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Biomedical subjects

K Nakano

Publications and source records attributed to K Nakano.

At least 163 records · Page 9Linked to original sources

Projections of the vestibular nuclei to the thalamus in the rat: a Phaseolus vulgaris leucoagglutinin study.

Injections of the anterograde axonal tracer Phaseolus vulgaris leucoagglutinin were made into individual nuclei of the vestibular nuclear complex of the rat to identify specific projections to the thalamus. The results showed that the superior vestibular nucleus and the medial vestibular nucleus, especially its rostral-to-middle parts, project to the lateral part of the parafascicular thalamic nucleus (corresponding to the centromedian nucleus in primates), the transitional zone between the ventrolateral thalamic nucleus (VL) and the ventral posterolateral thalamic nucleus (VPL) (the region considered to be the nucleus ventralis intermedius of Vogt [Vogt C. 1909. La myeloarchitecture du thalamus du cercopitheque. J Psychol Neurol 12:285-324.]), the lateral part of the centrolateral thalamic nucleus and the dorsal part of the caudal VL; the spinal vestibular nucleus projects to the lateral part of the parafascicular thalamic nucleus, the transitional zone between the VL and the VPL, the caudal part of the ventrobasal complex, and the suprageniculate thalamic nucleus. These results suggest that vestibular information is transmitted not only to the cerebral cortex (mainly area 2V and area 3a) but also to the striatum. They also suggest that vestibular activity may affect gaze control by means of vestibulothalamocortical pathway in addition to vestibulo-ocular and vestibulopremotoneuronal routes.

Afferent Pathways↗

Mitral valve repair by Carpentier-Edwards physio annuloplasty ring.

A semi-flexible annuloplasty ring (Physio-ring) was clinically used in 30 cases of mitral valve insufficiency. The Physio-ring has the characteristics in which the anterior section is rigid and has a saddle-shaped curve, while the posterior section is flexible to allow for changes in size and shape of the anulus during ventricular contraction. The patients were aged from 23 to 73 years (mean 53.8 +/- 12.5). The cause of mitral valve insufficiency was degenerative (in 24 patients), rheumatic (2), ischemic (1), endocarditis (1), congenital + degenerative (1), and traumatic (1). On the 6-month post-implant echocardiogram, 96.6% had grade 0 or +1 regurgitation. The effective valve orifice area was 2.61 +/- 0.82 cm2 (n = 19). There was no late death. However, there was 1 (3.3%) hospital death after the patient had received a simultaneous coronary artery bypass grafting, and then developed low output syndrome after surgery. Although there was no device-related complication, hemolysis of undetermined cause was observed in 1 (3.3%) patient. The findings from this study indicated a low incidence of device-related complication, while excellent valvular function was maintained.

Adult↗

Does neoadjuvant chemotherapy for carcinoma in the thoracic esophagus increase postoperative morbidity?

OBJECTIVES: The aims of this study were to examine whether neoadjuvant chemotherapy for a carcinoma in the thoracic esophagus increased the incidence of postoperative complications, and which clinicopathological factors may affect postoperative complications after esophagectomy. SUBJECTS AND METHODS: One hundred and forty-four patients who underwent neoadjuvant chemotherapy followed by esophagectomy for a carcinoma in the thoracic esophagus were reviewed in a retrospective study. Ninety-six patients received neoadjuvant chemotherapy and 48 did not. The postoperative complications were grouped either general complications (Complications A) or surgery-related complications (Complications B). Complications A consisted of pulmonary, cardiac, hepatic, renal, and neurological complications, and catheter sepsis. Complications B consisted of a gastrointestinal tract leak, gastrointestinal tract necrosis, an intrathoracic or intraabdominal abscess, hemorrhage, ileus, and vocal cord palsy. In these two categories of complications, 17 factors obtained from subjects were compared between patients with complications and those without by univariate and multivariate analyses. RESULTS: The patient characteristics did not differ between patients who received neoadjuvant chemotherapy and those without. The preoperative serum albumin level was higher in patients without complication than in those with complication in both two categories of complications (Complications A: p = 0.001, Complications B: p = 0.05). The proportion of patients who received neoadjuvant chemotherapy did not differ between patients with complication and those without complication in either category of complications. Multivariate analysis showed that preoperative Onodera's Prognostic Nutritional Index was the only factor reducing the incidence of complications A (p = 0.02, Odds ratio: 0.63). CONCLUSION: Neoadjuvant chemotherapy was well tolerated and was not associated with any increased morbidity or mortality after esophagectomy for a carcinoma in the thoracic esophagus.

