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Biomedical subjects

M Kawai

Publications and source records attributed to M Kawai.

At least 145 records · Page 8Linked to original sources
PubMed1999

Inhibition of human B cell activation by a novel nonsteroidal anti-inflammatory drug, indometacin famesil.

Indometacin farnesil (INF) is a prodrug of indomethacin (IND) designed to reduce the occurrence of side-effects by esterification of the carboxyl group on IND with farnesol. Previous studies have shown that INF has the characteristics of disease-modifying anti-rheumatic drug (DMARD) in that it has a component of slow-acting effect in treatment of rheumatoid arthritis (RA), in which abnormal B cell functions are considered to be involved. The current studies therefore examined the effects of INF on human B cells. Ig 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 were induced from highly purified T cells by stimulation with immobilized mAb to CD3. At pharmacologically attainable concentrations, INF, but not IND, suppressed the production of IgM and IgG of B cells, whereas neither suppressed the T cell proliferation and IFN-gamma production. The inhibition of Ig production by INF is not due to its IND structure, but is most likely due to its farnesil component, since farnesol alone comparably suppressed the Ig production. INF and farnesol did not suppress the expression of early activation markers, including CD98, CD25, and CD71, on SA-stimulated B cells, but appeared to inhibit the maturation of B cells following the initial activation. These results indicate that INF preferentially suppresses the human B cell functions. Thus, the data suggest that INF may have more beneficial effects than IND in treatment of RA.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1999

Epidermolysis bullosa simplex associated with muscular dystrophy: phenotype-genotype correlations and review of the literature.

BACKGROUND: Epidermolysis bullosa simplex associated with muscular dystrophy (EBS-MD; OMIM# 226670) is an autosomal recessive disorder caused by genetic defects in the plectin gene. Because EBS-MD is relatively rare, and gene defects have been elucidated only in a limited number of patients, the precise phenotype-genotype correlations have not yet been fully elucidated. OBJECTIVE: The purpose of this study was to define clinical features of EBS-MD and to clarify its phenotype-genotype correlations. METHODS: Clinical, ultrastructural, immunohistochemical, and molecular features of 4 unrelated Japanese patients with EBS-MD were recorded. In addition, 6 cases with defined plectin gene mutations reported in the literature were reviewed. RESULTS: In skin of the EBS-MD patients, the blister formation always occurs just above the hemidesmosomes, and expression of plectin is absent or markedly reduced in all cases examined. All 10 patients, including 6 cases in the literature, showed generalized blistering at birth or soon thereafter, and experienced nail deformities. In addition, decayed teeth (5 cases), urethral strictures (3), mild palmoplantar hyperkeratosis (2), infantile respiratory complications (2), alopecia (1), and laryngeal webs (1) were present. All 8 patients who were older than 9 years demonstrated considerable muscle weakness, and the majority of them ended up being wheelchair bound. Among the 10 patients, 7 were products of consanguineous marriage, 9 have premature termination codon (PTC) mutations in both alleles of the plectin gene, and 7 cases were homozygous for the mutation. One patient who is homozygous for a 2719del9 in-frame deletion mutation that resulted in elimination of 3 amino acids, QEA, could still walk at the age of 46 and showed milder clinical severity. CONCLUSION: EBS-MD reveals clinical features not only characteristic of EBS and MD, but also other manifestations including urethral, dental, and respiratory complications. The majority of patients are products of consanguineous marriage and have homozygous plectin gene mutations. Whereas patients with PTC mutations in both alleles typically showed severe clinical features of EBS-MD and ended up being wheelchair bound, a homozygous patient for an in-frame deletion mutation showed positive, yet attenuated, plectin expression and milder clinical phenotype. Thus plectin immunofluorescence, combined with identification of the underlying plectin mutations, is of value in predicting the severity of the muscle involvement that occurs later in life of patients with EBS-MD.

Child↗
PubMed1999

Newborns spontaneous arm movements are influenced by the environment.

