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Biomedical subjects

H Kawabata

Publications and source records attributed to H Kawabata.

At least 55 records · Page 3Linked to original sources

Role of energy metabolism in drug-induced acute gastric mucosal injuries in humans.

BACKGROUND: In various drug-induced gastric mucosal injuries, it has been speculated that changes in gastric mucosal energy metabolism differ according to the cause of injury. This study was conducted to investigate the role of energy metabolism in two drug-induced gastric mucosal injuries in humans. METHODS: The subjects were patients with acute gastric mucosal injury due to non-steroidal anti-inflammatory drugs (NSAID) or steroids, and normal controls. Two sets of tissue specimens from the antrum and corpus of the stomach were obtained. One specimen from each area was used for histological analysis and the other was stored in liquid nitrogen. The stored tissues were homogenized. Adenosine triphosphate (ATP), adenosine diphosphate (ADP) and adenosine monophosphate (AMP) were measured by the luciferin-luciferase method. RESULTS AND CONCLUSIONS: In the NSAID group, the ATP levels and the total adenine nucleotide (TAN) levels in both the antrum and corpus were significantly lower than in the control group. In the steroid group, no significant differences were observed in either the ATP or TAN levels. The NSAID decreased energy metabolism in the entire stomach while the steroid had a negligible effect on energy metabolism.

Adenosine Diphosphate↗

High prevalence of varicella-zoster virus reactivation in herpes simplex virus-seronegative patients with acute peripheral facial palsy.

Varicella-zoster virus (VZV) and herpes simplex virus (HSV) are considered to be the major causes of acute peripheral facial palsy (APFP). One hundred and forty-two patients with APFP were analyzed by serological assays and polymerase chain reaction analysis. Ramsay Hunt syndrome was diagnosed in 21 patients. Of the remaining 121 patients clinically diagnosed with Bell's palsy, VZV reactivation without zoster (zoster sine herpete) was detected in 35 patients (29%). The prevalence of antibodies to HSV among patients with Bell's palsy was significantly higher than the prevalence among those with VZV reactivation (Ramsay Hunt syndrome or zoster sine herpete). In contrast, a high incidence (88%) of VZV reactivation among HSV-seronegative patients with APFP was observed. Our data indicate that VZV is one of the major etiologic agents of clinically diagnosed Bell's palsy and that VZV reactivation causes APFP in most patients who lack antibodies to HSV.

Adolescent↗

Genomic differences in Streptococcus pyogenes serotype M3 between recent isolates associated with toxic shock-like syndrome and past clinical isolates.

Genomic differences among past Streptococcus pyogenes serotype M3 strains isolated in 1973 and before from patients with streptococcal pharyngitis, recent (1990s) serotype M3 clinical isolates from patients with pharyngitis, and recent M3 isolates from patients with toxic shock-like syndrome were investigated by restriction landmark genomic scanning and by modified random-amplified polymorphic DNA-polymerase chain reaction. Similar polymorphic DNA fragments were identified between the older M3 isolates and the recent isolates; also, the recent M3 clinical isolates from patients with pharyngitis were genetically indistinguishable, by the methods used, from the M3 isolates of patients with toxic shock-like syndrome. Although nucleotide sequences of these regions showed no apparent homology with known virulence factors, the DNA fragments could distinguish the recent M3 strains from the past strains. These results suggested that the recent strains have emerged because of genetic divergence.

Humans↗

Effect of beta-blocker on metabolism and contraction of doxorubicin-induced cardiotoxicity in the isolated perfused rabbit heart.

