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Biomedical subjects

S Kawai

Publications and source records attributed to S Kawai.

At least 91 records · Page 5Linked to original sources
PubMed2001

[Diagnostic imaging in osteoporosis (CT and MRI)].

Osteoporosis is a systemic skeletal disease characterized by low bone mass and micro-architectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture risk. In the past decade, considerable progress has been made in the development of methods for assessing the skeleton non-invasively, so that osteoporosis can be managed more effectively. Recently, attention has been focused on deriving measures that provide information about not only bone mineral density but also microstructure. Magnetic resonance imaging (MRI) and computed tomography (CT) are such new techniques which potentially may provide information pertaining to bone density and structure as well as to occult fracture detection. For example, quantitative CT (QCT), peripheral QCT and quantitative MRI are promising tools for the measurements of the bone density. Micro-CT and magnetic resonance microscopy are potentially available tools to image and quantify the three-dimensional structure of trabecular bone. These potentially useful techniques for assessing osteoporosis and predicting fracture risk are reviewed in this paper.

English Abstract↗
PubMed2000

The prevalence of TT virus infection in renal transplant recipients in Brazil.

BACKGROUND: Recently, TT virus (TTV) was discovered as a potential causative agent for non-A-E hepatitis. Little is known about the prevalence of TTV infection in renal transplant recipients. METHODS: One hundred and seventeen Brazilian renal transplant recipients and 100 normal subjects were examined to determine the prevalence of TTV infection. The TTV DNA in serum and its genotype were examined using polymerase chain reaction and restriction enzyme length polymorphism, respectively. RESULTS: TTV DNA was detected in 63/117 (53.8%) renal transplant recipients in contrast to its detection in 10/100 (10%) normal subjects (P<0.001). There was no statistical difference in the distribution of TTV genotypes between these groups. There was no significant difference in clinical backgrounds between TTV positive and negative patients. CONCLUSIONS: These results indicate a risk for TTV infection in renal transplant recipients in Brazil. They also indicate that TTV itself might not have a strong correlation with the pathogenicity of liver diseases.

Adolescent↗
PubMed2000

Inorganic Polyphosphate/ATP-NAD kinase of Micrococcus flavus and Mycobacterium tuberculosis H37Rv.

An enzyme with both inorganic polyphosphate [poly(P)]- and ATP-dependent NAD kinase activities was isolated from Micrococcus flavus. The enzyme was a dimer consisting of 34 kDa subunits, and was named poly(P)/ATP-NAD kinase. Internal amino acid sequences of the enzyme showed homologies with some function-unknown proteins released on the GenBank database. Among such proteins, hypothetical Rv1695 protein (Accession No. Z98268-16), which was encoded by a gene named "Rv1695" on genomic DNA of Mycobacterium tuberculosis H37Rv, was proposed to be poly(P)-dependent NAD kinase. By cloning and expression in Escherichia coli, Rv1695 was shown to encode poly(P)/ATP-NAD kinase and named ppnk. The ppnk product, recombinant-poly(P)/ATP-NAD kinase (Ppnk) was purified and characterized. The enzyme was a tetramaer consisting of 35 kDa subunits when expressed in E. coli. Poly(P)/ATP-NAD kinases of M. flavus and Ppnk of M. tuberculosis H37Rv specifically and completely phosphorylated NAD by utilizing commercially available poly(P)s and nucleoside triphosphates as phosphoryl donors.

Amino Acid Sequence↗
PubMed2000

Santonin-related compound 2 inhibits the expression of ICAM-1 in response to IL-1 stimulation by blocking the signaling pathway upstream of I kappa B degradation.

Santonin-related compounds (SRCs) were synthesized from the starting material L-alpha-santonin and tested for the biological activity on the expression of intercellular adhesion molecule-1 (ICAM-1) in response to IL-1 stimulation on human adenocarcinoma cells. One of the bromoketone derivatives termed SRC2 [11S-2 alpha-bromo-3-oxoeudesmanno-13,6 alpha-lactone] strongly inhibited the ICAM-1 expression at an IC(50) value of 5.9 microM, whereas L-alpha-santonin itself was totally inactive up to 100 microM. The blockage of ICAM-1 expression by SRC2 was not due to the direct inhibition of de novo RNA and protein synthesis. The nuclear translocation of NF-kappaB subunit p65 was markedly prevented by SRC2. Moreover, I kappa B alpha degradation upon IL-1 stimulation was strongly inhibited by SRC2. These observations suggest that SRC2 blocks the IL-1 signaling pathway upstream of I kappa B degradation.

