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Biomedical subjects

H Kawabata

Publications and source records attributed to H Kawabata.

At least 91 records · Page 5Linked to original sources

Mg2+- or Mn2+-dependent endonuclease activities of human myeloid leukemia cells capable of producing nucleosomal-size DNA fragmentation.

The presence of at least two distinct Mg2+- or Mn2+-dependent, Ca2+-independent endonuclease activities was shown in the myeloid leukemia cell line P39. One of them was recovered from nuclear extracts and the other from a cytoplasmic fraction. The molecular size of the former was 30 kDa in both gel filtration and activity gel and that of the latter approximately 130-140 kDa in gel filtration and 65-70 kDa in activity gel. These two activities were almost completely inhibited by 0.1 mM ZnCl2 or 0.1 mM aurintricarboxylic acid, common inhibitors of apoptosis. Both could produce nucleosomal-size DNA fragmentation when incubated with diethyl-pyrocarbonate-treated nuclei as substrates, and the pattern of cleavage was 3'-OH and 5'-P. Taken together, either or both of these activities may be associated with apoptosis of myeloid leukemia cells.

Chromatography, Gel↗

Enzymatic production of ethyl (R)-4-chloro-3-hydroxybutanoate: asymmetric reduction of ethyl 4-chloro-3-oxobutanoate by an Escherichia coli transformant expressing the aldehyde reductase gene from yeast.

The asymmetric reduction of ethyl 4-chloro-3-oxobutanoate (COBE) to ethyl (R)-4-chloro-3-hydroxybutanoate (CHBE) using Escherichia coli JM109 (pKAR) cells expressing the aldehyde reductase gene from Sporobolomyces salmonicolor AKU4429 as a catalyst was studied. The reduction required NADP+, glucose and glucose dehydrogenase for NADPH regeneration. In an aqueous system, the substrate was unstable, and inhibition of the reaction by the substrate was also observed. Efficient conversion of COBE to (R)-CHBE with a satisfactory enantiomeric excess (ee) was attained on incubation with transformant cells in an n-butyl acetate/water two-phase system containing the above NADPH-regeneration system. Under the optimized conditions, with the periodical addition of COBE, glucose and glucose dehydrogenase, the (R)-CHBE yield reached 1530 mM (255 mg/ml) in the organic phase, with a molar conversion yield of 91.1% and an optical purity of 91% ee. The calculated turnover of NADP+, based on the amounts of NADP+ added and CHBE formed, was about 5100 mol/mol.

Aldehyde Reductase↗

Ca2+/Mg(2+)-dependent endonuclease in marrow CD34 positive and erythroid cells in myelodysplasia.

Endonucleases capable of producing internucleosomal DNA cleavage are one of the key enzymes in apoptosis. We examined endonuclease activities contained in nuclei of CD34+ and erythroid cells in the bone marrow (BM) from 12 patients with the myelodysplastic syndromes. The levels of Mg(2+)-dependent and acidic endonucleases showed little changes as compared with those from normal BM. By contrast, the level of Ca2+/Mg(2+)-dependent endonuclease was appreciably higher in MDS erythroid cells than normal counterparts, although the activity varied markedly in CD34+ and erythroid cells. Our results suggested that Ca2+/Mg(2+)-dependent endonuclease is related to ineffective erythropoiesis in MDS.

Adult↗

Effect of thromboxane A2 synthetase inhibitor on metabolism and contractility in ischemic reperfused rabbit heart.

The effect of thromboxane A2 synthetase inhibitor (OKY-046) on myocardial metabolism and contractility during ischemia and reperfusion was examined by the phosphorus 31-nuclear magnetic resonance (31P-NMR) in Langendorff rabbit hearts with use of an artificial blood substitute, perfluorochemical emulsion Fluosol-43. After normothermic fifteen-minute global zero-flow ischemia or fifteen-minute global low-flow ischemia (coronary perfusion pressure = 20 mmHg), reperfusion of sixty minutes was carried out. OKY-046 was administered from forty-five minutes prior to the global ischemia. Adenosine triphosphate (ATP), creatine phosphate (CrP), inorganic phosphate (Pi), pH, left ventricular systolic developed pressure (LV Dev.P) and coronary flow were continuously measured. Twenty-eight heart were divided into four experimental groups consisting of 7 hearts each; Group I consisted of controls with zero-flow ischemia; Group II, perfusion with OKY-046 (10(-6) M) in zero-flow ischemia; Group III, controls with low-flow ischemia; and Group IV, perfusion with OKY-046 in low-flow ischemia. Group II showed a significant inhibition of the increase in Pi and of the decrease in ATP, CrP, and pH during global ischemia compared with Group I, and a suppression of the overshoot of CrP observed after postischemic reperfusion. Group IV also showed a significantly marked improvement of ATP, CrP, and pH and significant suppression in Pi during low-flow ischemia compared with Group III. These were no differences in LV Dev.P and coronary flow among any groups. In conclusion, OKY-046 has a significantly beneficial effect on metabolism during both myocardial ischemia and reperfusion.

