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Biomedical subjects

H Kato

Publications and source records attributed to H Kato.

At least 631 records · Page 35Linked to original sources
PubMed1998

Exanthematous disease induced by toxic shock syndrome toxin 1 in the early neonatal period.

BACKGROUND: We have seen a number of patients who developed systemic exanthema and thrombocytopenia in the first week of life. Although nearly 100% of the patients were carriers of meticillin-resistant Staphylococcus aureus (MRSA), no clear link between MRSA and this exanthematous disease has yet been made. METHODS: 20 neonates with exanthema and thrombocytopenia were selected for study. To see whether superantigenic exotoxins from MRSA are involved in the pathogensis of the exanthematous disease, we studied the production of these exotoxins by MRSA isolates from the neonates. We studied the expression of T-cell-receptor Vbeta and CD45RO in T cells taken from four of the neonates. We also analysed the DNA sequences of 16 cloned Vbeta2-positive T-cell-receptor-chain genes taken from two of the neonates. FINDINGS: Although most of the patients recovered within 5 days of onset of the exanthematous disease without any active treatment, two preterm infants died in the recovery phase. All patients showed colonisation by MRSA. The MRSA produced toxic shock syndrome toxin-1 (TSST-1). The number of T cells positive for T-cell-receptor Vbeta2, reactive to TSST-1, was increased in the four patients studied (p<0.0001), and these T cells expressed CD45RO (p=0.0185). None of the Vbeta2 clones had the same junctional sequences. INTERPRETATION: The polyclonal expansion of Vbeta2-positive T cells in patients colonised by TSST-1-producing MRSA suggests that the pathogenic micro-organism of this neonatal exanthematous disease is S aureus, mainly MRSA, and that in its pathogenesis it activates T cells by TSST-1. Although the pathogenesis of both this exanthematous disease and toxic shock syndrome are fundamentally the same, a diagnosis of toxic shock syndrome cannot be made in this case, based on the clinical criteria for toxic shock syndrome. We propose neonatal toxic-shock-syndrome-like exanthematous disease (NTED) as the name for this disease.

Bacterial Toxins↗
PubMed1998

A non-peptide compound which can mimic the effect of thrombopoietin via c-Mpl.

Thrombopoietin (TPO) is a cytokine which plays a central role in megakaryopoiesis and platelet production by binding to its cell surface receptor, termed c-Mpl. In the present study, two benzodiazepinones that compete with the binding of TPO to the extracellular region of c-Mpl were identified, and one of them stimulated the proliferation of a human TPO-dependent megakaryocytic cell line, UT-7/TPO. It stimulated the activation of signal transducer and activator of transcription 5 in UT-7/TPO cells. These results suggest that a non-peptide compound can mimic the effect of TPO via c-Mpl.

Benzodiazepinones↗
PubMed1998

Anti-HIV-1 and chemotactic activities of human stromal cell-derived factor 1alpha (SDF-1alpha) and SDF-1beta are abolished by CD26/dipeptidyl peptidase IV-mediated cleavage.

CD26 is a leukocyte-activation antigen that is expressed on T lymphocytes and macrophages and possesses dipeptidyl peptidase IV (DPPIV) activity, whose natural substrates have not been identified yet. CXC chemokines, stromal cell-derived factor 1alpha (SDF-1alpha) and 1beta (SDF-1beta), sharing the receptor CXCR-4, are highly efficacious chemoattractants for resting lymphocytes and CD34(+) progenitor cells, and they efficiently block the CXCR-4-mediated entry into cells of T cell line tropic strains of HIV type 1 (HIV-1). Here we show that both the chemotactic and antiviral activities of these chemokines are abrogated by DPPIV-mediated specific removal of the N-terminal dipeptide, not only when the chemokines are produced in transformed mouse L cell line to express human CD26 but also when they were exposed to a human T cell line (H9) physiologically expressing CD26. Mutagenesis of SDF-1alpha confirmed the critical requirement of the N-terminal dipeptide for its chemotactic and antiviral activities. These data suggest that CD26-mediated cleavage of SDF-1alpha and SDF-1beta likely occurs in human bodies and promotes HIV-1 replication and disease progression. They may also explain why memory function of CD4(+) cells is preferentially lost in HIV-1 infection. Furthermore, CD26 would modulate various other biological processes in which SDF-1alpha and SDF-1beta are involved.

Animals↗
PubMed1998

High SDF-1 expression in HIV-1 carriers does not correlate with CD8+ T-cell-mediated suppression of viral replication.

