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Biomedical subjects

K Nishi

Publications and source records attributed to K Nishi.

At least 19 recordsLinked to original sources
PubMed1992

Effects of phorbol ester on lower urinary tract smooth muscles in rabbits.

The contractile effects of phorbol 12,13-dibutyrate (PDBu) on rabbit urinary bladder dome and urethra were investigated using muscle bath techniques. PDBu caused concentration-dependent contractions in both tissues, and these responses were not affected by pretreatment with atropine, phentolamine, hexamethonium or indomethacin. In both tissues, 1-(5-isoquinolinyl-sulfonyl)-2-methylpiperazine (H-7), a potent inhibitor of protein kinase C (PKC), inhibited PDBu-induced contractions in a concentration-dependent manner. The maximum PDBu-induced contractions in bladder dome and urethra were 33.5 +/- 3.4 and 33.3 +/- 4.1% of KCl-induced maximum contractions, respectively. In Ca(2+)-free solution or after pretreatment with nifedipine (10(-6) M), PDBu-induced contractions were reduced but not completely abolished. Although pretreatment with PDBu (10(-8) M) did not have a significant effect on the contractile responses induced by carbachol (in bladder dome) and phenylephrine (in urethra), pretreatment with H-7 (100 microM) had an inhibitory effect on carbachol- and phenylephrine-induced contractions; tonic phase contractions were more sensitive than phasic contractions. These results indicate that PDBu has significant contractile effects in rabbit bladder dome and urethra, and that the effects may be partly mediated by activation of PKC. PKC activation might also contribute to agonist-induced contractile responses in these tissues.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1992

Synthesis of 2-O-(2-acetamido-2-deoxy-beta-D-glucopyranosyl)-5a-carba-alpha-D- mannopyranose, and 5a-carba-2-O- and 3,6-di-O-(alpha-D-mannopyranosyl)-alpha-D-mannopyranoses.

Protected derivatives of the title carba-trisaccharide 1, and carba-disaccharides 4 and 6 have been synthesised by conventional glycosylation of the precursors 8, 9, or 22 of 5a-carba-alpha-D-mannopyranose with sugar halides. These are carba-sugar analogues of the oligosaccharide chains frequently occurring as structural units in biologically important glycoconjugates, and could be utilised as the building blocks for construction of higher carba-oligosaccharides of biological interest.

Carbohydrate Sequence↗
PubMed1992

The oligosaccharides in a recombinant hepatitis B virus surface antigen (HBsAg) carrying the pre-S2 region derived from yeast.

The N- and O-linked oligosaccharides in a yeast-derived HBsAg M protein (pre-S2 + S) were analyzed. Two major structures of the N-linked oligosaccharides bound to residue Asn4 were determined to be high-mannose type oligosaccharides, Man7GlcNAc2 and Man8GlcNAc2, by two-dimensional sugar mapping of the corresponding pyridylamino oligosaccharides. Peptide mapping of the M protein, sequence analysis of the glycopeptides after beta-elimination under reducing conditions and sugar-composition analysis revealed that the O-linked oligosaccharides were composed solely of mannose and bound to residue Ser5, Thr6, Thr7, Ser27, Ser28, Ser29 and Thr31 in the pre-S2 region.

Amino Acid Sequence↗
PubMed1992

ABH-related antigens in human male genital tract. A histochemical examination.

The localization of ABH related antigens in human male reproductive tract was examined using monoclonal antibodies and an avidin biotin complex method. No positive reaction with blood group antibodies on spermatozoa was observed in testis and ductus epididymidis apart from erythrocytes and endothelial cells. The expression of ABH and ABH related antigens in ductuli efferents testis, ductus epididymidis, seminal vesicle and prostate was complexly coded by a combination of H, Se, Le and X genes. The results obtained in this study indicate that the ABH antigens detected on spermatozoa of seminal stains are coating antigens and not inherent to the cell membrane, and the ABO, H, Se, Le and X genes are subjected to a tissue-dependent differential expression.

ABO Blood-Group System↗
PubMed1992

Correlation between epidermal growth factor receptor concentration and the growth of human gastric cancer xenografts in nude mice.

