Biomedical subjects

K Kawashima

Publications and source records attributed to K Kawashima.

At least 127 records · Page 7Linked to original sources

PubMed1998

[Clinical study on prostate cancer initially presenting with disseminated intravascular coagulation syndrome].

We experienced five patients with prostate cancer with disseminated intravascular coagulation syndrome (DIC) at the first presentation at Gunma University Hospital and affiliated institutions between 1991 and 1997. Their average age was 68 years, average DIC score at the first presentation was 10 and prostate specific antigen (PSA) level was more than 700 ng/ml. All of them had multiple bone metastases. The therapy for DIC and hormonal therapy for prostate cancer were simultaneously started at the first presentation before prostate needle biopsy, but all patients died. The average number of days from the start of DIC to death was 685 days. The patients initially showed a good response to therapy, but their conditions soon aggravated. The prognosis was extremely poor, but some proper therapies lead to the prognosis which was equal to that of prostate cancer in Stage D2 without DIC.

Adenocarcinoma↗

PubMed1997

Suppression of NF-kappa B and AP-1 activation by glucocorticoids in experimental glomerulonephritis in rats: molecular mechanisms of anti-nephritic action.

Transcription factors nuclear factor-kappa B (NF-kappa B) and activator protein-1 (AP-1) play an important role in the induction of pro-inflammatory factors such as cytokines and cell adhesion molecules, which could be involved in the pathogenesis of glomerulonephritis. We have recently reported the pathogenic significance of NF-kappa B activation in experimental glomerulonephritis in rats. In this study, we investigated the pathogenic relevance of AP-1 activation in nephrotoxic serum (NTS)-induced glomerulonephritis. Increased AP-1 DNA-binding activity was detected in nephritic glomeruli by a gel shift assay. The kinetics of AP-1 activation was similar to that of NF-kappa B. Activation of both NF-kappa B and AP-1 preceded proteinuria, an important pathophysiological parameter for glomerulonephritis. Treatment with prednisolone, a glucocorticoid hormone, prevented activation of both NF-kappa B and AP-1 in glomeruli and subsequent mRNA expression of NF-kappa B- and AP-1-regulated genes. Prednisolone was also effective therapeutically and reduced DNA-binding activities of NF-kappa B and AP-1 which are already activated in nephritic glomeruli. These results suggest that activated NF-kappa B and AP-1 may play an important pathogenic role in glomerulonephritis and the anti-nephritic action of glucocorticoids may be mediated through the suppression of these transcription factors.

Animals↗

PubMed1997

Expression of rat cGMP-binding cGMP-specific phosphodiesterase mRNA in Purkinje cell layers during postnatal neuronal development.

The cDNA encoding rat cGMP-binding, cGMP-specific phosphodiesterase (cGB-PDE) was isolated from a rat lung cDNA library. Although the deduced amino acid sequence showed 93.4% similarity with that of bovine cGB-PDE, the N-terminal portion of rat cGB-PDE was extremely different from that of bovine. Northern blot analysis indicated that cGB-PDE transcripts in rats were expressed not only in aorta and lung, but also in several other tissues including cerebellum. In situ hybridization analysis demonstrated that cerebellar expression of cGB-PDE was confined to Purkinje cell layers in adult rats. To clarify the role of cGB-PDE in the cerebellum, we investigated expression of cGB-PDE mRNA in rats of various ages. cGB-PDE mRNA was not observed in the cerebellum of newborn rats, but levels of a cGB-PDE mRNA were markedly increased between 4 days and 28 days of age and reached a maximum in eight-week-old rats. In this study, we suggest that cGB-PDE plays important roles not only in regulating the relaxation of vascular vessels, but also in establishing neuronal networks in the cerebellum at an early postnatal stage. In addition the NO/cGMP/cGB-PDE pathway appears to be essential for the induction of long-term depression.

3',5'-Cyclic-GMP Phosphodiesterases↗

PubMed1997

Demonstration of the facilitatory role of 8-OH-DPAT on cholinergic transmission in the rat hippocampus using in vivo microdialysis.