Stromal cell-derived factor 1 (SDF-1) inhibits T-cell tropic (T-tropic) HIV-1 infection in vitro. In this study, we examined the regulatory role of SDF-1 on HIV-1 replication in peripheral blood mononuclear cells (PBMC) of HIV-infected individuals. We found that the amount of SDF-1 mRNA in freshly isolated PBMC of HIV-1 carriers was higher than in healthy donors. Moreover, PBMC from some asymptomatic carriers (ACs) exhibited high levels of SDF-1 mRNA expression. The level of SDF-1 expression in PBMC did not correlate with the magnitude of CD8+ T-cell-mediated suppression of HIV-1 among ACs SDF-1 inhibited HIV-1 replication at the viral entry step, whereas a single-cycle HIV-1 infection system showed that the major part of the CD8+ T-cell-mediated suppression occurs after intracellular penetration of the virus. Our results suggest that SDF-1 acts as a suppressor of virus replication in a CD8+ T-cell-independent mechanism in HIV-infected individuals.

Base Sequence↗
PubMed1998

Telomerase activity in lung cancer cells obtained from bronchial washings.

BACKGROUND: Telomerase, a ribonucleoprotein enzyme that functions in the maintenance of telomeres (specialized structures at the ends of chromosomes), has been reported to be a novel diagnostic marker for malignant diseases. We sought to determine whether measurement of telomerase activity in bronchial washings is of value in the diagnosis of lung cancer. METHODS: Extracts of cells in bronchial washings were analyzed for telomerase activity by use of a telomeric repeat amplification protocol (TRAP) assay. Telomerase activity inside cells was evaluated by use of an in situ TRAP assay. The results of both TRAP assays were compared with those obtained from cytologic examination, which employed standard Papanicolaou staining. RESULTS: When results from the two TRAP assays were combined, telomerase activity was detected in bronchial washings from 18 (82%; 95% confidence interval [CI] = 60%-95%) of 22 patients with lung cancer. In contrast, cancer cells were detected by cytologic examination in the bronchial washings of nine (41%; 95% CI = 21%-64%) of the same 22 patients, a statistically significant difference (two-sided P = .0061). In patients with lung cancer, telomerase-positive cells could be detected in bronchial washings irrespective of tumor location--11 of 14 (79%; 95% CI = 49%-95%) peripheral cancerous lesions and seven of eight (88%; 95% CI = 47%-100%) central cancerous lesions were detected by use of TRAP assays (for comparison, two-sided P = .5349). CONCLUSIONS: A high percentage of patients with lung cancers had detectable telomerase activity in bronchial washings. Thus, the use of a cell extract-based or an in situ TRAP assay in addition to cytologic examination may make the diagnosis of lung cancer more reliable.

Adult↗
PubMed1998

Development of a three-electrode-lens drift tube for time-of-flight mass spectrometry.

A three-electrode-lens drift tube for time-of-flight mass spectrometry (TOF-MS) has been developed for utilizing a detector to observe photon-stimulated desorption (PSD). In spite of a small detection area, the detector has a high detection efficiency and durability to reactive gas atmosphere at high pressure. The TOF-MS performance of the drift tube was examined for PSD using single-bunch-mode synchrotron radiation on a dichlorosilane (SiH(2)Cl(2))-saturated Si(001) surface. The measured acceleration and focusing-voltage dependences of the time of flight, intensity and full width at half-maximum for the peak of H(+) and Cl(+) PSD ions are discussed in terms of the numerical calculations of ion trajectories and focusing characteristic of the drift tube.

Journal Article↗
PubMed1998

Crystal structures of two tropinone reductases: different reaction stereospecificities in the same protein fold.

A pair of tropinone reductases (TRs) share 64% of the same amino acid residues and belong to the short-chain dehydrogenase/reductase family. In the synthesis of tropane alkaloids in several medicinal plants, the TRs reduce a carbonyl group of an alkaloid intermediate, tropinone, to hydroxy groups with different diastereomeric configurations. To clarify the structural basis for their different reaction stereospecificities, we determined the crystal structures of the two enzymes at 2.4- and 2.3-A resolutions. The overall folding of the two enzymes was almost identical. The conservation was not confined within the core domains that are conserved within the protein family but extended outside the core domain where each family member has its characteristic structure. The binding sites for the cofactor and the positions of the active site residues were well conserved between the two TRs. The substrate binding site was composed mostly of hydrophobic amino acids in both TRs, but the presence of different charged residues conferred different electrostatic environments on the two enzymes. A modeling study indicated that these charged residues play a major role in controlling the binding orientation of tropinone within the substrate binding site, thereby determining the stereospecificity of the reaction product. The results obtained herein raise the possibility that in certain cases different stereospecificities can be acquired in enzymes by changing a few amino acid residues within substrate binding sites.