Seven human gastric cancer xenografts with different concentrations of EGF receptor were established in nude mice. The expression of EGF receptor in the tumors was demonstrated by Western blotting with anti-EGF receptor antibody, binding assay with 125I-EGF and immunohistochemistry with anti-EGF receptor antibody. Western blotting revealed EGF receptor doublet bands at molecular masses of 150 KDa and 170 KDa in all of the samples. The concentration of 125I-EGF binding activity in the tumors ranged from 36.0 to 11,000 fmol/mg protein, with a mean of 345 fmol/mg protein. EGF receptor was also demonstrated immunohistochemically on the apical border of the glands and the cell membrane of the tumor cells. There seemed to be a close correlation between the concentration of 125I-EGF binding activity and the doubling time of these tumors in nude mice (gamma = -0.68). However, no definite correlation was observed between EGF ligand binding and histological features of intestinal type or diffuse type. The expression of EGF receptor appears to facilitate the growth of human gastric cancer xenografts in nude mice.

Animals↗
PubMed1992

Juvenile parkinsonism: ventricular CSF biopterin levels and clinical features.

Total biopterin (T-BP) levels in the ventricular cerebrospinal fluid (CSF) and clinical features of 19 patients with juvenile parkinsonism (JP: Parkinson's disease manifesting below the age of 40) were evaluated and compared with 61 patients with classical Parkinson's disease (classical PD: symptoms developing at the age of 40 or above). The JP patients were divided into two subgroups: JP-I; those with good response to levodopa followed by marked motor fluctuations and dopa-induced dyskinesias (DID), JP-II; those with milder response than JP-I with less fluctuations and DID being more similar to classical PD. Both of the mean ventricular CSF T-BP concentrations in the JP and classical PD patients were significantly lower than that in neurological controls. Moreover, the mean T-BP level in the JP-I was markedly lower than that in the JP-II or classical PD. Total biopterin levels revealed a gaussian distribution in the classical PD. However, a bimodal distribution was noted in the JP, with the lower peak consisting of only JP-I patients. These results seem to indicate that JP-II represents early-onset classical PD, while JP-I represents a distinct subgroup having a different physiopathology from classical PD.

Adult↗
PubMed1992

Significance of CSF total neopterin and biopterin in inflammatory neurological diseases.

Total neopterin (T-N), a by-product in the biopterin biosynthesis and an indicator of activation of the cellular immune system, and total biopterin (T-B) levels in cerebrospinal fluid (CSF), were measured in patients with various inflammatory neurological diseases and Parkinson's disease, and the following results were obtained. (1) In patients with neuro-sarcoidosis, neuro-Behçet's disease and meningitis, CSF T-N levels were markedly elevated in the exacerbation or acute stages of their neurological symptoms and remarkably decreased in the remission or chronic stages. In the neuro-sarcoidosis and neuro-Behçet's disease patients, however, CSF T-B levels showed no substantial change. (2) There was a significant positive correlation between CSF T-N levels and CSF/serum albumin ratios only in the meningitis patients. However, increases of CSF T-N levels were not associated with those of plasma T-N levels. (3) In the Parkinson's disease patients, CSF T-N levels remained normal, although CSF T-B levels significantly decreased. (4) A gradient for the CSF T-N value (lumbar greater than ventricular CSF), being reverse to the CSF T-B value, was observed. These results indicate that the significance of CSF T-N is quite different from CSF T-B, and that CSF T-N appears to be a valuable biochemical marker for evaluating the activity of inflammation within the central nervous system. Its measurement seems useful for therapeutic monitoring, especially of patients showing the chronic exacerbating-remitting course.

Adult↗
PubMed1992

Thymus of abused/neglected children.

Forty-six cases of child abuse/neglect autopsied during the period of 1967 to 1990 were investigated. The weight and histological findings of the thymus were compared with those of control children. In most abused and/or neglected children, the weight of the thymus decreased conspicuously. Involution correlated well to the degree and period of maltreatment. In cases without weight loss of the thymus, i.e. spasmodic abuse by a mentally deranged parent or foster parent, a short history of maltreatment was noted. On the other hand, marked involution was observed in cases of prolonged physical abuse and/or neglect. Microscopically, a decrease in the number and pyknosis of lymphocytes were observed in the involuted thymus. Atrophy of the thymus was more conspicuous in the cortex than in medulla. Immunohistochemically, CD-1a positive cells (immature thymocytes) decreased in cases with thymic involution. This involution appears to be an important index of the degree and duration of child abuse/neglect. Furthermore, thymic involution in the early stage of childhood may also be related to insufficiency of the immune system.