Adenosine Triphosphate↗

Pharmacological properties of the new centrally acting muscle relaxant (R)-(+)-3-phenyl-5-[2-(1-pyrrolidinylmethyl)butyryl]isoxazole hydrochloride.

The pharmacological properties of (R)-(+)-3-phenyl-5-[2-(1-pyrrolidinylmethyl)butyryl]isoxazole hydrochloride (CAS 144576-50-1, MS-322), a new centrally acting muscle relaxant, were investigated and compared with those of eperisone-HCl (CAS 56839-43-1) in experimental animals. MS-322 (1.5-6 mg/kg i.v.) reduced both anemic and intercollicular decerebration-induced rigidity in rats. Similar doses were required for these effects. The activity of MS-322 (200 mg/kg p.o.) against intercollicular decerebration-induced rigidity was greater and longer lasting than that of the same dose of eperisone-HCl. MS-322 (0.75-6 mg/ kg i.v.) inhibited the flexor reflex in anesthetized cats in a dose-dependent manner and more strongly than eperisone-HCl. MS-322 had no effect on the neuromuscular junction in anesthetized rats. The muscle relaxant activity of MS-322 in mice, demonstrated by the traction and rota-rod tests was stronger than that of eperisone-HCl, whereas MS-322 affected spontaneous motor activity in mice less than eperisone-HCl. The results of this study suggest that MS-322 is a potent centrally acting muscle relaxant with relatively weak depressant activity at other central nervous system pathways.

Animals↗

[Sensitivity loss of short wavelength sensitive cones in myopic eyes by blue-on-yellow perimetry].

A decrease of the short wavelength sensitive cone (S-cone) sensitivity has been reported in myopic eyes in addition to glaucoma and retinal diseases such as retinal detachment and diabetic retinopathy. In order to investigate early changes of visual function in myopic eyes, blue-on-yellow perimetry (B on Y) which could detect S-cone sensitivity and white-on-white perimetry (W on W) were measured with a computed perimeter program. Young subjects with good visual acuity, normal color vision, and normal intraocular pressure were selected. They had no other ophthalmoscopic abnormalities except for tigroid fundus. Mean deviations of W on W were reduced in mild and high myopic groups. In both tests, the sensitivities decreased as the refractive errors increased in all the tested areas (p < 0.0001). The sensitivity in B on Y decreased more remarkably than in W on W with an increase of refractive error (p < 0.05). We concluded that B on Y perimetry was significantly sensitive to identify early changes of visual function in myopic eyes.

Contrast Sensitivity↗

Lengthening of the lower limbs in patients with achondroplasia and hypochondroplasia.

Ten years of experience in lower limb lengthening achieved in 35 patients with achondroplasia and seven patients with hypochondroplasia is reported. A uniform method of callus distraction (callotasis) was used in all cases, although the order of lengthening of each bone differed among the cases. The mean age of the patients at the time of first operation was 14.5 years; at followup, the mean age was 18.8 years. The mean lengthening achieved in the femur was 7.2 cm (range, 4.5-12 cm) and in the tibia 7.1 cm (range, 4.5-13 cm). More lengthening was achieved in the more recent cases. The function of lengthened limbs, evaluated by physical strength tests, was better at followup than before lengthening in the growing children, although the mechanical axes of the lengthened bones were not necessarily in correct alignment.

Achilles Tendon↗

Apoptosis as a cell biological abnormality in myelodysplasia.