Alcohol Oxidoreductases↗
PubMed1998

The clinicopathologic significance of small areas unstained by Lugol's iodine in the mucosa surrounding resected esophageal carcinoma: an analysis of 147 cases.

BACKGROUND: Small areas unstained with Lugol's iodine are often observed in the mucosa surrounding esophageal carcinomas. METHODS: For light microscopic evaluation, the histologic features of 131 small areas unstained by Lugol's iodine in 12 selected cases were investigated. For clinicopathologic evaluation, the numbers of small areas unstained by Lugol's iodine in the mucosa surrounding 147 consecutively resected esophageal carcinomas, including these 12 cases, were counted. The relation between the incidence of such areas and the development of multiple primary cancers in the upper aerodigestive tract was examined together with data on the patients' tobacco and alcohol consumption. RESULTS: Ninety-two percent (131) of the small areas unstained by Lugol's iodine contained dysplastic lesions. Seventeen (12%) of the 147 resected specimens contained fewer than 5 small unstained areas, whereas 52 (35%) had 6-10 and 78 (53%) had more than 11 such areas. The incidence of multicentric cancer in the upper aerodigestive tract and the average alcohol index scores were significantly higher for patients who had more than 11 unstained areas than for patients who had fewer than 5 such areas (P < 0.01). CONCLUSIONS: Lugol's iodine staining method is useful for detecting groups at high risk of multicentric cancer in the upper aerodigestive tract.

Adult↗
PubMed1998

Structural requirements of human tissue factor pathway inhibitor (TFPI) and heparin for TFPI-heparin interaction.

Heparin affinity chromatography of synthetic peptide fragments mimicking tissue factor pathway inhibitor (TFPI) indicated that the minimal heparin binding sequence consists of 12 amino acid residues located at the C-terminal tail. Within this minimal sequence, Arg-257 and Arg-259 appeared to contribute most significantly to interaction with heparin. Affinity chromatography of TFPI using immobilized heparin derivatives regiospecifically desulfated at O-6 of the glucosamine residue, N-2 of the glucosamine residue, and/or O-2 of the iduronic acid residue indicated that all the sulfate groups in heparin appeared to be required for TFPI-heparin interaction. Among them, however, the 6-O-sulfate groups appeared to make the largest contribution to the interaction, while the 2-O-sulfate groups contributed the least. In vitro experiments on the inhibition of factor Xa by TFPI enhanced with native and chemically modified heparins afforded similar results.

Amino Acid Sequence↗
PubMed1998

Three novel missense mutations in unrelated Japanese patients with type I and type II protein S deficiency and venous thrombosis.

A molecular analysis of protein S deficiency in three unrelated Japanese patients was performed. An approximately 50% reduction in both functional and immunologic levels of protein S was detected in the plasmas from two unrelated patients, designated protein S Osaka 1 and protein S Osaka 2. An approximately 50% reduction in the functional level, but a normal immunologic level of protein S, was detected in plasma from a third patient, designated protein S Osaka 3. All of the exons and exon/intron junctions of the protein S gene were studied using a strategy combining polymerase chain reaction amplification and rapid non-radioactive single-strand conformational polymorphism analysis. We identified a G-to-A change in exon X of the protein S gene in protein S Osaka 1. This mutation resulted in the substitution of Gly for Ser at position 295 in the sex hormone-binding globulin-like region. In protein S Osaka 2, a G-to-C change at the position of the 3' end of exon III was identified, leading to the amino acid substitution of Val46 by Leu in the aromatic stack region. In protein S Osaka 3, an A-to-G change in exon II was identified, leading to the substitution of Lys9 by Glu in the Gla domain. It was concluded that the Gly295-to-Ser mutation and Val46-to-Leu mutation cause type I protein S deficiency and that the Lys9-to-Glu mutation causes type II deficiency.

Adult↗
PubMed1998

A kinetic analysis of the interaction of human recombinant tissue factor pathway inhibitor with factor Xa utilizing and immunoassay and the effect of antithrombin III/heparin on the complex formation.