Age Factors↗
PubMed1992

A leptomycin B resistance gene of Schizosaccharomyces pombe encodes a protein similar to the mammalian P-glycoproteins.

Screening for leptomycin B (LMB)-resistant transformants in a gene library constructed in Schizosaccharomyces pombe with the chromosomal DNA of an LMB-resistant mutant of S. pombe and with multicopy plasmid pDB248' as the vector led to the isolation of a gene, named pmd1+, encoding a 1362-amino-acid protein. This protein showed great similarity in amino acid sequence to the mammalian P-glycoprotein encoded by the multidrug resistance gene, mdr, and the Saccharomyces cerevisiae a-factor transporter encoded by STE6. In addition, computer analyses predicted that the protein encoded by pmd1+ formed an intramolecular duplicated structure and each of the halves contained six transmembrane regions as well as two ATP-binding domains, as observed with the P-glycoproteins and the STE6 product. Consistent with this was that S. pombe cells containing the pmd1+ gene on a multicopy plasmid showed resistance not only to LMB but also to several cytotoxic agents. The pmd1 null mutants derived by gene disruption were viable and hypersensitive to these agents. All these data suggest that the pmd1+ gene encodes a protein that is a structural and functional counterpart of mammalian mdr proteins.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1992

Effects of pyridoxalated hemoglobin polyoxyethylene conjugate and stroma free hemoglobin on pulmonary vascular responsiveness to vasoactive substances in isolated perfused rat lungs.

We examined the effects of pyridoxalated hemoglobin polyoxyethylene conjugate (PHP) and stroma free hemoglobin (SFH) on vascular responsiveness to various vasoactive substances in isolated perfused rat lungs. The lungs isolated from rats were perfused with 6% PHP, 6% SFH, or 6% hydroxyethylstarch (HES) solution, and the effects of intrapulmonary arterial injection of norepinephrine (NE), angiotensin II (ANG-II), acetylcholine (ACh), and nitroglycerin (NG) were examined by measuring perfusion pressure. NE and ANG-II produced a dose-dependent increase in perfusion pressure in all groups. The NE response in the PHP- or SFH-perfused group was significantly larger than that in the HES-perfused one. ACh decreased perfusion pressure in both PHP- and HES-perfused groups but increased perfusion pressure in the SFH-perfused group. NG decreased perfusion pressure in all groups. Present results indicate that pulmonary arterial responses to endothelium-derived relaxing factor (EDRF) induced by ACh would not be affected in the presence of PHP.

Acetylcholine↗
PubMed1992

Synthesis of interleukin-1 and prostaglandin E2 by lens epithelial cells of human cataracts.

To test our hypothesis that pseudophakic inflammation, including the fibrin reaction, may be caused by cytokines, prostaglandins (PG), or both, synthesised by residual lens epithelial cells (LECs), we measured interleukin-1 alpha (IL-1 alpha) and PGE2 in the incubation medium of cultures of human LECs obtained by capsulotomy during cataract surgery. After 1 week radioimmunoassay showed that there were 1.46 (0.62) ng of PGE2/10(6) cells (mean (SD) six cultures), and after 4 weeks, there were 5.50 (2.20) ng of PGE2/10(6) cells (seven cultures). During culture the cells proliferated and underwent fibroblast-like cell changes on exposure to the plastic of the wells. In the medium of control plates to which sodium diclofenac had been added PGE2 was not detected. Some IL-1 alpha was found in four of 10 samples, each of which contained media from 12 cultures; 207 pg/10(6) cells in one of the two pools of 2-week cultures, 120 pg/10(6) cells in one pool and 139 pg/10(6) cells in another of the three pools of 3-week cultures, and 111 pg/10(6) cells in the one pool of 4-week cultures. PGE2 and IL-1 alpha may therefore be produced in vivo by residual LECs after cataract surgery, and may be involved in postoperative inflammation, including the fibrin reaction.

Cataract↗
PubMed1992

Heparin adheres to the damaged arterial wall and inhibits its thrombogenicity.

