVIII Hiroshima. Our ELISA system is a simple and useful method of evaluating the proteolytic cleavage by thrombin at Arg1689.

Arginine↗
PubMed1994

Prognostic significance of loss of a chromosome 17p and p53 gene mutations in blast crisis of chronic myelogenous leukaemia.

In 31 cases of chronic myelogenous leukaemia (CML) we examined the prognostic significance of chromosomal loss of a 17p and p53 mutations at the onset of blast crisis (BC). p53 mutations were closely related to a shortened survival in CML-BC (P < 0.005 by the logrank test), whereas loss of a 17p by itself was not a poor prognostic indicator. The prognostic significance of loss of a 17p, however, emerged when combined with its predominance in the metaphases analysed. This predominance might easily and rapidly be screened by polymerase chain reaction-based analysis in about half of the cases.

Adolescent↗
PubMed1994

Multiple aberrant splicing of the p53 transcript without genomic mutations around exon-intron junctions in a case of chronic myelogenous leukaemia in blast crisis: a possible novel mechanism of p53 inactivation.

We found three truncated p53 transcripts in a patient with chronic myelogenous leukaemia in blast crisis carrying chromosome 17 abnormalities. Sequencing of these transcripts revealed complete absence of the entire exons 7, 8 and 9 in one, exons 8 and 9 in another, and exon 10 in the other. Sequencing analysis of genomic DNA, however, revealed no mutation in exons 6-10 and their flanking introns. These results suggest that the aberrant p53 transcripts in this case might not result from splicing mutations but from an unknown affected splicing process.

Base Sequence↗
PubMed1994

Novel antitumor sesquiterpenoids in Achillea millefolium.

Three new antitumor sesquiterpenoids, achimillic acids A, B and C, were isolated as methyl esters from Achillea millefolium and their structures were determined spectroscopically. The compounds were found to be active against mouse P-388 leukemia cells in vivo.

Animals↗
PubMed1994

Mapping of the human gene for inducible heme oxygenase to chromosome 22q12.

Heme oxygenase is an essential enzyme in heme catabolism that cleaves heme to form biliverdin, releasing carbon monoxide and iron. There are two isozymes of heme oxygenase: heme oxygenase 1 (HO-1) and heme oxygenase 2, each of which is encoded by a separate gene. It is noteworthy that HO-1 is inducible by various environmental factors, while heme oxygenase 2 is not. Here we have localized the human HO-1 gene to chromosome 22 by polymerase chain reaction (PCR) analysis of human-hamster somatic cell hybrids. The precise region of the HO-1 locus was then determined by fluorescence in situ hybridization, revealing that the human HO-1 gene is localized to 22q12.

Animals↗
PubMed1994

Syntheses of o-methacryloyl-N-acyl tyrosines and their adhesiveness to un-etched human dentin.

O-Methacryloyl-N-acyl tyrosines (MAATY) having acyl groups with the various chain length were synthesized and the strength of bonding agents, consisting of MAATY as an adhesive monomer, to unetched human dentin was studied to elucidate the relationship between the molecular structure of MAATY and its adhesive characteristics. Increasing the flexibility of the carboxyl group of tyrosine favors the interaction with the tooth substrate, causing strict bonding. Also, the properties of the neighboring carboxyl group, i. e., steric hindrance and hydrophobicity, hydrophobic-hydrophilic balance in the monomer, and shrinkage of the monomer at copolymerization, are considered important. Especially, steric hindrance of the substituted group neighboring the carboxyl group of tyrosine would play an extremely important role in the adhesion of O-methacryloyl-N-octanoyl tyrosine. The maximum tensile bond strength was obtained with a bonding agent consisting of O-methacryloyl-N-hexanoyl tyrosine (15 mol%) and hydroxyethyl methacrylate (85 mol%), and the strength (4.75 MPa) was the maximum in all methacrylates with phenylalanine as a bone structure.

Acid Etching, Dental↗
PubMed1994

[Reflux nephropathy within first year of life. Studies of its clinical features and kidney scar-formation according to treatment modalities].

