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Biomedical subjects

K Komatsu

Publications and source records attributed to K Komatsu.

At least 271 records · Page 15Linked to original sources
PubMed1993

Dose-rate effects of neutrons and gamma-rays on the induction of mutation and oncogenic transformation in plateau-phase mouse m5S cells.

The dose-rate effect of 252-californium neutrons was investigated using confluent cultures of mouse m5S cells. The relative biological effectiveness (RBE) of neutrons for oncogenic transformation was increased from 3.3 to 5.1 when the dose-rate was reduced from 1.8 to 0.12 cGy/min. Similarly, neutron RBE values for HPRT- mutation were 4.9 and 7.4 at dose-rates of 1.8 and 0.12 cGy/min, respectively. The increases in RBE as dose-rate was reduced were due mainly to diminished transformation- and mutation-induction by gamma-rays (the standard radiation). The yields of neutron-induced oncogenic transformation as well as neutron-induced mutation were constant for both dose rates. Our observation contrasts with reports by others using proliferating cells where both oncogenic transformation and mutation were enhanced with neutron exposure at a reduced dose-rate, the so-called inverse dose-rate effect. Since m5S cells are sensitive to postconfluent inhibition of cell division, this observation could be ascribed to cell growth conditions used in these experiments. The mechanism of the inverse dose-rate effect of neutrons suggests that the enhancement of neutron-induced mutation and oncogenic transformation at a reduced dose-rate is strongly associated with cell proliferation during exposure.

Animals↗
PubMed1993

Murine scid cells complement ataxia-telangiectasia cells and show a normal post-irradiation response of DNA synthesis.

The murine severe combined immunodeficient mutation (scid) is characterized by a lack of both B and T cells, due to a defect in lymphoid variable-(diversity)-joining (V(D)J) rearrangement. Scid cells are highly sensitive to both radiation-induced killing and chromosomal aberrations. Significantly reduced D0 and n values were demonstrated in scid cells and were similar to ataxia-telangiectasia (AT) cells (a unique human disease conferring whole body radiosensitivity). However, the kinetics of DNA synthesis after irradiation were different between the two cell types. In contrast with the radioresistant DNA synthesis of AT cells, DNA synthesis of scid cells was markedly inhibited after irradiation. The existence of different mutations was also supported by evidence of complementation in somatic cell hybrids between scid cells and AT cells. Our results indicate that the radiobiological character of scid is similar to AT but is presumably caused by different mechanisms.

Animals↗
PubMed1993

Functional complementation in mouse-human radiation hybrids assigns the putative murine scid gene to the pericentric region of human chromosome 8.

Fragments of human chromosome 8 were introduced into cells derived from murine scid mice via X-irradiation and somatic cell fusion. The resulting hybrid clones contained human DNA fragment(s) which complemented the hyper-radiosensitivity of the scid cells. Alu-PCR products from these hybrids were used for chromosome painting using the technique of chromosome in situ suppression hybridization, allowing assignment of the human HYRC (hyper-radiosensitivity of murine scid mutation, complementing) gene, a candidate for a V(D)J recombinase gene, to human chromosome 8q11.

Animals↗
PubMed1993

The absence of a surface protease, OmpT, determines the intercellular spreading ability of Shigella: the relationship between the ompT and kcpA loci.

A large plasmid-encoded protein, VirG, on the bacterial surface is essential for the spreading of Shigella by eliciting polar deposition of filamentous actin in the cytoplasm of epithelial cells. VirG expression from the large plasmid is diminished greatly when it is introduced into Escherichia coli K-12 from Shigella. In an attempt to identify factors affecting VirG expression, we found that the absence of the ompT gene, encoding outer membrane protease OmpT, restored full production of VirG protein to E. coli K-12. Conversely, upon introduction of the ompT gene of E. coli K-12 into Shigella, spreading ability was completely abolished, probably because of the proteolytic degradation of VirG protein by OmpT. Analysis of the DNA sequence of the ompT region indicated that the absence of the ompT gene occurred in Shigella and enteroinvasive E. coli strains, and that the absent DNA segment corresponded to a remnant lambdoid phage structure found in E. coli K-12, which encompasses a 21 kb DNA segment spanning from argU through to the ompT genes. Since ompT is located near purE in E. coli K-12 and a virulence locus for provoking keratoconjunctivitis in the eyes of guinea-pigs, named kcpA, is located near purE in S. flexneri, and the two loci are involved in VirG expression, the KcpA- mutants of S. flexneri 2a constructed were examined for correlation between acquisition of ompT and VirG degradation. Our data suggest that the previous recognition of a kcpA locus in S. flexneri is the result of transfer of the ompT gene from E. coli K-12, giving rise to a KcpA- phenotype. These results indicate that the lack of OmpT protease confers upon Shigella the ability to spread into adjacent epithelial cells.