Chemotherapy, Adjuvant↗

Regulation of histamine synthesis in mouse CD4+ and CD8+ T lymphocytes.

OBJECTIVES: Previously, we have shown that mouse T lymphocytes produce de novo histamine in response to mitogens. The aim of this study was to examine which subsets of T cells produce histamine and to clarify the regulatory mechanisms of the reaction. MATERIALS: CD4+ and CD8+ T lymphocytes were separated from spleen cells of mast cell-deficient WBB6/F1 (W/Wv) mice using anti-CD4- and anti-CD8-coupled magnetic beads, respectively. RESULTS: Both CD4+ T cells and CD8+ T cells released histamine when treated with Con A as a function of incubation time. Since histamine bound to each cell fraction was negligible before and after the treatment, it is highly likely that this indicates de novo synthesis of histamine by these cells. Granulocyte/macrophage colony-stimulating factor (GM-CSF) or IL-3 strongly enhanced the Con A-induced histamine formation. IL-1-alpha also potentiated the Con A-dependent histamine production. Dexamethasone, but not progesterone, significantly inhibited the Con A-dependent as well as Con A-independent histamine synthesis. Both GM-CSF and IL-3 caused a marked accumulation of histidine decarboxylase (HDC, EC 4.11.22) mRNAs in the cells. CONCLUSIONS: These results suggest that GM-CSF and IL-3 enhance histamine synthesis in CD4+ T cells and CD8+ T cells.

Animals↗

Genetic contribution of the BAT2 gene microsatellite polymorphism to the age-at-onset of insulin-dependent diabetes mellitus.

The BAT2 gene lies within the class III region of the major histocompatibility complex. We investigated the frequency of the BAT2 microsatellite alleles (BAT2) in 74 young-onset insulin-dependent diabetes mellitus (IDDM) patients, 51 adult-onset IDDM patients, and 85 normal control subjects, and assessed the associations among these BAT2 alleles, TNFa microsatellite alleles (TNFa), and HLA-DRB1 alleles. The frequency of the BAT2.9 allele was significantly increased in the young-onset IDDM patients (12.8 vs 4.1%, Pc=0.04896), whereas the frequency of BAT2.12 allele was significantly decreased in young-onset IDDM patients (0.0 vs 11.8%, Pc=0.00002) compared with control subjects. The BAT2.9 allele was strongly associated with TNFa9 in the young-onset IDDM patients, although no association was found between the BAT2.9 and HLA-DRB1 alleles. The BAT2.12 allele was strongly associated with TNFa13, and with DRB1*1502 in control subjects. These results suggest that the BAT2 microsatellite polymorphism is associated with the age-at-onset of IDDM and possibly with the inflammatory process of pancreatic beta-cell destruction during the development of IDDM. However, this association is not independent of TNFa polymorphisms.

Adolescent↗

Malignant rhabdoid tumor of the colon: report of a case.

