PubMed Health⌕ Search

Biomedical subjects

T Naka

Publications and source records attributed to T Naka.

At least 73 records · Page 4Linked to original sources
PubMed1997

A two-dimensional compartment model for the reaction-diffusion system of acetylcholine in the synaptic cleft at the neuromuscular junction.

A minimal compartment model of the reaction-diffusion system (RD system) of a neurotransmitter in a two-dimensional space of axis-symmetrical disc is proposed to represent the chemical transmission process of a quantum of acetylcholine (ACh) in the synaptic cleft at the neuromuscular junction. The behavior of the RD system for ACh is expressed by a two-dimensional diffusion equation with nonlinear reaction terms due to the rate processes for ACh receptor and acetylcholinesterase. The simulation analysis of the RD system reveals that the radial diffusion process of ACh has more distinctive effects on spontaneous generation of the miniature endplate current (MEPC) than the transverse process. The anisotropic diffusion is effective in the RD system since the diffusion coefficient of ACh in the radial direction is evaluated to be about 1.0 x 10(-6) cm2 sec-1 for appropriate characterization of the MEPC, on which the diffusion coefficient in the transverse direction larger than 2.0 x 10(-6) cm2 sec-1 has virtually no effects. The compartment model is thus appropriately constructed to comprise three elements on the transverse coordinate and ten elements on the radial coordinate in the disc with 500 nm of radius and 50 nm of height.

Acetylcholine↗
PubMed1997

Purification and characterization of polyamine aminotransferase of Arthrobacter sp. TMP-1.

Polyamine aminotransferase of Arthrobacter sp. TMP-1 was induced by 1,3-diaminopropane (DAP), N-3-aminopropyl-1,3-diaminopropane (norspermidine), spermidine, and spermine, but not by putrescine. The enzyme was purified to homogeneity. Its molecular weight and subunit size were 129,000 and 64,000, respectively. Its absorption spectrum had maxima at 280 and 420 nm and a shoulder at about 350 nm, and changes were observed upon the addition of DAP, putrescine, and sodium borohydride. The spectrum and its changes indicated that the enzyme contained pyridoxal-5'-phosphate as the coenzyme. The coenzyme content was found to be 1 mol per mol of subunit. DAP, putrescine, norspermidine, spermidine, and spermine were active amino donors and gave relative rates of 100, 73, 24, 30, and 23%, respectively. Pyruvate was the most active amino acceptor, while 2-ketoglutarate and oxaloacetate were inert. The equilibrium constant of the DAP-pyruvate transamination was 0.34. DAP was suggested to be a minor product of the norspermidine-pyruvate reaction.

Arthrobacter↗
PubMed1997

Action of polyamine aminotransferase on norspermidine.

The norspermidine-pyruvate reaction catalyzed by polyamine aminotransferase from Arthrobacter sp. TMP-1 formed N-3-aminopropyl-3-aminopropionaldehyde (APAPAL), L-alanine, 1,3-diaminopropane (DAP), allylamine, and acrolein, and the relative rates of formation of the latter four products were 24, 3.3, 2.3, and 1.2%, respectively, of the rate of the DAP-pyruvate transamination. The identification of APAPAL was done by 13C-NMR after it had been enzymatically oxidized to N-3-aminopropyl-beta-alanine followed by isolation of the oxidized product. The DAP was also isolated and identified by 13C-NMR. The allylamine and acrolein were identified by HPLC and a specific color reaction with m-aminophenol, respectively. In the absence of pyruvate, the enzyme catalyzed the elimination of DAP from norspermidine to yield allylamine, and the addition of DAP to allylamine to yield norspermidine with relative rates of 0.007 and 0.095%, respectively. When allylamine was incubated with the enzyme as the sole substrate, it was converted to N-allyl-1,3-diaminopropane and an unidentified product.

Acrolein↗
PubMed1997

Cytokeratin subtyping in chordomas and the fetal notochord: an immunohistochemical analysis of aberrant expression.