The role of the serotonin (5-HT)1A receptor in the regulation of acetylcholine (ACh) release in the hippocampus was investigated using an in vivo microdialysis technique and a sensitive radioimmunoassay specific for ACh. The mean (+/- S.E.M.) basal ACh contents in the hippocampal perfusate of conscious, freely moving rats was 60 +/- 4 (n = 29) and 3691 +/- 265 fmol/30 min (n = 31), respectively, in the absence and presence of physostigmine (Phy) in the perfusion fluid. Systemic administration of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, 0.5 mg/kg, s.c.), a 5-HT1A agonist, significantly enhanced ACh release both in the presence and absence of Phy. Local application of 8-OH-DPAT (3-30 microM) into the hippocampus through the microdialysis probe significantly potentiated ACh release only in the presence of Phy, whereas no significant effect was observed in its absence. Pretreatment with NAN-190 (3 mg/kg, i.p.), a 5-HT1A antagonist, eliminated the increasing effect of systemically applied 8-OH-DPAT on ACh release, while NAN-190 alone had no effect on basal ACh release either in the absence or presence of Phy. Consistent with the time course of ACh release, systemic administration of 8-OH-DPAT evoked hyperlocomotion, which was reversed by NAN-190. However, local hippocampal application of 8-OH-DPAT did not affect the locomotor activity of the rats. These findings suggest that at least two different sites are involved in the 8-OH-DPAT-induced increase in the release of ACh in the rat hippocampus in vivo.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed1997

Nitric oxide increases stimulation-evoked acetylcholine release from rat hippocampal slices by a cyclic GMP-independent mechanism.

Nitric oxide (NO) is an endothelium-derived relaxing factor and its main mechanism of action is activation of soluble guanylyl cyclase. NO and NO-related compounds have been reported to affect several neuronal functions in the central nervous system. In this study, we investigated the effects of NO donors (sodium nitroprusside (SNP) and (+/-)-(E)-4-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexenamide (FK409)) on acetylcholine (ACh) release from rat hippocampal slices. SNP (10(-5) M) and FK409 (10(-4) M) increased electrical stimulation-evoked ACh release without affecting basal release. As dibutyryl cyclic GMP inhibited stimulation-evoked ACh release, the effects of these NO donors were not due to soluble guanylyl cyclase activation. Atropine increased stimulation-evoked ACh release by blocking presynaptic muscarinic autoreceptors, and SNP increased stimulation-evoked ACh release in the presence of atropine, suggesting that SNP and atropine increase stimulation-evoked ACh release by different mechanisms. The present results indicate that NO enhances some part of the excitation-secretion coupling pathway without inducing ACh release directly and these effects are mediated by cyclic GMP-independent mechanism.

Acetylcholine↗

PubMed1997

Preparation and biological activity of manno- and galacto-validamines, new 5a-carba-glycosylamines as alpha-glycosidase inhibitors.

Manno- and galacto-validamines, which are epimers of validamine, were semi-synthesized by the configurational inversion of validamine, a pseudo-sugar analogue of alpha-D-gluco-pyranose that has inhibitory activity for alpha-glucosidases. The inhibitory activities of these analogues were determined against several mannosidases and galactosidase. Manno-validamine shows potent inhibition for the alpha-mannosidases (competitive. K(i) = 4.6 x 10(-5) M for jack beans, and competitive, Ki = 2.8 x 10(-5) M for almonds), and galacto-validamine shows weak inhibition for the alpha-galactosidases (coffee bean and E. coli). The inhibitory effect of the epimers on the N-linked oligosaccharide-processing mannosidases involved in glycoprotein biosynthesis and lysosomal mannosidase from rat liver were also examined. Mannovalidamine shows potent inhibition on the endoplasmic reticulumal alpha-mannosidase (competitive, K(i) = 1.2 x 10(-6) M), Golgi mannosidases IA, II (competitive, K(i) = 2.8 x 10(-5) M), and lysosomal alpha-mannosidase (competitive, Ki = 1.7 x 10(-5) M).

Animals↗

PubMed1997

Maintenance of constant blood acetylcholine content before and after feeding in young chimpanzees.

We have shown that acetylcholine (ACh) is present in the blood of various species of mammals using a specific, sensitive radioimmunoassay. In the present study, the effect on blood and plasma ACh levels of feeding after overnight fasting was studied in one male and five female 4- to 7-year-old chimpanzees. The mean basal ACh concentrations of the blood and plasma were 3143 +/- 380 and 184 +/- 10 pg/ml (+/-SEM, n = 6), respectively. Feeding each chimpanzee 500 g boiled sweet potatoes as breakfast at 1000 h and tap water given ad libitum did not affect the ACh content of the blood and plasma, and constant values of the blood and plasma ACh contents were observed for 4 h after the feeding. Hematocrit and plasma acetylcholinesterase (AChE) activity were also insensitive to feeding. No correlation was observed between plasma AChE activity and either blood or plasma ACh content. The results of the present study indicate that the blood ACh of chimpanzees is distributed mainly in the blood cell fraction, and that the blood ACh content is not regulated directly by cholinergic nerve activity or by plasma AChE activity.

