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Biomedical subjects

M Nishimura

Publications and source records attributed to M Nishimura.

At least 1,099 records · Page 61Linked to original sources

Beige rat: a new animal model of Chediak-Higashi syndrome.

Although Chediak-Higashi syndrome (CHS) has been found in various mammalian species, it has not been described in rats. Since giant granules characterizing CHS are easily recognizable in mast cells of beige (CHS) mice, we screened mast-cell granules in the auricle of some mutant rats, of which coat color was diluted by mutation. Giant granules of mast cells were found in a mutant trait that occurred in the inbred colony of the DA strain rat maintained in Hamamatsu University School of Medicine. Giant granules were also observed in neutrophils and pigment cells of the eye. In this mutant, either spontaneous migration or chemotaxis of neutrophils was impaired, and the bleeding time was prolonged. Blood serotonin level of the mutant was about one tenth that of the normal congenic rat, and injection of serotonin normalized the bleeding time of the mutant. Moreover, the natural killer activity of the mutant was significantly impaired. These results indicated that this mutation was comparable to CHS of humans and mice, and we designated it as "beige." Since rats are more favorable than mice for some types of experiments, the beige rat is potentially useful as an animal model of CHS.

Animals↗

[An analysis of DNA histogram and the expression of carbohydrate antigens regarding the degree of malignancy in gastric cancer].

We investigated both DNA histogram and the expression of carbohydrate antigens concerning to 168 patients with gastric cancer. Gastric cancer with type II DNA ploidy pattern showed a high incidence of vascular invasion and liver metastasis in the DNA analysis. Furthermore, ten patients with Stage II died of recurrence of gastric cancer within 2 years, of these nine patients showed type II or III DNA ploidy pattern. Then, gastric cancer with type II or III DNA ploidy pattern showed a high incidence of the expression of carbohydrate antigens, where they tended to distribute to cytoplasm and stroma. In conclusion, an analysis of nuclear DNA content appeared useful to predict prognosis in gastric cancer, in which type II DNA ploidy pattern showed the highest degree of malignancy, and both the expression of carbohydrate antigens and their localization possibly fill the role of parameter of the degree of malignancy.

Antigens, Tumor-Associated, Carbohydrate↗

An immunohistological study of gastric cancer--with special reference to the expression of carbohydrate antigens and nuclear DNA ploidy patterns.

The expression of carbohydrate antigens specific to Span-1, CA 19.9, and SLEX in cancer tissues and nuclear DNA ploidy patterns were studied from tissue specimens of lesions excised from 137 patients with gastric cancer. The frequency of detection of each antigen was augmented with advanced invasion depth and progress in regional lymph node metastasis. In the cases which were positive for all three kinds of antigens, lymph node metastasis and lymphatic or venous invasion were detected with significantly higher frequencies than in the negative cases. The DNA histograms showed a DNA ploidy pattern of Type Ia or Ib in the cases negative for these antigens and a non-diploid or aneuploid pattern of Type II or III in many of the positive cases. These findings suggest that an immunohistological study of gastric cancer using monoclonal antibodies, combined with a nuclear DNA ploidy analysis, might be useful for understanding malignancy of the tumour.

Adenocarcinoma↗

Analysis of granulomatous arteritis in MRL/Mp autoimmune disease mice bearing lymphoproliferative genes. The use of mouse genetics to dissociate the development of arteritis and glomerulonephritis.

MRL/Mp mice bearing the lymphoproliferation gene (lpr) spontaneously develop systemic granulomatous arteritis coincident with glomerulonephritis (GNP). Although the association of lpr-dependent lymphoproliferation in these mice seems to be a prerequisite for the development of granulomatous arteritis, the genetic basis is poorly understood. The first approach to this problem was to study the ability of another, nonallelic, lymphoproliferative gene, gld (generalized lymphoproliferative disease), inducing arteritis in MRL/Mp mice. The gld gene was placed on an MRL/Mp background by producing reciprocal (MRL/Mp-+/+ X C3H/Hej-gld/gld)F2 hybrid mice. Seventeen percent of these mice with lymphoproliferation had arteritis and GNP, suggesting that more than one lymphoproliferative gene could induce GNP and arteritis in an MRL/Mp background. Next, the effect of rearrangements in the genetic background of MRL/Mp-lpr/lpr mice by hybridization with non-autoimmune lpr-bearing mice was examined. This was done by making MRL/Mp-lpr/lpr X reciprocal (MRL/Mp-lpr/lpr X C57BL/6-lpr/lpr)F1 mice. Thirty-three percent of these mice developed arteritis, but one third of these did not get GNP, thus showing that susceptibility to arteritis was separate from GNP. The histopathologic features of the arteritis in both the F2 hybrids and the backcross mice were granulomatous and were identical to those seen in MRL/Mp-lpr/lpr mice. These findings suggested that it might be possible to dissociated two components (arteritis and GNP) of a severe autoimmune disease of MRL/Mp mice and to study their pathogenesis separately.