Chordoma is a well-known bone tumor that shows epithelioid features and in which the expression of cytokeratins (CKs) has been reported to appear very frequently. Numerous immunohistochemical analyses of CK expression have been conducted using such monoclonal antibodies as CAM5.2, which react with CK8, CK18, and CK19, and AE1/AE3, which react with CKs 1-8, 10, 14-16 and 19 in chordoma. No detailed analysis, however, of the expression of each component of CK has yet been conducted in chordoma; thus, the subsets of CK expressed there have yet to be clarified. With the use of immunohistochemical techniques with a panel of monoclonal antibodies against each subset of CK, the authors studied the expression of CKs in 16 specimens of classic chordoma and 14 specimens of the fetal notochord to clarify the subsets of CK expressed in chordoma and to evaluate the similarities and differences of CK expression between chordoma and the fetal notochord. All of the chordoma specimens showed a strong positive immunoreactivity for CK8 and CK19, whereas nine (56.3%) chordoma specimens showed a positive immunoreaction for CK18. In addition, four chordoma specimens were focally positive for keratin-903, which reacts with high molecular weight CKs such as CK1, CK5, CK10, and CK14; one specimen also showed a strong CK7 expression. All of the notochord specimens were also positive for CK8 and CK19, but none showed a positive immunoreaction for keratin-903, CK7, or CK18. In addition, none of the chordoma or notochord specimens showed immunoreactivity for CK20. The expression of CK8 and CK19, observed in all of the chordoma and notochord specimens, was thus considered to be maintained throughout the neoplastic transformation, although some aberrant CK expressions (CK7, CK18, and keratin-903) also occurred in the chordoma specimens examined in this study.

Adult↗
PubMed1997

Expression of c-met proto-oncogene product (c-MET) in benign and malignant bone tumors.

The expression of c-met proto-oncogene product (c-MET) has been reported to be related to invasive growth or tumor stage in some tumors, but little is known concerning the significance of c-MET expression in bone tumors. With use of formalin-fixed, paraffin-embedded tissue specimens and polyclonal antibody for c-MET, we studied the expression of c-MET in 122 cases of malignant bone tumors (43 osteosarcomas, 24 chondrosarcomas, 21 malignant fibrous histiocytomas of bone, 16 Ewing's sarcoma versus primitive neuroectodermal tumors, 18 chordomas), 65 cases of benign tumors and tumor-like lesions (including 8 giant cell tumors of bone, 8 chondroblastomas, 12 enchondromas, 7 osteochondromas, 10 fibrous dysplasias), 7 cases of articular cartilaginous tissue, and 10 cases of fetal vertebral tissue consisting of foci of enchondral ossification and notochordal tissue. In malignant tumors, c-MET expression was most frequently detected in chordoma (94.4%), followed by chondrosarcoma (54.2%) and osteosarcoma (23.3%). Among the osteosarcoma specimens, c-MET expression was frequently detected in the chondroblastic subtype (66.7%), but the incidence was low in the cases with other subtypes of osteosarcoma. We found no significant correlation between the c-MET expression and the histologic grade of malignancy in either osteosarcoma or chondrosarcoma. c-MET expression was either rarely observed or completely negative in malignant fibrous histiocytomas of bone (4.8%) and primitive neuroectodermal tumors (0%). In benign tumors and tumor-like lesions, c-MET expression was frequently detected in cartilaginous tumors, such as chondroblastoma (62.5%), enchondroma (66.7%), and osteochondroma (71.4%), but no expression was observed in giant cell tumors of bone or any other benign tumors or tumor-like lesions. In normal tissue, c-MET expression was frequently detected in the articular cartilage (100%) and notochord (70.0%) specimens examined. We conclude that c-MET expression as frequent as that observed in the notochordal tissue, chordomas, articular cartilage, and cartilaginous tumors is related to the development of both normal tissue and chondroid tumors.