A malignant rhabdoid tumor of the colon is very rare and only three cases have been previously described. A 76-year-old man was admitted to the hospital complaining of epigastralgia. An elastic mass was palpable in the right upper abdomen. A barium enema and endoscopic examination showed a giant gyrate tumor arising from the cecum. Abdominal ultrasonography and a computed tomography scan revealed the tumor to be located in the colon associated with multiple liver metastases and gallbladder stones. A right colectomy and cholecystectomy were thus performed. The tumor was histologically composed of sheets of large round and polygonal nuclei with vesicular chromatin, and abundant acidophilic cytoplasm, often containing hyalin-like inclusion. The cytoplasm was positive for vimentin and neuron-specific enolase, and hyaline globules of the rhabdoid tumor cells stained positive for cytokeratin in some cells. Transmission electron microscopy showed characteristic rhabdoid cells with an aggregation of intermediate filaments. A histologic diagnosis of malignant rhabdoid tumor of the colon was made. The tumor demonstrated several unusual findings for malignant rhabdoid tumors including diploidy by a flow cytometric analysis, and positive nuclear immunohistochemical staining for p53 protein and Ki-67 antigen. We report herein the third known case of a pure colonic rhabdoid tumor.

Aged↗

Surgical treatment of Behçet's disease involving aortic regurgitation.

BACKGROUND: Behçet's disease involving aortic regurgitation is rare, and prosthetic valve detachment after aortic valve replacement is one of the most serious complications reported. We investigated the surgical results in 10 patients with aortic regurgitation caused by Behçet's disease. METHODS: Between 1981 and 1997, 10 patients with aortic regurgitation secondary to Behçet's disease had surgery. There were 8 men and 2 women, and their ages ranged from 33 to 60 years (mean, 46+/-8 years). The surgical procedures for aortic regurgitation were aortic valve replacement in 6 patients and Bentall type operation in 4. RESULTS: No patient died during the hospital stay. The follow-up periods ranged from 11 to 185 months (mean, 87 months). Two patients died during the follow-up period. The acturial survival rate was 89% at 5 years and 67% at 10 years. Prosthetic valve detachment or suture detachment requiring redo operation occurred in 4 patients, 3 of whom had redo operations twice. Four patients had a composite graft replacement, and 1 patient died after the operation. No prosthetic valve detachment was noted in 64% of the patients at 5 years and in 43% at 10 years. CONCLUSIONS: The rate of prosthetic valve detachment was 40% (4 of 10 patients), with a higher incidence in patients with Behçet's disease than in those treated during the same period at the same hospital for aortitis caused by other diseases. Surgical techniques for treatment of this condition should be modified to improve the surgical outcome in these patients.

Adult↗

Influence of TNF microsatellite polymorphisms (TNFa) on age-at-onset of insulin-dependent diabetes mellitus.

The TNF-alpha gene is located in the HLA region and has been implicated in the pathogenesis of Type I (insulin-dependent) diabetes mellitus (IDDM). We investigated the frequency of TNFa microsatellite alleles in 76 young-onset IDDM patients, 65 adult-onset IDDM patients, and 90 control subjects. We also examined the association of these TNFa alleles with HLA-DRB1 alleles, HLA-class I alleles, and TNF-alpha production. The frequency of the TNFa2 and TNFa9 alleles was increased in the young-onset IDDM patients compared to control subjects, but the increased frequency of TNFa2 was not significant after the correction for the number of comparisons was made. We did not find any association of TNFa2 or TNFa9 with any of the HLA-DRB1 alleles. In contrast, the frequency of the TNFa13 allele was decreased in both the young-onset and the adult-onset IDDM patients compared to the control subjects, but the difference lost significance after the correction was made in the adult-onset IDDM. The TNFa13 allele was strongly associated with DRB1*1502. Patients with TNFa2 or TNFa9 had greater TNF-alpha production, while those positive for TNFa13 had lower TNF-alpha production than patients with non-TNFa2, a9, and a13 alleles. These results suggest that TNFa polymorphisms are associated with age-at-onset of IDDM and influence the inflammatory process of pancreatic beta cell destruction in the development of IDDM.

Adolescent↗

A novel adenovirus E1B19K-binding protein B5 inhibits apoptosis induced by Nip3 by forming a heterodimer through the C-terminal hydrophobic region.