Acetylcholine↗

PubMed1997

Oral administration of KW-5092, a novel gastroprokinetic agent with acetylcholinesterase inhibitory and acetylcholine release enhancing activities, causes a dose-dependent increase in the blood acetylcholine content of beagle dogs.

Acetylcholine (ACh) was detected in the blood and plasma of beagle dogs using a specific, sensitive radioimmunoassay. The mean basal ACh contents in the blood and plasma of beagle dogs were 451 +/- 65 and 83.5 +/- 12.3 pg/ml (+/- SEM, n = 7), respectively, and were lower than the contents in humans reported previously by our laboratory. Oral administration of KW-5092 (10-30 mg/kg), a gastroprokinetic agent with acetylcholinesterase (AChE) inhibitory and ACh release enhancing activities, caused a dose-dependent increase in the ACh content of both the blood and plasma, as well as several behavioral side effects due to peripheral cholinergic stimulation. The size of the increase in the plasma ACh content at each dose of KW-5092 was greater than that in the blood, indicating that KW-5092 caused the increase in the blood ACh content through elevation of the plasma ACh content, by inhibition of AChE and facilitation of ACh release. These results demonstrate that the blood ACh of beagle dogs is present mainly in the blood cells and to a lesser degree in the plasma, and that KW-5092 increased the blood ACh content mainly by increasing the plasma ACh concentration.

Acetylcholine↗

PubMed1997

Eicosapentaenoic acid enhances nitric oxide production by cultured human endothelial cells.

It is unclear whether the abnormal relaxation seen in diabetes is due to decreased levels of nitric oxide (NO) and how eicosapentaenoic acid (EPA, C20:5 omega 3) affects the endothelial production of NO. We investigated the effects of EPA ethyl ester (EPA-E) and elevated glucose on NO production by human endothelial cells (HUE). EPA-E (0.3 mM) significantly enhanced [NO2] production and the intracellular concentration of free Ca2+ within 3 min after EPA-E was added to the cultures. High levels of glucose (27.5 mM) significantly increased endothelial glucose, sorbitol and fructose, and inhibited [NO2-] production. However, EPA-E (0.3 mM) prevented the inhibition of [NO2-] production due to the activation of the Ca(2+)-calmodulin system of NO synthase. EPA-E decreased the glucose-mediated inhibition of NO production by HUE. These results suggest this agent might ameliorate endothelial dysfunction associated with diabetes.

Calcium↗

PubMed1997

A randomized study comparing VMCP and MMPP in the treatment of multiple myeloma.

PURPOSE: To compare VMCP, a multidrug combination chemotherapy comprising vincristine (VCR), melphalan (MPH), cyclophosphamide (CPM) and prednisolone (PSL), with MMPP comprising MPH, ranimustine (MCNU), procarbazine, and PSL as induction, to elucidate the value of alternating combination chemotherapy, and to search for an appropriate maintenance therapy in multiple myeloma. METHODS: At 16 institutions in the Nagoya City area, we carried out a randomized trial of VMCP versus MMPP as the initial treatment. Patients who were refractory or resistant to the initial therapy were crossed over into the other arm (crossover trial). For patients who achieved a partial response (PR) or a minor response (MR) and in whom the paraprotein level ceased to decrease, the maintenance therapy was randomized either to an MPH/PSL combination (MP) or to alternating combination therapy (AT) with VMCP and MMPP. RESULTS: In the 94 evaluable patients of the 111 enrolled, the response rate (PR rate) was 27.7% (13/47) in the VMCP arm and 44.7% (21/47) in the MMPP arm (P = 0.0859). The crossover trial resulted in a PR rate of 15.8% (3/19) for the VMCP-->MMPP crossover and 14.3% (2/14) for the MMPP-->VMCP crossover. The median survival time was 23.4 months for those initially begun in the VMCP arm and 24.9 months for those in the MMPP arm, showing a tendency for better survival during a follow-up of 2-6 years with MMPP treatment, but without statistical significance. The survival time of patients with progressive disease was significantly shorter than that of patients with PR, MR or no change (NC). However, there was no significant difference in the survival rate among those who achieved PR, MR, or NC. As to the maintenance therapy, there was no significant difference in survival between MP therapy and AT. Patients who reached a plateau phase survived significantly longer than those who did not. Except for six cases of grade 3 or 4 neurotoxicity in the VMCP arm, there was no significant difference in the hematologic or gastrointestinal toxicity between the two arms. CONCLUSIONS: We conclude that VMCP is less effective for myeloma than MMPP as the induction treatment, that alternating noncrossresistant chemotherapeutic combinations do not offer an advantage in multiple myeloma, and that patients who reach a plateau phase have a significantly longer survival time.