Heparin binds to thrombogenic extracellular matrices as well as to smooth muscle cells of the vascular wall in vitro. The inhibitory effects of heparin on thrombogenicity of the damaged arterial wall were examined in vivo using small mesenteric arteries of rats and a video recording system attached to a microscope. To induce thrombosis, we damaged the vessel wall over a short segment by compression and exposed the media to the blood stream. A platelet-rich thrombus enlarged gradually at the damaged site, occluded the vascular lumen for a short period, and then flowed away. Compression damage induced such thrombus formation several times. Heparin (500 units/ml) was given in three different ways: intravenous and intra-arterial administration (both 300 units/kg) and intraluminal application under stopped-flow conditions (less than 0.01 ml) for 1-2 minutes with subsequent draining out. Intravenous heparin significantly decreased both the total duration and the number of thrombotic occlusions, whereas intra-arterial heparin abolished thrombotic occlusion. Both routes of heparin administration similarly prolonged the blood coagulation time. Intraluminal application of heparin significantly inhibited subsequent thrombus formation after restoring the flow without changes in the blood coagulation time. After an intra-arterial administration or intraluminal application of fluorescein isothiocyanate-bound heparin, strong fluorescence was observed only at the damaged vascular segment. A heparin fraction with low affinity to antithrombin III or chondroitin sulfate A did not inhibit thrombosis. To clarify anticoagulant activity of vascular wall-bound heparin, damaged carotid arterial segments of rats were incubated (inside out) in platelet-poor plasma with thrombin, and fibrin clot formation around the segments with or without heparin binding was measured.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Requirement of c-kit for development of intestinal pacemaker system.

A discovery that the protooncogene encoding the receptor tyrosine kinase, c-kit, is allelic with the Dominant white spotting (W) locus establishes that c-kit plays a functional role in the development of three cell lineages, melanocyte, germ cell, and hematopoietic cell which are defective in W mutant mice. Recent analyses of c-kit expression in various tissues of mouse, however, have demonstrated that c-kit is expressed in more diverse tissues which are phenotypically normal in W mutant mice. Thus, whether or not c-kit expressed outside the three known cell lineages plays a functional role is one of the important questions needing answering in order to fully elucidate the role of c-kit in the development of the mouse. Here, we report that some of the cells in smooth muscle layers of developing intestine express c-kit. Blockade of its function for a few days postnatally by an antagonistic anti-c-kit monoclonal antibody (mAb) results in a severe anomaly of gut movement, which in BALB/c mice produces a lethal paralytic ileus. Physiological analysis indicates that the mechanisms required for the autonomic pacing of contraction in an isolated gut segment are defective in the anti-c-kit mAb-treated mice, W/Wv mice and even W/+ mice. These findings suggest that c-kit plays a crucial role in the development of a component of the pacemaker system that is required for the generation of autonomic gut motility.

Animals↗
PubMed1992

Deamidation at asparagine-88 in recombinant human interleukin 2.

Reversed-phase high-performance liquid chromatography (RP-HPLC) and protein-chemical analysis revealed that only Asn88 in recombinant human interleukin 2 (rIL-2) is liable to be deamidated during a long period of storage in aqueous solutions (pH 5.0) at 25 degrees C, even though there are eight asparagine and six glutamine residues. The deamidation occurred more easily at 40 degrees C than at 25 degrees C but did not occur at all at temperatures below 5 degrees C. The biological activity of Asn88-deamidated rIL-2 was found to be almost the same as that of intact rIL-2, whereas its isoelectric point (pI 7.6) is different from that of intact rIL-2 (pI 7.9).

Amides↗
PubMed1992

Locally invasive pulmonary aspergillosis in a healthy man successfully treated with oral fluconazole.

A 74-year-old healthy man with locally invasive form of pulmonary aspergillosis (PA) is reported. Chest X-ray film showed a segmental infiltration of right upper lobe (RUL) without cavitation, and the transbronchial lung biopsy specimen contained numerous hyphae of aspergillus species. Complication of bronchial asthma, or bronchiectasis were absent, and hyphae of aspergillus were present at only one segment of RUL. After 5 months of therapy with oral fluconazole, the PA had dramatically improved. Fluconazole was found to be effective for the locally invasive form of PA in a healthy man.

Administration, Oral↗