Amino Acid Sequence↗
PubMed1993

Eight genes in region 5 that form an operon are essential for invasion of epithelial cells by Shigella flexneri 2a.

The 7-kb region 5 on the large 230-kb plasmid pMYSH6000 in Shigella flexneri 2a YSH6000 is one of the virulence-associated DNA segments required for the invasion of epithelial cells (C. Sasakawa, K. Kamata, T. Sakai, S. Makino, M. Yamada, N. Okada, and M. Yoshikawa, J. Bacteriol. 170:2480-2484, 1988). To elucidate the functional organization of region 5 and to determine the virulence-associated genes encoded by region 5, we performed insertion and deletion mutagenesis, DNA subcloning, and complete nucleotide sequencing of region 5 and found that region 5 contained 11 open reading frames (ORFs) named ORF-1 through ORF-11 which could be translated into proteins with molecular masses of 15.1, 47.5, 13.2, 33.0, 33.4, 24.2, 9.4, 28.5, 39.9, 9.1, and 10.4 kDa, respectively. Complementation tests of the 14 Tn5-induced noninvasive mutants of region 5 with the above plasmid constructs have indicated that region 5 consists of an operon and that ORF-2 through ORF-9, but not ORF-1, ORF-10, and ORF-11, are essential for invasion, and 7 of 8 ORFs (ORF-2 and ORF-4 through ORF-9) and presumably the remaining ORF (ORF-3) are required for secretion of the Ipa proteins. The transcriptional organization, as determined by a promoter-proving vector, S1 nuclease protection, and primer extension RNA sequencing analysis revealed that region 5 is transcribed from a promoter located 47 bp upstream of the 5' end of ORF-2 for the 47.5-kDa protein and that the promoter activity identified was regulated by the virB gene, the transcriptional activator on the 230-kb plasmid.

Amino Acid Sequence↗
PubMed1993

Pulmonary capillary pressure measured with a pulmonary arterial double port catheter in surgical patients.

We developed a pulmonary artery (PA) double port catheter technique for reliable clinical measurements of pulmonary capillary pressure (Ppc). In seven elective surgical patients, the PA double port catheter with the second PA port 1 cm proximal to the balloon was inserted. The two PA ports, connected to identical pressure measuring systems, provided the pulmonary arterial pressures (Ppa) distal and proximal to the balloon. After general anesthesia was stabilized, the two Ppas were measured simultaneously during a PA occlusion maneuver during 10 s of apnea. The instant of occlusion was determined precisely as the time when the two Ppa traces sharply diverged. A single exponential equation was fitted to the segment of distal Ppa tracing starting 0.3 s after the instant of occlusion. Ppc was determined as the value of the exponential fit extrapolated to time 0. In six of seven patients, PA occlusion occurred consistently in the early systolic phase regardless of the timing of balloon inflation. Mean Ppa, Ppc, and pulmonary arterial wedge pressure were 16.6, 11.8, and 7.6 torr. The ratio of venous to total resistance ranged from 0.37 to 0.54 (mean:0.46). We conclude that this technique is clinically feasible and valuable in precise definition of the instant of PA occlusion. By defining PA occlusion consistently, this technique can provide reliable Ppc estimation in the clinical settings.

Catheterization, Swan-Ganz↗
PubMed1993

Pharmacological properties of galenical preparation. XVI. Pharmacokinetics of evodiamine and the metabolite in rats.

In an attempt to evaluate its pharmacokinetics, [3H]evodiamine, which is one of the characteristic alkaloids of Evodia fruit was synthesized. The pharmacokinetics of [3H]evodiamine were investigated in rats. In plasma, the main source of radioactivity was a metabolite of d-evodiamine (EM). One hour after oral administration of 200 micrograms/kg of [3H]evodiamine, the radioactivity level in the plasma was maximal. The radioactivity declined in a biphasic manner with half-life times of 1.6 and 78.4 h. The distribution volume was 560 ml/kg. Radioactivity in tissues was higher in the liver, kidney, heart, lung, and adipose tissue than in plasma, but radioactivity in other tissues it was lower than that in plasma. In all tissues the radioactivity proportionally decreased to the level of that in plasma. At 24h after administration, 19% and 63% of orally administered radioactivity was excreted in urine and bile, respectively.

