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Biomedical subjects

T Nakazawa

Publications and source records attributed to T Nakazawa.

At least 163 records · Page 9Linked to original sources
PubMed1998

Optic disc edema associated with spinocerebellar degeneration.

A 58-year-old man presented with optic disc edema as a rare association with spinocerebellar degeneration (SCD). The patient also had chronic idiopathic intestinal pseudo-obstruction with hypoalbuminemia. No elevation of intraspinal pressure and no intracranial lesion was observed. The hypoalbuminemia reacted promptly to treatment, whereas the optic disc edema regressed gradually. An association between SCD and optic atrophy has often been described, but to our knowledge this is the first report of SCD in association with optic disc edema.

Fluorescein Angiography↗
PubMed1998

Human skin mast cells produce TNF-alpha by substance P.

Using in situ hybridization and the reverse transcriptase polymerase chain reaction (RT-PCR) we show that messenger RNA for IL-4, IL-5 and tumor necrosis factor-alpha (TNF-alpha) is induced by cross-linkage of high-affinity Fc(epsilon) receptors (Fc(epsilon)RI) on human skin mast cells, but that only TNF-alpha mRNA is selectively induced by substance P. Skin mast cells were purified using the Percoll density technique. T cells were removed by serial negative selection using a CD2 monoclonal antibody (mAb) to achieve a final mast cell purity >95%. Purified mast cells were precultured with recombinant human stem cell factor (rhSCF; 10 ng/ml) and myeloma IgE (3 microg/ml) for 16 h before challenge with sheep polyclonal antihuman IgE antibody (anti-IgE; 1 or 10 microg/ml) in the presence of rhSCF (50 ng/ml). Using in situ hybridization, we demonstrated that IgE-dependent stimulation induces the expression of IL-4, IL-5 and TNF-alpha mRNA in skin mast cells. We have investigated the expression of IL-4, IL-5 and TNF-alpha mRNA by substance P, with the result that substance P, 0.003-30 microM, selectively induced TNF-alpha mRNA. However, substance P did not induce IL-4 mRNA and did not enhance IL-5 mRNA. Furthermore, we confirmed the release of TNF-alpha by substance P from skin mast cells using an ELISA technique. These findings demonstrate the capacity of human skin mast cells to transcribe IL-4, IL-5 and TNF-alpha by immunological activation and to transcribe and release TNF-alpha by substance P.

Base Sequence↗
PubMed1998

Distribution of Chlamydia pneumoniae infection in the athersclerotic carotid artery.

BACKGROUND AND PURPOSE: Chlamydia pneumoniae infection has recently become noteworthy in relation to atherosclerosis. We investigated by immunohistochemistry the distribution of C pneumoniae infection in the atherosclerotic carotid artery. METHODS: Twenty carotid atherosclerotic lesions that were resected during carotid endarterectomy were investigated. Parallel sections were stained immunohistochemically with monoclonal antibodies for a C pneumoniae-specific antigen, macrophages, and smooth muscle cells. RESULTS: Immunoreactivity for the C pneumoniae-specific antigen was observed in 11 of 20 specimens (55%), and intense immunoreactivity was observed in 7 of 20 (35%). C pneumoniae infection was observed in endothelial cells, macrophages and in smooth muscle cells that had migrated into the atheromatous plaque, as well as in smooth muscle cells and small arteries in the media underlying the atheromatous plaques. C pneumoniae infection was most prominently observed in smooth muscle cells. The severity of the infection as demonstrated by immunohistochemistry was not significantly related to general risk factors for atherosclerosis. CONCLUSIONS: C pneumoniae widely infects endothelial cells, macrophages, and smooth muscle cells in the atherosclerotic carotid artery. The results of the present study can help us to understand how C pneumoniae infection contributes to the progression of carotid atherosclerosis.

Aged↗
PubMed1998

Expression of cell adhesion molecules in tubulointerstitial nephritis associated with Sjögren's syndrome.