We have recently shown that a complex formation of tissue factor pathway inhibitor (TFPI) and factor Xa (Xa) promotes a clearance of proteoglycans-associated TFPI. In the current studies, the interaction between human recombinant TFPI (h-rTFPI) and Xa were kinetically analyzed by utilizing both a protease inhibitor, p-(amidophenyl) methanesulfonyl fluoride hydrochloride, and a specific enzyme-linked immunosorbent assay for the complex of h-rTFPI with Xa. We further investigated the effect of antithrombin III on the complex formation between h-rTFPI and Xa. We found that the h-rTFPI/Xa complex formed in a time-dependent manner: the second-order rate constant (K1) for the complex formation was calculated to be 0.86x10(6) M(-1)s(-1). The addition of antithrombin III to the h-rTFPI solution modestly reduced the rate of the complex formation between h-rTFPI and Xa. Heparin strikingly enhanced antithrombin III's inhibition of Xa and resulted in complete abrogation of the complex formation between h-rTFPI and Xa in the absence or presence of acidic phospholipids. Furthermore, antithrombin III induced dissociation of the preformed h-rTFPI/Xa complex in the presence of heparin. These results suggest that in the presence of heparin, antithrombin III interferes with the catabolism of TFPI mediated via Xa.

Antithrombin III↗
PubMed1998

Decrease in benzodiazepine receptor binding in the brains of adult patients with Rett syndrome.

To evaluate benzodiazepine (BZD) receptor binding in the brains of patients with the Rett syndrome (RS), three Japanese adult females with stage IV RS were evaluated by single-photon emission computed tomography (SPECT) using [123I] iomazenil. The iomazenil images were obtained 20 min and 3 h post-injection and analyzed for BZD receptor binding. The binding potential (BP) for the BZD receptor was significantly decreased in the fronto-temporal cortex of the RS patients (P<0.05). They also exhibited a decreased BP ratio (BP of each region/BP of cerebellum) in the fronto-temporal (P<0.01), occipital and parietal (P<0.05) cortical gray matter as compared with the ratios observed in five healthy male volunteers. In one RS patient, a marked decrease of iomazenil binding was observed in the late SPECT images, while the early SPECT images showed well preserved cerebral perfusion. This difference strongly suggests that changes in the BZD receptor in RS are primary abnormality, not secondary to a decrease in cerebral blood flow.

Adult↗
PubMed1998

Interleukin-6 produced by pancreatic carcinoma cells enhances humoral immune responses against tumor cells: a possible event in tumor regression.

Production of interleukin-6 (IL-6) by human pancreatic carcinoma cells inversely correlates with potentials for blood-borne metastasis to the liver in nude mice. IL-6 cDNA was transfected to PCI-43, one of our cultured pancreatic carcinoma cell lines that does not produce IL-6 and generates numerous metastases to the liver. An IL-6 high-producer clone (PCI-43h) generated few metastases; IL-6 production thus has a direct effect on metastasis, whereas other transfectants (PCI-43l and PCI-43n), which are IL-6 low-, and IL-6 non-producers, respectively, did generate metastases. Tumor-reactive IgG, which mediated antibody-dependent cellular cytotoxicity (ADCC) in vitro, was detected in sera from recipient nude mice inoculated with PCI-43h but not in sera from mice given PCI-43l, PCI-43n or parent PCI-43. Tumor-reactive IgM was detected in sera from all mice, irrespective of inoculated PCI-43 species, with a slight augmentation being noted in PCI-43h-inoculated nude mice. Severe combined immunodeficiency (SCID) beige mice were then used as recipients for PCI-43 species, and tumorigeneity was examined by s.c. inoculation of a suboptimal number of PCI-43 transfectants (1 x 10(6)/0.1 ml). Only PCI-43h formed palpable masses in SCID beige mice, whereas it first grew to be palpable but subsequently became not palpable in nude mice, thereby revealing a dual action of tumor-derived IL-6. Thus, tumor-derived IL-6 confers growth promotion in SCID beige mice, while the same cytokine exhibits anti-tumorigenic functions, presumably through humoral immune responses, in nude mice.

Animals↗
PubMed1998

Depolarization triggers intracellular magnesium surge in cultured dorsal root ganglion neurons.

