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Biomedical subjects

H Nishikawa

Publications and source records attributed to H Nishikawa.

At least 55 records · Page 3Linked to original sources
PubMed2001

Anxiety-like behavior in elevated plus-maze tests in repeatedly cold-stressed mice.

To clarify the relationship between SART (specific alternation of rhythm in temperature) stress (repeated cold stress) and anxiety, the effects of various types of stress on the behavior of mice were studied in elevated plus-maze tests and then the effects of anxiolytics were evaluated. The percentage of time spent in the open arms of the plus-maze apparatus decreased in mice subjected to SART stress without change in the total number of arm entries. No change was noted in mice subjected to other stresses, such as 1-h, 2-day and 5-day cold stress and 1-h, 15-h and 5 x 15-h restraint stress. The reduction in the percentage of time spent in the open arms caused by SART stress was inhibited by single and repeated administrations of diazepam and alprazolam and by a single administration of buspirone, which have no influence on the percentage of time spent in the open arms in nonstressed mice, but not by flumazenil, WAY-100635 and chronic treatment with buspirone. The effects of diazepam and buspirone were antagonized by flumazenil and WAY-100635, respectively. The behavior of SART-stressed mice in the plus-maze would thus appear to arise from anxiety, to which benzodiazepine and serotonin receptors are related, but the diazepam binding inhibitor, an endogenous anxiogenic protein, is not. Thus SART-stressed animals may be useful for investigating the psychopharmacological and neuropharmacological basis of anxiety.

Animals↗
PubMed2001

Histological study of rat masseter muscle following experimental occlusal alteration.

It has been suggested that occlusal interference results in masticatory muscle dysfunction. In our previous study, occlusal interference reduced the rat masseter energy level during masticatory movements. The purpose of this study was to investigate the histological alterations of rat masseter muscles following experimental occlusal alteration with unilateral bite-raising. A total of eight male adult Wistar rats were equally divided into control and experimental groups. The experimental rats wore bite-raising splints on the unilateral upper molar. However, 4 weeks after the operation, the anterior deep masseter muscles were removed and then stained for succinic acid dehydrogenase (SDH), haematoxylin eosin (HE) and myofibrillar ATPase. Most of the muscle fibres in experimental rats remained intact, although partial histological changes were observed, such as extended connective tissue, appearance of inflammatory cells in the muscle fibres and existence of muscle fibres with central nuclei and central cores. Moreover, the fibre area-fibre frequency histograms of experimental muscle indicated a broad pattern than that of controls. These results indicated that occlusal interference caused histological changes in masseter muscles and that this may be related to the fact that the masseter energy level was reduced during masticatory movements in unilateral bite-raised rats.

Animals↗
PubMed2001

Clinical evaluation of physical fitness in male obese Japanese.

OBJECTIVE: To establish an effective exercise prescription, the exercise capacity of obese subjects was investigated. METHODS: In 71 male obese (body mass index: BMI > or = 26.4) Japanese, aged 26-77 years, the body composition and physical fitness such as aerobic exercise level, muscle strength and flexibility were determined and compared with those of age- and sex-matched 71 borderline (24.2 < or = BMI < 26.4) and 71 normal Japanese men (19.8 < or = BMI < 24.2). The relationship between body composition and other parameters was evaluated in obese subjects. RESULTS: In obese subjects, body weight, BMI, body fat percentage, waist hip ratio, and skinfold thickness were higher than those of borderline and normal subjects. Lower aerobic exercise level and weight bearing index (WBI) were noted in obese subjects. There was a negative correlation between waist hip ratio and aerobic exercise level (oxygen uptake at ventilatory threshold) (r = -0.509, P < 0.01) and also between waist hip ratio and WBI (r = -0.315, P < 0.01). CONCLUSIONS: Lower physical fitness is considered to be a general characteristic of male obese Japanese, and the accumulation of visceral adipose tissue might affect exercise capacity.

Adult↗
PubMed2000

Mechanism for bone invasion of oral cancer cells mediated by interleukin-6 in vitro and in vivo.