The tissue distribution of cellular adhesion molecules (ICAM-1, ELAM-1, VCAM-1) was studied in specimens from six normal human kidneys and in six biopsies from kidneys with tubulointerstitial nephritis associated with Sjögren's syndrome. In addition, the expression of cellular adhesion molecules was examined both in four renal biopsies from cases of tubulointerstitial nephritis of diverse pathogenesis and in six lip biopsies from cases of Sjögren's syndrome. ICAM-1 was expressed on vascular endothelial cells in normal kidneys, in all specimens of tubulointerstitial nephritis and in salivary glands. On tubular epithelial cells, ICAM-1 appeared slightly in normal kidneys; otherwise tubular epithelial ICAM-1 was observed in and around the foci of cellular infiltration in all cases of tubulointerstitial nephritis. ELAM-1 and VCAM-1 were observed on the newly generated vessels in massive cellular infiltrates in some cases of tubulointerstitial nephritis associated with Sjögren's syndrome; by contrast, they were not seen in normal kidneys and in cases of tubulointerstitial nephritis of diverse pathogenesis. In the lip biopsies from salivary glands, ICAM-1 was observed on ductal epithelial cells in and around the foci of cellular infiltration, and ELAM-1 and VCAM-1 occasionally appeared on the newly generated vessels in massive cellular infiltrates. Chronic and progressive inflammation may be facilitated by such ELAM-1 and VCAM-1 expression on newly generated vessels. The adhesion molecules were thought to play a role in the pathogenesis of tubulointerstitial nephritis and sialoadenitis associated with Sjögren's syndrome. It was thus concluded that the same inflammatory process that took place in the salivary glands to induce the characteristic tissue change of Sjögren's syndrome likely was operative in the renal tubulointerstitial tissue as well.

Adolescent↗
PubMed1998

Chemotaxis of Helicobacter pylori: a urease-independent response.

Helicobacter pylori has adapted to a very specialized niche; namely, the highly acidic, viscous, and somewhat anaerobic gastric mucus of humans. The enzyme urease is essential for colonization of the stomach, as it provides protection against gastric acidity. A spiral morphology as well as sheathed flagella have been claimed to give the bacteria an advantage in colonizing mucus. Wild type strain of H. pylori and its isogenic urease-negative mutant showed a chemotactic response to urea, flurofamide (a potent urease inhibitor), sodium ion, and bicarbonate ion. These chemotactic responses are also observed in the viscous environment. Thus, it appears that H. pylori has chemotactic movement that is independent of urease activity. The chemotactic response was inhibited by carbonyl cyanide m-chlorophenylhydrazone (CCCP), a potent H+ pump inhibitor, but not by Na+ pump-inhibiting amiloride, suggesting this response is forced by H+-driven flagellar movement. Since urea and sodium bicarbonate are secreted from the gastric epithelial surface, this chemotactic response may contribute to the colonization by H. pylori and the persistence of its infection.

Chemotaxis↗
PubMed1998

[Seizures in the acute phase of aseptic and bacterial meningitis].

We studied seizures that occur during the acute phase of aseptic and bacterial meningitis in childhood. Of the 108 children with aseptic meningitis, five had seizures (4.7%). Four patients developed them within 24 hours of the onset of the initial symptom (fever in 3 cases), and three had repeated seizures on the first day. One case had SIADH complication, but another neurologic abnormalities were not observed. On the 18 children with bacterial meningitis, three cases (16.7%) had seizure, which occurred on the second day of illness. Disturbance of consciousness and cerebral hypertension were observed in 2 cases each, and abnormal cerebral CT findings in all the three. The NSE level in the cerebrospinal fluid was elevated in 2 cases. Thus, seizures occurring in the acute phase of aseptic meningitis may reflect transient cerebral functional abnormality accompanying fever or SIADH, whereas those in bacterial meningitis may result from neural tissue damage due to encephalopathy or angitis. In aseptic and bacterial meningitis, the presence of seizures in the acute phase was not correlated with the neurological outcome.