The adenovirus E1B19K protein inhibits apoptosis induced by E1A and other divergent signals. The cellular proteins that interact with E1B19K have been analyzed by isolating cDNA clones by the yeast two hybrid system. One of these clones encodes B5 which consists of 219 amino acid residues and contains the putative BH3 and transmembrane regions. B5 binds strongly to Nip3 and itself, weakly to E1B19K, but not to Bcl-2 and localizes in nuclear envelope, endoplasmic reticulum and mitochondria. B5 has sequence homology with Nip3 in the middle and C-terminal regions, but not in the N-terminal region. Unlike other E1B19K binding BH3 proteins so far characterized, B5 does not induce apoptosis, but inhibits apoptosis induced by Nip3. However the deletion mutant B5Delta1-31 lacking the N-terminus does induce apoptosis, although weaker than does Nip3, suggesting that the N-terminal region is masking the apoptosis-inducing capacity of B5.

Adaptor Proteins, Signal Transducing↗

Protective activity of the purified protein antigen of Erysipelothrix rhusiopathiae in pigs.

We purified the protein antigen (P64), which contains 66 and 64 kDa proteins, from the alkaline extract (AE) of whole cells of Erysipelothrix rhusiopathiae strain Agata (serovar 5) to determine the protective activity of the antigen against E. rhusiopathiae infection in pigs. The serum titre of antibody against P64 rapidly increased in pigs immunized with 500 and 100 micrograms of P64 and reached maximum values at 3 weeks after the first immunization (1 week after the second immunization). However, the serum antibody titres were not increased in pigs immunized with 20 micrograms of P64 and in nonimmunized pigs. In the pigs immunized with live cell vaccine (acriflavin-fast attenuated strain Koganei 65-0.15), the serum titres of antibody against P64 also increased at 1-2 weeks after immunization. In a pig challenge test performed on immunized and nonimmunized pigs, all nonimmunized pigs showed typical clinical signs of swine erysipelas (fever, erysipeloid, arthritis), while all pigs immunized with 500 and 100 micrograms of P64 and live cell vaccine showed no clinical signs of this disease. In Western blot analysis, sera from pigs immunized with P64 and live cell vaccine strongly reacted with the 64 kDa protein. In contrast, the serum from nonimmunized pigs did not react with any proteins. From these results, it was suggested that a specific antibody against the 64 kDa protein could be increased in pigs immunized with P64 or live cell vaccine and that this anti-P64 antibody has a strong protective effect against E. rhusiopathiae infection in pigs.

Animals↗

Distinct actions and cooperative roles of ROCK and mDia in Rho small G protein-induced reorganization of the actin cytoskeleton in Madin-Darby canine kidney cells.

Rho, a member of the Rho small G protein family, regulates the formation of stress fibers and focal adhesions in various types of cultured cells. We investigated here the actions of ROCK and mDia, both of which have been identified to be putative downstream target molecules of Rho, in Madin-Darby canine kidney cells. The dominant active mutant of RhoA induced the formation of parallel stress fibers and focal adhesions, whereas the dominant active mutant of ROCK induced the formation of stellate stress fibers and focal adhesions, and the dominant active mutant of mDia induced the weak formation of parallel stress fibers without affecting the formation of focal adhesions. In the presence of C3 ADP-ribosyltransferase for Rho, the dominant active mutant of ROCK induced the formation of stellate stress fibers and focal adhesions, whereas the dominant active mutant of mDia induced only the diffuse localization of actin filaments. These results indicate that ROCK and mDia show distinct actions in reorganization of the actin cytoskeleton. The dominant negative mutant of either ROCK or mDia inhibited the formation of stress fibers and focal adhesions, indicating that both ROCK and mDia are necessary for the formation of stress fibers and focal adhesions. Moreover, inactivation and reactivation of both ROCK and mDia were necessary for the 12-O-tetradecanoylphorbol-13-acetate-induced disassembly and reassembly, respectively, of stress fibers and focal adhesions. The morphologies of stress fibers and focal adhesions in the cells expressing both the dominant active mutants of ROCK and mDia were not identical to those induced by the dominant active mutant of Rho. These results indicate that at least ROCK and mDia cooperatively act as downstream target molecules of Rho in the Rho-induced reorganization of the actin cytoskeleton.