BACKGROUND: Osteoclastic bone resorption is an important step in bone invasion in several malignancies. Although interleukin (IL)-6 accelerates osteoclastic bone resorption, it remains unclear whether IL-6 may be involved in bone invasion of oral cancer. METHODS: The pit formation assay with calf femur-derived bone slices was performed to examine the bone-resorbing activity of osteoclasts and cancer cells. The chemotaxis activity of the culture media was analyzed by the use of Boyden chamber technique. Nude mice, which were inoculated with IL-6-producing oral cancer cells into masseter, were treated with anti-IL-6 neutralizing antibody, and mandibular-bone invasion of the cells was assessed. RESULTS: BHY, a bone-invasive oral cancer cell line, but not HNT, a noninvasive cell line, produced large amounts of IL-6. In a pit formation assay, addition of conditioned medium (CM) derived from BHY but not HNT increased osteoclastic bone resorption, and the effects were inhibited by anti-IL-6 antibody. BHY-secreted IL-6 showed significant chemotaxis activity for osteoclasts. Of note, CM from the cocultivation of osteoclasts and BHY markedly enhanced the cancer cell migration, and the chemotaxis activity was significantly reduced when anti-IL-6 antibody was added into the coculture and then CM were collected, but not when the antibody was added into the CM after they were collected. Furthermore, treatment with anti-IL-6 antibody almost completely inhibited mandibular bone invasion of BHY in nude mice. CONCLUSIONS: These results strongly suggest that IL-6 secreted by oral cancer cells plays a significant role in bone invasion.

Animals↗
PubMed2000

Characterization of the protease-activated receptor-1-mediated contraction and relaxation in the rat duodenal smooth muscle.

Activation of protease-activated receptor-1 (PAR-1) produces a dual action, apamin-sensitive relaxation followed by contraction, in the rat duodenal smooth muscle, which is partially dependent on activation of L-type Ca2+ channels, protein kinase C (PKC) or tyrosine kinase (TK), and resistant to tetrodotoxin. The present study further characterized the PAR-1-mediated duodenal responses. Removal of extracellular Ca2+ as well as SK&F96365 reduced the contraction due to the PAR-1 agonist TFLLR-NH2 (TFp-NH2) by 60-80% that was similar to the extent of the inhibition by nifedipine. Lowering of the extracellular Na+ concentration, but not IAA-94, a Cl- channel inhibitor, reduced both the PAR-1-mediated contraction and relaxation by about 50%. U73122, a phospholipase C (PLC) inhibitor, or wortmannin, a phosphatidyl inositol 3'-kinase (PI3K) inhibitor, significantly reduced the PAR-1-mediated contraction, but not the relaxation, by itself, as the PKC inhibitor GF109203X and the TK inhibitor genistein did. U73122 or wortmannin, like GF109203X, when applied in combination with genistein, significantly reduced the PAR-1-mediated relaxation. The relaxation was resistant to antagonists of PACAP receptors, VIP receptors and P2 purinoceptors. Thus, the PAR-1-mediated contraction is considered to be dependent on intracellular and extracellular Ca2+, the influx of the latter being induced through activation of L-type Ca2+ channels triggered by the enhanced Na+ permeability, and that PLC and PI3K, in addition to PKC and TK, are involved in the PAR-1-mediated dual responses. Furthermore, non-adrenergic, non-cholinergic nerve neurotransmitter candidates that may modulate K+ channels do not appear to contribute to the relaxation by PAR-1 activation.

Androstadienes↗
PubMed2000

Involvement of direct inhibition of NMDA receptors in the effects of sigma-receptor ligands on glutamate neurotoxicity in vitro.