Acute-Phase Reaction↗
PubMed1997

Theophylline accelerates human granulocyte apoptosis not via phosphodiesterase inhibition.

Theophylline, in addition to its bronchodilator effect, is reported to have an antiinflammatory action that may account for its clinical effectiveness in the reduction of inflammatory cells in the airway. In bronchial asthma, such inflammatory cytokines as GM-CSF and IL-5 are upregulated and have been proposed to cause granulocyte infiltration (neutrophils and eosinophils) in the airway by inhibition of granulocyte apoptosis. We examined the abilities of theophylline to counteract the prolongation of human granulocyte survival caused by cytokines. Theophylline was shown to shorten granulocyte survival in a dose-dependent manner. Upon incubation with a therapeutical concentration of theophylline (0.1 mM; 18 microg/ml), percentages of GM-CSF (10 ng/ml)-induced delayed apoptosis increased from 18+/-2% to 38+/-3% (p < 0.02) in neutrophils and from 21+/-2% to 35+/-2% (p < 0.02; 24-h incubation) in eosinophils. The percentage of IL-5 (5 ng/ml)-induced delayed eosinophil apoptosis also increased from 22+/-4% to 33+/-2% (P < 0. 05). In contrast, cyclic AMP (cAMP)-increasing agents (3-isobutylmethylxanthine, dibutyryl cAMP, and rolipram) inhibited granulocyte apoptosis in the control and anti-Fas antibody-treated cells. In eosinophils, the expression of bcl-2 protein decreased after incubation with theophylline. These findings suggest that theophylline accelerates granulocyte apoptosis, which may play an essential role in inflammation, and controls granulocyte longevity regardless of the elevation of intracellular cAMP levels.

1-Methyl-3-isobutylxanthine↗
PubMed1997

Synthetic peptides derived from the melanocyte-stimulating hormone receptor MC1R can stimulate HLA-A2-restricted cytotoxic T lymphocytes that recognize naturally processed peptides on human melanoma cells.

Human melanoma-specific HLA-A2 restricted CTLs have recently been shown to recognize antigens expressed by melanoma lines and normal melanocytes, including Melan-A/Mart-1, gp100, gp75, and tyrosinase. Herein, we define HLA-A2-restricted CTL epitopes from a recently cloned melanocortin 1 receptor (MC1R), which belongs to a new subfamily of the G-protein-coupled receptors expressed on melanomas and melanocytes. Thirty-one MC1R-derived peptides were selected on the basis of HLA-A2-specific motifs and tested for their HLA-A2 binding capacity. Of a group of 12 high or intermediate HLA-A2 binding peptides, three nonamers, MC1R244 (TILLGIFFL), MC1R283 (FLALIICNA), and MC1R291 (AIIDPLIYA), were found to induce peptide-specific CTLs from peripheral blood mononuclear cells of healthy HLA-A2+ donors after repeated in vitro stimulation with peptide-pulsed antigen-presenting cells. The CTLs raised against these three HLA-A2+-restricted peptides could recognize naturally processed peptides from HLA-A2+ melanomas and from Cos7 cells cotransfected with MC1R and HLA-A2. CTLs induced by the MC1R291 peptide (but not induced or induced only to a very low extent by the other two MCR1 peptide epitopes) showed cross-reactions with two other members of the melanocortin receptor family, which are more broadly expressed on other tissues. Taken together, our findings have implications in relation both to autoimmunity and immunotherapy of malignant melanomas.

Animals↗
PubMed1997

Biocompatibility of alumina ceramic and polyethylene as materials for pivot bearings of a centrifugal blood pump.

