Biomedical subjects

M Kawai

Publications and source records attributed to M Kawai.

At least 127 records · Page 7Linked to original sources

PubMed2000

[A case report of TS-1 in a patient with advanced gastric cancer].

TS-1 is an oral anticancer drug that produces biochemical modulation. TS-1 is composed of FT (tegafur), CDHP (gimestat, which inhibits 5-FU degradation enzyme), and Oxo (otastat potassium, which reduces 5-FU gastrointestinal toxicities), in a molar ratio of 1:0.4:1. We administered TS-1 to a 68-year-old female gastric cancer patient, after distal gastrectomy (Stage IV, cur C). As a result of abdominal CT, the diameter of metastatic lymph node increased before and after surgery, and before TS-1 (45 x 35 mm), but it was reduced after 1 course of TS-1 (37 x 25 mm), 2 courses of TS-1 (35 x 20 mm), 3 courses of TS-1 (30 x 20 mm), 4 courses of TS-1 (30 x 20 mm), and 6 months after 4 courses of TS-1 (20 x 20 mm). The reduction rate is 74.6%. The value of CA125 was reduced 74.4 to 8.6 after TS-1. Anorexia and back pain, which occurred after operation, disappeared after TS-1. There was no side effect over grade 3.

Aged↗

PubMed2000

[Overloading to neck extensor muscles is an aggravating factor to induce further neck drop in isolated neck extensor myopathy (Katz). A case report].

A 78-year-old woman was hospitalized because of progressive anterior neck drop over 4 months prior to admission. She was normal except for mild weakness of her neck, trapezius and biceps brachii muscles. EMG revealed mild myopathic changes in the neck extensors, trapezius, deltoid and sternocleidomastoid muscles. Bilateral splenius capitis muscles had high intensities on T2-weighted and STIR pulse-sequenced MRI. However, there were no inflammatory changes in the right splenius muscle biopsy. Accordingly, the abnormal MRI finding seems not to result from an inflammatory process but from an physiological increase of intracellular water content due to sustained muscle contraction. Because apparent neuromuscular diseases responsible for neck drop were excluded, her clinical features met the criteria of isolated neck extensor myopathy (INEM, Katz). After strict bed-rest for one month, her neck drop improved dramatically. When she returned to the previous life style after discharge, her symptoms of the neck drop reappeared. Although the cause of INEM remains unclear, the present case indicates that the condition is reversible at least in the early stage of the disease, and the overloading to the neck extensor muscles is an aggravating factor of the neck drop in INEM.

Aged↗

PubMed2000

[Juvenile parkinsonism with symmetrical hypoperfusion in the cerebellum--a case report].

We report a 24-year-old female presenting levodopa-responsive juvenile parkinsonism with symmetrical hypoperfusion in the cerebellum. At the age of 21, she noticed difficulty in brushing her teeth and writing with the right hand. She developed resting tremor in the right hand. These symptoms were dramatically relieved by levodopa. One year prior to the admission, she noticed dystonia and drug-induced motor fluctuations and her symptoms became worse. Neurological examinations disclosed resting and postural tremor in both hands and the right leg. Bradykinesia and cogwheel rigidity were noted on the right side. Deep tendon reflexes were slightly increased on the right side, while Babinski sign was negative. Slight lateropulsion was observed without retropulsion. Sensory, autonomic and cerebellar disturbances were not observed. No abnormalities were found in parkins gene or in the genes of spinocerebellar ataxia (SCA) 1,2,3,6,7,8 and alpha-synuclein. Cranial CT scan and brain MRI were normal, but technetium-99m ethyl cysteinate dimer (ECD) single photon emission computed tomography (SPECT) showed symmetrical hypoperfusion in the cerebellum. Other 5 patients presenting juvenile parkinsonism and 10 aged-matched normal controls in our hospital did not show hypoperfusion in the cerebellum on ECD SPECT. Cerebellar blood flow has not been measured in the previously reported cases of juvenile parkinsonism. These results suggested that etiopathogenesis in this patient was different from that in previously reported cases.

Adult↗

PubMed2000

[Painful unilateral gynecomastia in a patient with myotonic dystrophy].

A 54-year-old patient with myotonic dystrophy presented unilateral painful gynecomastia, which occurred 3 months after aggravation of diabetes mellitus. Serum luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels were slightly high. LH was elevated than 2 years before. Breast pain and gynecomastia disappeared by daily administration of 10 mg tamoxifen. He could not have intramuscular injection therapy because of marked muscle atrophy. Painful gynecomastia may be one of the endocrine complications in myotonic dystrophy.