Clinical data of 106 patients (177 renal units) with vesicoureteral reflux diagnosed within first year of life were reviewed to clarify its clinical feature and reflux nephropathy. 1) 82.1% (87/106) of them were boy, 83.1% (147/177) of renal units had high grade reflux (VUR grade III or more). These findings suggested that some of them were Fetal Vesicoureteral Reflux. 2) At presentation, 57.1% (101/177) of renal units showed renal parenchymal scars and 18.9% (20/106) of cases had renal dysfunction (s-Cr > or = 0.6 mg/dl). Renal dysplasia or hypoplasia was found in rather high incidence of 8.5% (15/177) suggested that normal fetal nephrogenesis is also disturbed in early infants having VUR. 3) The patients having multiple renal scarring bilaterally had significant impaired both tubular and glomerular function, showing reflux nephropathy. 4) During more than 2 years follow-up on 102 renal units, totally 29 of them (28.4%) showed new scar-formation and/or scar-advancement. Among the kidneys more than grade III reflux and undergone antireflux surgery, those with delayed surgery had the incidence of new scar-formation and/or scar-progression as high as 48.6% (18/37). On the other hand, in those with immediate surgery, the incidence was much lower of 14.3% (5/35). In addition, the incidence in case of non-surgery was 38.5% (5/13). Indication or timing of antireflux surgery for infants is still controversial however, the above results suggest that early antireflux surgery which aimed to eliminate reflux and risk of upper urinary tract deterioration from infantile immatured kidney is more beneficial in order to prevent progression of renal scarring and attain normal renal development.(ABSTRACT TRUNCATED AT 250 WORDS)

Cicatrix↗
PubMed1994

[Scrotal calcification associated with hydrocele testis in a child: a case report].

Scrotal calcification is a rare complication of childhood hydrocele testis. Herein, a 12-year-old boy who suffered from left hydrocele testis with intrascrotal calcification is reported. The boy had experienced scrotal pain about 6 months prior to the first visit to our hospital, and gradually noted scrotal swelling. Physical examination revealed left scrotal enlargement with transillumination. Sonographic examination revealed a left hydrocele testis, and a 1.5 cm discrete focus of calcification was found immediate cranio-lateral to the left testis, contour, size and consistency of which were palpated normally. In left hydrocelectomy, no appendix epididymidis was found. A smooth, white, spherical, firm body connecting to the head of the epididymidis was removed. A microscopic examination revealed multiple layers of collagenous tissue with the necrotic tissue in the core. We concluded that this case presented with hydrocele testis secondary to a growing calcification reacting to the infarction due to the repeated torsion of the appendix epididymidis.

Calcinosis↗
PubMed1994

Pharmacokinetic properties of E3810, a new proton pump inhibitor, in healthy male volunteers.

E3810 is a new H+,K(+)-ATPase inhibitor with a substituted benzimidazole, which is under clinical investigation for peptic ulcer treatment in Japan and the USA. Three separate studies were conducted to evaluate the safety and to establish the pharmacokinetic profile of E3810 after oral administration to healthy male subjects. E3810 was administered as: single oral doses (1, 3, 10, 20, 40 and 80 mg) in fasting conditions, a single oral dose (20 mg) after a meal and repeated oral doses (20 and 40 mg) once daily for 7 days. The concentrations of E3810 and its metabolites in plasma and urine were determined by HPLC methods with UV detection. E3810 was generally well tolerated by all subjects. In the single-dose study, Cmax and AUC increased with increasing doses in the dose range examined. The mean plasma half-life was about 1.0 hour and was dose-independent. The apparent oral clearance of E3810 ranged from 4.37 to 8.40 ml/min/kg. No significant deviation from linear pharmacokinetics was observed. Approximately, 30% of a dose was excreted into the urine as thioether carboxylic acid-E3810 and its glucuronide. The mean serum protein binding was 96.3%. No effect of food intake on the Cmax and AUC was observed while tmax after a meal was 1.7 hours longer than that in the fasting conditions. No appreciable change in drug pharmacokinetics was observed during repeated oral dosing of E3810.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1994

[Clinical effects of a combination treatment with fosfomycin and clavulanic acid/ticarcillin for infections in patients complicated with hematological disorders].

We evaluated clinical effects and toxicities of a combination of fosfomycin (FOM) and clavulanic acid/ticarcillin (CVA/TIPC) for treatment of infections complicated with hematological disorders in 61 patients. Fifty-eight patients were evaluable, including 40 with acute leukemia, 13 with malignant lymphoma and 5 with other hematological disorders. Clinical efficacies were excellent in 21 cases, good in 13 cases, fair in 2 cases and poor in 22 cases. The efficacy rate was 58.6% (34 cases/58 cases). This treatment was also effective in 12 of 20 cases in which granulocyte counts were less than 500/microliters through the course of administration. No subjective side effects were observed. Abnormal values in laboratory tests were noted in 1 case. Mild elevations of GOT and GPT were observed. Thus, the combination of FOM and CVA/TIPC is an effective and safe regimen for the treatment of infections in patients complicated with hematological disorders.