The double pivot bearings in the Gyro C1E3 centrifugal blood pump incorporate a high-purity alumina (Al2O3) ceramic and an ultra-high-molecular-weight polyethylene (UHMWPE). This centrifugal pump has been developed as a completely sealless pump for long-term usage. The combination of Al2O3 and UHMWPE are the materials of choice for the acetabular bearing in artificial joints, which have proven to be clinically reliable for over 10 years. Previous studies have examined the biocompatibility of Al2O3 and UHMWPE as bulky implant materials. The present study investigated this material as a blood-contacting material using a standard assessment in vitro and in vivo analysis. The examined items were systemic toxicity, sensitization (guinea pig maximization test), cytotoxicity (elution test), mutagenicity (Ames test), direct contact hemolysis, and thrombogenicity. The studies were performed according to the United States Pharmacopoeia and published previous studies. The samples of both Al2O3 and UHMWPE demonstrated no differences from the negative controls in all tests. These findings indicate that both Al2O3 and UHMWPE are biocompatible materials for double-pivot bearings in the centrifugal blood pump.

Aluminum Oxide↗
PubMed1997

Uterine carcinosarcoma is derived from a single stem cell: an in vitro study.

Expression of intermediate filaments (IFs) has been suggested to be a reliable marker for differentiating epithelial and non-epithelial tumors. Moreover, the c-erbB-2 and p53 genes are considered to be involved relatively early in the process of human carcinogenesis. In order to elucidate the origin of uterine carcinosarcomas, we analyzed IF, c-erbB-2 and p53 expression in and the ultrastructural characteristics of clones derived from a human uterine-carcinosarcoma cell line, EMTOKA. The expression of IFs and other proteins in the EMTOKA clones was identical to that in the EMTOKA cell line. It and its 7 clones all expressed cytokeratins 8, 17, 18 and 19, vimentin, epithelial membrane antigen, S-100, myoglobin, type-II collagen, alpha-smooth-muscle actin, placental alkaline phosphatase and epidermal-growth-factor receptor. The c-erbB-2 and p53 expression levels of all the cell types of the EMTOKA cell line and its clones were the same. Interestingly, an ultrastructural study showed that the EMTOKA cell line and its clones at early and late passages possessed the characteristics of epithelial cell types without either transitional forms between the epithelial and stromal components or differentiation into sarcomatous components. The results of this study lend particular support to the combination tumor hypothesis that a precursor (stem) cell gives rise both to epithelial and to mesenchymal components during the histogenesis of uterine carcinosarcoma, the epithelial component of which appears to be dominant, suggesting that the established cell lines derived from a common stem cell.

Biomarkers, Tumor↗
PubMed1997

Fiber-optic-based biomonitoring of benzene derivatives by recombinant E. coli bearing luciferase gene-fused TOL-plasmid immobilized on the fiber-optic end.

TOL plasmid in Pseudomonas putida mt-2 has a series of genes for the degradation of xylene, toluene, and their derivatives to pyruvate and acetaldehyde (or propionaldehyde). Two operons, i.e., upper operon and meta operon, play indispensable roles for the digestion of xylene derivatives: When XyIR protein recognizes xylene derivatives, another controlling gene, xyIS, is activated, which results in the activation of meta operon. Therefore, we have constructed a fusion gene between TOL plasmid and the firefly luciferase gene under the control of XyIR and the promoter of xyIS gene; i.e., by using fusions of the meta operon with promotorless luciferase expression vector from firefly, we have constructed and tested biomonitors for benzene derivatives. Bioluminescence specified by Escherichia coli (pTSN316), carrying xyIR and xyIS promoters, Ampr and luc, was measured in either a benzene derivative-saturated or o-methylbenzyl alcohol-dissolved medium both in the case of cell suspension and in the case of immobilized cell form. The utility of the biosensing system for monitoring in chemical plant drainage was demonstrated with samples supplemented with benzene derivatives. The xyIR-xyIS promoter-lux fusion carried by pTSN316 responded to a benzene-related chemical in sample solutions. Immobilization of the transformed E. coli, at one end of fiber optic, bearing firefly luciferase gene fused to TOL plasmid, has been demonstrated to fabricate a luminescent remote biomonitoring device for the protection of environmental deterioration. Due to the luminescent detection, the detection limits for benzene-related aromatics that are recognized by a binding protein (XyIR) were parts-per-million. We had already submitted a preliminary report concerning the possibility of environmental monitoring based on the above idea by using the transformed E. coli in a cell-suspended solution. This paper describes mainly a fiber-optic-based biomonitoring device for the protection of environmental deterioration.