This study was performed to examine the roles of the N-methyl-D-aspartate (NMDA) receptor/phencyclidine (PCP) channel complex in the protective effects of sigma-receptor ligands against glutamate neurotoxicity in cultured cortical neurons derived from fetal rats. A 1-h exposure of cultures to glutamate caused a marked loss of viability, as determined by Trypan blue exclusion. This acute neurotoxicity of glutamate was prevented by NMDA receptor antagonists. Expression of sigma(1) receptor mRNA in cortical cultures was confirmed by reverse transcription polymerase chain reaction (RT-PCR). sigma Receptor ligands with affinity for NMDA receptor channels including the PCP site, such as (+)-N-allylnormetazocine ((+)-SKF10,047), haloperidol, and R(-)-N-(3-phenyl-1-propyl)-1-phenyl-2-aminopropane ((-)-PPAP), prevented glutamate neurotoxicity in a concentration-dependent manner. In contrast, other sigma-receptor ligands without affinity for NMDA receptors, such as carbetapentane and R(+)-3-(3-hydroxyphenyl)-N-propylpiperidine ((+)-3-PPP), did not show neuroprotective effects. Putative endogenous sigma receptor ligands such as pregnenolone, progesterone, and dehydroepiandrosterone did not affect glutamate neurotoxicity. The protective effects of (+)-SKF10,047, haloperidol, and (-)-PPAP were not affected by the sigma(1) receptor antagonist rimcazole. These results suggested that a direct interaction with NMDA receptors but not with sigma receptors plays a crucial role in the neuroprotective effects of sigma receptor ligands with affinity for NMDA receptors.

Animals↗
PubMed2000

Effect of probucol on repeat revascularization rate after percutaneous transluminal coronary angioplasty (from the Probucol Angioplasty Restenosis Trial [PART]).

To address the issue of whether probucol reduces clinical events after percutaneous transluminal coronary angioplasty (PTCA), we surveyed clinical status at 1 year after PTCA of 101 patients who had entered the Probucol Restenosis Angioplasty Trial. Repeat angioplasty at index lesions were required in 5 patients in the probucol group and in 12 in the control group, suggesting that probucol administered beginning 4 weeks before PTCA reduces repeat revascularization rates for 1 year.

Angioplasty, Balloon, Coronary↗
PubMed2000

Activation of protease-activated receptor-2 (PAR-2) triggers mucin secretion in the rat sublingual gland.

Protease-activated receptor-2 (PAR-2) is distributed throughout the gastrointestinal systems. The present study investigated the role for PAR-2 in the rat salivary glands. PAR-2 mRNA was detected in the sublingual, submaxillary, and parotid glands by a reverse-transcriptase polymerase chain reaction. In the isolated sublingual gland that exhibited the strongest signal for PAR-2, Ser-Leu-Ile-Gly-Arg-Leu-NH(2), a PAR-2-activating peptide, and trypsin, a PAR-2-activating enzyme, but not thrombin that can activate PARs 1, 3, and 4, triggered secretion of N-acetylneuraminic acid, an indicator of mucin, that was a unique major sialic acid detectable after hydrolysis of the sublingual mucin with 0.1 N HCl. The PAR-2-mediated secretion of mucin was attenuated by genistein, a tyrosine kinase inhibitor, but not by inhibitors of protein kinase C and phosphatidyl inositol 3'-kinase. Thus, PAR-2 is expressed by the three distinct salivary glands in the rat, and sublingual PAR-2 appears to play a role in triggering mucin secretion, at least in part, via activation of tyrosine kinase.

Animals↗
PubMed2000

p75-mediated neuroprotection by NGF against glutamate cytotoxicity in cortical cultures.

Accumulating evidence suggests that the neurotrophin receptors, Trks and p75, play distinct roles in regulating cells survival and death, with Trks important for cell survival, and p75 acting to induce cell death. Here, we provide evidence that, in neuronal cultures from rat cerebral cortex, nerve growth factor (NGF) exerts neuroprotective actions via p75. Incubating cultures with NGF for 1-24 h protected cortical neurons from delayed cytotoxicity induced by brief exposure to glutamate. Delayed neurotoxicity induced by a calcium ionophore, ionomycin, or nitric oxide (NO) donors such as S-nitrosocysteine (SNOC) and 3-morpholinosydnonimine (SIN-1), was also attenuated by pretreatment with NGF. RT-PCR analysis revealed the presence of p75 and trkB transcripts in cortical cultures, but did not detect transcripts of trkA, a high-affinity receptor for NGF. Brain-derived neurotrophic factor (BDNF), but not NGF, induced tyrosine phosphorylation of Trks, indicating that NGF does not activate Trks in cortical neurons. Concurrent application of anti-p75 neutralizing antibody markedly reduced the neuroprotective effect of NGF, but resulted in only a modest reduction of that of BDNF. BDNF-induced neuroprotection, but not NGF-induced neuroprotection, was inhibited by a protein synthesis inhibitor cycloheximide. Distinct signaling pathways mobilized by NGF and BDNF were also revealed in that NGF but not BDNF stimulated significant production of ceramides, whereas BDNF but not NGF caused persistent activation of mitogen-activated protein kinases. These results indicate that, although NGF and BDNF both protect cortical neurons from excitotoxicity, the mechanisms involved in their effects are totally different. The present results are, to our knowledge, the first to demonstrate the principal involvement of p75 in cytoprotective actions of neurotrophins.