Diabetes Complications↗

PubMed1999

Evolutionally conserved plant homologue of the Bax inhibitor-1 (BI-1) gene capable of suppressing Bax-induced cell death in yeast(1).

The plant homologue of Bax Inhibitor-1, a gene described to suppress the cell death induced by Bax gene expression in yeast, was isolated from Oryza sativa L. (rice) and Arabidopsis. The amino acid sequence of the predicted protein was well conserved in both animal and plant (45% in amino acids) and contained six or seven membrane-spanning segments. Northern blot analysis showed that OsBI-1 transcripts were present in all tissues examined. The OsBI-1 cDNA suppressed cell death induced by mammalian Bax in yeast, suggesting functional conservation of this BI-1 homologue in the plant kingdom.

Amino Acid Sequence↗

PubMed1999

Cellular co-localization of phosphorylated tau- and NACP/alpha-synuclein-epitopes in lewy bodies in sporadic Parkinson's disease and in dementia with Lewy bodies.

The precursor of the non-Abeta-component of Alzheimer's disease (AD) amyloid (NACP, alpha-synuclein) aggregates into insoluble filaments of Lewy bodies (LBs) in Parkinson's disease (PD) and dementia with LBs (DLB). The microtubule-associated protein tau is an integral component of filaments of neurofibrillary tangles (NFTs). NFTs are occasionally found in brains of PD and DLB; however, the presence of NFTs or tau-epitopes within LB-containing neurons is rare. Double-immunofluorescence study and peroxidase-immunohistochemical study in serial sections, performed to examine the co-localization of tau- and NACP-epitopes in the brainstem of PD and DLB, demonstrated that four different epitopes of tau including phosphorylation-dependent and independent ones were present in a minority of LBs, but more often than previously considered. A tau (tau2)-epitope was localized to filaments in the outer layers of brainstem-type LBs by immunoelectron microscopy. Therefore, we conclude that tau is incorporated into filaments in certain LBs. Extensive investigation has enabled us to classify this co-localization into four types: type 1, LBs with ring-shaped tau-immunoreactivity; type 2, LBs surrounded by NFTs; type 3, NACP- and tau-immunoreactive filamentous and granular masses; and type 4, NACP- and tau-immunoreactive dystrophic neurites. This study raises a new question whether aggregation and hyperphosphorylation of tau in PD and DLB are triggered by the collapse of intraneuronal organization of microtubules due to NACP-filament aggregation in neuronal perikarya and axons.

Aged↗

PubMed1999

Nonpathogenic common variants of IFNGR1 and IFNGR2 in association with total serum IgE levels.

Atopy is an immune disorder in which a Th2 dominant mechanism leads to high IgE levels and the clinical disorder asthma. It has been postulated that the Th1 cytokine IFNgamma, acting through its heterodimeric receptors, IFNgammaR1 and IFNgammaR2, in the induction/proliferation of Th1 cells, might suppress the Th2 responses that may underlie atopic asthma. However, neither murine nor human variants of IFNgamma associate with atopy. Several dysfunctional mutations have been identified in IFNgamma receptor genes (IFNGR1 and IFNGR2) in relation to severe and selective infections with poorly pathogenic organisms. However, little is known about common polymorphisms and their functional role in atopy. To test whether such variants of IFNGR1 and IFNGR2 relate to atopic asthma, we conducted a genetic association study in both British (n = 300) and Japanese (n = 200) populations. An intronic variant of IFNGR1 showed marginal association with total serum IgE levels in the British population compared with those with total IgE levels <30 IU/ml and those with >120-500 IU/ml [odds ratio = 2.00 (95% CI 1. 00-4.07), P = 0.048]. A coding variant, Gln64Arg of the IFNGR2, also associated with total serum IgE levels in the British population [chi(2) = 5.08, P = 0.024]. Further genetic and functional analyses are needed to clarify the role of variants of IFNgamma receptor genes in atopic immune disorder among different ethnic groups.

Asthma↗

PubMed1999

Production of tissue factor in CD14-expressing human umbilical vein endothelial cells by lipopolysaccharide.