Bacterial Proteins↗
PubMed1997

B cell subpopulations separated by CD27 and crucial collaboration of CD27+ B cells and helper T cells in immunoglobulin production.

B cell immunoglobulin production is regulated by helper T cells through direct interaction and secreted cytokines. In the present study, we functionally analyzed CD27 in cord and peripheral blood B cells. Adult peripheral blood B cells were separated into CD27+ and CD27- cells, which differed in their morphology. Cord blood B cells did not express CD27, and CD27 expression on peripheral blood B cells increased with age. Only CD27+ B cells had the ability to produce immunoglobulin, which was increased by contact with a tumor necrosis factor-related transmembrane ligand, CD70. Adult peripheral blood CD27+ B cells can be further subdivided into two discrete subtypes: IgD- CD27+ and IgD+ CD27+ B cells. IgD- CD27+ B cells produce IgG, IgM and IgA, whereas IgD+ CD27+ B cells predominantly produce IgM. The addition of activated CD4+ CD45RO T cells expressing CD70 caused down-regulation of CD27 expression on activated B cells, and this down-modulation was completely blocked by anti-CD70 monoclonal antibody, indicating direct T-B cell contact via CD27/CD70. The triggering via CD27 and CD40 additively increased the immunoglobulin production under Staphylococcus aureus Cowan strain plus interleukin-2 stimulation. Taken together, our findings demonstrate that peripheral blood B cells are separated into subpopulations by CD27 and IgD expression and that CD27+ B cells produce large amounts of immunoglobulin by interaction with the CD70 molecule.

Adult↗
PubMed1997

Effect of long-term treatment with complete Freund's adjuvant on KK-Ay mouse, a model of non-insulin-dependent diabetes mellitus.

Nonspecific stimulation with immunoadjuvants significantly improves glucose tolerance in animal models for non-insulin-dependent diabetes mellitus (NIDDM). In this study, we observed the effect of long-term treatment with complete Freund's adjuvant (CFA) on serum factors and histology of various organs in KK-Ay mice with NIDDM. The mice were injected with CFA weekly or every 2 weeks for 12 weeks. Glucose tolerance was significantly improved in the CFA-treated mice throughout the experiment. At the end of the experiment, hypertriglyceridemia was significantly reduced, but serum total protein, glutamic pyruvic transaminase, creatinine, and nonfasting insulin levels were not changed by the treatment. Fatty change of the liver and index of glomerular lesions of the kidney were significantly inhibited in the CFA-treated mice, whereas the pancreatic islet morphology remained unchanged. No toxic effect was observed by the CFA treatment. These results imply that the novel treatment with CFA could control NIDDM and inhibit the development of diabetic glomerular lesions in KK-Ay mice.

Animals↗
PubMed1997

p53 accumulation and apoptosis in embolized meningiomas.

Preoperative embolization of meningiomas is performed to decrease blood loss at surgery. While it is also expected to reduce tumor recurrence by producing necrosis at the site of dural attachment, very little has been described about what happens to the non-necrotic tumor cells. We investigated how the proliferative activities of meningiomas were modified after embolization. In nine meningiomas which were embolized preoperatively, proliferative potentials and expression of cell cycle inhibitors were assessed immunohistochemically using MIB-1, anti-53 (DO-1 and DO-7), and anti-p21 (WAF1/CIP1) monoclonal antibodies. To determine whether a cell underwent apoptotic death besides necrosis, we applied the terminal deoxynucleotidyl transferase-mediated dUTP-digoxigenin nick end labeling method. Results were compared with control meningiomas without embolization. MIB-1 positive cells often gathered in perinecrotic areas, although the mean MIB-1 staining index of the embolized meningiomas was not significantly different from the control. p53 and its downstream effector p21 accumulated mainly in the perinecrotic areas in eight of the nine embolized meningiomas. Apoptosis was also observed in the concomitant areas. Double staining for both MIB-1 and p21 frequently showed positive cells for both antibodies. The accumulation of MIB-1 positive cells in the embolized meningiomas may not be a sign of fast growth or malignancy, but it may implicate arrest of cell cycle by the p21. This study indicates that embolized meningiomas exhibit not only necrosis but also apoptosis and cell cycle arrest. The latter effects appear to be at least partly p53 dependent.