Adolescent↗
PubMed1997

Candesartan cilexetil: a review of its preclinical pharmacology.

Candesartan is a highly potent, long-acting and selective angiotensin II type 1 (AT1) receptor blocker. It is administered orally as the inactive prodrug candesartan cilexetil which is rapidly and completely converted to candesartan during gastrointestinal absorption. In vitro studies have shown that candesartan acts as an insurmountable angiotensin II receptor antagonist, binding tightly to and dissociating slowly from the AT1 receptor. The above characteristics are thought to contribute to the marked and long-lasting antihypertensive effects of candesartan cilexetil in several animal models of hypertension. These included rodent models of renal hypertension in which candesartan cilexetil also demonstrated efficacy equivalent to or greater than enalapril. In other animal models, candesartan cilexetil reduced the incidence of stroke, renal dysfunction and renal disease while reducing cardiac and vascular hypertrophy. Furthermore, candesartan cilexetil conferred some protection against cerebral and renal damage at a dose that had no blood pressure-lowering effect. In toxicity and general pharmacology studies, candesartan cilexetil was shown to possess a 'clean' profile with a large safety margin. Also it did not potentiate chemical- or autocoid-induced cough or anaphylactoid reactions.

Angiotensin Receptor Antagonists↗
PubMed1997

[A family with facioscapulohumeral muscular dystrophy and hereditary long QT syndrome].

We describe a family with facioscapulohumeral muscular dystrophy (FSHD) and hereditary long QT syndrome (LQT) for three generations. The proband, a 50-year-old woman, had noticed difficulty in raising the upper extremities since the age of 40. At the age of 48, she was admitted to our hospital because of arrhythmia attack. She, her mother, and one of her three children were diagnosed as having LQT. These three individuals and the proband's two siblings were clinically diagnosed as having FSHD which was confirmed by genetic analysis using EcoR1. FSHD is an autosomal dominant disorder and the gene locus is mapped to chromosome 4q35-ter, but the gene has not been isolated. LQT is a group of disorders which cause syncope and sudden death from ventricular arrhythmia in an autosomal dominant fashion. Four loci for this syndrome (LQT1-4) have been known, and three of the genes have been shown to encode ion-channels. Genetic analysis of the proband failed to detect any of previously known mutations in the LQT1, LQT2, and LQT3 genes. The locus for LQT4 has been mapped to chromosome 4q25-7. There have so far been no report of FSHD associated with LQT. Although the pathogenesis is unclear, we speculate that these two diseases are linked each other on chromosome 4q.

Chromosomes, Human, Pair 4↗
PubMed1996

Synthesis and angiotensin II receptor antagonistic activities of benzimidazole derivatives bearing acidic heterocycles as novel tetrazole bioisosteres.

The design, synthesis, and biological activity of benzimidazole-7-carboxylic acids bearing 5-oxo-1,2,4-oxadiazole, 5-oxo-1,2,4-thiadiazole, 5-thioxo-1,2,4-oxadiazole, and 2-oxo-1,2,3,5-oxathiadiazole rings are described. These compounds were efficiently prepared from the key intermediates, the amidoximes 4. The synthesized compounds were evaluated for in vitro and in vivo angiotensin II (AII) receptor antagonistic activities. Most were found to have high affinity for the AT1 receptor (IC50 value, 10(-6)-10(-7)M) and to inhibit the AII-induced pressor response (more than 50% inhibition at 1 mg/kg po). The 5-oxo-1,2,4-oxadiazole, 5-oxo-1,2,4-thiadiazole, and 5-thioxo-1,2,4-oxadiazole derivatives showed stronger inhibitory effects than the corresponding tetrazole derivatives, while their binding affinities were weaker. This might be ascribed to their improved bioavailability by increased lipophilicity. The 5-oxo-1,2,4-oxadiazole derivative 2 (TAK-536) and 5-oxo-1,2,4-thiadiazole derivative 8f showed efficient oral bioavailability without prodrug formation. This study showed that the 5-oxo-1,2,4-oxadiazole ring and its thio analog, the 5-oxo-1,2,4-thiadiazole ring, could be lipophilic bioisosteres for the tetrazole ring in nonpeptide AII receptor antagonists.