Production of tissue factor (TF) in response to lipopolysaccharide (LPS) was examined in human umbilical vein endothelial cells (HUVECs) transfected with human CD14 DNA. The expression of CD14 on HUVECs dramatically enhanced the production of TF at a low concentration of LPS in the absence of fetal calf serum (FCS). On the other hand, mock-transfected HUVECs did not respond to even a high concentration of LPS. TF production in CD14-expressing HUVECs was significantly inhibited by anti-CD14 monoclonal antibody. Addition of FCS to the culture of CD14-expressing HUVECs markedly augmented the LPS-induced TF production, whereas only a marginal effect was observed in mock-transfected HUVECs. The findings suggested that the integration of membrane CD14 rendered HUVECs highly sensitive to LPS in the production of TF irrespective of the presence of FCS.

Antibodies, Monoclonal↗

PubMed1999

Variants of endothelin-1 and its receptors in atopic asthma.

Endothelin-1 (ET-1) is a 21 amino acid peptide released from several types of bronchial cells. It operates through two types of receptors, type A(ET-RA) and type B(ET-RB) and has various activities in the pathophysiology of atopic asthma. These genes are localised on different chromosomes where genome-wide searches have identified linkage for atopic asthma, thus supporting the candidacy of ET-1 and its receptors for atopic asthma. A genetic association study was performed with variants of these three genes in both British (n = 300) and Japanese populations (n = 200). No significant association was found between variants of EDN1 and EDNRB genes, and atopic asthma in either population. However, variants of EDNRA gene showed a marginal association with atopy [odds = 0.39(95% CI: 0.17-0.89), p = 0.022, Pc = 0.066], especially with antigen specific IgE levels [odds = 0.31 (95% CI: 0.20-0.77), p = 0.006, Pc = 0.018] in the British population. These findings suggest that EDNRA is a major candidate locus for atopy on chromosome 4.

Antibody Specificity↗

PubMed1999

Colocalization of leptin receptor (OB-R) mRNA and placental lactogen-II in rat trophoblast cells: gestational profile of OB-R mRNA expression in placentae.

The present study was designed to clarify the cellular localization and expression of leptin receptor(s) [OB-R(s)] mRNA including its splice variants and their correlation with the cells which secrete placental hormone, placental lactogen-II (PL-II), in rat placentae. By in situ hybridization analysis, hybridization signals for OB-Rb and the common extracellular domain of OB-R were first detectable in some cells of the labyrinth zone of the placentae on day 14 of pregnancy and then a lot of cells dispersed in the entire area of the labyrinth zone expressed OB-Rb during the latter half of pregnancy. However, no expression was observed in the decidua and the junctional zone of the placentae during pregnancy. Double staining study revealed that signals for OB-R expressing trophoblast cells showed PL-II immunoreactivity in the labyrinth zone of the placentae. In Northern blot analysis, two bands (2.8 kb and 5.1 kb) of OB-R mRNA expression were observed in the placentae from day 17 to 21 of pregnancy and the expression of both increased markedly up to day 21 of pregnancy. RT-PCR analysis revealed that OB-Rb, OB-Ra, and OB-Re are expressed in the placentae on days 19 and 21 of pregnancy. These results suggest that the OB-R may have a physiological significance in the placental function during the latter half of pregnancy.

Alternative Splicing↗

PubMed1999

Cutting edge: dominant effect of Ile50Val variant of the human IL-4 receptor alpha-chain in IgE synthesis.

Two variants of the IL-4R alpha-chain (IL-4Ralpha) gene have been recently identified in association with different atopic disorders. To clarify the etiological relationship between the two variants, we analyzed responsiveness to IL-4 of transfectants with four kinds of IL-4Ralpha carrying either Val or Ile at 50 and either Gln or Arg at 551. The substitution of Ile for Val augmented STAT6 activation, proliferation, and transcription activity of the Iepsilon promoter by IL-4, whereas that of Arg for Gln did not change these IL-4 signals. Arg551 was not associated with atopic asthma in the Japanese population. CD23 expression and IgE synthesis by IL-4 were augmented in Ile50-bearing PBMC, compared with those bearing Val50. Taken together, substitution of Arg551 does not enhance the IL-4 signal for generation of germline epsilon transcript, whereas the substitution of Ile50 contributes to enhancement of IgE synthesis.

Amino Acid Substitution↗

PubMed1999

Optical resolution and absolute configuration of N-benzyloxycarbonyl-alpha-alkoxyglycines

Optical resolution of racemic N-benzyloxycarbonyl-protected alpha-alkoxyglycines, (+/-)-Cbz-Gly(OR)-OH (R = Et and Pr(i)), was achieved by means of fractional crystallization of diastereomeric salts with (+)-(1S,2S)-2-amino-1-phenyl-1,3-propanediol or diastereomeric esters of (+)- or (-)-menthol. The D- and L-configurations were assigned to the (+)- and (-)-Cbz-Gly(OR)-OH, respectively, based on L-enantioselective enzymatic hydrolysis of (+/-)-Cbz-Gly(OR)-OR' (R = Me, Et, and Pr(i); R' = CH(2)CF(3) and Me) using porcine pancreatic lipase and papain. Chiroptical properties and HPLC retention times of D- and L-Gly(OR)-residue (R = Me and Pr(i))-containing peptides were compared in relation to their configurational assignments. Copyright 1999 Wiley-Liss, Inc.