Intracellular magnesium concentration ([Mg2+]i) of cultured dorsal root ganglion (DRG) neurons was measured using the magnesium indicator Mag-Fura-2/AM. [Mg2+]i was 0.48 +/- 0.08 mM (mean +/- SEM, n = 23) at rest, and it increased 3-fold by depolarization with a 60-mM K+ solution. The [Mg2+]i increase was observed in the absence of extracellular Mg2+, but the increase disappeared in the absence of extracellular Ca2+. 50 microM cadmium or 100 microM verapamil, a Ca2+ channel blocker, also diminished the rise of [Mg2+]i. The additional measurement of an intracellular Ca2+ concentration ([Ca2+]i) indicated that the [Mg2+]i rise requires a threshold concentration of [Ca2+]i to be reached; above 60 nM. The present results indicate that depolarization induces a Ca2+-influx through voltage dependent Ca channels and this causes the release of Mg2+ from intracellular stores into the cytoplasm.

Animals↗
PubMed1998

Post-thymic maturation of migrating human thymic single-positive T cells: thymic CD1a- CD4+ T cells are more susceptible to anergy induction by toxic shock syndrome toxin-1 than cord blood CD4+ T cells.

To determine whether human CD4+ T cells undergo post-thymic maturation, we compared the susceptibility to anergy induction in human thymic CD1a- CD4+ single-positive (CD4+), cord blood (CB) CD4+, and adult peripheral blood (APB) CD4+ T cells by stimulation with toxic shock syndrome toxin-1 (TSST-1). Most TSST-1-induced T cell blasts derived from either T cell preparation expressed TCR Vbeta2, which determines the potential reactivity to TSST-1. Most thymic CD4+ T cell blast preparations exhibited little or no production of IL-2 and IL-4 after restimulation with TSST-1 and only marginal responses after stimulation with rIL-2 or a combination of PMA and calcium ionophore, while the APB CD4+ T cell blasts showed high responses to these stimuli. The responses of CB CD4+ T cell blasts to these stimuli varied, ranging from minimal to relatively high. Studies of DNA fragmentation showed that there was no significant cell death of thymic CD4+ T cell blasts. Most thymic CD1a- CD4+ and CB CD4+ T cells were CD38 positive. APB CD4+ T cell blasts derived from the CD38+ fraction and from the CD38- fraction exhibited equally high responses to restimulation with TSST-1. These results indicate that thymic CD1a- CD4+ and CB CD4+ T cells are inherently highly susceptible to anergy induction by bacterial superantigens and that thymic CD1a- CD4+ T cells are less mature than CB CD4+ T cells, suggesting that post-thymic maturation in thymic T cells migrating to the periphery is required for acquisition of full reactivity to antigenic stimulation.

ADP-ribosyl Cyclase↗
PubMed1998

Bioactive bone cement: comparison of apatite and wollastonite containing glass-ceramic, hydroxyapatite, and beta-tricalcium phosphate fillers on bone-bonding strength.

A study was conducted to compare the bone-bonding strengths of three types of bioactive bone cement, consisting of either apatite- and wollastonite-containing glass-ceramic (AW-GC) powder, hydroxyapatite (HA) powder, or beta-tricalcium phosphate (beta-TCP) powder as an inorganic filler and bisphenol-a-glycidyl methacrylate (Bis-GMA) based resin as an organic matrix. Seventy percent (w/w) filler was added to the cement. Rectangular plates (10 x 15 x 2 mm) of each cement were made and abraded with #2000 alumina powder. After soaking in simulated body fluid for 2 days, the AW cement (AWC) and HA cement (HAC) formed bonelike apatite over their entire surfaces, but the TCP cement (TCPC) did not. Plates of each type of cement were implanted into the tibial metaphyses of male Japanese white rabbits, and the failure loads were measured by a detaching test at 10 and 25 weeks after implantation. The failure loads of AWC, HAC, and TCPC were 3.95, 2.04, and 2.03 kgf at 10 weeks and 4.36, 3.45, and 3.10 kgf at 25 weeks, respectively. The failure loads of the AWC were significantly higher than those of the HAC and TCPC at 10 and 25 weeks. Histological examination by contact microradiogram and Giemsa surface staining of the bone-cement interface revealed that all the bioactive bone cements were in direct contact with bone. However, scanning electron microscopy and energy-dispersive X-ray microanalysis showed that only AWC had contacted to the bone via a Ca-P rich layer formed at the interface between the AW-GC powder and the bone, which might explain its high bone-bonding strength. Neither the HAC nor the TCPC contacted the bone through such a layer between each powder and the bone, although the HAC and TCPC directly contacted with bone. Our results indicate that all three types of abraded and prefabricated cement have bonding strength to bone, but AWC has superior bone-bonding strength compared to HAC and TCPC.

Animals↗