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Biomedical subjects

N Kitamura

Publications and source records attributed to N Kitamura.

At least 289 records · Page 16Linked to original sources
PubMed1994

[Quadruple coronary artery bypass grafting with arterial grafts--application of internal thoracic artery and right gastroepiploic artery].

Arterial graft has been widely applied for coronary artery bypass because of its excellent long-term patency. However, when more than four coronary bypass graftings should be carried out using internal thoracic arteries (ITAs) and right gastroepiploic artery (GEA), some surgical techniques must be devised. We performed quadruple coronary artery bypass grafting using three arterial grafts; bilateral ITAs and GEA, and obtained good results. We used free RITA graft for sequential grafting in one case. In another case, GEA was divided into two segments and used as two free grafts. From our experience, we believe it is possible to perform multiple coronary revascularization using only arterial grafts with one median skin incision.

Abdominal Muscles↗
PubMed1994

[A case report of disappearance of free internal thoracic artery graft stenosis].

We have experienced an interesting case of spontaneous disappearance of stenosis of the injured free internal thoracic artery graft six months after coronary artery bypass grafting. A 61-year-old male underwent coronary bypass surgery with in situ left internal thoracic artery (LITA)-left anterior descending (LAD) and free right internal thoracic artery (RITA)-first diagonal branch (D1) bypass at our hospital. Postoperative angiogram showed the stenosis of the distal portion of the free RITA. We judged it was the injury by the electrocautery when dissecting the RITA. He was admitted to our hospital and received repeat angiography because of recurrence of angina six months after surgery. Repeat angiogram showed the good patency of LITA and complete disappearance of the stenosis of the free RITA. We consider that this case proved the free ITA can be a living graft.

Coronary Artery Bypass↗
PubMed1994

Structure of the enteric nervous system in the sheep omasum as revealed by neurofilament protein-like immunoreactivity.

The general structure of the enteric nervous system in the omasum of sheep was investigated by immunohistochemical techniques using antineurofilament protein antibody. The myenteric plexus consisted of polygonal ganglia and interganglionic nerve bundles. The meshwork of the plexus in the oral region was denser than the middle and aboral regions. Intraganglionic laminar endings were present in the myenteric ganglia. The submucosal plexus was divided into sublaminar and intralaminar plexuses. The latter was denser near the free border of the omasal laminae than in the region near the omasal wall. There were no ganglion cells showing neurofilament protein-like immunoreactivity in the submucosal and mucosal layers. Probable mucosal receptors were found in the horny omasal papillae near the reticulo-omasal orifice. The findings demonstrate a complicated structure for the enteric nervous system in the omasum, presumably reflecting its regulatory activities.

Animals↗
PubMed1993

Evidence for involvement of furin in cleavage and activation of diphtheria toxin.

Proteolytic cleavage (nicking) of diphtheria toxin (DT) in the 14-amino acid loop subtended by the disulfide bond between Cys186 and Cys201 is required for the cytotoxic action of DT. The loop includes the consensus motif for cleavage by a membrane-anchored protease, furin. We found that a soluble form of furin cleaves intact DT between Arg103 and Ser194 in vitro. LoVo cells, a human colon carcinoma cell line, do not produce functional furin. We show here that intact DT is not cleaved by LoVo cells. The cells are resistant to intact DT, although they are sensitive to DT nicked by furin before it is added to the medium. When intact DT is added to LoVo/Fur1 cells, a stable transfectant of LoVo cells expressing mouse furin, nicked DT associated with the cells is observed. LoVo/Fur1 cells are sensitive to both intact and nicked DT. These results indicate that furin is involved in the toxicity of intact DT. Bafilomycin A1, an inhibitor of intracellular vesicle acidification, did not inhibit cleavage of intact DT by LoVo/Fur1 or Vero cells, indicating that cleavage can proceed in a neutral environment. Inhibitors of endocytosis decreased DT cleavage but did not eliminate it. We also found a small amount of nicked DT in the culture medium. These results may indicate that intact DT is cleaved age by cell-associated furin on the cell surface as well as in endocytotic vesicles.

Animals↗
PubMed1993

Stimulation of prostaglandin production by hepatocyte growth factor in human gastric carcinoma cells.