The spontaneous arm movements of 28 healthy full-term newborn infants were observed for 1 min in four different environmental conditions: each infant was placed in a vertical position in a bathtub filled with water with the water level up to her or his neck in a vertical position in water with the water level up to her or his waist in a supine position out of the water in a vertical position out of the water. It was hypothesised that these different environmental constraints would influence the infants spontaneous activity. From video recordings spontaneous arm movements were categorised according to the classifications of Hannan (Hannan TE. Young infant's hand and finger expressions: An analysis of category reliability. In: Field T, Fogel A, editors. Emotion and Early Interaction. New Jersey: Elbaum 1982;253-265). The statistical analyses showed, firstly, that the frequency of occurrence of various arm movements is greater out of the water than in the water. Secondly, for those out of the water the frequency of occurrence of various arm movements is greater in the vertical position in comparison to the supine position. Thirdly, the infants showed more active arm movements (more upward movements) in the vertical position out of the water in comparison to the two water and supine conditions. These findings lead to the conclusion that different environmental constraints influenced the spontaneous arm movements.

Arm↗
PubMed1999

Oral administration of peptidergic growth hormone (GH) secretagogue KP102 stimulates GH release in goats.

To assess the oral activity of KP102 (also known GHRP-2) on growth hormone (GH) release in ruminant animals, 5 or 10 mg/kg body weight (BW) of KP102 dissolved in saline was orally administered twice at 2 hr-intervals to either 1- or 3-mo-old goats (n = 5-6). Plasma GH concentrations in the 1-mo-old goats were elevated at 15 min after the first administration of both 5 and 10 mg/kg BW of KP102. Significant elevation of GH concentrations continued until 180 min after 10 mg/kg BW of KP102, whereas the elevated GH levels after the administrations of 5 mg/kg BW of KP102 subsided to basal concentrations within 90 min. The second administration of 10 mg/kg BW of KP102 failed to elevate the GH concentration, but 5 mg/kg BW of KP102 abruptly stimulated GH release. Plasma GH concentrations in the 3-mo-old goats were also significantly elevated after the administration of both 5 and 10 mg/kg BW of KP102. The plasma GH responses to 5 and 10 mg/kg BW of KP102 were almost identical. The elevated GH levels after the first administration of KP102 tended to be maintained throughout the experiment, and a transient increase in plasma GH levels was observed after the second administration. However, the stimulatory effect of KP102 on GH release in the 3-mo-old goats was small and less abrupt than that in the 1-mo-old goats. The concentrations of insulin-like growth factor-I were not increased by KP102 during the brief sampling periods used in this experiment. These results show that the oral administration of the peptidergic GH secretogogue KP102 stimulates GH release in a ruminant species, and that the oral activity of KP102 on GH release is modified by the age.

Aging↗
PubMed1999

Dose-response relationships between drinking and serum tests in Japanese men aged 40-59 years.

Alcohol intake per Japanese adult has been increasing year by year. To show biological effects of drinking, the dose-response relationships between alcohol use and serum indices were analyzed in 5919 Japanese men aged 40-59 years. The subjects were classified into nine groups: a nondrinking (ND, n = 1827) group and eight drinking (1D-8D) groups, by self-reported drinking habit. The 1D (the lightest drinking, n = 699), 5D (n = 942), and 8D (the heaviest drinking, n = 46) groups consumed alcohol less than 30 g per week, 25-30 g alcohol per day, and 100 g alcohol per day or more, respectively. Ten serum indices, total cholesterol, HDL cholesterol, triglyceride, total/HDL cholesterol ratio, LDL cholesterol, gamma-glutamyl transpeptidase, aspartate aminotransferase, alanine aminotransferase, glucose, and uric acid, were used. The dose-response analysis was statistically controlled for age, body mass index, smoking, and habitual exercise, and showed that drinking, even a small amount of alcohol, always had both beneficial and adverse effects on humans. However, alcohol less than 30 g per day may be tolerable for middle-aged Japanese men, because it improved serum lipids profile but did not induce apparent liver cell damage, hyperglycemia, or hyperuricemia.

Adult↗
PubMed1999

Endothelin-1 activates p38 mitogen-activated protein kinase via endothelin-A receptor in rat myocardial cells.