Adipose Tissue↗
PubMed1993

[Stability of allantoin and identification of its degradation compounds].

The stability of allantoin was studied in pH 3.0, 6.0, and 8.0 buffer solutions at 50 degrees C for 55 d. Allantoin was determined by high performance liquid chromatography (HPLC) with a cation exchange mode and colorimetry. The known degradation compounds, allantoic acid and glyoxylic acid, were simultaneously determined by ion chromatography. Urea was determined by HPLC with an ion pair mode. In the stability studies on pH 6.0 and 8.0 solutions, new degradation compounds of allantoin were identified as two growing unknown peaks in the HPLC chromatogram. Isolation of these compounds by preparative HPLC and 1H, 15N and 13C-NMR spectra revealed that they were condensates of allantoin and glyoxylic acid, which also reacted positively in phenylhydrazine colorimetry. The amounts of these compounds were calculated from the determination results of other allantoin related compounds in the buffer solutions and were estimated as the biggest amount among all other compound. As they were found to be stable in an alkaline solution, conditions for hydrolysis in the colorimetric determination of allantoin were further examined. It was found that the longer hydrolysis gave more than 90% recovery in the colorimetry.

Allantoin↗
PubMed1993

Testosterone normalizes plasma vasopressin response to osmotic stimuli in men with hypogonadism.

We studied plasma vasopressin concentrations during hypertonic saline infusions in 5 men with hypogonadism and 10 normal men to investigate the effect of gonadal steroid on hypothalamo-neurohypophyseal function. All the subjects received the infusion of 5% saline, and plasma vasopressin concentrations were determined by radioimmunoassay (RIA). Three of the 5 men were patients with isolated hypogonadotropic hypogonadism (IHH) and the other two were patients with Klinefelter's syndrome. None of them had any symptoms of diabetes insipidus. Although there was no difference between basal plasma osmolality in the patients and the normal subjects (287.2 +/- 2.1 vs. 285.3 +/- 1.8 mmol/kg), the basal level of plasma vasopressin in the patients was lower than that in the normal subjects (0.62 +/- 0.17 vs. 1.36 +/- 0.15 pg/ml, P < 0.05). Hypertonic saline infusion revealed varying degrees of subnormal vasopressin responses in the patients except one patient with Klinefelter's syndrome. The mean vasopressin response to osmotic stimuli (delta plasma vasopressin/delta plasma osmolality) in the 5 patients was lower than in the normal subjects (0.04 +/- 0.01 vs. 0.16 +/- 0.02, P < 0.05). Three patients with IHH and one patient with Klinefelter's syndrome were re-examined after pulsatile gonadotropin-releasing hormone (GnRH) infusion or testosterone enanthate i.m. injection. After the treatment with testosterone or GnRH, the response of plasma vasopressin to hypertonic saline infusion was normalized in three patients who had subnormal vasopressin response before treatment (delta plasma vasopressin/delta plasma osmolality: 0.04 +/- 0.01 vs. 0.09 +/- 0.01, P < 0.05). These results suggest that testosterone improves the subnormal vasopressin response to osmotic stimuli in men with hypogonadism.

Adolescent↗
PubMed1993

Improved survival following pediatric cardiac transplantation in high-risk patients.