The effect of beta-blocker (propranolol) on the metabolism and contraction of doxorubicin-induced cardiomyopathy during pacing or ischemia was examined by the phosphorus 31-nuclear magnetic resonance (31 P-NMR) in Langendorff hearts of chronically treated rabbits after cumulative doses of 16 mg doxorubicin/kg. After 8 weeks of doxorubicin treatment, beta-blocker (propranolol) was given orally over a period of 2 weeks for a cumulative dose of 1.4 mg/kg. Isolated hearts were paced at higher heart rates, or hearts were perfused on low flow. Adenosine triphosphate (ATP), creatine phosphate (PCr), inorganic phosphate (Pi), pH, left ventricular systolic developed pressure (LVDev P), and coronary flow were measured. The hearts were divided into three experimental groups: Group I consisted of controls, Group II consisted of doxorubicin treatment, and Group III consisted of doxorubicin treatment with propranolol. Group II showed a significant decrease of ATP during pacing (48 +/- 2%) and during low flow (61 +/- 6%) compared with Group I (86 +/- 9% at pacing, 94 +/- 6% on low flow). But Group III showed a significantly marked improvement of ATP during pacing (95 +/- 10%) and during low flow (83 +/- 3%) compared with Group II. Furthermore, Group II showed a significant decrease of LVDev P during pacing (69 +/- 6 mm Hg) and during low flow (63 +/- 3 mm Hg) compared with Group I (101 +/- 5 mm Hg at pacing, 95 +/- 9 mm Hg on low flow). But Group III showed a significantly marked improvement of LVDev P during pacing (93 +/- 5 mm Hg) and during low flow (83 +/- 14 mm Hg) compared with Group II. In conclusion, propranolol had a significant beneficial effect on metabolism and contraction during high-energy demand and during low oxygen supply of doxorubicin cardiomyopathy.

Administration, Oral↗

Comparative study of superoxide dismutase in normal and hereditary cataract (UPL) rats.

In the present study, the levels of SOD activity and Cu, Zn-SOD mRNA in the brain, kidney, liver and eye of normal and Upjohn Pharmaceutics Limited (UPL) rats, a new hereditary cataract model derived from Sprague-Dawley rats, were measured. Although the levels of SOD activity in the eye and brain of UPL rats were significantly decreased compared with those of normal rats 3 and 5 weeks after birth, the levels of SOD activities in the kidney and liver were the same in both groups. The levels of Cu, Zn-SOD mRNA in kidney and liver of UPL rats were the same as those of normal controls. The level of Cu, Zn-SOD mRNA in the brain of normal rats 5 weeks after birth was about twofold greater than that of UPL, and that in the eye of UPL rats 3 weeks after birth was significantly decreased compared with that of normal controls. The sequences of cDNA encoding Cu, Zn-SOD and the sequences of the regulatory region of the Cu, Zn-SOD gene were confirmed to be the same in normal and UPL rats. These results indicated that the decreases in levels of SOD activity and Cu, Zn-SOD mRNA in the brain and eye of UPL rat were not due to mutation of the genomic Cu, Zn-SOD gene in UPL rats or differences in the sequence of the regulatory region of the Cu, Zn-SOD gene between normal and UPL rats.

Animals↗

Effect of angiotensin converting enzyme inhibitor and angiotensin II type 1 receptor antagonist on metabolism and contraction in ischemia-reperfused rabbit heart.

The effect of angiotensin converting enzyme (ACE) inhibitor, temocaprilat and/or angiotensin II type 1 (AT1) receptor antagonist, CV-11974 on myocardial metabolism and contraction during ischemia and reperfusion was examined by phosphorus 31-nuclear magnetic resonance (31P-NMR) in Langendorff rabbit hearts. After normothermic 15 min global ischemia, postischemic reperfusion of 60min was carried out. Temocaprilat and/or CV-11974 were administered from 40 min prior to the global ischemia. Adenosine triphosphate (ATP), creatine phosphate (PCr), inorganic phosphate (Pi), intracellular pH (pHi), left ventricular developed pressure (LVDevP), left ventricular end-diastolic pressure (LVEDP) and coronary flow were measured. Twenty-eight hearts were divided into 4 experimental groups consisting of 7 hearts each: group I consisted of controls, group II was perfused with temocaprilat (10(-6)mol/L), group III was perfused with CV-11974 (10(-6)mol/L), and group IV was perfused with temocaprilat (10(-6)mol/L) in combination with CV-11974 (10(-6) mol/L). Groups II and III showed a significant (p<0.05) inhibition of an overshoot phenomenon of PCr during postischemic reperfusion compared with group I. Group IV also showed a more pronounced significant (p<0.01) inhibition of the overshoot of PCr during reperfusion compared with group I. Groups II, III and IV showed a significant (p<0.05) inhibition of the decrease in ATP during global ischemia (59+/-2, 54+/-3 and 54+/-7%, respectively) compared with group I (45+/-3%). Groups II and IV showed a significant (p<0.05) early recovery of ATP during reperfusion (81+/-2, 80+/-6%) compared with group I (71+/-3%) and group II (73+/-2%). Group IV showed no more significant recovery in ATP than group III. There were no differences in LVDevP, LVEDP and coronary flow among these groups. In conclusion, temocaprilat in combination with CV-11974 has significant potential for improving myocardial energy metabolism during both myocardial ischemia and reperfusion.