Biological Transport↗
PubMed2000

Lipophilic HMG-CoA reductase inhibitor has an anti-inflammatory effect: reduction of MRNA levels for interleukin-1beta, interleukin-6, cyclooxygenase-2, and p22phox by regulation of peroxisome proliferator-activated receptor alpha (PPARalpha) in primary endothelial cells.

We examined the effects of four 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (pravastatin, simvastatin, fluvastatin, and cerivastatin) on the production and expression of inflammatory cytokines and on enzyme expression involving prostaglandin and superoxide production in cultured human umbilical vein endothelial cells (HUVEC). All HMG-CoA reductase inhibitors significantly reduced interleukin-1beta and -6 mRNA expression and their protein levels in the culture medium, and also inhibited cyclooxygenase-2 mRNA expression and their protein levels. And these drugs induced peroxisome proliferator-activated receptor alpha (PPARalpha) and PPARgamma mRNA expression and their protein levels in HUVEC and hepatocyte. Moreover, the mRNA levels of p22phox, a 22-kD subunit and the protein levels of p47phox, a 47-kD subunit of nicotine adenine dinucleotide phosphate (NADPH) oxidase, was decreased by treatment with either simvastatin, fluvastatin or cerivastatin, and this effect was reversed by mevalonate, geranylgeraniol, farnesol, and cholesterol. The changes induced by HMG-CoA reductase inhibitors might be due to regulation of cellular cholesterol content level, cellular cholesterol metabolic pathway, and cellular PPARalpha activity, which was related with inflammation. This unique anti-inflammatory effect in addition to its hypolipidemic action, may be beneficial in preventing the vascular complications that are induced by hyperlipidemia.

Anti-Inflammatory Agents↗
PubMed2000

Mouse smad8 phosphorylation downstream of BMP receptors ALK-2, ALK-3, and ALK-6 induces its association with Smad4 and transcriptional activity.

Smads are intracellular signaling mediators for TGF-beta superfamily. Smad1 and Smad5 are activated by BMP receptors. Here, we have cloned mouse Smad8 and functionally characterized its ability to transduce signals from BMP receptors. Constitutively active BMP type I receptors, ALK-3 and ALK-6, as well as ALK-2, were phosphorylated Smad8 and induced Smad8 interaction with Smad4. Nuclear translocation of Smad8 was stimulated by constitutively active BMP type I receptors. In contrast, constitutively active TGF-beta type I receptor, ALK-5, did not exhibit any action on Smad8. Smad8 and Smad4 cooperatively induced the promoter of Xvent2, a homeobox gene that responds specifically to BMP signaling. Dominant-negative Smad8 was shown to inhibit the increase of alkaline phosphatase activity induced by BMP-2 on pluripotent mesenchymal C3H10T1/2 and myoblastic C2C12 cell lines. The presence of Smad8 mRNA in mouse calvaria cells and osteoblasts suggests a role of Smad8 in the osteoblast differentiation and maturation.

Activin Receptors↗
PubMed2000

Novel antiarthritic agents with 1,2-isothiazolidine-1,1-dioxide (gamma-sultam) skeleton: cytokine suppressive dual inhibitors of cyclooxygenase-2 and 5-lipoxygenase.

Various 1,2-isothiazolidine-1,1-dioxide (gamma-sultam) derivatives containing an antioxidant moiety, 2,6-di-tert-butylphenol substituent, were prepared. Some compounds, which have a lower alkyl group at the 2-position of the gamma-sultam skeleton, showed potent inhibitory effects on both cyclooxygenase (COX)-2 and 5-lipoxygenase (5-LO), as well as production of interleukin (IL)-1 in in vitro assays. They also proved to be effective in several animal arthritic models without any ulcerogenic activities. Among these compounds, (E)-(5)-(3,5-di-tert-butyl-4-hydroxybenzylidene)-2-ethyl-1, 2-isothiazolidine-1,1-dioxide (S-2474) was selected as an antiarthritic drug candidate and is now under clinical trials. The structure-activity relationships (SAR) examined and some pharmacological evaluations are described.