Adult↗

PubMed1997

Immunohistopathological characterization of pig pneumonia caused by a combined Aujeszky's disease virus and Actinobacillus pleuropneumoniae infection.

Nine pigs were inoculated endobronchially with Actinobacillus pleuropneumoniae serotype 1 (App-1) 6 days after infection with Aujeszky's disease virus (ADV); four died within 3 days and the remainder were killed after 1-6 days. Immunohistopathologically, there were two types of pneumonic lesion: pleuropneumonia, characterized by coagulative necrosis, oedema and fibrinous thrombosis; and necrotizing interstitial pneumonia, characterized by bronchitis, bronchiolitis and alveolitis. The former type of lesion was associated with App-1 antigen, and the latter with ADV antigen. These results indicated that a combined ADV and App-1 infection produced severe haemorrhagic pleuropneumonia; and that ADV and App-1 each produced a characteristic pneumonic lesion.

Actinobacillus pleuropneumoniae↗

PubMed1997

Congenital right diaphragmatic hernias through posterolateral and anterolateral defects associated with extralobar pulmonary sequestration: a case report.

Multiple diaphragmatic hernias in the unilateral diaphragm are extremely rare. The authors report a neonate with diaphragmatic hernias through two defects in the right diaphragm: a posterolateral defect without a hernia sac and an anterolateral defect with one. After excision of the anterolateral hernia sac, each defect was closed. Histology studies showed extralobar pulmonary sequestration in the removed hernia sac. The presence of sequestrated pulmonary tissue indicates the possibility of interference with the closure of the pleuroperitoneal canal and muscularization in the diaphragm, which may result in multiple defects.

Bronchopulmonary Sequestration↗

PubMed1997

Restoration of nitric oxide production by aldose reductase inhibitor in human endothelial cells cultured in high-glucose medium.

The effects of elevated glucose and aldose reductase inhibitor (ARI:ONO-2235) on nitric oxide (NO) production in cultured human umbilical endothelial cells (HUVEC) were evaluated. Aldose reductase and nitric oxide synthase(NOS) share NADPH as an obligate cofactor, therefore it is suggested that the enhanced of glucose flux (27.5 mM) by aldose reductase inhibited NO production by blunting NOS activity. However, the addition of ONO-2235 (100 microM) prevented the inhibition of [NO2-] production. Since ARI decreases glucose-mediated inhibition of NO production in HUVEC. this agent might ameliorate endothelial function associated with diabetes.

Aldehyde Reductase↗

PubMed1997

Suppression of arthritis by the inhibitors of dipeptidyl peptidase IV.

Dipeptidyl peptidase IV (DP IV, CD26) is a serine exoprotease which selectively cleaves the penultimate proline residue of polypeptides. This enzyme is also expressed as a surface marker on activated T cells. In order to assess the relevance of DP IV in immunological disorders, we evaluated the in vivo effects of specific DP IV inhibitors using two arthritis models, one which was induced by collagen one by alkyldiamine. These animal models share several pathological features associated with rheumatoid arthritis. The transition state substrate analog of DP IV, (S)-Alanylpyrrolidine-boronic Acid (Ala-boroPro), suppressed hind paw swelling, which was associated with collagen-induced and alkyldiamine-induced arthritis. A competitive inhibitor of DP IV, Lys(Z(NO2))-thiazolidide and an irreversible inhibitor, Ala-Pro-nitrobenzoylhydroxylamine also suppressed alkyldiamine-induced arthritis dose-dependently. We also analyzed the pharmacological effects of Lys(Z(NO2))-thiazolidide on several immune responses in vitro, in order to determine its mode of action. This inhibitor suppressed mitogen-induced and antigen-induced proliferation of T cells. However, studies using splenic cells from DP IV deficient rats showed that the inhibition of lymphocyte proliferation was not exerted through the inhibition of DP IV.

Animals↗

PubMed1997

Developmental toxicity evaluation of phthalic acid, one of the metabolites of phthalic acid esters, in rats.