Animals↗
PubMed2000

Induction of Th1-type cytokines by lipoteichoic acid-related preparation isolated from OK-432, a penicillin-killed streptococcal agent.

We have isolated the lipoteichoic acid (LTA)-related molecule (OK-PSA) from OK-432, a streptococcal preparation, by an affinity chromatography on CNBr-activated Sepharose 4B-bound TS-2 monoclonal antibody (mAb) that neutralizes interferon (IFN)-gamma-inducing activity of OK-432. In in vitro experiments using human peripheral blood mononuclear cells (PBMC), OK-PSA induced IFN-gamma, interleukin (IL)-2, IL-12, IL-18, tumor necrosis factor (TNF)-alpha and TNF-beta that are generally called "Th1-type cytokines" both in protein and in mRNA levels. Furthermore, the neutralizing test using cytokine-specific antibodies demonstrated that IL-18 plays a most significant role for IFN-gamma- and killer cell-inducing ability of OK-PSA among the other cytokines tested. These findings clearly indicated that OK-PSA, an LTA-related molecule, is a main effective component of OK-432, and is a potent inducer of Th1-type cytokines by T cell and natural killer (NK) cell activation mediated by monocytes-derived IL-18, and that it may be a useful immunotherapeutic agent for the patients with malignancies better than original OK-432.

Animals↗
PubMed2000

Purification and characterization of cytokine-inducing protein of seed extract from Aeginetia indica L., a parasitic plant.

We have isolated 55 kDa protein from the seed extract of Aeginetia indica L. (AIL), a parasitic plant, by an affinity chromatography on N-hydroxysuccinimide (NHS)-activated Sepharose High Performance column bound F3 monoclonal antibody which neutralizes cytokine-inducing and antitumor effect of AIL. In in vitro model using human peripheral blood mononuclear cells (PBMC), the 55 kDa protein (AILb-A) induced multiple cytokines, such as IFN-gamma, tumor necrosis factor (TNF)-alpha, granulocyte macrophage-colony stimulating factor (GM-CSF), IL-2, IL-6, IL-10, IL-12 and IL-18, and also accelerated killer cell activities of PBMC. When compared with a commonly used immunotherapeutic agent OK-432, AILb-A induced Th1 cytokines are greater than OK-432. Of the Th2 cytokines, the amounts of IL-6 and IL-10 induced by AILb-A were lower than those by OK-432. No significant induction of IL-4 and IL-13 was observed in AILb-A-stimulated PBMC. TNF family including TNF-alpha, TNF-beta, Fas ligand (FasL) and TNF-related apoptosis-inducing ligand (TRAIL) were suggested to be important for AILb-A-induced killing activity of PBMC by reverse transcription-polymerase chain reaction (RT-PCR) analysis. Furthermore, the neutralizing test using cytokine-specific antibodies demonstrated that IL-18 plays a most significant role for IFN-gamma- and killer cell-inducing ability of AILb-A among the cytokines tested. These findings clearly indicated that AILb-A, a 55 kDa protein of AIL, is a potent Th1 cytokine inducer and may be a useful immunotherapeutic agent for the patients with malignancies.

Adjuvants, Immunologic↗
PubMed2000

Clinical evaluation of muscle strength in 20-79-years-old obese Japanese.