Angiotensin Receptor Antagonists↗
PubMed1996

Proliferative activities in conventional chordoma: a clinicopathologic, DNA flow cytometric, and immunohistochemical analysis of 17 specimens with special reference to anaplastic chordoma showing a diffuse proliferation and nuclear atypia.

Chordoma shows various degrees of atypia histologically, however, the relationship between the histological features and the biological behavior still remains controversial. The authors subclassified 17 specimens with chordoma into two groups (ie, trabecular type showing a trabecular patterns and solid type mainly consisting of a diffuse proliferation of tumor cells). The histological grading was performed according to the degree of nuclear atypia on a scale of 1 to 3. Using DNA flow cytometric and immunohistochemical techniques, both the proliferative index (% S + G2 + M phase) and the MIB-1 labeling index (LI) of the tumor cells were estimated regarding their proliferative activities. In addition, p53 overexpression was also investigated using immunohistochemical techniques. There were eight (47.1%) specimens of trabecular type and nine (52.9%) of solid type. In nine specimens of solid type, those with higher nuclear atypia (grade 2 or 3) were significantly more frequent (five specimens, 55.6%) than in trabecular type in which all of the eight specimens were grade 1 (P = 0.44). The proliferative index was significantly higher in grade 2 or 3 lesions than in grade 1 lesions (P = .014), and the MIB-1 LI tended to be higher in solid type than in trabecular (P = .088). p53 overexpression was detected in two specimens of solid type, and the MIB-1 LI in these two specimens was significantly higher (P = .037) than that in the specimens without p53 overexpression. It was considered that the preceding anaplastic histological features, including either diffuse proliferation or high grade nuclear atypia, together with p53 overexpression, were thus closely related to the proliferative activities in chordomas.

Adolescent↗
PubMed1996

Overexpression of bcl-2 protein in synovial sarcoma: a comparative study of other soft tissue spindle cell sarcomas and an additional analysis by fluorescence in situ hybridization.

The expression of bcl-2 protein was analyzed in 19 synovial sarcomas and 29 additional soft tissue spindle cell sarcomas as controls by the immunohistologic staining of paraffin-embedded specimens; 15 of 19 (79%) synovial sarcoma cases were positive, but all other spindle cell sarcomas were negative including 20 leiomyosarcomas, 4 malignant peripheral nerve sheath tumors, and 4 fibrosarcomas. In 4 cases of bcl-2-positive synovial sarcoma (3 biphasic and 1 focally glandular type), bcl-2 protein staining was much stronger in the spindle cells than in the epithelial cells. A fluorescence in situ hybridization (FISH) analysis with centromeric and whole chromosome painting probes for chromosome 18 and X was performed on 7 synovial sarcomas. The six cases of bcl-2-positive synovial sarcoma consisted of five cases with the t(X; 18) and one case with tetrasomy of chromosome 18 and X. It has been speculated that bcl-2 protein expression is caused by the 14; 18 translocation and other abnormalities of chromosome 18. This study thus showed the feasibility of such a correlation between bcl-2 protein expression and the characteristic cytogenetic abnormality in the synovial sarcoma-X; 18 translocation. In addition, bcl-2 protein also appears to be a characteristic marker of synovial sarcoma and is thus considered to be potentially useful in distinguishing synovial sarcoma from other spindle cell sarcomas.

Chromosomes, Human, Pair 18↗
PubMed1996

Functional disturbance of naive T lymphocytes in very high IgE producers: depletion of interleukin-4-induced interleukin-4-producing cells.