Angiotensin Receptor Antagonists↗

Effect of a novel cardioprotective agent, JTV-519, on metabolism, contraction and relaxation in the ischemia-reperfused rabbit heart.

The effect of a novel cardioprotective agent, JTV-519 on myocardial metabolism and contraction during ischemia and reperfusion was investigated by means of phosphorus 31-nuclear magnetic resonance (31P-NMR) in Langendorff rabbit hearts. Normothermic, 20-min, global ischemia was followed by 30-min of postischemic reperfusion and JTV-519 was administered from 40 min prior to the global ischemia. Adenosine triphosphate (ATP), creatine phosphate (PCr), inorganic phosphate (Pi), intracellular pH (pHi), left ventricular developed pressure (LVDP), left ventricular end-diastolic pressure (LVEDP) and coronary flow were measured. Fourteen hearts were divided into 2 experimental groups of 7: Group I were controls and Group II were perfused with JTV-519 (10(-6) mol/L). During ischemia, Group II showed a significant (p<0.01) inhibition of the increase in Pi and LVEDP and the decrease in ATP and pHi, compared with Group I. After postischemic reperfusion, Group II also showed a significant (p<0.01) improvement in ATP and pHi as compared with Group I. There were no differences in LVDP or coronary flow during ischemia and reperfusion between the 2 groups. In conclusion, JTV-519 had a significant beneficial effect on myocardial energy metabolism and relaxation during both myocardial ischemia and reperfusion.

Adenosine Triphosphate↗

Molecular cloning of transferrin receptor 2. A new member of the transferrin receptor-like family.

Transferrin receptor (TfR) plays a major role in cellular iron uptake through binding and internalizing a carrier protein transferrin (Tf). We have cloned, sequenced, and mapped a human gene homologous to TfR, termed TfR2. Two transcripts were expressed from this gene: alpha (approximately 2.9 kilobase pairs), and beta (approximately 2.5 kilobase pairs). The predicted amino acid sequence revealed that the TfR2-alpha protein was a type II membrane protein and shared a 45% identity and 66% similarity in its extracellular domain with TfR. The TfR2-beta protein lacked the amino-terminal portion of the TfR2-alpha protein including the putative transmembrane domain. Northern blot analysis showed that the alpha transcript was predominantly expressed in the liver. In addition, high expression occurred in K562, an erythromegakaryocytic cell line. To analyze the function of TfR2, Chinese hamster ovary TfR-deficient cells (CHO-TRVb cells) were stably transfected with FLAG-tagged TfR2-alpha. These cells showed an increase in biotinylated Tf binding to the cell surface, which was competed by nonlabeled Tf, but not by lactoferrin. Also, these cells had a marked increase in Tf-bound (55)Fe uptake. Taken together, TfR2-alpha may be a second transferrin receptor that can mediate cellular iron transport.

Amino Acid Sequence↗

Stereoselective reduction of ethyl 4-chloro-3-oxobutanoate by Escherichia coli transformant cells coexpressing the aldehyde reductase and glucose dehydrogenase genes.

The asymmetric reduction of ethyl 4-chloro-3-oxobutanoate (COBE) to ethyl (R)-4-chloro-3-hydroxybutanoate [(R)-CHBE] using Escherichia coli cells, which coexpress both the aldehyde reductase gene from Sporobolomyces salmonicolor and the glucose dehydrogenase (GDH) gene from Bacillus megaterium as a catalyst was investigated. In an organic solvent-water two-phase system, (R)-CHBE formed in the organic phase amounted to 1610 mM (268 mg/ml), with a molar yield of 94.1% and an optical purity of 91.7% enantiomeric excess. The calculated turnover number of NADP+ to CHBE formed was 13,500 mol/mol. Since the use of E. coli JM109 cells harboring pKAR and pACGD as a catalyst is simple, and does not require the addition of GDH or the isolation of the enzymes, it is highly advantageous for the practical synthesis of (R)-CHBE.

