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Biomedical subjects

S Kakinuma

Publications and source records attributed to S Kakinuma.

At least 37 records · Page 2Linked to original sources

Pertussis toxin-sensitive signal controls the trafficking of thymocytes across the corticomedullary junction in the thymus.

We investigated a role of chemokines in thymocyte trafficking. Genes encoding stromal cell-derived factor-1 and its receptor CXCR4 were detected in the cortex by in situ hybridization. Early immigrant cells did not express CXCR4, whereas their descendant CD44+CD25+CD4-CD8- cells did. CXCR4 expression was down-modulated when CD4+CD8+ double-positive cells became CD4+CD8- or CD4-CD8+ single-positive (SP) cells. Positively selected CD69+CD3intermediate cells gained CCR4, of which ligand, thymus activation-regulated chemokine, was expressed in the medulla. At the next developmental stage, CD69-CD3high cells lost CCR4 but gained CCR7. These results suggest that thymocytes use different chemokines along with their development. Blockade of chemokine receptor-mediated signaling by pertussis toxin perturbed the normal distribution of SP cells and resulted in the accumulation of SP cells in the cortex. Thus, a pertussis toxin-sensitive event controls the trafficking of SP cells across the corticomedullary junction.

Animals↗

Movement velocity dependent muscle strength in Parkinson's disease.

We measured isokinetic muscle strength of knee extension and flexion in 18 patients with Parkinson's disease who showed marked laterality in symptom severity and compared strength between the sides in the same patient. In all patient groups, the maximum peak torque of the more affected side was significantly less than for the less affected side at 15 revolutions per minute (r.p.m.) and 30 r.p.m. with the difference between the sides being larger at 30 r.p.m. than at 15 r.p.m., while at 5 r.p.m. there were no significant differences between sides. In the Yahr stage I group, the maximum peak torque in both extension and flexion at each velocity showed no significant difference between the sides. In contrast, in the stage II and III groups the maximum peak torque at 5 r.p.m. showed no significant difference between the sides, while at 15 r.p.m. and 30 r.p.m. these values showed a tendency and a significant difference between the sides, respectively, with the more affected side being weaker. These results suggest that muscle weakness in patients with Parkinson's disease increases with performance velocity, especially as the disease progresses.

Acceleration↗

Low frequency of Ras gene mutation in spontaneous and gamma-ray-induced thymic lymphomas of scid mice.

Scid mice, which have a defect in the capacity to repair DNA double-strand breaks, were highly prone to the induction of thymic lymphomas after exposure to ionizing radiation; approximately 70% of mice developed lymphomas within 1 year after exposure to 1-3 Gy, whereas approximately 20% of unirradiated control mice developed lymphomas. To gain information on the possible role of Ras activation in development of thymic lymphomas in scid mice, we have examined both the frequency and the spectrum of Kras and Nras mutations in spontaneous and radiation-induced lymphomas. Neither activated Kras nor Nras genes were detected in spontaneous lymphomas, while Kras mutations increased in a dose-dependent manner in radiation-induced lymphomas. However, Kras mutations were infrequent (6% in lymphomas in mice exposed to 1 Gy, 12.5% in those exposed to 2 Gy, 16.7% in those exposed to 3 Gy), and no mutations were detected in Nras genes, suggesting that Ras mutation was not significantly involved in the development of thymic lymphomas in scid mice. Analysis of the spectrum of Kras mutations demonstrated unique mutations in both codons 13 (GGC to GAC) and 61 (CAA to CTA) in addition to the commonly identified substitution of GAT for GGT in codon 12 of Kras.

Animals↗

Muscle weakness in Parkinson's disease: isokinetic study of the lower limbs.

Isokinetic strength of knee extension and flexion was measured at two speeds of movement in 23 patients with Parkinson's disease, to clarify whether muscle weakness is inherent to the disease. To counteract normal variation among subjects, we selected patients with symptoms completely or largely confined to one side and compared sides for each patient. The affected side was weaker than the other in both slow and fast movements early in the disease. In more advanced disease, the difference between sides diminished at the slow speed but remained significant at the faster speed. These observations suggest that weakness is inherent to Parkinson's disease and influenced by movement speed.

Aged↗

Increased serum vascular endothelial growth factor levels and intrathyroidal vascular area in patients with Graves' disease and Hashimoto's thyroiditis.