ADP Ribose Transferases↗

Frequency of HLA-A alleles in Japanese patients with head and neck cancer.

BACKGROUND: Association between certain human leukocyte antigen (HLA) types such as HLA-A1 and -A3 and squamous cell carcinoma of the head and neck (SCCHN) has been demonstrated in the Caucasian population. HLA typings in these studies were performed by conventional serological methods. However, recent comparison studies between serological and molecular typings have revealed that the former are often inaccurate. METHODS: The frequency of HLA-A alleles in 100 Japanese patients with SCCHN and 100 control subjects was determined by the polymerase chain reaction, with primers specific for the HLA-A locus, in combination with dot-blot hybridization with 31 sequence-specific oligonucleotides. RESULTS: The frequencies of HLA-A*2602 and HLA-A*3303 were higher and those of HLA-A*2603 and HLA-A*3101 were lower in the patients with SCCHN than in healthy controls, but these differences were not statistically significant. In the 39 male patients with laryngeal carcinoma, the most common malignancies in Japanese patients with SCCHN, the frequency of HLA-A*2402 was significantly lower than that in the 80 male controls; however, after correction of the P value, statistical significance was not confirmed. In oral carcinoma patients, the frequency of HLA-A*2402 was significantly higher than that in healthy controls. CONCLUSIONS: These results suggest that the contribution of certain HLA-A alleles to susceptibility to SCCHN may differ between sites in the head and neck regions, despite these cancers being of an identical histological type, and that HLA-A*2402 may influence the development of oral carcinoma in Japanese patients.

Adult↗

Analysis of 57 nonagenarian cancer patients treated by radical radiotherapy: a survey of eight institutions.

BACKGROUND: As the human society grows more aged, it is considered important to elucidate factors essential in applying radical radiotherapy (RT) to the elderly, with ages as high as 90 years and greater. METHODS: A retrospective survey was conducted for patients 90 years of age or older who received radiotherapy with radical intent in eight leading institutions in Japan from 1990 through 1995. RESULTS: Fifty-seven nonagenarian patients were studied. Their ages ranged up to 98 (median 91) and there was a strong female preponderance (M/F: 16/41). The distribution by site was as follows: head and neck, 16; skin and adnexae, 11; uterine cervix, 7; esophagus, 6. The prevailing histopathological diagnosis was squamous cell carcinoma (34), followed by adenocarcinomas (8). The highest age at RT was 98 years [female, skin cancer, died of senility 2.5 years after treatment, with no evidence of disease (NED)] and the longest survivor is 102 years old (female, glottic cancer T2, age at RT 93, alive NED for 8 years, uses wheel-chair). The rate of completion of treatment was 75% (43/57), if the treatment field was limited to the gross primary tumor volume only and if the cumulative dose was above 80% of the tolerable adult dose. Familial escort was necessary for most of the patients in completing the day-to-day RT. CONCLUSION: Radiotherapy is feasible with radical intent even in the elderly, if the treatment field is limited to the gross primary tumor volume only, if the cumulative dose is above 80% of the tolerable adult dose and if familial support is adequate.

Aged↗

Delayed development or congenital absence of a single first permanent molar in Japanese child patients.