It is well known that obesity is closely related to non-insulin-dependent diabetes mellitus, hyperlipidemia, hypertension and cardiovascular disease, and the insulin resistance associated with obesity is supposed to play a central role for the development of these diseases. Thus, effective prevention and treatment of obesity need to be explored. In 357 obese (body mass index > or =26.4) subjects, aged 20-79 years, grip and leg strength were determined and compared with age- and sex-matched 1683 nonobese control subjects. Age-dependent alteration of body composition, evaluated by waist-hip ratio and the relative fat mass volume, was also compared. Finally, the relationship between the number of risk factors related to atherosclerosis and muscle strength was evaluated. Grip and leg strength in obese subjects were obviously stronger than controls under the age of 60 in both sexes. However, in the subjects over 60 years old, muscle strength was similar between obese subjects and controls. Weight bearing index (WBI) (leg strength (kg)/body weight (kg)) in obese subjects was remarkably lower than that in controls in all generations. In obese subjects, the waist-hip ratio and relative percentage of fat increased with aging, and obese subjects with multiple risk factors had higher waist-hip ratio and a tendency for lower muscle strength. Reduced WBI was considered to be a fundamental feature of obese subjects, and obese subjects increased fat composition with aging, which may be linked with low muscle strength. Thus, we need to design the most effective protocols to maximize and maintain quantitative and qualitative properties of muscle.

Adult↗
PubMed2000

Proteinase-activated receptor-2 (PAR-2): regulation of salivary and pancreatic exocrine secretion in vivo in rats and mice.

Proteinase-activated receptor-2 (PAR-2) is expressed throughout the gastrointestinal tract including the pancreas, and may be involved in digestive functions. The aim of our study was to evaluate a potential role for PAR-2 in regulating salivary and pancreatic exocrine secretion in vivo. PAR-2-activating peptides (PAR-2-APs), but not selective PAR-1-APs, administered intravenously, increased salivary secretion in the mouse or rat; this effect of the PAR-2-APs was unaffected by atropine, phentolamine, propranolol or indomethacin. Secretion (amylase) by rat parotid gland slices in vitro was also stimulated by PAR-2-APs and trypsin, but not by activation of other PARs. PAR-2-APs, administered to rats in vivo, caused a prompt effect on pancreatic exocrine secretion. PAR-2 mRNA, known to be present in pancreatic tissue, was also detected in parotid tissue. Our results indicate that in addition to a potential role in regulating cardiovascular and respiratory functions, PAR-2 may also play a general role in vivo for the direct regulation of glandular exocrine secretion.

Animals↗
PubMed2000

Dual modulation by thrombin of the motility of rat oesophageal muscularis mucosae via two distinct protease-activated receptors (PARs): a novel role for PAR-4 as opposed to PAR-1.

Since protease-activated receptors (PARs) are distributed throughout the gastrointestinal tract, we investigated the role of PARs in modulation of the motility of the rat oesophageal muscularis mucosae. Thrombin produced contraction of segments of the upper and lower part of the smooth muscle. Trypsin contracted both the muscle preparations only at high concentrations. SFLLR-NH(2) and TFLLR-NH(2) (PAR-1-activating peptides), but not the PAR-1-inactive peptide FSLLR-NH(2), evoked a marked contraction. In contrast, the PAR-2 agonist SLIGRL-NH(2) and the PAR-4 agonist GYPGKF-NH(2) caused no or only a negligible contraction. In oesophageal preparations precontracted with carbachol, thrombin produced a dual action i.e. relaxation followed by contraction. TFLLR-NH(2) further contracted the precontracted preparations with no preceding relaxation. GYPGKF-NH(2), but not the inactive peptide GAPGKF-NH(2), produced marked relaxation. Trypsin or SLIGRL-NH(2) caused no relaxation. The PAR-1-mediated contraction was completely abolished in Ca(2+)-free medium and considerably attenuated by nifedipine (1 microM) and in a low Na(+) medium. The PAR-4-mediated relaxation was resistant to tetrodotoxin (10 microM), apamin (0.1 microM), charybdotoxin (0.1 microM), L-N(G)-nitroarginine methyl ester (100 microM), indomethacin (3 microM), propranolol (5 microM) or adenosine 3', 5'-cyclic monophosphorothioate, 8-bromo, Rp-isomer (30 microM). Thus, thrombin plays a dual role in modulating the motility of the oesophageal muscularis mucosae, producing contraction via PAR-1 and relaxation via PAR-4. The PAR-1-mediated effect appears to occur largely through increased Na(+) permeability followed by activation of L-type Ca(2+) channels and subsequent influx of extracellular Ca(2+). Our data could provide evidence for a novel role of PAR-4 as opposed to PAR-1, although the underlying mechanisms are still open to question.