Animals↗
PubMed2000

Hyperleptinemia in female patients with ossification of spinal ligaments.

In order to examine the involvement of leptin in the ossification of spinal ligaments (OSL), the present study examined (i) serum levels of leptin and insulin in OSL patients and controls, (ii) serum leptin levels in children of OSL females with severe obesity, (iii) the expression of leptin receptor mRNA in human spinal ligaments, and (iv) effects of leptin on cultured human ligament cells. In the OSL females, serum leptin levels were significantly higher than those of the control females, and the levels were positively correlated to the serum insulin levels, while in the control females, there was a tendency of inverse correlation. The daughters of OSL females with severe obesity also had high serum leptin levels, although they had not developed OSL. The expression of leptin receptor mRNA was confirmed in the ligaments, but leptin did not influence the alkaline phosphatase activity nor procollagen type I carboxyl-terminal peptide content of the ligament cells. These findings suggest that leptin is involved genetically and indirectly with the pathogenesis of OSL in female patients.

Adolescent↗
PubMed2000

Erythrocytosis caused by an erythropoietin-producing hepatocellular carcinoma.

A case of erythrocytosis caused by a hepatocellular carcinoma (HCC) that produced erythropoietin (Epo) is described. A 64-year-old man, with a huge HCC tumor in the right lobe of the liver, showed a high concentration of hemoglobin and increased levels of serum Epo, alpha-fetoprotein (AFP), and protein induced by vitamin K absence II (PIVKA-II). Right lobectomy of the liver was performed. Histological findings of the specimen showed a moderately differentiated HCC. The existence of Epo was confirmed immunohistochemically only in the tumor tissue and not in the normal liver tissue. Erythrocytosis disappeared and the serum levels of Epo, AFP, and PIVKA-II returned to the normal range after the operation. Within 2 months after the operation, recurrent tumors appeared in the remnant liver, and the patient died 13 months after the operation.

Biomarkers↗
PubMed2000

A major metabolite of aceclofenac, 4'-hydroxy aceclofenac, suppresses the production of interstitial pro-collagenase/proMMP-1 and pro-stromelysin-1/proMMP-3 by human rheumatoid synovial cells.

OBJECTIVE AND DESIGN: We examined the effects of aceclofenac and its metabolites on the production of pro-collagenase-1/pro-matrix metalloproteinase-1 (proMMP-1), pro-gelatinase A/proMMP-2, pro-stromelysin-1/proMMP-3 and tissue inhibitor of metalloproteinases-1 (TIMP-1) by rheumatoid synovial cells. MATERIALS: Synovial cells were obtained from patients with rheumatoid arthritis. TREATMENT: Cultures of confluent cells were treated with interleukin-1beta (IL-1beta)(1 ng/ml) and/or test drugs (0.3-30 microM) for 48 h. METHODS: Production of proMMPs and TIMP-1 was monitored by Western blotting or gelatin zymography. Prostaglandin E2 (PGE2) was measured by an enzyme immunoassay. RESULTS: 4'-Hydroxy aceclofenac, a major metabolite of aceclofenac, down-regulated both basal and IL-1beta-induced production of proMMP-1 and proMMP-3 at a concentration sufficient to suppress PGE2 production without modulating proMMP-2 or TIMP-1, whereas aceclofenac itself had no marked effect on the production of proMMPs. CONCLUSIONS: Down-regulation of proMMP-1 and proMMP-3 production by 4'-hydroxy aceclofenac may contribute to the therapeutic effect of aceclofenac on rheumatoid arthritis and osteoarthritis.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2000

Accumulation of butyltin and phenyltin compounds in various fish species.