We examined the capacity of T cells from normal individuals and allergic patients with very high IgE to differentiate into interleukin-4(IL-4)-producing cells in vitro. T cells incubated with anti-CD3 monoclonal antibody plus IL-4 or plus anti-IL-4 antibody in the presence of antigen-presenting cells for 7 days were restimulated and their capacity to express IL-4 mRNA was examined by RT-PCR. In T cells from normal individuals, there was a marked increase in the expression of IL-4 mRNA following the addition of IL-4. After fractionation of normal T cells into naive T (CD45RA+) and memory T (CD45RO+) cells, induction of the increase of IL-4 mRNA was restricted to the naive T cell population. In contrast, in T cells from allergic patients, the stimulation of whole or naive T cells with anti-CD 3 monoclonal antibody in the presence of IL-4 induced much less IL-4 mRNA. These findings suggest the presence of a functional abnormality in IL-4-dependent development of IL-4-producing T cells in the peripheral-blood naive T cells from allergic patients.

Adjuvants, Immunologic↗
PubMed1996

Peripheral blood T lymphocytes and basophils, freshly isolated from house-dust-mite-sensitive patients, produce interleukin-4 in response to allergen-specific stimulation.

We examined the capacity of interleukin-4 (IL) production from lymphocytes and basophils, isolated from the peripheral blood of allergic patients sensitive to house dust mite, after stimulation with mite extract. IL-4 production was measured by a sensitive bioassay based on coculture with CT.h4S (a human IL-4-responsive cell line). Lymphocytes and basophils from patients with elevated serum IgE specific to mite allergen [radioallergosorbent test (RAST) score > 3] could produce detectable levels of IL-4 in response to mite extract, whereas those from patients with a RAST score of less than 2 or normal volunteers could not. The sensitivity of basophils to mite extract was high, so that a lower concentration of mite extract (1-10 ng/ml) could induce maximal IL-4 production. On the other hand, a higher concentration (10 micrograms/ml) was required for maximal IL-4 production from the lymphocytes. These findings demonstrate that allergen-specific IL-4-producing cells, lymphocytes and basophils, are generated in vivo in allergic patients and also that there exist characteristic differences between lymphocytes and basophils related to the in vivo source of IL-4.

Allergens↗
PubMed1995

Osteosarcoma versus malignant fibrous histiocytoma of bone in patients older than 40 years. A clinicopathologic and immunohistochemical analysis with special reference to malignant fibrous histiocytoma-like osteosarcoma.

BACKGROUND: It is often difficult to discriminate between osteosarcoma and malignant fibrous histiocytoma (MFH) of bone, especially in older patients because of the clinical similarities, including the lytic radiologic appearance. A histologic analysis of MFH-like osteosarcoma, which closely resembles MFH of bone both clinically and radiologically, has not yet been conducted thoroughly, and therefore this issue remains controversial. METHODS: Using clinicopathologic and immunohistochemical techniques, the authors studied 24 cases of osteosarcoma arising in patients older than 40 years of age and compared them with 20 cases of MFH of bone from similarly aged patients. RESULTS: Radiography revealed that 68.2% of the osteosarcoma cases were predominantly lytic, whereas all cases of MFH of bone showed either a predominantly or purely lytic pattern. Histologically, osteosarcoma was subclassified as conventional osteoblastic (54.2%), MFH-like (29.2%) containing various amounts of tumor osteoid and/or bone in each of the cases, and conventional fibroblastic (4.2%), whereas all the cases of MFH of bone had a storiform-pleomorphic pattern. Immunohistochemically, no overexpression of p53 protein was found in MFH-like osteosarcoma, whereas it tended to occur more frequently in osteoblastic osteosarcoma (66.7%) and MFH of bone (50.0%). The Ki-67 labeling index was significantly lower in MFH-like osteosarcoma than in MFH of bone. The 5-year survival rate was 18.2% in patients with osteoblastic osteosarcoma, 66.7% in patients with MFH-like osteosarcoma, and 21.5% in patients with MFH of bone. A significant difference in the survival curve was observed between osteoblastic and MFH-like osteosarcoma. CONCLUSIONS: It is proposed that MFH-like osteosarcoma, which shows characteristically different clinical and histologic features from that of conventional osteosarcoma, thus may be considered a variant of osteosarcoma.