Acetoacetates↗

Visual completion of partly occluded grating in infants under 1 month of age.

Four groups of eight infants (3 weeks of age on average) were each habituated to one of four displays consisting of a grating of either low (0.4 cpd) or high (1.2 cpd) spatial frequency, whose central portion was covered up with a horizontal occluder which was either narrow (1.33 degrees) or broad (4.17 degrees). These habituation displays are referred to as LN (low spatial frequency grating and narrow occluder), LB (low and broad), HN (high and narrow), and HB (high and broad) displays. Posthabituation-test displays consisted of a complete grating (CG) of the same frequency as the habituated grating along with a separate grating (SG) whose central portion was replaced with a black gap of the same height as the occluder in the habituation displays. Infants habituated to the LN display looked significantly longer at the SG than the CG display during posthabituation-test trials. Infants habituated to the LB and HN displays looked at the CG and SG displays, almost equally. In contrast, infants habituated to the HB display looked longer at the CG than the SG display. These results show that infants under 1 month of age can perceive the continuation of the grating behind the occluder, and that their visual completion on habituation displays can be evoked according to the interaction between the spatial frequency of the grating and the occluder height.

Evoked Potentials, Visual↗

Occurrence of multiple ethyl 4-chloro-3-oxobutanoate-reducing enzymes in Candida magnoliae.

Multiple ethyl 4-chloro-3-oxobutanoate (COBE)-reducing enzymes were isolated from a cell-free extract of Candida magnoliae. A NADPH-dependent COBE-reducing enzyme, distinct from the carbonyl reductase and aldehyde reductase previously reported, was purified to homogeneity using five steps, including polyethylene glycol treatment. The relative molecular mass of the enzyme was estimated to be 86,000 on high performance gel-permeation chromatography and 29,000 on sodium dodecyl sulfate polyacrylamide gel electrophoresis. The enzyme catalyzed the reduction of COBE to the corresponding (S)-alcohol with a 51% enantiomeric excess. The substrate specificity of the enzyme was different from those of the other COBE-reducing enzymes of the same strain. The partial amino acid sequences of the enzyme showed that it belongs to the short chain alcohol dehydrogenase/reductase (SDR) family. This is the first report of multiple COBE-reducing enzymes with various stereoselectivities occurring in the same strain but belonging to different (super)families.

Journal Article↗

An electrophysiological follow-up study on acquired unilateral nyctalopia.

PURPOSE: To describe the clinical picture and electrophysiological findings in acquired unilateral nyctalopia. METHODS: A patient who had acquired unilateral visual loss with normal fundus was followed for a period of 2.5 years with basic ophthalmological examinations including standard electroretinogram and photopic on and off responses. RESULTS: A 46-year-old woman suffered from acquired unilateral nyctalopia. She complained of photopsia and blurred vision in her left eye. The initial examination of the left eye showed 1+ cells in the anterior chamber and a granular appearance in the fovea. After 1 month of treatment she still complained of photopsia in her left eye. Ophthalmoscopy and fluorescein angiography revealed no abnormality in either eye. A bright flash electroretinogram (ERG) in the left eye was a negative shape. Photopic ERG elicited by a 150 ms stimulus showed a depressed b-wave and enhanced a- and d-waves in the left eye. CONCLUSIONS: This ERG waveform suggested that the transmission between photoreceptor and on-bipolar cell might be affected by idiopathic retinal disease.

Electroretinography↗

Myelodysplastic syndrome in a patient with adult T-cell leukaemia.

A 53-year-old female who developed myelodysplastic syndrome (MDS) after chemotherapy for adult T-cell leukaemia (ATL) is described. The latent period of therapy-related MDS (t-MDS) from the time of diagnosis of ATL was approximately 35 months. Cytogenetic analysis of the bone marrow cells at the time of diagnosis of t-MDS revealed a clonal abnormality; 46,XX,add(7)(p13), der(17)t(3;17)(p11;p13). Although monoclonal integration of human T lymphotropic virus type I (HTLV-I) proviral DNA was detected in the peripheral blood lymphocytes at ATL diagnosis, bone marrow cells at t-MDS diagnosis did not show monoclonal integration of HTLV-I. To our knowledge, this is the first report of t-MDS associated with ATL.

Adolescent↗