Concentrations of organotins (OTs) were measured in the muscle of 11 species of fishes from the Port of Osaka and Yodo River, Japan. Tributytin (TBT) and triphenyltin (TPT) compounds were detected in the range of 0.011-0.182 mg/kg wet weight and < 0.001-0.130 mg/kg wet weight, respectively. Concentrations of TBT were higher than those of TPT in the muscle of fish. Concentrations of OTs in fish from sea areas were higher than those from rivers, and the ratios of TBT to total butyltins (BTs) in fish from sea areas were also higher than those from rivers. A similar trend was found for TPT. Logarithm of bioconcentration factor (BCF) of TBT in fish was in the range of 2.7-3.9. No sex differences in TBT and TPT concentrations in Japanese sea perch were observed, and the concentrations of TBT and TPT were not related to total length of fish. No correlation was also observed between the concentration of TBT or TPT and lipid content. The concentrations of BTs and phenyltins (PTs) in organs and tissues of three fish species were determined. TBT was higher concentration in liver, brain, and muscle of white croaker and yellowtail. The ratios of TBT to the total BTs were 30-40%, and the ratios of TPT to total PTs in these fishes were greater than 50% of the total PT concentrations.

Animals↗
PubMed2000

Surgical treatment of old pelvic fractures.

We report on 4 patients, aged 24-51 years, with untreated pelvic ring fractures. The chief complaints were gait disturbances and pain in the buttocks and lower limb. The period between the initial injury and the surgical treatment ranged from 2.5 months to 3 years. Palsy was not improved, but pain and gait ability was improved in all patients.

Accidental Falls↗
PubMed2000

Innervation of nociceptors in the menisci of the knee joint: an immunohistochemical study.

Using histology, we studied the innervation of nociceptors in the medial and lateral menisci of the knee joint. Specimens examined were taken from 16 patients during arthroplasty. The patients were 6 men and 10 women, with ages ranging from 14 to 76 years (mean 56 years). Immunohistochemistry with the unlabeled antibody biotin-streptavidin method was employed to detect protein gene product 9.5 (PGP 9.5) or substance P (SP) in the specimen. The antibody for PGP 9.5 detected nerve tissues in the menisci. Most but not all of the nerve fibers were associated with blood vessels. Nerve fibers and sensory receptors were found mainly in the peripheral, vascular zone, representing the outer one-third of the meniscus, and the innervated area was wider in the anterior and posterior horns. Pacinian and Ruffini corpuscles as well as free nerve endings were identified in these areas. Larger fibers coursed circumferentially in the peripheral zone, with smaller branches of nerve fibers running radially into the meniscus. Nerve fibers positive for SP were also detected in the menisci, but were fewer in number. Their branches also were fewer, oriented radially and paralleling blood vessels. This study showed that some of the pain in cases of meniscal tear could originate in the meniscus itself, especially with peripheral tears that may be accompanied by bleeding.

Adolescent↗
PubMed2000

Molecular structure of a novel gypsy-Ty3-like retrotransposon (Kabuki) and nested retrotransposable elements on the W chromosome of the silkworm Bombyx mori.

We previously characterized a female-specific randomly amplified polymorphic DNA (RAPD), designated W-Kabuki, derived from the W chromosome of the silkworm, Bombyx mori. To further analyze the W chromosome of B. mori, we obtained a lambda phage clone which contains the W-Kabuki RAPD sequence and sequenced the 18.1-kb DNA insert. We found that this DNA comprises a nested structure of at least seven elements; three retrotransposons, two retroposons, one functionally unknown insertion, and one Bombyx repetitive sequence. The non-LTR retrotransposon BMC1, the retroposon Bm1, a functionally unknown inserted DNA (FUI), and a copia-like LTR retrotransposon (Yokozuma) are themselves inserted into a novel gypsy-Ty3-like LTR retrotransposon, named Kabuki. Furthermore, this Kabuki element is itself inserted into another copy of Bm1. The BMCI and Yokozuna elements inserted in the Kabuki sequence are intact. Moreover, the Kabuki element is largely intact. These results suggest that many retrotransposable elements have accumulated on the W chromosome, and these elements are expected to evolve more slowly than those on other chromosomes.

Amino Acid Sequence↗