BACKGROUND: Preoperative hemodynamic support, complex congenital heart disease, and elevated pulmonary vascular resistance present particular challenges for pediatric heart transplantation. This study was performed to identify preoperative factors that influence survival after pediatric heart transplantation over two eras of pediatric heart transplant experience. METHODS AND RESULTS: We retrospectively analyzed demographic, clinical, and hemodynamic data from 67 pediatric patients who underwent heart transplantation between February 1982 and June 1992 and compared survival between two eras (early experience versus late experience). During the early experience (group 1: February 1982 to August 1989), univariate analysis identified congenital heart disease, pretransplant extracorporeal membrane oxygenator (ECMO) support, inotropic and/or ventilatory support (UNOS status I), elevated transpulmonary gradient (at least 15 mm Hg), and elevated pulmonary vascular resistance index (at least 4 Wood units.m2) as preoperative risk factors for early death after pediatric heart transplantation. However, in the late experience (group 2: September 1989 to June 1992), the only risk factor for premature death by univariate analysis was elevated transpulmonary gradient. By multivariate analysis, elevated transpulmonary gradient was the only risk factor for our early, late, and entire experiences. One-year survival after transplantation for congenital heart disease was improved from 46% in group 1 to 73% in group 2 (P < .05). In group 1, only one patient (25%) with pretransplant ECMO support survived 1 year, whereas 66% (four of six) survived more than 1 year in group 2. CONCLUSIONS: Although elevated transpulmonary gradient continues to be a significant risk factor for pediatric heart transplantation, candidates with congenital heart disease, UNOS status I, and pretransplant ECMO support now can be successfully transplanted with reasonable hope for extended survival.

Cardiomyopathies↗
PubMed1993

Hantavirus in the southwestern United States: epidemiology of an emerging pathogen.

In May of this year, an outbreak of sudden, unexplained, and highly fatal respiratory illness of unknown etiology was identified in the four-corners region of the southwestern United States. Within 3 weeks after the collaborative response launched by the state and local health agencies in the affected area, laboratory studies from the federal Centers for Disease Control and Prevention suggested that an acute infection with a previously unrecognized Hantavirus species was responsible for the reported cluster of cases. The hantavirus associated with this outbreak has since been isolated in tissue culture, and diagnostic test systems specific for the newly identified hantavirus have been developed. This article summarizes the history of the outbreak as experienced by investigators from the Arizona Department of Health Services and reviews the epidemiologic and clinical aspects of both the current epidemic and hantaviruses in general. The sudden occurrence of acute illnesses in the Southwest due to a previously unrecognized hantavirus reaffirms that the potential for the emergence of new infectious diseases exists at any place or time in the United States. The response to the outbreak also illustrates how community clinicians and federal, state, and local health agencies work together to promptly identify the emergence of new disease threats, rapidly determine new etiologic agents, and develop and swiftly implement appropriate disease prevention and control strategies.

Adult↗
PubMed1993

Human chromosome 8 (p12-->q22) complements radiosensitivity in the severe combined immune deficiency (SCID) mouse.

The severe combined immune deficiency (SCID) mouse shows two kinds of phenotypic abnormalities, a high radiosensitivity and an abnormal immunoglobulin gene recombination. A genetic study has revealed that a mutation exists in chromosome 16. However, several attempts to isolate the gene responsible for these phenotypes have been unsuccessful. By making use of the characteristics of radiosensitivity, we conducted complementation experiments to identify a human chromosome which contains the responsible gene. Radioresistant cells were selected from the hybrid cells of the SCID mouse and human fibroblasts. Based on this approach, the gene complementing the SCID phenotype was assigned to human chromosome 8 p12-->q22.

Animals↗
PubMed1993

[Vitamin K].

In this paper, highly sensitive methods for measuring of vitamin K in serum, feces and milk are described. Vitamin K1 and the menaquinone family from the serum, feces and milk were separated by high performance liquid chromatography. The separated K1 and menaquinone families were detected by a fluorescence spectrophotometer after their reduction with sodium borohydride or platinum catalyst column. In these methods, minimum detectable quantities of K1, menaquinone-4 and menaquinone-7 were 10, 10 and 50 pg, respectively. More than 95% of supplemented vitamin K1, menaquinone-4 and menaquinone-7 were recovered in the serum and feces. Furthermore, the method of Hirauchi et al. for measurement of vitamin K1 2,3-epoxide in human plasma is introduced.

Chromatography, High Pressure Liquid↗
PubMed1992

Cloning and disruption of the cefG gene encoding acetyl coenzyme A: deacetylcephalosporin C o-acetyltransferase from Acremonium chrysogenum.