Adolescent↗
PubMed1994

N-ras mutation and karyotypic evolution are closely associated with leukemic transformation in myelodysplastic syndrome.

We performed a longitudinal analysis of the karyotypes and N-ras gene configuration of bone marrow cells in 35 patients with myelodysplastic syndrome (MDS). Karyotypic evolution was found in eight patients, and was associated with disease progression, including leukemic transformation, in all the patients. We identified N-ras mutations in six patients, using a polymerase chain reaction (PCR) technique, in which oligonucleotide primers were constructed with induced mismatches, followed by endonuclease digestion. Direct sequencing confirmed single base substitutions at codon 12 in two patients and at codon 13 in four. The incidence of N-ras gene mutations was significantly higher in the karyotypically evolved group (five of eight patients) than in the stable group (one of 27 patients). All of five patients harboring both karyotypic evolution and an N-ras mutation showed concomitant disease progression to overt leukemia or refractory anemia with excess of blasts in transformation (RAEB-T). Two of four patients with either karyotypic evolution or N-ras mutation and six of 26 patients without any of these alterations also progressed to overt leukemia. Our results indicate that the accumulation of these genetic alterations is closely associated with leukemic transformation of MDS, although other genetic alterations may also play a key role in the remaining patients.

Adult↗
PubMed1994

Analysis of mutations and expression of GAP-related domain of the neurofibromatosis type 1 (NF1) gene in the progression of chronic myelogenous leukemia.

We investigated mutations in the GTPase activating protein-related domain of the neurofibromatosis type 1 gene (NF1-GRD) and its expression in each phase of chronic myelogenous leukemia (CML). Samples from 45 cases in chronic phase (CP), 41 in acute phase, and four CML cell lines were examined for mutations in the NF1-GRD by single-strand conformation polymorphism (SSCP) analysis and allele specific restriction analysis (ASRA). No mutations were detected in the exon where frequent mutations have recently been reported in human tumors, namely the FLR exon. We also examined for point mutations of the N-ras gene but found no mutations either. In 23 samples from CML cases and four CML cell lines, expression of two types of the NF1-GRD transcripts, type I and type II, were examined by NF1-GRD-specific polymerase chain reaction-based densitometric analysis and by the quantitative assay with coamplification of the NF1-GRD and beta-actin transcripts. Consequently, although expression level of type I transcripts varied among the samples, type II expression was increased in CML cell lines and a minor increase in type II expression was observed in the samples in acute phase compared with CP. However, this difference in type II expression between CP and acute phase was so small that changes of NF1-GRD transcripts as well as NF1-GRD or N-ras mutations might not be responsible for the progression of CML.

Alleles↗
PubMed1993

Amplification of bacteriophage Mu DNA by rolling circle DNA replication in vitro.

When mini-Mu DNA was allowed to transpose and replicate in vitro over a prolonged period, the products consisted not only of simple inserts and cointegrates but also high molecular weight DNA many times the unit length of mini-Mu. This high molecular weight product contained predominantly full-length mini-Mu DNA and relatively little non-Mu DNA (the vector harboring the mini-Mu element and the target for transposition in the reaction system). It arose from rolling circle DNA replication of templates created by intramolecular strand transfer, which is catalyzed by Mu transposition proteins. A donor substrate, which is a supercoiled plasmid bearing a mini-Mu element, gave rise to large amounts of the high molecular weight product provided that the vector segment outside the mini-Mu element was 2 kilobase pairs or more. When a donor substrate had a vector segment of only 600 base pairs, the mini-Mu element first had to transpose to a larger circular target before giving rise to the high molecular weight product. These results suggest a mechanism by which Mu DNA can be amplified for lytic development without transposing multiple times. By establishing a circular template, multiple copies of Mu can be processively generated from a single initiation event.

Bacteriophage mu↗
PubMed1993

Determination of aspoxicillin in broncho-alveolar lavage fluid by high-performance liquid chromatography with photolysis and electrochemical detection.

A determination method for the penicillin antibiotic aspoxicillin in broncho-alveolar lavage fluid has been developed, involving high-performance liquid chromatography and post-column photolysis. The method enabled the determination of aspoxicillin at concentrations below 100 ng/ml, with a linear calibration curve at concentrations of 1-1000 ng/ml for 100 microliters of lavage fluid. The detection limit was 1 ng/ml at a signal-to-noise ratio of 3:1.

Amoxicillin↗