Vascular endothelial growth factor (VEGF) is one of the angiogenic factors. We examined both thyroid volume and intrathyroidal vascular area by color flow Doppler ultrasonography in patients with Graves' disease (GD), Hashimoto's thyroiditis (HT), and subacute thyroiditis. The serum concentrations of thyroid hormones, TSH, TSH receptor antibodies, and VEGF were also examined. There was a significant increase in serum VEGF levels in patients with untreated GD and goitrous HT compared with those in healthy subjects. The serum VEGF levels in untreated patients with subacute thyroiditis were significantly higher than those in patients with untreated GD or HT. There was a significant correlation between serum VEGF levels and the ratio of intrathyroidal vascular area and thyroid area in untreated patients with GD who had a goiter larger than or equal to 40 cm3. There was also a significant correlation between serum VEGF and TSH levels in patients with HT who were hypothyroid and had a goiter. Serum VEGF levels decreased significantly in these patients after treatment; this was accompanied by a significant decrease in intrathyroidal vascular area and thyroid volume. Our study demonstrates that VEGF appears to play an important role in intrathyroidal angiogenesis in patients with GD and goitrous HT.

Adult↗

Occult Boerhaave's syndrome without vomiting prior to presentation. Report of a case.

Boerhaave's syndrome (spontaneous esophageal perforation) is an uncommon clinical entity that frequently presents with an antecedent history of marked vomiting followed by chest or abdominal pain. We report a case of spontaneous rupture of the esophagus in 53-year-old male who was referred to our hospital with a chest discomfort. A chest radiogram revealed pleural effusion and pneumomediastinum. Nine hours after onset, the diagnosis of Boerhaave's syndrome become evident. She underwent operative repair and, after a prolonged stay, was discharged in relatively good condition 55 days after admission. The absence of vomiting prior to presentation is the distinguishing feature of this particular case. This is the seventh case in the English literature to our knowledge.

Diagnosis, Differential↗

Suppression of autoimmune disease and of massive lymphadenopathy in MRL/Mp-lpr/lpr mice lacking tyrosine kinase Fyn (p59fyn).

MRL/Mp-lpr/lpr (MRL/lpr) mice suffer from a generalized autoimmune disease that includes autoantibody production and glomerulonephritis and develop massive lymphadenopathy characterized by an expanded population of CD4- CD8- B220+ T cells that is derived from autoreactive T cells in the periphery. Some of us previously reported that these atypical T cells overexpressed a gene for tyrosine kinase p59fyn (Fyn). To define the role of Fyn in the renal disease and lymphadenopathy in MRL/lpr mice, we have generated Fyn-deficient MRL/lpr mice whose fyn gene is replaced by the gene for beta-galactosidase. Fyn-deficient MRL/lpr mice developed markedly limited disease and lived more than twice as long as the conventional MRL/lpr mice. In the mutant mice, the production of IgG3 anti-DNA autoantibody was significantly (p < 0.005%) reduced, and glomerular deposits of IgG3 and C3 were remarkably diminished. Ag receptor-mediated proliferative responses of Fyn-deficient splenic T cells were markedly impaired. The mutant mice showed delayed accumulation of the atypical CD4- CD8- B220+ T cells that exhibited a significantly lower activity of ZAP-70 compared with those in the conventional MRL/lpr mice. These data demonstrated that Fyn is involved as a positive regulator in the disease of MRL/lpr mice. Fyn provides a signal for both the expansion of autoreactive T cells and the production of IgG3 anti-DNA autoantibody by B cells. Thus, manipulation of Fyn may improve systemic autoimmune disease in humans.

Animals↗

Gastric mucosal blood flow and gastric secretion following intravenous administration of 5-fluorouracil in anesthetized rats.

Acute gastric mucosal lesions are often observed after the intravenous administration of high doses of anticancer drugs. To investigate the acute toxic effects of such anticancer therapy on the gastric mucosa, 5-fluorouracil (5-FU) was administered intravenously to anesthetized rats. Gastric mucosal blood flow (GMBF) was measured continuously using laser Doppler velocimetry. Acid secretion was measured using a perfusion method for 1 h after the administration of 5-FU. No significant change was observed with a low dose of 5-FU (50 mg/kg), but a high doses of 5-FU (100 or 200 mg/kg) caused a significant decrease in GMBF in a dose-dependent manner. The selective antagonist of the muscarinic acetylcholine receptor, pirenzepine, prevented the decrease in GMBF with high doses of 5-FU. Acid secretion decreased after the administration of 5-FU, but not significantly. This study indicates that a decrease in GMBF may be an important factor in gastric mucosal injury induced by chemotherapy. Pirenzepine may prevent the gastric mucosal lesions which are induced by the administration of 5-FU.

Animals↗

Sequence analysis of a 50 kb region between spo0H and rrnH on the Bacillus subtilis chromosome.

The 49630 bp spo0H-rrnH region of the Bacillus subtilis genome has been fully sequenced. The sequence contains one partial and 62 complete ORFs, one partial and three complete rRNA genes and a cluster of six tRNA genes. The direction of the transcription and translation of 61 ORFs is the same as that of the movement of the replication fork. A homology search of 40 ORFs in newly determined sequence revealed that 27 of them had significant similarity to known proteins such as elongation factor G, elongation factor Tu, pseudouridine synthase I and ribsosomal proteins. Two adjacent genes, ybaD and ybaE, appeared to encode proteins belonging to the ATP-binding cassette (ABC) family.