Acetyl CoA: deacetylcephalosporin C o-acetyltransferase(DCPC-ATF) catalyses the final step in the biosynthesis of cephalosporin C (CPC) in Acremonium chrysogenum. The gene encoding DCPC-ATF, cefG, has been isolated from an A. chrysogenum genomic library using a DCPC-ATF cDNA probe. Nucleotide sequence analysis revealed that cefG contains two short introns of 79bp and 65bp. The gene was found to be closely linked to the cefEF gene encoding deacetoxycephalosporin C synthetase/deacetylcephalosporin C synthetase, which catalyses the preceding two steps in the pathway. The two genes are separated by a 1114 bp segment from which they are divergently transcribed. Introduction of the cloned cefG gene to A.chrysogenum resulted in an increased level of DCPC-ATF activity. A plasmid carrying a cefG gene interrupted in the coding region by a selectable marker for resistance to hygromycin B was constructed and used to disrupt the cefG locus in A.chrysogenum. The cefG-disrupted strains were found to lack the ability to produce CPC, and accumulated its precursor, deacetylcephalosporin C in the culture broth. Southern hybridization analysis confirmed that the disruption resulted from a gene replacement event at the cefG locus.

Acetyltransferases↗
PubMed1992

Molecular cloning of acetyl coenzyme A: deacetylcephalosporin C o-acetyltransferase cDNA from Acremonium chrysogenum: sequence and expression of catalytic activity in yeast.

Acetyl CoA: deacetylcephalosporin C o-acetyltransferase(DCPC-ATF) catalyses the final step in the biosynthesis of cephalosporin C, the conversion of deacetylcephalosporin C to cephalosporin C. A cDNA encoding DCPC-ATF has been isolated from a cDNA library of a cephalosporin C producing fungus Acremonium chrysogenum using oligonucleotide probes based on N-terminal amino acid sequences of the enzyme. The cDNA contains a single large open reading frame for a putative precursor consisting of 12 amino acid(AA) leader peptide of unknown function, 274 AA large subunit and 126 AA small subunit at the carboxyl end. The cDNA was expressed in yeast exhibiting a functional DCPC-ATF activity. It was also indicated that the leader peptide was not essential for expression of the enzyme activity. The primary structure of DCPC-ATF shows significant homology with those of acetyl CoA: homoserine o-acetyltransferase in Saccharomyces cerevisiae and Ascobolas immersus.

Acetyltransferases↗
PubMed1992

The influence of pelvic nerve transection on the neuromuscular system of the canine urinary bladder.

We previously reported that bladder overdistension led to denervation and subsequent supersensitivity of the detrusor muscle to acetylcholine. Therefore, to exclude the influence of bladder overdistension, we produced a low-pressure bladder in female mongrel dogs using an indwelling urethral catheter, and performed pelvic neurectomy (decentralization). We examined the effects of decentralization on the neuromuscular system of the bladder. The contraction response levels of bladder strips in dogs 1 and 2 weeks after neurectomy was low, and significantly different from that of bladder strips in the control group. The dose-response curves of dogs 4 and 8 weeks after neurectomy showed a shift to the left when compared to those of the control group, indicating a significant increase in sensitivity of the bladder strips. Many cholinergic terminal and varicosity profiles had a normal ultrastructure in all of the groups subjected to neurectomy, while some had degenerating profiles representing clear axoplasm without any recognizable organelles. Microphotographs of bladder obtained from dogs with spontaneous catheter loss showed degenerating axons, which were observed more frequently than in bladders kept empty with indwelling urethral catheters. Micturition in the dogs with spontaneous catheter loss was achieved by overflow incontinence without catheterization. These findings suggest that post-synaptic nerve degeneration may be augmented by impairment of micturition, followed by decentralization. Our observations also suggest that post-synaptic nerve degeneration (denervation) plays an important role in the increased sensitivity of the detrusor muscle to acetylcholine in the parasympathetically decentralized urinary bladder, whether denervation is due to trans-synaptic degeneration or impairment of micturition.

Acetylcholine↗
PubMed1992

A case of tubulo-interstitial nephritis with exfoliative dermatitis and hepatitis due to phenobarbital hypersensitivity.

Severe exfoliative dermatitis and liver dysfunction developed in a 5-year-old girl 3 weeks after initiation of phenobarbital therapy. Liver function improved gradually after discontinuation of phenobarbital. During the convalescent stage an initially mild renal dysfunction was exacerbated by episodes of post-transfusion haemolysis. Liver biopsy revealed moderate parenchymal damage with subacute cellular infiltration. Renal biopsy demonstrated the cardinal findings of interstitial nephritis, excluding the possibility of acute tubular necrosis caused by haemolysis. Serial lymphocyte transformation studies and skin patch tests gave positive results for phenobarbital, supporting the view that these were unusual complications of phenobarbital hypersensitivity.

Chemical and Drug Induced Liver Injury↗