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Biomedical subjects

N Kitamura

Publications and source records attributed to N Kitamura.

At least 145 records · Page 8Linked to original sources

Distribution of hepatocyte growth factor activator inhibitor type 1 (HAI-1) in human tissues. Cellular surface localization of HAI-1 in simple columnar epithelium and its modulated expression in injured and regenerative tissues.

We used a specific monoclonal antibody to human hepatocyte growth factor activator inhibitor type 1 (HAI-1) in immunohistochemical procedures to determine the distribution and localization of HAI-1 in human tissues. In normal adult tissues, HAI-1 was predominantly expressed in the simple columnar epithelium of the ducts, tubules, and mucosal surface of various organs. In all cases, HAI-1 was localized predominantly on the cellular lateral (or basolateral) surface. By contrast, hepatocytes, acinar cells, endocrine cells, stromal mesenchymal cells, and inflammatory cells were hardly stainable with the antibody, and stratified squamous epithelium showed only faint immunoreactivity on the surface of cells of the basal layer. In the gastrointestinal tract, the surface epithelium was strongly stained. RNA blot analysis confirmed the presence of specific mRNA transcript in the gastrointestinal mucosa, and in situ hybridization revealed that HAI-1 mRNA showed a similar cellular distribution pattern. Although HAI-1 was not expressed in normal hepatocytes, strong immunoreactivity was observed on the epithelium of pseudo-bile ducts and on the surface of scattered hepatocytes in fulminant hepatitis. The enhanced expression was also noted in regenerating tubule epithelial cells of the kidney after infarction. We conclude that HAI-1 is preferentially expressed in the simple columnar epithelium of the mucosal surface and duct, that the predominant localization of HAI-1 is the cell surface, and that the expression of HAI-1 can be modulated by tissue injury and regeneration.

Antibodies, Monoclonal↗

Morphological study on pigmented cells in the horse testis.

One of the most attractive characteristics of a horse testis is the change of the weight during development. As the testicular weight changes and the number of Leydig cells decreases, pigments appear in interstitial tissues. In the present study, the characteristics of the pigments found in the interstitial tissues were examined histochemically and ultrastructurally. Specific stainings indicated that the pigmented granules showed almost all of the histological and histochemical characteristics of ceroid or ceroid-like pigment. The cells showed positive reaction for acid phosphatase while the pigmented cells contained a lot of lysosomes ultrastructurally. These results suggest that macrophages might phagocytize Leydig cells, and store their digested materials as ceroid-like pigment.

Animals↗

Immunohistochemical survey of the gut endocrine cells in the common tree shrew (Tupaia belangeri).

Regional distribution and relative frequency of endocrine cells in the gastrointestinal tract of the common tree shrew (Tupaia belangeri) were studied immunohistochemically. Ten types of immunoreactive endocrine cells were localized in the gastric mucosa, i.e., chromogranin-, serotonin-, gastrin-, somatostatin-, bovine pancreatic polypeptide (BPP)-, enteroglucagon-, pancreatic glucagon-, peptide tyrosine tyrosine (PYY)-, motilin-, and substance P (SP)-immunoreactive (IR) cells. In the intestine, 13 types of immunoreactive cells were observed, i.e., chromogranin-, serotonin-, somatostatin-, gastrin-, BPP-, enteroglucagon-, PYY-, secretin-, cholecystokinin (CCK)-, gastric inhibitory peptide (GIP)-, motilin-, neurotensin-, and SP-IR cells. The regional distribution and relative frequency of the cell types varied along the gastrointestinal tract. Basically, the types, distribution, and relative frequency of the gut endocrine cells were similar to those reported in other mammalian species. However, some characteristic findings were noted in the present study: (1) the considerably large number of gastrin-IR cells in the pyloric region; (2) numerous serotonin-IR cells in the stomach; (3) appreciable number of BPP-IR cells in the transitional region of the stomach; and (4) wide distribution of PYY- and motilin-IR cells in the gut.

Animals↗

Activation of protein C by arginine-specific cysteine proteinases (gingipains-R) from Porphyromonas gingivalis.

In order to determine the effect of bacterial proteinases on activation of the protein C system, a negative regulator of blood coagulation, two arginine-specific cysteine proteinases (gingipains R) from Porphyromonas gingivalis, a causative bacterium of adult periodontitis, were examined. Each enzyme activated human protein C in a dose- and incubation time-dependent manner. Interestingly, the form of enzyme being composed of a non-covalent complex containing both catalytic and adhesion domains (RgpA) produced activated protein C 14-fold more efficiently than RgpB which contained the catalytic domain alone. The kcat/Km value of RgpA was 18-fold higher than that of RgpB and comparable to that of the thrombin-thrombomodulin complex, the physiological activator of protein C. RgpA catalyzed protein C activation was augmented 1.4-fold by phospholipids, ubiquitous cell membrane components. Furthermore, RgpA, but not RgpB, could activate protein C in plasma and this resulted in a decrease of the protein C concentration in plasma, which is often observed in patients with sepsis during the development of disseminated intravascular coagulation (DIC). These data indicate that RgpA is a more potent activator of protein C than RgpB and suggest that only the former enzyme can cause protein C activation in vivo. The present study further suggests that bacterial proteinases may possibly contribute to the consumption of plasma protein C which predisposes to DIC and/or promotes a thrombotic tendency towards DIC in sepsis.

Adhesins, Bacterial↗

[Crohn's disease with the onset resembling systemic lupus erythematosus].