Hepatocyte growth factor (HGF), a protein with pleiotropic biological activity affecting cell growth and motility, was found to markedly activate prostaglandin production in human gastric carcinoma TMK-1 cells. HPLC analysis revealed that HGF stimulated the production of prostaglandin E2 (PGE2), which is the major prostaglandin produced in these cells. HGF maximally stimulated PGE2 production at a concentration of 10 ng/ml, and it was a more potent stimulator of PGE2 production than epidermal growth factor (EGF), which is known to stimulate prostaglandin production in various cell lines. The simultaneous addition of HGF and EGF caused no further stimulation of the PGE2 production observed in HGF-treated cells. We showed also that HGF increased the arachidonate release from TMK-1 cells, which release was completely suppressed by the addition of phospholipase A2 (PLA2) inhibitors. Further studies in vitro showed that HGF enhanced cellular activities of cytosolic PLA2 and cyclooxygenase 1.5-fold each. These results indicate that HGF stimulates prostaglandin production through increases in both cytosolic PLA2 and cyclooxygenase activities.

Chromatography, High Pressure Liquid↗
PubMed1993

Activation of the zymogen of hepatocyte growth factor activator by thrombin.

Hepatocyte growth factor activator (HGF activator) is a serine protease which converts single-chain HGF to the active two-chain form. HGF activator purified from human serum has a molecular mass of 34 kDa and consists of two chains held together by a disulfide bond. The nucleotide sequence of HGF activator cDNA shows that HGF activator is derived from the COOH-terminal region of a precursor of 655 amino acids by proteolytic cleavage of the bonds between Arg372 and Val373 and between Arg407 and Ile408 and that the precursor consists of multiple domains homologous to those observed in blood coagulation factor XII. In this study, we identified the precursor of HGF activator in human plasma using an enzyme-linked immunosorbent assay system. The precursor was purified from plasma by a five-step procedure. The purified precursor did not activate single-chain HGF. The precursor was efficiently cleaved in vitro by thrombin, at the bond between Arg407 and Ile408, in the presence of negatively charged substances. The cleaved precursor activated single-chain HGF. These findings led us to conclude that HGF activator is present in plasma as an inactive zymogen and that the zymogen is activated by the cleavage of the bond between Arg407 and Ile408 by thrombin. Characteristic structural domains in the NH2-terminal region of the zymogen may be involved in the binding of the zymogen to negatively charged substances, which stimulates the activation of the zymogen by thrombin.

Amino Acid Sequence↗
PubMed1993

A mutation of furin causes the lack of precursor-processing activity in human colon carcinoma LoVo cells.

Furin has been proposed to be the endoprotease responsible for precursor cleavage at Arg-X-Lys/Arg-Arg (RXK/RR) sites within the constitutive secretory pathway. However, there was a possibility that other protease(s) is involved in this cleavage. We here characterized furin in human colon carcinoma LoVo cells, since these cells lacked the endogenous processing activity toward RXK/RR sites and recovered the activity by transfection of furin cDNA. Furin cDNA cloned from LoVo cells had one nucleotide deletion in the region covering the homo B domain which is essential for the endoproteolytic activity. LoVo cells transfected with a furin construct with the mutation showed no activity. Based on these data, we conclude that furin is the endoprotease that is involved in the precursor cleavage at RXK/RR sites within the constitutive secretory pathway.

Amino Acid Sequence↗
PubMed1993

Proteolytic processing of the hepatocyte growth factor/scatter factor receptor by furin.

The hepatocyte growth factor/scatter factor (HGF/SF) receptor consists of an alpha- and a beta-subunit, which are derived from a single-chain precursor by endoproteolytic processing. The precursor is not proteolytically processed in LoVo colon carcinoma cells. The uncleaved receptor immunopurified from the cells was cleaved in vitro by furin. Furthermore, the HGF/SF receptor was proteolytically processed in LoVo cells transfected with furin cDNA. These results indicate that furin is a processing endoprotease for the HGF/SF receptor. Tyrosine autophosphorylation of the uncleaved receptor was induced by HGF/SF, and the growth of the cells expressing the uncleaved receptor was stimulated by HGF/SF, indicating that the proteolytic processing of the receptor is not essential for the signal transduction of HGF/SF.

Amino Acid Sequence↗
PubMed1993

Increase in [3H]cAMP binding sites and decrease in Gi alpha and Go alpha immunoreactivities in left temporal cortices from patients with schizophrenia.