Bacillus subtilis↗

Nucleotide sequence of feline immunodeficiency virus: classification of Japanese isolates into two subtypes which are distinct from non-Japanese subtypes.

Seven isolates of feline immunodeficiency virus (FIV), Shizuoka, Yokohama, Sendai-1, Sendai-2, Fukuoka, Aomori-1, and Aomori-2, were isolated from FIV-seropositive domestic cats in Japan, and their proviral DNAs were amplified by PCR. The nucleotide sequences of their env and gag genes were determined and compared with those of previously described isolates: U.S. and European isolates and one Japanese isolate, TM2. Phylogenetic analyses of complete env gene sequences demonstrate that worldwide isolates are classified into three subtypes: Japanese TM2, Japanese Shizuoka, and non-Japanese subtypes (U.S. and European isolates), with 20% amino acid distances from each other. This pattern indicates that an evolutionary radiation of these three subtypes of FIV occurred at approximately the same time. The sequence data of gag genes also confirmed these results. Furthermore, the Sendai-1 isolate was identified as an imported FIV isolate.

Amino Acid Sequence↗

Inhibitory effect of rikkunshi-to, a traditional Chinese herbal prescription, on tumor promotion in two-stage carcinogenesis in mouse skin.

We report the inhibitory effect of topical application of extracts of a traditional Chinese herbal prescription on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation in mice. Methanol and water extracts obtained from 22 traditional Chinese herbal prescriptions were assayed and their inhibition ratios calculated. In general, the methanol extracts produced more effective inhibition than the water extracts. Of the various traditional Chinese herbal prescriptions, the methanol extract of Rikkunshi-to was more effective than other prescriptions as far as inhibition of TPA-induced inflammation was concerned. Hoelen, Glycyrrhizae Radix, Atractylodis Rhizoma, components of Rikkunshi-to markedly inhibited the inflammatory activity involved by TPA in mice. Furthermore, topical application of the methanol extract of Rikkunshi-to markedly inhibited TPA-induced tumor promotion in two-stage carcinogenesis in mouse skin.

Animals↗

Production of the new antibiotic tetrahydrokalafungin by transformants of the kalafungin producer Streptomyces tanashiensis.

The new antibiotic tetrahydrokalafungin was produced by the transformants of kalafungin producing S. tanashiensis and kalafungin-nonproducing mutants carrying the recombinant plasmid pKU523. This plasmid consists of pKU501 (J. Antibiotics 44: 995 approximately 1005, 1991) which contains the gene cluster for kalafungin biosynthesis, and additional 5 kb stability region of SCP2*.

Anti-Bacterial Agents↗

Sequencing and characterization of the ntp gene cluster for vacuolar-type Na(+)-translocating ATPase of Enterococcus hirae.

We have previously reported the DNA and amino acid sequences for the three genes (ntpA, ntpB, and ntpK) encoding the A, B, and K (proteolipid) subunits, respectively, of Na(+)-translocating ATPase of a eubacterium Enterococcus hirae (Kakinuma, Y., Kakinuma, S., Takase, K., Konishi, K., Igarashi, K., and Yamato, I. (1993) Biochem. Biophys. Res. Commun. 195, 1063-1069). In this paper we report the entire nucleotide sequence of the ntp gene cluster coding for this multisubunit enzyme. The cluster contained eight other genes; the order of these 11 genes was ntpF, -I, -K, -E, -C, -G, -A, -B, -D, -H, and -J, encoding proteins with predicted molecular weights of 14,255, 75,619, 16,036, 22,699, 38,162, 11,409, 65,766, 51,139, 27,093, 7,164, and 48,869, respectively. The deduced amino acid sequences of these products suggested that NtpI and NtpJ are hydrophobic proteins and others are hydrophilic. The ntpI gene product, which possesses six membrane-spanning segments in its carboxyl-terminal half, resembled the 116-kDa subunit of vacuolar (V)-ATPase in clathrin-coated vesicles. In addition, the NtpE, NtpC, NtpG, and NtpD proteins resembled bovine kidney ATPase E subunit, Saccharomyces cerevisiae Vma6p, Manduca sexta V-ATPase 14-kDa subunit, and Sulfolobus acidocaldarius gamma subunit, respectively, although the similarities between their amino acid sequences were moderate. Other gene products (NtpF and NtpH) did not show significant sequence similarity to other V-ATPase subunits. Since NtpA, NtpB, and NtpK are homologous counterparts of V-ATPase, these findings suggest that the molecular architecture of E. hirae Na(+)-ATPase complex corresponds to the V-type H(+)-ATPase complex distributed in various eukaryotic endomembrane systems. The sequence of the NtpJ product was similar to those of K+ transport systems of S. cerevisiae (Trk1 and Trk2); its meaning will be discussed. This is the first demonstration of a eukaryotic V-ATPase-like Na+ pump in bacteria.