Evidence is accumulating to indicate that alterations in the control of apoptosis can contribute to a variety of disorders. Among the disorders associated with abnormal regulation of apoptosis, MDS stands out unequaled in that apoptosis is related, in apparently opposite directions, to ineffective hematopoiesis and leukemic transformation of MDS; notably, excessive apoptosis in the former and deranged apoptosis or escape from apoptotic control in the latter. In this review, we want to focus on the role of apoptosis in various stages of MDS, and to discuss its possible relevance to further therapeutic interventions.

Acute Disease↗

Multifocal electroretinogram in myopia.

PURPOSE: To investigate early changes of retinal function in myopic eyes, patients with various degrees of myopia underwent multifocal electroretinography (multifocal ERG). METHODS: Thirty young patients (mean age, 26.1 years) were divided into three groups according to the degree of refractive error: emmetropia/low, medium, and high myopia. All groups were matched by sex and age. All subjects had good corrected visual acuities of better than 1.0 and normal color vision. No other ophthalmoscopic abnormalities except for tessellated fundus existed. Three grouping programs (all-traces, rings, and quadrants) were used, and all-traces grouping waveforms, six-ring grouping waveforms, and four-quadrant grouping waveforms were determined from 103 local responses. We studied the differences of amplitudes and latencies of the waves among the myopic groups and their relation to refractive error and axial length. RESULTS: Amplitudes were reduced and latencies were delayed as the refractive errors increased. The amplitudes in the peripheral areas were more reduced in the myopic groups. CONCLUSIONS: The reduced amplitude and delayed latency of each wave of multifocal ERG in myopia resulted primarily from cone function loss, which may occur even when the only noted retinal change is tessellated fundus.

Adult↗

A novel mutation in L1CAM gene in a Japanese patient with X-linked hydrocephalus.

L1CAM is a member of the immunoglobulin gene superfamily of neural adhesion molecule. Abnormality of the L1CAM gene is associated with X-linked recessive form of congenital hydrocephalus (HSAS; hydrocephalus due to congenital stenosis of aqueduct of Sylvius) and some allelic disorders. Four new patients with congenital hydrocephalus consistent with the X-linked type were described. One of them had a novel mutation in the L1CAM gene.

Child↗

The origin and significance of spinal cord pulsation.

We studied the origin and mechanism of spinal cord pulsation in ten dogs in order to elucidate its clinical significance. Under general anesthesia, a 6 cm length of the animals' cervical spinal cord was exposed and the cerebrospinal fluid removed. The amplitude of spinal pulsation was then measured by means of ultrasonography in Mode M. The measurements were made after the spinal cord was cut: (1) on the cranial side; (2) on the cranial as well as caudal side, with the nerve roots and radicular arteries intact; (3) on both sides as in (2), which was then supplemented with the severance of the nerve roots and radicular arteries. It was demonstrated that, while the pulsation amplitude stood at an average of 88.0 microns before the surgical treatment, it rose to 455.0 microns in (1) and 274.8 microns in (2), but dropped to nearly zero in (3). The 5.2-fold increase in pulsation following the cordotomy on the cranial side was attributed to two factors: (1) the increased spinal mobility due to the cordotomy; (2) the elevation of blood pressure. The results of the three different degrees of spinal detachment suggested that spinal pulsation derived mainly from the radicular arteries and that its presence indicated low tonicity in the spinal cord and favorable circulation in the radicular arteries.

Animals↗

Presence of common antigenic epitope in outer surface protein (Osp) A and OspB of Japanese isolates identified as Borrelia garinii.

Japanese Borrelia strains FujiP2, AP83, NT24, NT29 and HT2 which had a 31-kilodalton protein non-reactive with monoclonal antibody (MAb) H5332 to outer surface protein A (OspA) were identified as B. garinii by the DNA hybridization method. MAb P3134 raised to strain NT24 reacted with OspA and the OspB-ranging protein of these isolates and cross-reacted with the OspB-ranging protein of some other isolates. Since the reactive protein was extracted by the Triton X-114 phase partitioning method, the MAb recognized the common epitope present in OspA and OspB. To our knowledge, this is the first report of an MAb reactive to both OspA and OspB.

Antibodies, Bacterial↗

Comparison of OspA serotypes for Borrelia burgdorferi sensu lato from Japan, Europe and North America.