In myocardial cells (MCs), endothelin-1 (ET-1) exerts various effects such as hypertrophy, and causes cellular injury. Long-term treatment with an endothelin-A (ET(A)) receptor antagonist improves the survival of rats with heart failure, suggesting that myocardial endothelin system contributes to the progression of heart failure. p38 mitogen-activated kinase (MAPK) is a member of the MAPK family and activated by several forms of environmental stresses. We show here the effect of ET-1 on p38 MAPK activation and the role of ET-1-activated p38 MAPK on morphological changes in MCs. ET-1-stimulated p38 MAPK phosphorylation was detectable within 2 min and maximal at 5 min and was concentration dependent. The maximum effect was obtained at 10 nM. An ET(A) receptor antagonist, BQ-123, but not an endothelin-B receptor antagonist, BQ-788, inhibited these reactions. A p38 MAPK inhibitor, SB203580, failed to inhibit the morphological changes associated with ET-1-induced myocardial cell hypertrophy. These results indicate that p38 MAPK is activated by ET-1 but does not contribute to the development of ET-1-induced myocardial cell hypertrophy.

Animals↗
PubMed1999

Preparation and properties of novel gramicidin S analogs possessing a tri-, tetra- or pentamethylene bridge between ornithine side chains.

Gramicidin S (GS) analogs in which the Ndelta atoms of the two Orn side chains are linked by an oligomethylene bridge [-(CH2)n-; n=3-5] were prepared via the bis(p-nitrobenzenesulfonyl) derivative [Orn(NBS)2,2']GS. For comparison the nonbridged secondary amino group-containing analog [Orn(Me)2,2']GS was also prepared. 1H NMR and CD spectral analysis indicated that these analogs adopt the same beta-sheet conformation as GS. The antimicrobial activities of these analogs were very similar, but were slightly dependent on the bridge chain length, the trimethylene-bridged analog being the most potent.

Anti-Bacterial Agents↗
PubMed1999

Convenient preparation of [Orn(Tfa)2]- and [Orn(Boc)2, Orn(Tfa)2]gramicidin S, versatile unsymmetrically protected derivatives of gramicidin S.

Treatment of gramicidin S (GS) with trifluoroacetic anhydride afforded a derivative in which only one of the two Orn side chains was trifluoroacetylated in 72% yield, furnishing the first efficient method for the preparation of a monoprotected derivative of GS. The mono(Tfa) derivative [Orn(Tfa)2']GS was treated with di-tert-butyl dicarbonate to yield dually protected derivative [Orn(Boc)2,Orn(Tfa)2']GS from which another monoprotected derivative [Orn(Boc)2]GS was prepared in high yield. These unsymmetrically protected GS derivatives are versatile starting materials for the preparation of various other GS derivatives. As an example of application of the unsymmetrically protected derivatives, a dimeric GS derivative was prepared via a singly p-nitrobenzenesulfonyl(NBS)-activated derivative [Orn(Boc)2,Orn(NBS)2']GS.

Amino Acid Sequence↗
PubMed1999

Body mass index (weight/height2) or percentage body fat by bioelectrical impedance analysis: which variable better reflects serum lipid profile?

We present population data on percentage body fat (%BF) by bioelectrical impedance analysis (BIA) in 12,287 men and 6657 women aged 30-69 y. In addition, we examined relationships among BMI, %BF and serum lipids (total-cholesterol (TC), HDL-cholesterol (HDLC), TC/HDLC ratio, LDL-cholesterol (LDLC) and triglycerides (TG)) in order to determine whether body mass index (BMI, kg/m2) or %BF by BIA better reflected lipid metabolism. Women had larger %BF than men in all age groups. On the other hand, women aged < 60 y had smaller BMI than corresponding men. Regardless of age, BMI was obviously correlated with %BF (r = 0.743-0.924). As previously reported, high BMI and high %BF were strongly associated with high serum TC/HDLC ratio and TG, and low serum HDLC rather than high serum TC and LDLC. Compared with BMI, %BF by BIA was better correlated with the serum indices except for serum HDLC. These results were found in both sexes, and there was a trend in which younger subjects had stronger correlations among BMI, %BF and serum lipids. Consequently, %BF by BIA (an index of body composition) better reflects serum lipid profile than BMI.

