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Biomedical subjects

N Kawamura

Publications and source records attributed to N Kawamura.

At least 73 records · Page 4Linked to original sources

Fertilization and the first cleavage mitosis in insects.

Fertilization in animals is now considered to be of the "sea urchin type"; that is, haploid male and female pronuclei completely fuse shortly after sperm entry into the egg, followed by the formation of a mitotic spindle to allow cleavage mitoses to proceed. However, two other patterns of fertilization and early embryonic mitosis in some animal species are known: an Ascaris type and a gonomeric type. The gonomeric type of fertilization in insects and other arthropods is not well known and is quite different from the sea urchin and Ascaris types. In the present article, the author examines the peculiar gonomeric fertilization, using mainly the silkworm as an example.

Animals↗

Selective localization of G protein gamma5 subunit in the subventricular zone of the lateral ventricle and rostral migratory stream of the adult rat brain.

G proteins play important roles in transmembrane signal transduction, and various isoforms of each subunit, alpha, beta and gamma, are highly expressed in the brain. The Ggamma5 subunit is a minor isoform in the adult brain, but we have previously shown it to be highly expressed in the proliferative region of the ventricular zone in the rat embryonic brain. We show here that Ggamma5 is also selectively localized in a proliferative region in the adult rat brain, including the subventricular zone of the lateral ventricle and rostral migratory stream. The Galphai2 subunit colocalized with Ggamma5 in these regions, the two subunits being present in neuronal precursors and ependymal cells but not in proliferating astrocytes. In addition, intense staining of Ggamma5 was seen in axons of the olfactory neurons, which are known to regenerate. These results suggest specific roles for Ggamma5 in precursor cells during neurogenesis so that this isoform might be a useful biological marker.

Animals↗

Familial gastrointestinal stromal tumor with hyperpigmentation: association with a germline mutation of the c-kit gene.

We describe 2 siblings with multiple gastrointestinal stromal tumors (GISTs) and cutaneous hyperpigmentation. Both had a point mutation of the c-kit gene. The patients were sisters who had exhibited cutaneous hyperpigmentation since their late teens, but the diagnosis of multiple gastrointestinal submucosal tumors was not made until they were 41 and 45 years old. Histologic examination showed that these tumors were GISTs expressing CD34 and Kit protein. Both patients died of GISTs. Single-strand conformation polymorphism analysis showed a mutation of c-kit in tumor DNA extracted from paraffin-embedded specimens. Direct sequencing analysis showed that the point mutation occurred at codon 559 of exon 11 (Val-->Ala). The same single-point mutation was detected in DNA extracted from peripheral leukocytes obtained from the younger sister and her 2 children (who had similar general hyperpigmentation) as well as in DNA from a skin biopsy specimen taken from the older sister. The germline mutation at codon 559 of the c-kit gene found in the present familial GISTs differed from that in a previously reported case of familial GISTs. We propose that GISTs caused by a germline mutation of the c-kit gene should be referred to as GIST-cutaneous hyperpigmentation disease.

Adult↗

Na+/H+ exchange inhibitor SM-20220 attenuates leukocyte adhesion induced by ischemia-reperfusion.

Leukocytes play a key role in ischemia-reperfusion-induced tissue injuries. It has been suggested that blocking the Na+/H+ exchanger improves ischemic injuries such as stroke. In this study, we investigated the effect of the Na+/H+ exchanger inhibitor SM-20220 (N-[aminoiminomethyl]- 1-methyl-1H-indole-2-carboxamide methanesulfonate) on leukocyte-endothelial cell interactions during ischemia-reperfusion. SM-20220 (0.3-1.0 mg/kg i.v.) given after ischemia significantly attenuated the leukocyte adhesion in the mesenteric postcapillary venules that was induced by transient superior mesenteric artery occlusion. At 60 min after reperfusion, the numbers of adherent leukocytes in groups treated with vehicle or SM-20220 (0.3 mg/kg) were 15.1+/-2.9 cells/100 microm/3 min and 3.0+/-0.7 cells/100 microm/3 min (p < 0.01), respectively. In a transient middle cerebral artery occlusion model, i.v. infusion of SM-20220 (0.4 mg/kg per hour) for 1 h, beginning 1 h after the start of occlusion, significantly reduced both the infarct size and the increase in brain myeloperoxidase activity, compared with the vehicle group (p < 0.01 and p < 0.05, respectively). In summary, this is the first evidence that the leukocyte adhesion to the endothelium that is induced by ischemia-reperfusion is attenuated by the inhibition of Na+/H+ exchanger activity in vivo. Our results suggest that Na+/H+ exchanger inhibitors may prevent ischemia-reperfusion injuries such as stroke partly through the attenuation of leukocyte-endothelial cell interactions.

Amides↗

No leucine(7)-to-proline(7) polymorphism in the signal peptide of neuropeptide Y in Japanese population or Japanese with alcoholism.