The objective of this study was to evaluate the developmental toxicity of phthalic acid (PA), which is one of the metabolites of phthalic acid esters (PAEs). Pregnant rats were given PA at a dose of 0 (control), 1.25, 2.5, or 5.0% in the diet on day 7 through day 16 of pregnancy. Average daily intakes of PA were 1021 mg/kg for the 1.25% group, 1763 mg/kg for the 2.5% group, and 2981 mg/kg for the 5.0% group. Maternal toxicity occurred in the 2.5 and 5.0% groups as can be seen by significant decreases in the maternal body weight gain and food consumption during the administration period. No significant changes in maternal parameters were found in the 1.25% group. Neither deaths nor clinical signs of toxicity were noted in any groups. No significant changes induced by PA were detected in the incidence of postimplantation loss and number and sex ratio of live fetuses. Significant decreases in the weight of male fetuses and number of ossification center of the caudal vertebrae were found in the 5.0% group. Morphological examinations of fetuses revealed no evidence of teratogenesis. Thus it appears unlikely that PA may be responsible for the production of the developmental toxicity of PAEs.

Animals↗

PubMed1997

Characterization of molecularly cloned human 5-aminoimidazole-4-carboxamide ribonucleotide transformylase.

The cDNA encoding human 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) transformylase has been cloned from a placenta cDNA library, utilizing a PCR-derived probe. It encodes a peptide of 592 amino acids. The amino (N)-terminal sequence of this enzyme, purified from HeLa cells and CCRF-CEM cells, was found to be APGQLALF-. Both sequencing results revealed a difference of six N-terminal residues when compared to the reported sequence of cloned cDNA from a hepatoma cDNA library. Northern-blot analysis of human AICAR transformylase mRNA showed the expression of a single 2.0 kb mRNA in all tissues examined. With the cloned cDNA fragment, we constructed expression vectors for mature and GST-fused AICAR transformylase. Both recombinant molecules possessing AICAR transformylase activity were overproduced in Escherichia coli. GST-AICAR transformylase can be purified to homogeneity by a single-step affinity procedure with glutathione Sepharose. Mutational analysis, utilizing this expression system, showed that His213 and His267 were essential for AICAR transformylase activity.

Amino Acid Sequence↗

PubMed1997

The rectus abdominis myocutaneous flap combined with vascularized costal cartilages in reconstructive craniofacial surgery.

The efficacy of osteocutaneous or vascularized bone flaps for reconstruction of massive skeletal and soft-tissue defects has been supported by recent descriptions in the literature. In this article we presented an alternative technique, which is the rectus abdominis myocutaneous flap combined with vascularized eighth and ninth costal cartilages, for reconstruction of midfacial composite defects. The vascular pedicle of the composite flap is the deep inferior epigastric artery and vein. The costal cartilages are supplied by the perichondrial vascular network through the anterior intercostal vessels connecting with the deep epigastric vascular system. Vascularized costal cartilages are considered to reduce the incidence of postoperative complications and resorption of this material. This technique is a useful tool for restoration of craniofacial contour in reconstructive head and neck surgery.

Abdominal Muscles↗

PubMed1997

Calcium effect on the membrane preparation of segmented poly(ether/urethane/amide) (PEUN) as a biomedical material.

Poly(ether/urethane/amide) (PEUN), a segmented polyurethane, was characterized concerning phase relationship, viscosity in solution, hydraulic permeability, mechanical properties, and in vivo biocompatibility with tissue and blood. PEUN was dissolved at the highest concentration of 0.5% in N,N-dimethylformamide (DMF). Addition of calcium chloride at concentrations up to 3.1% progressively increased the solubility of PEUN in DMF PEUN2 membrane was prepared by casting from mixtures of PEUN, 3% calcium chloride, and DMF, from which calcium chloride was sufficiently removed. The PEUN2 membrane thus obtained was compared with PEUN membrane which was prepared by casting from DMF solution without the addition of calcium chloride. The water permeability across PEUN2 membrane was higher than that across PEUN membrane. PEUN2 membrane in the swollen state exhibited a lower tensile modulus and much greater elastic property than PEUN membrane. Tissue compatibility of PEUN2 membrane was better than that of PEUN membrane. Thromboresistance of PEUN membrane was good, while PEUN2-coated surface was thrombogenic to some extent in vivo. Our characterization suggested that PEUN2 membrane is more hydrophilic than PEUN membrane, possibly because of the assembly of polar groups on the segments of PEUN molecules which show affinity to calcium chloride in membrane processing.

Animals↗