Adipose Tissue↗
PubMed1999

Rapid enumeration of physiologically active bacteria in purified water used in the pharmaceutical manufacturing process.

Physiologically active bacteria in purified water used in the manufacturing process of pharmaceutical products were enumerated in situ. Bacteria with growth potential were enumerated using the micro-colony technique and direct viable counting (DVC), followed by 24 h of incubation in 100-fold diluted SCDB (Soybean Casein Digest Broth) at 30 degrees C. Respiring and esterase-active bacteria were detected by fluorescent staining with 5-cyano-2,3-ditolyl tetrazolium chloride (CTC) and 6-carboxyfluorescein diacetate (6CFDA), respectively. A large number of bacteria in purified water retained physiological activity, while most could not form colonies on conventional media. The techniques applied in this study enabled bacteria to be counted within 24 h so results could be available within one working day. These rapid and convenient techniques should be useful for the systematic monitoring of bacteria in water used for pharmaceutical manufacturing.

Bacteriological Techniques↗
PubMed1999

Four novel plectin gene mutations in Japanese patients with epidermolysis bullosa with muscular dystrophy disclosed by heteroduplex scanning and protein truncation tests.

Epidermolysis bullosa with muscular dystrophy (EB-MD) is a distinct variant of EB caused by mutations in the plectin gene (PLEC1). In this study, we have examined two Japanese patients with EB-MD using heteroduplex scanning or a protein truncation test for mutation detection analysis. The results revealed that both patients were compound heterozygotes for novel PLEC1 mutations (Q1936X/Q1053X and R2421X/12633ins4), which all caused premature termination of translation of the corresponding polypeptides. These cases, which demonstrate the utility of two complementary mutation detection strategies, add to the repertoire of plectin mutations in EB-MD.

Adult↗
PubMed1999

The effect of selective cyclooxygenase-2 inhibitor on corneal angiogenesis in the rat.

PURPOSE: Eicosanoids that are present in inflamed tissues are thought to play a significant role in angiogenesis. Cyclooxygenase, a key enzyme in eicosanoid synthesis, has recently been shown to exist in two isoforms: the constitutive COX-1 and the inducible COX-2. This study was undertaken to determine the role of COX-2 in the corneal angiogenic response. METHODS: Angiogenesis in the rat cornea was provoked by chemical cautery. Either NS-398, a selective COX-2 inhibitor, or indomethacin, a non-selective COX inhibitor, was applied topically 3 times daily for 4 days. Neovascularization was quantitated by digital image analysis in corneal flat preparations. To test their inhibitory effects on eicosanoid synthesis, normal or cauterized corneas were incubated in the culture medium with the inhibitor. Prostaglandin E2 in the medium was assayed using an enzyme-linked immunosorbent assay. RESULTS: Both NS-398 and indomethacin significantly inhibited corneal neovascularization with the % inhibition of 36.4 +/- 9.6%, and 38.5 +/- 9.0%, respectively, when applied topically at a concentration of 0.1% (p <.001). Neither reduced the angiogenic response at a concentration of 0.01% or below. PGE(2) production in the cauterized cornea was 2.0 times higher than that in the controls. In normal corneas, indomethacin inhibited PGE(2) synthesis by 80%, whereas NS-398 inhibited it by no more than 20%. In contrast, in injured corneas, both indomethacin and NS-398 inhibited PGE(2) synthesis in a similar fashion, with a maximal inhibition rate of 75 to 80%. CONCLUSIONS: Our results suggest that COX-2 induction in cauterized corneas increases the level of eicosanoids, which result in corneal angiogenesis.

Administration, Topical↗
PubMed1999

Characterization of novel cysteine proteases from germinating cotyledons of soybean [Glycine max (L.) Merrill].