Animals↗

[Three cases with an extensive lesion in the dependent portion of the lungs diagnosed by chest CT-scan].

Three patients whose lung diseases are diagnosed with CT-scan are reported. A patient showed severe hypoxemia without any abnormal shadow on chest X-P. CT-scan revealed a diffuse and extensive lesion in the dependent portion. We performed his respiratory care in prone position. CT-scan of the second patient with aspiration pneumonia revealed that the lesion existed in the dependent portion. Cardiogenic pulmonary edema of the third patient was found to be distributed mainly in the dependent portion by CT-scan. We consider that CT-scan is useful when chest X-P gives little information.

Humans↗

Acute renal failure secondary to rhabdomyolysis associated with dissecting aortic aneurysm.

Rhabdomyolysis, a massive necrosis of skeletal muscle, is caused by various traumatic and non-traumatic factors. We report on a 30-year-old male in whom dissecting aortic aneurysm diagnosed by computed tomography was responsible for the generation of rhabdomyolytic acute renal failure. The patient was successfully treated by repeated hemodialyses and corrective surgery for aortic regurgitation and dissecting aortic aneurysm (Bentall's operation).

Acute Kidney Injury↗

An analysis of the DNA ploidy patterns of gastric cancer.

This article deals with DNA measurements by fluorometry of nuclei in 33 freshly obtained specimens and in 109 fixed specimens of gastric cancer in Japanese patients. Histograms of the DNA measurements can be classified into four types (Ia, Ib, II, III). The nuclear DNA patterns had definite, if not significant, correlations with clinical and histologic parameters. For example, 88.2% of the cases classified as Type III were advanced stage disease, whereas early stage cases were predominant in Type Ia. Type II and III were frequently found in hepatic, peritoneal, and lymph node metastasis. The rate of occurrence of polyploid cells was significantly higher in the group with hepatic or lymph node metastasis than in the other group without metastasis. The results of this study show that fluorometric measurement of nuclear DNA is considered one method of determining the biological activity of gastric cancer cells.

Adenocarcinoma↗

[Physiological significance of plasma free and conjugated dopamine in healthy volunteers--with special reference to sympathetic nerve activity].

In order to elucidate the physiological significance of plasma dopamine, blood pressure, pulse rate (PR), plasma concentrations of free or conjugated dopamine (free or conjugated pDA), noradrenaline (pNA) and adrenaline (pAd) were measured in 9 healthy volunteers. Blood sampling for the measurements was performed at a basal condition maintaining a supine position for 60 minutes, after twenty minutes 60 degrees head-up tilt (tilt) and an intravenous infusion of 1000 ml 0.9% saline for 2 hours. Following tilt, mean values in diastolic and mean blood pressure, PR, pNA and pAd were significantly increased, while free, conjugated and total pDA were decreased. On the other hand, saline infusion yielded significant decreases in hematocrit, pNA, free, conjugated and total pDA, but blood pressure, PR and pAd remained at the same level. Free/conjugated pDA ratio did not change during tilt or saline infusion. The basal value of free, conjugated or total pDA did not significantly correlate with blood pressure, PR, pNA or pAd, respectively. Furthermore, no significant correlations between the changes in pDAs and hemodynamic parameters, pNA or pAd by tilt or saline infusion were observed. From these results, it was suggested that plasma free or conjugated dopamine in physiological conditions may not be released from sympathetic nerve endings or adrenomedullary glands. Further investigations are needed to clarify the physiological significance of plasma dopamine in humans.

Adult↗

Nucleotide sequence of cloned cDNA coding for pumpkin 11-S globulin beta subunit.

cDNA coding for preproglobulin beta, a precursor protein of 11-S globulin beta subunit, was cloned and the nucleotide sequence has been determined. The sequence covers the whole coding region (1440 base pairs) with 5' and 3' noncoding region (30 and 214 base pairs, respectively). The deduced amino acid sequence of preproglobulin beta consists of a 21-amino-acid N-terminal signal peptide, preceding the acidic gamma polypeptide region (275 amino acids) and the subsequent basic delta region (184 amino acids). The site for post-translational cleavage of the precursor polypeptide to make the gamma and delta chains is estimated to be located between the asparagine-glycine residues. The N-terminal amino acid of the gamma chain of mature 11-S globulin beta subunit was reported to be blocked by 5-oxoproline (pyroglutamic acid) [Ohmiya et al. (1980) Plant Cell Physiol. 21, 157-167]. It was shown that the blocked N-terminal amino acid is coded as a glutamine residue. The derived amino acid sequence was also compared with those of precursor proteins of other 11-S globulins such as soybean glycinin, cotton beta globulin, pea legumin and rape 11-S globulin by dot matrix analysis.