OBJECTIVE: Delayed eruption of the first permanent molar (M1) is a relatively rare finding. This report describes the occurrence of delayed development and eruption of a single M1 in Japanese child patients. DESIGN: Cases were identified by surveying 353 orthopantomograms taken of child patients attending a Dental Hospital. Dental age, crown morphology and the presence of third permanent molars (M3) were determined from radiographs and clinical examination. SETTING: Osaka University Dental Hospital in Japan. RESULTS: Nine cases were identified from radiographs. The occlusal morphology of the affected molars showed a reduction of the distolingual cusp. Dental ages correlated more closely to chronological ages when the affected teeth were assumed to be second permanent molars (M2) than they did when the teeth were assumed to be M1. M3 proximate to the affected molar was congenitally absent in the orthopantomograms of all affected subjects. CONCLUSIONS: It is suggested that in the cases seen here the affected teeth were likely to have been second permanent molars that had migrated mesially in association with the congenital absence of M1, although congenital absence of M1 has been reported to be extremely rare.

Adolescent↗

Histone deacetylase inhibitor activates the p21/WAF1/Cip1 gene promoter through the Sp1 sites.

Trichostatin A (TSA), a specific histone deacetylase inhibitor, induces histone hyperacetylation and modulates the expression of some genes. We examined the effects of TSA on MG63 cells. TSA induced growth arrest and expression of the p21/WAF1/Cip1 protein. A close correlation between the level of histone acetylation and induction of the p21/WAF1/Cip1 protein was detected. Using several mutant p21/WAF1/Cip1 promoter fragments, mutation of either of two Sp1 sites at -82 or -69 of the p21/WAF1/Cip1 promoter reduced the responsiveness to TSA. This finding indicates that TSA activates the p21/WAF1/Cip1 promoter through the Sp1 sites in a p53-independent manner.

Cyclin-Dependent Kinase Inhibitor p21↗

Comparison of the complete DNA sequences of human herpesvirus 6 variants A and B.

Human herpesvirus 6 (HHV-6), which belongs to the betaherpesvirus subfamily and infects mainly T cells in vitro, causes acute and latent infections. Two variants of HHV-6 have been distinguished on the basis of differences in several properties. We have determined the complete DNA sequence of HHV-6 variant B (HHV-6B) strain HST, the causative agent of exanthem subitum, and compared the sequence with that of variant A strain U1102. A total of 115 potential open reading frames (ORFs) were identified within the 161,573-bp contiguous sequence of the entire HHV-6 genome, including some genes with remarkable differences in amino acid identity. All genes with <70% identity between the two variants were found to contain deleted regions when ORFs that could not be expressed were excluded from the comparison. Except in the case of U47, these differences were found in immediate-early/regulatory genes, DR2, DR7, U86/90, U89/90, and U95, which may represent characteristic differences of variants A and B. Also, we have successfully typed 14 different strains belonging to variant A or B by PCR using variant-specific primers; the results suggest that the remarkable differences observed were conserved evolutionarily as variant-specific divergence.

DNA, Viral↗

Human herpesvirus 6 open reading frame U83 encodes a functional chemokine.

Some viruses including herpesviruses have undergone evolution to benefit viral infection and propagation by pirating and modifying host genes such as chemokine genes. Human herpesvirus 6 (HHV-6), acutely or persistently infects mononuclear cells in vitro. DNA sequence analysis of HHV-6 has revealed that the putative protein encoded by an open reading frame (ORF) of the U83 gene in HHV-6 variant B resembled a human chemokine. We have cloned the U83 gene and analyzed the biological function of this gene. The U83 gene contained an ORF encoding a 113-amino-acid peptide, starting at the first methionine and containing a possible signal peptide and the typical cysteine residues characteristic of the chemokines. Reverse transcription-PCR analysis of mRNA and immunofluorescent-antibody testing of infected cells both indicated that the encoded protein was a late protein. The ORF U83 gene fused to the Fc gene was expressed as a fusion protein in COS-7 cells by transfection, and the fusion protein was purified from the supernatant of transfected cells to test its biological function. The purified protein was capable of inducing transient calcium mobilization in THP-1 cells and of chemotactically activating THP-1 cells. These findings suggested that the U83 protein might play an important role in HHV-6 propagation in vivo by activating and trafficking mononuclear cells to sites of viral replication, thus aiding the development of superbly efficient virus production mechanisms.

Amino Acid Sequence↗