The enzymatic properties of novel cysteine proteases D3-alpha and beta which were purified from germinating soybean cotyledons were investigated. The enzyme activities were exhibited in the presence of a thiol reagent, such as 2-mercaptoethanol, and apparently inhibited by E-64, a cysteine protease inhibitor. Hydrolytic activities toward carbobenzoxy-Phe-Arg-MCA were detected at a pH above 4.0. The optimum temperature for activities was about 40 degrees C. The isoelectric point of D3-alpha and beta was 4.4 and 4. 7, respectively. The molecular mass of D3-alpha and beta, measured by MALDI/TOF mass spectrometry, was 26,178 and 26,429 Da, respectively. The substrate specificities of the enzymes were examined using peptide-MCAs and peptides, and cathepsin L-like broad specificity was observed at pH 4.0. These results demonstrated that these enzymes are cysteine endopeptidases [EC 3.4.22.-] like papain [EC 3.4.22.2].

Amino Acid Sequence↗
PubMed1999

Production of murine collagen-induced arthritis using Klebsiella pneumoniae O3 lipopolysaccharide as a potent immunological adjuvant.

Collagen-induced arthritis (CIA) was produced in mice with non H-2q and H-2r haplotypes by repeated immunization of porcine type-II collagen (CII) together with Klebsiella O3 lipopolysaccharide (KO3 LPS) as an immunological adjuvant. Histological changes that appeared in joints of repeatedly immunized mice were characterized by destruction of normal joint structure, synovial hyperplasia with proliferation of synovial cells, and infiltration of inflammatory cells. No such lesions were produced in mice receiving repeated injections of CII alone or KO3 LPS alone. Development of the humoral antibody and the delayed-type hypersensitivity to CII was exclusively found in mice immunized with the mixture of CII and KO3 LPS. It was therefore suggested that arthritis lesions induced by repeated immunization with the mixture of CII and KO3 LPS might be caused by an autoimmune mechanism, and that the experimental model might be useful for characterization of human rheumatoid arthritis (RA).

Adjuvants, Immunologic↗
PubMed1999

Digestible energy expenditure in grazing activity of growing horses.

Ten Thoroughbred yearlings (5 females and 5 males) were used to examine the effect of time of grazing on pasture forage and digestible energy (DE) intake, bodyweight gain and DE expenditure in grazing activity. Five females were grazed for 17 h/day (LTG), 5 males were grazed for 7 h/day (STG) and they were fed differently. As a result, DE intake from pasture forage of LTG horses and STG horses was 27.3 and 12.7-13.9 Mcal/day, respectively. The average daily gain (ADG) of LTG and STG horses was 0.37 and 0.39-0.61 kg/day, respectively. The regression lines between DE intake and ADG of both groups were parallel and the difference in DE intake between them was 10 Mcal of DE. It was suggested that DE expenditure in grazing activity (entirely at night) of growing horses was 1 Mcal/h under the conditions of this study.

Animal Feed↗
PubMed1999

Excitation-contraction coupling in rat ventricular myocytes after formamide-induced detubulation.

Formamide-induced osmotic shock has been used to detubulate isolated adult rat ventricular myocytes (i.e., disrupt the surface membrane-T tubule junction). Cell volume, calculated from cell length and width, rapidly decreased and increased upon application and removal of formamide, respectively. After treatment with formamide, membrane capacitance decreased by 26.4% (from 199.4 +/- 18.7 pF in control cells to 146.7 +/- 6.4 pF in formamide-treated cells; n = 13, P < 0.05). However, the amplitude of the L-type Ca(2+) current (I(Ca)) decreased by a greater extent (from 0.75 +/- 0.14 to 0.18 +/- 0.03 nA; n = 5, P < 0.05) so that the density of I(Ca) decreased by 74.5%. Simultaneous measurements of I(Ca) and Ca(2+) transients (monitored using fura 2) showed that both decreased rapidly upon removal of formamide. However, the Ca(2+) content of the sarcoplasmic reticulum showed little change. Cross-striations, visualized with the fluorescent dye di-8-aminonaphthylethenylpyridinium, were sparse or absent in cells that had been treated with formamide, suggesting that formamide can successfully detubulate cardiac cells and that I(Ca) is concentrated in the T tubules, which therefore play an important role in excitation-contraction coupling.

Animals↗