Animals↗
PubMed2000

Sialoblastoma.

Tumours of the salivary gland are very uncommon in children. We present a case of sialoblastoma, a very rare congenital salivary-gland tumour, initially recognised on antenatal ultrasound. After histological diagnosis, a superficial parotidectomy was performed at 21 days of age with preservation of the facial nerve. There is no recurrence at2 years.

Female↗
PubMed2000

Induction of cytokines and killer cell activities by cisplatin and 5-fluorouracil in head and neck cancer patients.

It has been suggested that certain antitumor agents stimulate antitumor immunity. In the present study, we examined whether cisplatin and 5-fluorouracil (5-FU) accelerate the antitumor host responses in head and neck cancer patients. Two groups of patients were studied, i.e. an untreated (UT) group and a treated, disease-free (TDF) group that received chemo-immunotherapy in combination with radiotherapy and operation. When peripheral blood mononuclear cells (PBMC) derived from head and neck cancer patients were treated with cisplatin or with 5-FU, interferon-gamma, tumor necrosis factor (TNF)-alpha, TNF-beta, interleukin (IL)-1beta, IL-6, IL-12 and IL-18 as well as killer cell activities were significantly induced in both groups. In this case, these activities induced by cisplatin in UT showed lower levels than those in TDF, whereas the activities induced by 5-FU in the UT group demonstrated almost similar levels to those in TDF. These activities were significantly inhibited by anti-asialo-GM1 antibody. Furthermore, cytokine levels in sera and killer activities of PBMC derived from the cancer patients were significantly increased after cisplatin administration. These findings suggest that cisplatin and 5-FU increase anticancer immunity mediated by induction of cytokines and killer cell activities in patients with head and neck cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

Sulfated glycosaminoglycan synthesis and its regulation by transforming growth factor-beta in rat clonal dental pulp cells.

Dental pulps contain sulfated glycosaminoglycans (GAGs), such as chondroitin 4-sulfate (CSA/4CS), dermatan sulfate (CSB/DS), and chondroitin 6-sulfate (CSC/6CS). Sulfated GAGs play important roles in mineralization and collagen fibrillogenesis during primary, secondary, and reparative dentin formations. Transforming growth factor-beta (TGF-beta) is a potent regulator for several extracellular matrix (ECM) components and modulates the proliferation and differentiation. Using rat clonal dental pulp cells (RPC-C2A), we investigated the constituents of GAGs synthesized by the cells and the effect of TGF-beta on their synthesis by measuring the radioactivity of [35S]sulfate incorporated into GAG fractions. Cellulose acetate electrophoresis analysis revealed that RPC-C2A cells synthesized CSA and CSB but not CSC and that 10 ng/ml of TGF-beta increased the production of CSA and CSB in the cell/ECM fraction. Measurement of [35S]sulfate incorporation showed a significant increase in the amount of GAGs by TGF-beta, 1.3-fold CSA, and 1.2-fold CSB in the cell/ECM fraction. In the medium fraction the most secreted GAG was CSA, whereas CSB was stored in the cell/ECM fraction. Secreted CSA in the medium was markedly increased by 10 ng/ml of TGF-beta (1.7-fold). These findings indicate that CSA and CSB are major sulfated GAGs synthesized by RPC-C2A cells and that TGF-beta acts as a stimulator of sulfated GAG synthesis in dental pulp cells.

Animals↗