To search for possible alterations in second messenger systems in the temporal cortex (Brodmann's area 22) of patients with schizophrenia, we measured the binding activities of [3H]adenosine 3',5'-cyclic monophosphate ([3H]cAMP) and [3H]4 beta-phorbol 12,13-dibutyrate ([3H]PDBu) which can label the regulatory subunit of cAMP-dependent protein kinase (protein kinase A) and the regulatory domain of Ca2+/phospholipid-dependent protein kinase (protein kinase C), respectively. We also immunoquantified the variable subunits of guanine nucleotide binding proteins (G-proteins), using specific polyclonal antisera against Gs alpha, Gi alpha and Go alpha. Brains were obtained at autopsy on 10 patients with schizophrenia and 10 age-matched control subjects. Representative Scatchard plots for specific [3H]cAMP bindings to the soluble fraction consisted of a single component with high affinity (Kd = 2.36 nM, Bmax = 737 fmol/mg protein). Among the tested adenyl and guanyl nucleotides, or neuroleptics, cAMP alone potently inhibited the binding (Ki = 4.95 nM). The binding sites for [3H]cAMP were discretely localized, and were in the order of: cerebral cortex = hypothalamus = amygdala > hippocampus = neostriatum = thalamus = nucleus accumbens > globus pallidus = cerebellum. Specific [3H]cAMP bindings to the soluble fractions were about 30% greater in the left temporal cortices of schizophrenic patients, as compared to findings in the right side of the patients and the left side of the control subjects, no control brain showed this asymmetry. The specific [3H]PDBu binding in schizophrenic and control groups did not change.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Molecular cloning and sequence analysis of the cDNA for a human serine protease reponsible for activation of hepatocyte growth factor. Structural similarity of the protease precursor to blood coagulation factor XII.

Hepatocyte growth factor (HGF) is a potent mitogen for parenchymal liver cells, epithelial cells, and endothelial cells and may play an important role in liver regeneration following hepatic injury. HGF is homologous to plasminogen and is first synthesized and secreted as an inactive single-chain precursor and then activated to a heterodimeric form by endoproteolytic processing. Recently, a novel serine protease responsible for this processing (HGF activator) has been purified from fetal bovine serum (Shimomura, T., Ochiai, M., Kondo, J., and Morimoto, Y. (1992) Cytotechnology 8, 219-229). In this study, we purified HGF activator from human serum and determined its partial amino acid sequence. Based on the amino acid sequence, we have molecularly cloned the cDNA for human HGF activator. The nucleotide sequence of the cDNA revealed that HGF activator is derived from the COOH-terminal half region of a precursor protein of 655 amino acids and that the precursor consists of multiple putative domains homologous to those observed in blood coagulation factor XII. These domains may be involved in the conversion of the precursor to the active form of HGF activator.

Amino Acid Sequence↗
PubMed1993

Characterization of the promoter region of the rat hepatocyte-growth-factor/scatter-factor gene.

Hepatocyte growth factor/scatter factor (HGF/SF) is a potent mitogen for hepatocytes in primary culture. In response to liver damage, the levels of HGF/SF mRNA change in various tissues. In this study, we isolated a genomic DNA fragment containing the promoter region of the rat HGF/SF gene and analyzed transcription-initiation sites and their utilization in response to acute liver injury. Rat HGF/SF-mRNA synthesis starts from at least three sites in the liver, spleen and kidney. One of these sites is preferentially utilized in the liver and spleen in response to acute liver injury. In the 5' flanking region, several cytokine-related sequence elements that might be involved in the regulation of HGF/SF-gene expression are located near the transcription-initiation sites. The effects of cytokines related to these sequence elements on the production of HGF/SF mRNA were examined using a cell culture system. Transforming growth factor-beta 1 (TGF-beta 1) inhibits the production of HGF/SF mRNA by Shay granulocytic sarcoma-derived cells. The TGF-beta 1-inhibitory element, one of the sequence elements present in the promoter sequence, may mediate the inhibition of HGF/SF-gene expression by TGF-beta 1.

Animals↗
PubMed1993

Differential changes in serotonin 5-HT1A and 5-HT2 receptor binding in patients with chronic schizophrenia.