Adult↗
PubMed1997

Receptor-dependent G protein-mediated Ca2+ sensitization in canine airway smooth muscle.

To determine the mechanisms of receptor-dependent Ca2+ sensitization in airway smooth muscle, canine tracheal smooth muscle (CTSM) was permeabilized with alpha-toxin or beta-escin. Although the effects of 5-hydroxytryptamine (100 microM), histamine (100 microM), and the thromboxane A2 analogue U-46619 (100 microM) were negligible, carbachol (100 microM) and endothelin-1 (ET-1, 1 microM) evoked additional contractions of 47.0 +/- 5.90% and 25.0 +/- 5.37% (n = 6) at pCa 6.7 with GTP (3 microM) (normalized to the maximum contraction at pCa 4.5) in alpha-toxin-permeabilized CTSM. GDP-beta-S (1 mM) reversed the carbachol and ET-1 responses completely. GTP-gamma-S (30 microM) and 4 beta-phorbol 12,13-dibutyrate (PDBu, 3 microM) increased the Ca2+ sensitivity (median effective pCa) of contraction by 1.8- and 4.4-fold, respectively (n = 4-11, P < 0.05). The effects of saturating concentrations of GTP-gamma-S and PDBu were additive. A synthetic peptide (T2) corresponding to the actin-binding site of calponin caused a dose-dependent contraction of beta-escin permeabilized CTSM, with the peak effect (25 +/- 4%, n = 4) at 1200 microM, PDBu (3 microM) caused contraction of the T2 peptide-treated CTSM. In conclusion, Ca2+ sensitization of CTSM depends on receptor type and is mediated by G proteins and protein kinase C whose effects are additive, with a partial contribution by calponin.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1997

Angiotensin converting enzyme inhibitors suppress production of tumor necrosis factor-alpha in vitro and in vivo.

It has been reported that angiotensin converting enzyme (ACE) inhibitors have beneficial effects on insulin resistance and congestive heart failure, in which elevations of serum tumor necrosis factor-alpha (TNF-alpha) level have been indicated. Therefore, in this study, we examined effect of ACE inhibitors on TNF-alpha production both in vitro and in vivo by using human blood mononuclear cells and mice, respectively. LPS (20 micrograms/ml)-induced in vitro TNF-alpha production, measured by bioassay and enzyme-linked immunosorbent assay, was significantly inhibited with captopril, delapril and cilazapril in a concentration of 10(-3) mol/l. A single, oral administration of captopril, delapril and cilazapril at more than 10-fold doses of common clinical use in man significantly inhibited LPS (2 mg/kg)-induced serum TNF-alpha activity in Balb/c mice. These results indicate that ACE inhibitors such as captopril, delapril and cilazapril have an inhibitory effect on TNF-alpha production not only in vitro as previously reported, but also in vivo, although relatively high concentrations and large doses were required in this study.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1997

Pure ovarian ependymoma: report of a case treated with surgery, chemotherapy, irradiation and hyperthermotherapy.

Ependymomas usually develop from neuroectodermal organs. Pure ovarian ependymoma is an extremely rare tumor. We report a patient with ovarian ependymoma who died at the age of 28, 9 years after initial surgery and subsequent intensive combination therapy (chemotherapy, irradiation and hyperthermotherapy) for repeated relapses and metastatic tumors. The diagnosis was confirmed by histopathological and immunohistochemical studies. For recurrent and persistent ependymoma, a combination of the treatment modalities described above is suggested to be beneficial in attenuating the rapid progress and spread of this disease.

Adolescent↗