Amino Acid Sequence↗

The central projection of masticatory afferent fibers to the trigeminal sensory nuclear complex and upper cervical spinal cord.

Retrograde and anterograde transport of horseradish peroxidase-wheat germ agglutinin (HRP-WGA) conjugate was used to study the organization of primary afferent neurons innervating the masticatory muscles. HRP applied to the nerves of jaw-closing muscles--the deep temporal (DT), masseter (Ma), and medial pterygoid (MP)--labeled cells in the trigeminal ganglion and the mesencephalic trigeminal nucleus (Vmes), whereas HRP applied to nerves of the jaw-opening muscles--anterior digastric (AD) and mylohyoid (My)--labeled cells only in the trigeminal ganglion. Cell bodies innervating the jaw-closing muscles were found with greater frequency in the intermediate region of the mandibular subdivision, while somata supplying the jaw-opening muscles were predominant posterolaterally. The distribution of their somatic sizes was unimodal and limited to a subpopulation of smaller cells. Projections of the muscle afferents of ganglionic origin to the trigeminal sensory nuclear complex (TSNC) were confined primarily to the caudal half of pars interpolaris (Vi), and the medullary and upper cervical dorsal horns. In the Vi, Ma, MP, AD, and My nerves terminated in the lateral-most part of the nucleus with an extensive overlap in projections, save for the DT nerve, which projected to the interstitial nucleus or paratrigeminal nucleus. In the medullary and upper cervical dorsal horns, the main terminal fields of individual branches were confined to laminae I/V, but the density of the terminals in lamina V was very sparse. The rostrocaudal extent of the terminal field in lamina I differed among the muscle afferents of origin, whereas in the mediolateral or dorsoventral axis, a remarkable overlap in projections was noted between or among muscle afferents. The terminals of DT afferents were most broadly extended from the rostral level of the pars caudalis to the C3 segment, whereas the MP nerve showed limited projection to the middle one-third of the pars caudalis. Terminal fields of the Ma, AD, and My nerves appeared in the caudal two-thirds of the pars caudalis including the first two cervical segments, the caudal half of the pars caudalis and the C1 segment, and in the caudal part of the pars caudalis including the rostral C1 segment, respectively. This rostrocaudal arrangement in the projections of muscle nerves, which corresponds to the anteroposterior length of the muscles and their positions, indicates that representation of the masticatory muscles in lamina I reflects an onion-skin organization. These results suggest that primary muscle afferent neurons of ganglionic origin primarily mediate muscle pain.(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗

Zinc antagonizes the effect of botulinum type A toxin at the mouse neuromuscular junction.

Zn2+ (10-100 microM) elevated the frequency of miniature end-plate potentials (MEPPs) in the mouse diaphragm. The effect did not depend on external Ca2+. Botulinum type A toxin (BTXA, 50 ng/ml) abolished MEPPs almost completely within 30 min. Zn2+ (100 microM) restored MEPPs and increased their frequency after they had been abolished by BTXA in Ca2+ -free solutions. The antagonistic effect of Zn2+ in the Ca2+ -free solution was reduced by exposing the diaphragm to the toxin in the Ca2+ -free solutions containing high K+. Thus, the action of BTXA is probably enhanced by depolarization of the motor nerve terminals.

Animals↗

Teratogenicity of the antiallergic Sm 857 SE in rats versus rabbits.

Sm 857 SE is an antiallergic drug chemically described as 11-Oxo-11H-pyrido(2,1-b)quinazoline-2-carboxylic acid that has activity against allergic bronchoconstriction in animal models. The purpose of this study was to investigate the teratogenic potential in pregnant rats and rabbits when administered during the critical period of organogenesis. The drug was suspended in aqueous 0.25% carboxymethylcellulose (CMC) solution. Daily doses of 20, 90, or 400 mg/kg were given orally by gavage to rats on days 7 through 17 of gestation and to rabbits on days 6 through 18. Two additional studies were done in rats dosed with 400 mg/kg, and with 90, 200, or 400 mg/kg, respectively. Doses of 20, 90, and 200 mg/kg had no meaningful effects on maternal animals of either species or on their offspring. A dose of 400 mg/kg was maternally toxic in rats as shown by the effects on body weight and food consumption. Among pregnant rabbits, two deaths and three miscarriages occurred at this dose. In rats, 400 mg/kg caused embryonic death, retarded fetal development, and two specific malformations, namely microphthalmia and vertebral-costal defects. A mild teratogenic action of 400 mg/kg also occurred in the first additional study but not in the second one. There was, however, one anophthalmia in a rat fetus of the 90 mg/kg group. In rabbits, no embryotoxic or teratogenic effects were observed. These species differences were explained by the concentration and protein binding in maternal serum as well as by the relatively high concentration of 14C-Sm 857 SE in the rat fetus.