Journal Article↗

PubMed1999

Synergistic inhibition of human B cell activation by gold sodium thiomalate and auranofin.

The mechanism of action of gold compounds, which are effective in the treatment of rheumatoid arthritis (RA), has not been clearly identified. Since one of the characteristic features of RA is chronic stimulation of B cells, the current studies compared the effects of parenteral gold (gold sodium thiomalate; GST) and orally active gold (auranofin; AUR) on human B cells. IgM production was induced from highly purified B cells obtained from healthy donors by stimulation with Staphylococcus aureus Cowan I (SA) plus IL-2. T cell proliferation and IFN-gamma production was induced from highly purified T cells by stimulation with immobilized mAb to CD3. AUR as well as GST suppressed B cell IgM production at much lower concentrations than those that suppressed T cell proliferation or IFN-gamma production. Thus, as little as 0.01 microg/ml AUR (0.015 microM) markedly suppressed IgM production, but neither T cell proliferation nor IFN-gamma production. AUR as well as GST is required at the initiation of cultures to exert optimal suppressive effects on IgM production. Moreover, AUR as well as GST suppressed the expression of CD98 and CD71 on SA-stimulated B cells. Of note, AUR and GST exerted a synergistic inhibitory effect on B cell production of IgM and IgG in a manner which was reversed by catalase, but not by ascorbate. The synergistic inhibitory effect is most likely to be due to thiomalate components of GST, since AUR and thiomalate exerted comparable synergistic inhibitory effects on B cell function. Finally, AUR and bucillamine, another antirheumatic drug with thiol groups, also showed synergistic inhibition of B cell function. These results indicate that AUR and GST preferentially inhibit the function of B cells by interfering with the initial activation of B cells. More importantly, the data indicate that AUR synergizes with GST or thiols to inhibit B cell function in a manner that depends upon the generation of hydrogen peroxide. These synergistic inhibitory effects of AUR and compounds with thiols on in vitro human B cell activation suggest the therapeutic efficacy of combinations of these compounds in RA.

Auranofin↗

PubMed1999

Nebulin is normally expressed in nemaline myopathy.

Since the nebulin gene is located in the candidate gene locus of autosomal recessive nemaline myopathy, 2q21.2-q22, we examined five muscle biopsy specimens with monoclonal and polyclonal antibodies against nebulin in combination with the modified Gomori trichrome stain. We were able to demonstrate immunohistochemically that there was no abnormality in nebulin in the muscle fibers both with and without nemaline bodies. Although the molecular weight of nebulin was normal, it was slightly reduced in amount on immunoblotting.

Humans↗

PubMed1999

Immunohistochemical and ultrastructural characterization of neuritic clusters around ghost tangles in the hippocampal formation in progressive supranuclear palsy brains.

We performed a detailed study of swollen neurite aggregation surrounding extracellular neurofibrillary tangles (ghost tangles, GTs) in brains of patients with progressive supranuclear palsy (PSP) by immunohistochemistry and electron microscopy (EM). The complex structures, designated as tangle-associated neuritic clusters (TANCs), were found in the hippocampus and parahippocampal cortex in all five PSP brains examined. TANCs measured from 20 to 40 microm across; twice as large as nearby neurons. Each neurite was globular or fusiform in shape, measured up to 10 microm in diameter, and was found between loosened fascicles of GTs or along their outer rims. There were several subsets of neurites that were argyrophilic or immunoreactive against antibodies to either phosphorylated tau protein, phosphorylated neurofilaments, ubiquitin, or synaptophysin. On EM, TANCs consisted of numerous axon terminals of varying size, which were filled with flocculate dense bodies, vesicular profiles, and synaptic vesicles, as well as normal-looking and degenerating cell organelles. Some axons had 13- to 15-nm-thick straight tubules that showed tau immunoreactivity; however, there was little neurofilament accumulation. Most of the swollen axon terminals conformed to the ultrastructural features of either reactive or degenerating terminals. The neurites identified by immunohistochemistry only represented a minority of the swollen axons visualized by EM. Tubules of GTs were dispersed in the extracellular space, but no amyloid fibrils were found. TANCs may constitute a distinctive form of neuronal degeneration in PSP cortices. We hypothesize that axon terminal accumulation may occur in response to GT-formation.