Adenosine Triphosphatases↗

[A case of painful involuntary contraction of the left latissimus dorsi muscle, successfully treated with left thoracodorsal nerve resection].

A 66-year-old Japanese man underwent the resection of the upper lobe of the left lung for primary lung cancer. One year later, his back muscles neighboring the operation scar gradually began to twitch upwards intermittently. The involuntary muscle twitch was accompanied with severe local pain, and intensity of the pain and contraction slowly increased. The abnormal muscle contractions were confined to the left latissimus dorsi muscle on needle EMG. The pain and movement ceased by blocking of either thoracodorsal nerve or brachial plexus, and disappeared finally by resection of the nerve. The impulses causing involuntary, painful contractions were thought to originate in the damaged thoracodorsal nerve, transmitted to CNS and re-transmitted to the thoracodorsal nerve.

Aged↗

[18p-syndrome with bilateral pyramidal tract signs, dystonia of the lower extremities and concentric visual field defect].

A case, diagnosed as 18p-syndrome by typical clinical appearance and by chromosomal analysis, presented with multiple nervous system defects consisting of bilateral pyramidal tract signs, weakness and focal dystonia of the lower extremities, and concentric visual field defect. Chromosomal analysis revealed karyotype 46, X, dic (Y;18) (p11;p11), inv(9) (p11q13), and the points of chromosomal breakages were thought to be in the short arm of chromosome 18 and in the short arm of Y chromosome. 18p-syndrome is caused by a chromosomal deletion, and presents with a wide variety of clinical appearances. Many cases have been reported since the original descriptions by de Grouchy in 1963, though with few mentions of neurological deficits other than mental retardation. Furthermore, there have been no reports of pyramidal tract signs, weakness and focal dystonia of the lower extremities, or visual field defect, without recognizable anatomical abnormalities. Our case of 18p-syndrome is quite rare because of multiple nervous system abnormalities mentioned above, not accompanied by malformations of the central nervous system.

Adult↗

[Correlation between fetal growth and platelet function in normal pregnancy].

Various interpretations have been attempted, but no definitive theory has yet been established as to the etiology of the low-birth-weight infant. We carried out the present study in an attempt to explore the relationship between platelet functions and fetal growth during normal pregnancy. For this purpose, we made a retrospective study of 130 pregnant women aged 23-35 with no clinical abnormalities throughout pregnancy or at delivery. Blood samples were taken at 29-30 weeks of gestation (referred to as the 2nd trimester) and 37-38 weeks of gestation (referred to as the 3rd trimester). The cases studied were divided into two groups: i) those with a birth weight of under 2,500g (n = 32), and ii) those with a birth weight of over 2,500g (n = 98). In these two groups, we studied the platelet functions in maternal blood in the 2nd and 3rd trimesters. The following results were obtained: 1) In the 2nd to 3rd trimester, the platelet count showed no significant variation with the birth weight. 2) In the 2nd to 3rd trimester, the platelet aggregation was found to be moderately depressed in cases with a birth weight of under 2,500g, while it was found to be moderately activated in cases with a birth weight of over 2,500g. 3) In the 2nd to 3rd trimester, platelet factor 4 was significantly lower (p < 0.005) in cases with a birth weight of under 2,500g, while it was moderately higher in cases with a birth weight of over 2,500g.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

A gene encoding the 16-kDa proteolipid subunit of Enterococcus hirae Na(+)-ATPase complex.

By further sequencing the cloned genome DNA of Enterococcus hirae that retains the genes encoding two major subunits of Na(+)-transport ATPase (Takase, K., Yamato, I., and Kakinuma, Y. (1993) J. Biol. Chem. 268, 11610-11616), we found a gene, ntpK, encoding a very hydrophobic protein of 156 amino acids (Mr = 16,036). The amino acid sequence deduced from the ntpK gene matched with the partial sequence of a 16-kDa protein purified as the proteolipid component of Na(+)-ATPase. The amino acid sequence and the hydropathy profile of the NtpK product were very similar with those of the 16-kDa proteolipids of vacuolar (V-) H(+)-ATPases in eukaryotes. The amino-terminal half of this sequence was highly homologous to the carboxyl-terminal half, suggesting that it was evolved from a common ancestral gene through duplication. The proteolipid of E. hirae Na(+)-ATPase belongs to that of the eukaryotic V-ATPase.

Adenosine Triphosphatases↗