Serotonin 5-HT1A and 5-HT2 receptors were examined in the postmortem brains of controls and patients with chronic schizophrenia. In the prefrontal cortex from patients with schizophrenia, 5-HT1A receptor binding was increased, while 5-HT2 receptor binding was decreased, when compared to controls. The increased 5-HT1A receptor binding or the decreased 5-HT2 receptor binding was observed in both the patients who had been medicated with neuroleptics at time of death and those who had not, at least 2 months prior to death. Thus, abnormalities of 5-HT receptor subtypes seem to exist in the brains of patients with chronic schizophrenia. 5-HT related agents might be beneficial for the treatment of schizophrenia.

Chronic Disease↗
PubMed1993

Immunohistochemical localization of lactoferrin in bovine exocrine glands.

The localization of lactoferrin (LF) was studied in bovine exocrine glands by the peroxidase-antiperoxidase method. In general, LF immunoreactivity was demonstrated in most of the serous demilunes of the mixed glands and in some but not all acinar cells of the serous glands. LF was not detected in the acinar cells of the mucous glands. LF immunoreactive cells were seen in the nasal and tracheal glands. The lacrimal and mammary glands were stained intensely, while the sweat glands were not stained. In the major and minor salivary glands, LF immunoreactivity was demonstrated in the serous demilunes and acini of the mixed glands and in some serous cells of the pure serous parotid gland. LF immunoreactivity was not seen in the gastrointestinal tract and pancreas, but the serous gland in the lamina propria of the bile duct was stained positively. In the male reproductive tracts, the prostate and bulbourethral glands were stained positively, but the vesicular gland was negative. In the female reproductive system, the uterine and Bartholin glands, the epithelial cells of the cervix and ampulla of the uterine tube reacted positively. However, the lesser vestibular gland did not react for LF. The present findings, that LF was demonstrated in the exocrine glands located mainly in the gateways of the digestive, respiratory and reproductive systems, may morphologically support the antibacterial role of LF.

Animals↗
PubMed1993

Reoperations on prosthetic heart valves: an analysis of outcome.

To evaluate risks and complications of reoperations on prosthetic heart valves, we reviewed data on 70 patients who underwent reoperations because of prosthetic valve malfunction. Overall hospital mortality was 13% (9/70 patients). The common cause of death was low cardiac output syndrome following surgery (4 patients). Respiratory failure and mediastinal infection accounted for 2 deaths each, and neurological complication for 1 death. However, hospital mortality was different according to the risk factors; reoperations for prosthetic valve endocarditis (18%, p < 0.05), advanced New York Heart Association (NYHA) class (50%, p < 0.001), and emergency operation (33%, p < 0.005) were the significant risk factors. In contrast, advanced age, female sex, type of prosthesis, valve position, and diagnosis (leak, structural deterioration, or valve thrombosis) did not appear to be significant risk factors. There were 7 late deaths (4 valve-related, 2 cardiac, and 1 noncardiac). Inasmuch as emergency operation, advanced NYHA class, and prosthetic valve endocarditis affected hospital mortality, these factors contributed to late death. Actuarial survival rate and freedom from valve-related mortality at 10 years were 75.8 +/- 2.8% and 87.2 +/- 2.3%, respectively. There were 8 valve-related complications, and freedom from valve-related complications at 10 years was 73.5 +/- 3.5%. As judged by these data, hospital mortality and late survival can be improved if hemodynamic conditions leading to myocardial damage can be prevented.

Adult↗
PubMed1993

Three-dimensional architecture of the subepithelial connective tissue in the omasal laminae of sheep and cattle.

The three-dimensional architecture of the subepithelial connective tissue in the omasal laminae of sheep and cattle was studied by scanning electron microscopy after treatment with 2 N NaOH solution. The omasal laminae were equipped with highly undulated subepithelial connective tissue showing various projections or ridges. In the sheep, the subepithelial connective tissue in the omasal papillae formed flat papillary projections in the oral and middle regions of the laminae. Ridges were arranged in cellular or rosette-like form in the aboral region. In the interpapillary space, the subepithelial connective tissue formed papillary projections in the oral region, parallel ridges with dentate projections in the middle region and smooth low ridges in the aboral region. In the cattle, the projections of the subepithelial connective tissue were more developed than in the sheep. The reticular or cellular ridges were uniformly arranged. The omasal papillae with horny tips located near the reticulo-omasal orifice showed various shapes of papillary projections. In the interpapillary space, round-edged and complex folded ridges with high undulations and deep grooves were observed. These findings may indicate regional and interspecies diversities in the function of the omasal mucosa.

Animals↗