UNLABELLED: Sixty-one Borrelia burgdorferi sensu lato strains from various sources (ticks, human, and wild animals) in Japan and two strains from ticks in Far Eastern Russia were classified on the basis of reactivity with 16 monoclonal antibodies (mAb) to outer surface protein A (OspA) and by DNA-DNA hybridization assay. Eleven OspA serotypes (J1 to J11) were recognized among the Japanese and the Far East Russian isolates (serotypes J1 to J9 were identified as B. garinii, serotype J10 was identified as B. afzelii, and serotype J11 corresponded to B. japonica), whereas 7 OspA serotypes for North American and European isolates previously reported (Bettina Wilske et al, J. Clin. Microbiol. 31:340-350,1993) were not observed except for OspA serotype 2 which showed identical reactivity with OspA serotype J10. This finding provides helpful information for understanding the geographical distribution of Lyme disease borrelia and the development of vaccine and diagnostic tests. IN CONCLUSION: 1.B. burgdorferi sensu stricto has not been observed in Japan, 2. Japanese B. afzelii isolates are closely related to those from Europe, 3. B. garinii isolates from Japan are highly heterogeneous and apparently different from European B. garinii isolates.

Animals↗

Effect of acetylsalicylic acid on metabolism and contractility in the ischemic reperfused heart.

The effect of acetylsalicylic acid (ASA) on high-energy phosphates (adenosine triphosphate: ATP, creatine phosphate: CrP, inorganic phosphate: Pi) and intracellular pH during myocardial ischemia and reperfusion was studied using phosphorus 31-nuclear magnetic resonance (31P-NMR) in the isolated rabbit hearts. Coronary flow, left ventricular systolic developed pressure (LV Dev.P) and left ventricular end-diastolic pressure (LVEDP) were also measured. Langendorff hearts perfused at 37 degrees C with the perfluorochemical emulsion Fluosol-43 were subjected to 15 min and 30 min of zero-flow ischemia and to 15 min of low-flow ischemia (coronary perfusion pressure = 20 mmHg) followed by 65 min of reperfusion (control, Group I). ASA (0.28 mmol/L) was infused either for the entire experimental period from beginning 45 min prior to ischemia (Group II) and infused immediately after reperfusion (Group III). During ischemia, Group II showed a significant suppression of the decrease in the ATP level and pH with both zero-flow and low-flow ischemia compared to those in the other groups, and moreover the increase in Pi and the decrease in CrP in low-flow ischemia were also suppressed. In Group III, the ATP level during reperfusion was significantly higher than that in Group I, but was not significantly different from that in 30 min zero-flow ischemia. In 30 min zero-flow ischemia, Pi, CrP and coronary flow after reperfusion in Group II tended to recover to preischemic values. There were no differences in LV Dev.P among the 3 groups. In conclusion, ASA has a protective effect on myocardial high-energy phosphates during ischemia and reperfusion in rabbit hearts.

6-Ketoprostaglandin F1 alpha↗

Characterization of Borrelia spp. isolated from the tick, Ixodes tanuki and small rodents in Japan.

Spirochetes were isolated from the tick, Ixodes tanuki, as well as wood mice (Apodemus speciosus) and voles (Clethrionomys rufocanus and Eothenomys smithii), caught in Fukui, Tokushima, and Hokkaido, Japan, from 1991 to 1993. Spirochetes were characterized on the basis of protein profiles, reactivities with monoclonal antibodies (mAbs), Outer surface protein A gene (ospA) and Outer surface protein B gene (ospB) amplification analysis, rRNA gene and flagellin gene restriction fragment length polymorphism (RFLP) analysis, and DNA homology values. Protein profiles of all isolates were homologous and reacted with mAb to OspA, OspB, OspC, flagellin, and heat shock protein 60. The primer reactivity to ospA and ospB were different from those of Borrelia burgdorferi sensu stricto, B. afzelii, B. japonica, and B. garinii. Based on the DNA/DNA homology value and RFLP analysis of rRNA and flagellin gene, these Borrelia sp. isolates are a new group of B. burgdorferi sensu lato. The isolates from ticks and the host rodents were identical in these assays. We propose that these Borrelia sp. are adapted to I. tanuki and are maintained in these field rodents.

Animals↗