Aged↗

PubMed1999

Breached cerebral glia limitans-basal lamina complex in Fukuyama-type congenital muscular dystrophy.

We have reported breaches of glia limitans (GL)-basal lamina (BL) complex with protruding neuroglial tissue in Fukuyama-type congenital muscular dystrophy (FCMD) fetus brain and suggested that some basic deficits in the GL-BL complex may have a pivotal role in formation of micropolygyria in FCMD. We therefore investigated the cerebral GL-BL complex in seven FCMD cases (12-27 years of age), in three cases of Duchenne muscular dystrophy (17-25 years of age) and in two non-neurological controls (28 and 33 years of age). The frontal lobe cortex was examined immunocytochemically using antibodies against collagen type IV and laminin in each case, and ultrastructurally in an adult case of FCMD. In FCMD, the BL of the cortical surface was frequently breached with protruding neural tissue that ultrastructurally showed frequent synapses, neurites that had parallel arranged microtubules, and astrocytic processes. The outermost surface of this tissue was only partly lined by a BL. In the region of the gyral adhesion of micropolygyria, the perivascular space of the apparently entrapped meningeal blood vessels was occupied by neuroglial tissue, which is assumed to have invaded through the occasionally seen breaches of the perivascular GL-BL complex. Electron microscopy of the intruding tissue showed frequent synapses, microtubule-containing neurites and astrocytic processes. No breached GL-BL complex was found in any of the non-FCMD cases. These findings indicate that in FCMD, the cerebral GL-BL complex continues to have a crucial deficit with resulting breaches through which neuroglial tissue protrudes, promoting adhesion of the adjacent cerebral gyri during brain development before and after birth.

Adolescent↗

PubMed1999

Does thin filament compliance diminish the cross-bridge kinetics? A study in rabbit psoas fibers.

The effect of thin filament compliance on our ability to detect the cross-bridge kinetics was examined. Our experiment is based on the facts that in rabbit psoas the thin filament (1.12 micrometer) is longer than half the thick filament length (0.82 micrometer) and that the thick filament has a central bare zone (0.16 micrometer). Consequently, when sarcomere length is increased from 2.1 to 2.4 micrometer, the same number of cross-bridges is involved in force generation but extra series compliance is introduced in the I-band. Three apparent rate constants (2pia, 2pib, and 2pic) were characterized by sinusoidal analysis at pCa 4.66. Our results demonstrate that 2pia and 2pib increased 13-16% when sarcomere length was increased from 2.0 to 2.5 micrometer, and 2pic decreased slightly (9%). This slight decrease can be explained by compression of the lattice spacing. These observations are at variance with the expectation based on increased series compliance, which predicts that the rate constants will decrease. We also determined compliance of the I-band during rigor. I-band compliance during rigor induction was 35% of sarcomere compliance at sarcomere length 2.4 micrometer, and 24% at sarcomere length 2.1 micrometer. We conclude that the presence of thin filament compliance does not seriously interfere with our ability to detect cross-bridge kinetics using sinusoidal analysis.

Animals↗

PubMed1999

Ophthalmic artery velocimetry in normotensive and preeclamptic women with or without photophobia.

OBJECTIVE: To compare ophthalmic arterial velocimetry in normotensive and preeclamptic gravidas with and without photophobia. METHODS: Ophthalmic arteries were studied by color-flow Doppler ultrasonography in 118 normotensive pregnant women, 20 gravidas with preeclampsia and no visual symptoms, and 11 with preeclampsia, photophobia, and retinal edema. RESULTS: The ophthalmic arterial pulsatility index (PI) correlated negatively with gestational age (y = -0.01x + 1.84, r = -0.41, P<.01). Pulsatility index in preeclamptics with photophobia (0.71+/-0.17) was lowest among the three groups (P<.01) and was highest in normotensive pregnant women (1.41+/-0.21, P<.01). Mean velocity in normotensive pregnant women (0.19+/-0.05 m/second) was highest among the groups (P<.01) and was not significantly different in preeclamptic women with no visual symptoms (0.27+/-0.03 m/second) and with photophobia (0.30+/-0.02 m/second). CONCLUSION: Preeclamptic women, especially those with photophobia, have orbital vascular vasodilation or hyperperfusion, or both.

Adult↗