Adult↗
PubMed1995

[Clinical significance of IgG rheumatoid factor in patients with rheumatoid arthritis].

We studied 135 patients with rheumatoid arthritis (RA) from February 1991 through June 1992 (mean period: 9 months) to measure serum IgG rheumatoid factor (IgG-RF) by the method of enzyme linked immunosorbent assay. In order to evaluate clinical significance of serum IgG-RF we compared the level of IgG-RF with some of the clinical and laboratory markers including disease activity index of RA and titers of IgM rheumatoid factor (IgM-RF) and IgA rheumatoid factor (IgA-RF). Positive IgG-RF (more than 2.0 on IgG-RF index) was observed only in 22.2% (30 patients) with the examination of the first collected serum samples but was increased to 41.5% (56 patients) by the case of total test samples. The number of patients with positive IgM-RF or positive IgA-RF test was significantly smaller in seronegative patient group than in seropositive patient group, whereas IgG-RF test showed no significant differences between these two groups. These indicate usefulness of consecutive test of IgG-RF for diagnosis of RA especially in seronegative patients. The mean of total score indicating radiographic bone destruction by Sharp's modified method was significantly higher in positive patients than in negative patients of IgG-RF. Multivariate analysis showed positive correlations between serum IgG-RF levels and erythrocyte sedimentation rates as well as between serum IgG-RF levels and Lansbury's indexes. These results suggest that the test of serum IgG-RF level is beneficial for daily management of patients with RA.

Arthritis, Rheumatoid↗
PubMed1994

The absence of IgE antibody-mediated augmentation of immune responses in CD23-deficient mice.

The CD23 antigen, a low-affinity receptor for IgE (Fc epsilon RII), is a type II membrane-bound glycoprotein expressed on various cells, particularly mature B cells. A number of functions have been ascribed to CD23, including specific regulation of IgE production, IgE-mediated cytotoxicity and release of mediators, IgE-dependent antigen focusing, promotion of B-cell growth, prevention of germinal center B cells from apoptosis, proliferation of myeloid precursors, and maturation of early thymocytes. It is not clear whether these activities represent in vivo functions. To explore in vivo functions of CD23, we have produced CD23-deficient mice. These mice displayed normal lymphocyte differentiation and could mount normal antibody responses, including IgE responses upon immunization with T-dependent antigens and infection with Nippostrongyrus brasiliensis. Germinal center formation after immunization and in vitro proliferative response of B cells were not affected in mutant mice. However, antigen-specific IgE-mediated enhancement of antibody responses was severely impaired.

Animals↗
PubMed1994

The immune responses in CD40-deficient mice: impaired immunoglobulin class switching and germinal center formation.

An engagement of CD40 with CD40 ligand (CD40L) expressed on activated T cells is known to provide an essential costimulatory signal to B cells in vitro. To investigate the role of CD40 in in vivo immune responses, CD40-deficient mice were generated by gene targeting. The significant reduction of CD23 expression on mature B cells and relatively decreased number of IgM bright and IgD dull B cells were observed in the mutant mice. The mutant mice mounted IgM responses but no IgG, IgA, and IgE responses to thymus-dependent (TD) antigens. However, IgG as well as IgM responses to thymus-independent (TI) antigens were normal. Furthermore, the germinal center formation was defective in the mutant mice. These results suggest that CD40 is essential for T cell-dependent immunoglobulin class switching and germinal center formation, but not for in vivo T cell-dependent IgM responses and T cell-independent antibody responses.

Animals↗