We have screened 200 Japanese workers and 105 Japanese patients with alcoholism for the mutation in the signal peptide of pre-pro-neuropeptide Y resulting in a substitution of proline for leucine at position 7. This polymorphism was reported in the Finnish and Dutch populations recently. None of our subjects displayed the mutation at this site. Therefore, this allele does not play any role in the development of alcoholism in the Japanese population.

Alcoholism↗

5-HT2A promoter polymorphism is not associated with anorexia nervosa in Japanese patients.

Genetic factors have been implicated in playing a significant role in susceptibility to anorexia nervosa (AN). Among many candidate genes for AN, an association with the A allele of the -1438G/A polymorphism in the promoter region of the 5-HT2A receptor has been reported. However, these findings are controversial and all patients studied to date have been Caucasian. This study was designed to determine whether this association is reproducible in Japanese subjects. This case-control study of a cohort of 75 female Japanese AN sufferers and 127 normal female control subjects revealed no significant association between the 5-HT2A promoter polymorphism and AN. Thus, at least for Japanese subjects, the A-allele of the -1438G/A polymorphism in the promoter region of the 5-HT2A receptor gene does not contribute to a predisposition to AN.

Alleles↗

Analysis of tumor necrosis factor-alpha gene promoter polymorphisms in anorexia nervosa.

Elevated plasma tumor necrosis factor-alpha (TNFalpha) levels and enhanced spontaneous TNFalpha release from peripheral blood mononuclear cells in patients with anorexia nervosa (AN) have been reported. TNFalpha activates the hypothalamic-pituitary-adrenal axis and reduces food intake, which is characteristic of eating disorders. Recently, three novel polymorphisms in the 5'-flanking region of the TNFalpha gene were reported at positions -1031 (T --> C substitution), -863 (C --> A) and -857 (C --> T). Differences in these alleles are reportedly related to altered TNFalpha-transcriptional promoter activity. Therefore, we performed a case-control association analysis to determine whether any of those three polymorphisms in the TNFalpha promoter region were involved in a predisposition to AN. The results of our analysis of a cohort of 79 female Japanese AN sufferers and 127 normal female control subjects provide no support for the hypothesis that -1031T/C, -863 C/A and -857C/T polymorphisms in the TNFalpha gene promoter region influence the susceptibility to AN.

Adult↗

Lesions in lateral hypothalamic areas increase splenocyte apoptosis.

OBJECTIVE: The lateral hypothalamic area (LHa) is involved in various functions such as feeding, drinking, sexual and reward behavior, among others. Recently, we demonstrated that the LHa can regulate cellular immunity in the spleen. In experiments involving the LHa, it was noticed that the spleen shrinks noticeably after LHa destruction. To explore this phenomenon further, the effect of LHa lesioning on splenocyte apoptosis was investigated. METHODS: Male Wistar-King-Aptekman rats underwent bilateral lesioning of their LHa and consequent spleen weights, splenocyte numbers and apoptosis were measured. For the detection of splenocyte apoptosis, both ELISA, which measures DNA fragmentation within the splenocytes, and flow cytometry, which measures the percentage of apoptotic lymphocytes in the spleen, were used. RESULTS: In the LHa-lesioned rats, spleen weights and the number of splenocytes decreased significantly within 24 h. Additionally, in the spleen, lymphocyte apoptosis significantly increased compared to the control after 6 h. CONCLUSION: These results suggest that the LHa may play a role in immunoregulation by affecting lymphocytes in the spleen through apoptosis and may be relevant to the pathway of stress-induced apoptosis.

Animals↗

Suppression of cellular immunity in men with a past history of posttraumatic stress disorder.

OBJECTIVE: High rates of medical morbidity have been reported in subjects with posttraumatic stress disorder (PTSD). The authors examined immune function in subjects in remission from past PTSD. METHOD: The initial study group was composed of 1,550 Japanese male workers. Japanese versions of the Events Check List, the Impact of Event Scale-Revised, and the Diagnostic Interview Schedule for DSM-IV were used to identify subjects who had a past history of PTSD. Twelve of the workers were identified as having such a history. These men were matched in age and smoking habits, which affect immunity, to 48 comparison subjects who had similar stressful life experiences but no current or past history of PTSD. Natural killer (NK) cell activity, lymphocyte subset counts, and production of interferon gamma (IFN-gamma) and interleukin-4 (IL-4) were measured in the 60 men by means of phytohemagglutinin stimulation. RESULTS: The number of lymphocytes, number of T cells, NK cell activity, and total amounts of IFN-gamma and IL-4 were significantly lower in the 12 men with a past history of PTSD. CONCLUSIONS: PTSD leaves a long-lasting immunosuppression and has long-term implications for health.

Adult↗

Na+/H+ exchange inhibitor SM-20220 improves endothelial dysfunction induced by ischemia-reperfusion.