Abnormalities, Drug-Induced↗

Electron microscopic study on brain of macular mutant mouse after copper therapy.

The hemizygote of the macular mutant mice, which is clinically and neuropathologically considered to be a model of Menkes kinky hair disease (MKHD), were injected intraperitoneally four times with 10, 20, 20 and 30 micrograms of cupric chloride on days 4, 6, 8 and 10 after birth, respectively. Their cerebral and cerebellar cortices were chronologically examined by electron microscopy. In the cerebral cortex, only a few abnormal mitochondria with electron-lucent matrix and short peripherally located cristae were scattered in the neurons on day 14, and these had almost entirely vanished after day 21. In the cerebellar cortex, abnormal mitochondria were frequently found on day 14 in the dendrites of the Purkinje cells, whereas they were only occasionally observed in their cytoplasm. Those in the dendrites had decreased in number on day 30, and only a few of them were seen in the cerebellum after day 45. These results show that the copper therapy reduced ultrastructural abnormalities in the hemizygote of this mutant mouse.

Animals↗

Restriction fragment length polymorphism and chromosome mapping of a mouse homeo box gene, Hox-2.1.

Restriction endonuclease fragment length polymorphisms (RFLPs) were found using the cDNA probe Hox-2.1 for the homeo box-2.1 gene in the mouse. Polymorphism was detected in restriction patterns generated by fragments from HindIII digestion. The great majority of laboratory strains of mice carries the Hox-2.1a allele. Only two laboratory strains carry the Hox-2.1b allele. Among strains of wild origin, the European subspecies (Mus m. domesticus, M. m. brevirostris, and M. m. musculus) and some Asian subspecies (M. m. castaneus) carry the Hox-2.1a allele. The subspecies from Far Eastern countries (M. m. molossinus, Chinese mice of wild origin, and M. m. yamashinai) carry the Hox-2.1b allele. Using the RFLP, the Hox-2.1 gene was mapped on chromosome 11. Three-point cross test data showed that the recombination frequency is 29.6% between the Hba and the Hox-2.1 genes and 23.5% between the Hox-2.1 and the Es-3 genes. The gene order of Hba-Hox-2.1-Es-3 has been confirmed.

Animals↗

Human T cell lines established from the cerebrospinal fluid of patients with human T lymphotropic virus type I-associated myelopathy (HAM).

T cell lines were established from the cerebrospinal fluid (CSF) lymphocytes of two patients with human T lymphotropic virus type I (HTLV-I)-associated myelopathy (HAM). These two interleukin-2 (IL-2)-dependent T cell lines have been cultured for more than 8 months without any accessory cells. The surface phenotype of these cells was CD2(+), CD4(+), CD8(-), Ia(+) and Tac(+). Southern blot hybridization analysis revealed the presence of HTLV-I provirus in these cells and C-type retrovirus particles were identified by electron microscopy. These findings indicate the presence of HTLV-I infected helper T lymphocytes in the CSF of the patients with HAM. These HTLV-I(+) T cell lines may be valuable for investigating the possible neutrotropism of HTLV-I and the role of HTLV-I in the pathogenesis of HAM.

Antigens, Differentiation, T-Lymphocyte↗

Analysis of the provirus genome integrated in T cell lines established from the cerebrospinal fluid of patients with human T lymphotropic virus type I-associated myelopathy (HAM).

T cell lines were established from the cerebrospinal fluid (CSF) lymphocytes of three patients with human T lymphotropic virus type I (HTLV-I)-associated myelopathy (HAM). To elucidate the possible changes of the provirus nucleotide sequences integrated in HAM-derived T cell line cells, DNA from these cells was digested with PstI, which cleaved the provirus genome of HTLV-I at several sites, and three common bands were detected by Southern blot analysis in all cases. These bands were identical in size to those detected in T cell lines established from peripheral blood lymphocytes of adult T cell leukemia (ATL) patients. These results were confirmed with restriction enzymes HindIII and BamHI. These findings suggest that the provirus genome detected in T cell lines derived from CSF of HAM patients is identical to HTLV-I.

Adult↗