Endothelial cells play an important role in the physiologic homeostasis of the cerebral circulation. Previously, we showed that the Na+/H+ exchanger (NHE) inhibitor SM-20220 (N-(aminoimino-methyl)-1-methyl-1H-indole-2-carboxamide methanesulfonate) improved ischemic brain injury. In this study, we investigated the effect of SM-20220 on cerebrovascular dysfunction after ischemia-reperfusion, focusing on the kinds of dysfunction that involved endothelial function. In cultured bovine brain microvascular endothelial cells (BBMCs), the IC50 value for the NHE activity of SM-20220 was 4 x 10(-8) M. SM-20220 also reduced the cell injury induced by hypoxia/aglycemia-reoxygenation in BBMCs, with statistical significance at 10(-7) M (P<0.05). Next, the effect of SM-20220 on disruption of the blood-brain barrier and cerebral blood flow were evaluated using transient middle cerebral artery (MCA) occlusion models. Intravenous infusion of SM-20220 (0.4 mg/kg per hour for 1 h) attenuated the extravasation of Evans blue, a blood-brain barrier disruption indicator, into cerebral tissue on the day after transient ischemia (P<0.05). The occlusion of the MCA decreased the cerebral blood flow in the MCA territory by about 20%, and only about 45% of the preischemic value was recovered at 1-h reperfusion. A bolus injection of SM-20220 (1 mg/kg, i.v.) improved the postischemic hypoperfusion by about 75%, without causing changes in the systemic blood pressure. These results indicate that the protective effect of NHE inhibitor on ischemic brain injury may be at least partially mediated by the prevention of endothelial dysfunction.

Amides↗

Are there one million nerve fibres in the human medullary pyramid?

It has been the accepted opinion that there are one million nerve fibres in the human medullary pyramid. This seemed to be confirmed in several old reports. But we cannot agree with this opinion. We made nitrocellulose-embedded sections from three normal male brains, and stained them by our modification of Masson-Goldner method. With this method, myelinated axons appeared in blue, whereas the glial processes were coloured in red, which allowed easy discrimination between the two. After morphometric evaluation of the pyramidal axons under the microscope, it appeared without the slightest doubt, that the number of axons does not exceed one-tenth of one million.

Adult↗

Metachromasia of the endocervical epithelium in women treated with gonadotropin releasing hormone agonist.

Endocervical epithelium from women treated with gonadotropin releasing hormone agonist (GnRH agonist) were compared with those from untreated women, using metachromatic stain with toluidine blue and immunohistochemistry, for estrogen and progesterone receptors. Smaller endocervical epithelium with lower intraepithelial mucus and more prominent nuclear distribution of estrogen receptors were seen in a woman who was treated for twelve months with GnRH agonists, as compared with those from an untreated premenopausal woman.

Adult↗

Association of the shrinkage of uterine leiomyoma treated with GnRH agonist and deletion of long arm of chromosome 7.

Specific chromosomal abnormalities, such as del(7q), t(12;14), 12 trisomy, or the rearrangement of 6p, are seen in approximately 30% of uterine leiomyomas despite their benign status. We investigated the association between the shrinkage of uterine leiomyomas treated with a GnRH agonist and the interstitial deletion of chromosome 7q, which is one of the most common chromosomal abnormalities in uterine leiomyomas. This study covered 29 women with uterine leiomyomas who were treated with a GnRH agonist before surgery. The volume of the largest myoma nodule was measured by means of MRI before and at 12 weeks after the beginning of GnRH agonist treatment, and the percentage of the reduction in volume was calculated. Genomic DNA was extracted from leiomyoma tissue and peripheral blood, and amplified by PCR using fluorescently-tagged oligonucleotide primers of twelve microsatellite loci on chromosome 7. The PCR products were analyzed for loss of heterozygosity (LOH) using an automated fluorescent DNA sequencer. Of the 29 informative tumors, five (17%) showed LOH with deletion of the common region, D7S491. The mean percentages of the reduction in volume of the largest myomas with LOH or without LOH were 32+/-13 and 18+/-58%, respectively (not significant). One tumor showing interstitial deletion of both alleles (homo-deletion) reduced in volume by 19%. Another tumor showing an extraband increased in volume by 13%. Although tumor specific chromosomal deletion suggested the existence of tumor suppressor genes in this region, there was no significant association between the shrinkage of uterine leiomyomas treated with a GnRH agonist and the interstitial deletion of chromosome 7q.

Adult↗

Anti-alpha-fodrin autoantibody is an early diagnostic marker for childhood primary Sjögren's syndrome.

OBJECTIVE: alpha-fodrin is a recently identified autoantigen associated with adult primary Sjögren's syndrome (SS). We tested whether anti-alpha-fodrin antibody could also be used as a diagnostic marker for childhood SS. METHODS: We performed immunoblot analysis of sera from 7 patients with childhood primary SS using glutathione-S-transferase alpha-fodrin fusion protein as an antigen. RESULTS: Anti-alpha-fodrin antibody was detected in sera from all 7 patients with childhood primary SS, 2 of 4 with secondary SS, and one of 7 with systemic lupus erythematosus, but in no other healthy controls. CONCLUSION: The anti-alpha-fodrin autoantibody was detected before anti-SSA or SSB antibody became positive; thus anti-alpha-fodrin antibody could be a useful marker for the early diagnosis of SS.

Adolescent↗