We described a 37-year-old man with Crohn's disease (CD) resembling systemic lupus erythematosus (SLE) at his disease onset. He was admitted to the municiple Akiru Hospital in October 1986 by fever, aphtous oral ulcerations, sore throat and polyarthralgia. Hematologic examination showed leukocytopenia, lymphocytopenia, positive tests for antinuclear antibody, anti-DNA antibody and LE cell phenomenon. He has had episodes of convulsion and conciousness loss of unknown etiology when he was 17 years old. The diagnosis of SLE was made, and oral medication of prednisolone was started. Several weeks later, most of symptoms and autoantibodies disappeared, although the oral aphtous ulcerations and leukocytopenia remained. In May 1987, he admitted to the other hospital because of bloody vomiting. Endoscopic examination showed the esophagial ulceration, and histology of biopsied-specimen was nonspecific esophagitis. The combination of prednisolone and oral cyclophosphamide or methotrexate was employed thereafter. However, the leukocytopenia, oral aphtous ulceration and esophagial ulceration continued in spite of these treatments. All the immunosuppressive treatment was stopped at March 1992. In October 1995, he admitted to our hospital because of body weight loss and continuous diarrhea with occasional bloody stool. Barium enema and endoscopic examination of the colon revealed the findings compatible with CD. The patient responded favorably to methylprednisolone pulse therapy followed by oral sulphasalazine. This case indicated that cases with inflammatory bowel diseases like CD could show similar clinical signs and symptoms to SLE, and in some cases of CD might satisfied the classification of criteria for SLE.

Administration, Oral↗

Recovery from metabolic impairments after hypothermic cardiopulmonary bypass: postoperative changes in arterial-venous carbon dioxide tension difference.

Arterial-venous carbon dioxide tension differences (Pv-aCO2) are known to increase during the resuscitation phase following several types of shock. We hypothesized that Pv-aCO2 increases immediately following hypothermic cardiopulmonary bypass (CPB) because of the metabolic impairments that occur during CPB. Fifty-six adult patients underwent hypothermic CPB for cardiac surgery. Arterial and mixed venous blood gases were analyzed every 6 hours for the first 24 hours following cardiac surgery. Immediately after surgery, the Pv-aCO2 was elevated (8.2 +/- 2.9 mmHg), but gradually returned to a normal range within 12 hours (6.2 +/- 3.2 mmHg, p < 0.001). Factors (X) which correlated significantly with the postoperative Pv-aCO2 (Y) included the minimum rectal temperature during CPB (Y= 27.3 - 0.664X, p = 0.011) and the duration of CPB (Y= 5.6 + 0.0172X, p = 0.047). The abnormally high Pv-aCO2 during the early postoperative period may be caused by metabolic impairments during hypothermic CPB. The recovery stage following open heart surgery is therefore similar to the resuscitation phase after shock.

Aged↗

[Stentless aortic root bioprosthesis (freestyle) to patients of bicuspid aortic valve with abnormal positioning of the coronary ostia].

Stentless aortic root bioprosthesis (Freestyle) was implanted to two patients of bicuspid aortic valve stenosis with anatomically abnormal positioning of the coronary ostia. In a patient of LR type bicuspid valve, the left coronary artery was located at 180 degrees against the right coronary ostium. To match the Valsalva sinus of the patient with bioprosthesis, the left half of the native annulus, 23 mm in the diameter, was plicated corresponding to the one third of the Freestyle inflow, 21 mm in the diameter. In the other patient of AP type bicuspid valve, both coronary ostia were closely positioned at 90 degrees. To keep both ostia in the sinus of bioprosthesis, careful trimming and suturing were required in the narrow part of both ostia. Their postoperative courses were uneventful and no regurgitation has been observed in either case.

Aged↗

Direct expiratory gas analysis after hypothermic cardiopulmonary bypass.

We hypothesized that patients who have undergone hypothermic cardiopulmonary bypass may have abnormal oxygen metabolism after cardiac surgery because of oxygen debts that occurred during cardiopulmonary bypass. A prospective study was designed to determine oxygen consumption and carbon dioxide production using an indirect calorimeter in 45 adult patients who underwent hypothermic cardiopulmonary bypass. Inspiratory and expiratory gases were analyzed and the respiratory exchange ratio (carbon dioxide production/ oxygen consumption) was obtained every 6 hours up to 24 hours after surgery. The respiratory exchange ratio immediately following cardiopulmonary bypass was abnormally high then gradually decreased. The respiratory exchange ratio at 18 or 24 hours after surgery was significantly lower than the one on admission to the intensive care unit. Duration of cardiopulmonary bypass was the most significant parameter which correlated to the respiratory exchange ratio on admission to the intensive care unit (r = 0.82, p < 0.001). We conclude that the respiratory exchange ratio can be used to monitor systemic metabolism, especially during the recovery phase from metabolic abnormality following hypothermic cardiopulmonary bypass.

Adult↗

[Clinical results of surgical repair for thoracic aortic aneurysms: intraoperative blood loss and morbidity].

Clinical results of 64 patients who underwent surgical repair for thoracic aortic aneurysms were studied, focusing on the relationship between intraoperative blood loss and postoperative morbidity. Operative mortality was 22% in the urgent repair group and 9% in the elective repair group. Deep hypothermia, operative death, postoperative complication were the factors which significantly correlated to the amount of intraoperative blood loss. In patients who received deep hypothermia, larger blood loss and higher incidence of mortality and morbidity were observed. There was a significant relationship between the lowest core temperature during cardiopulmonary bypass and the lowest platelet count. Intraoperative blood loss revealed as a strong risk factor to directly influence postoperative clinical outcome of thoracic aortic operation.

Aortic Aneurysm, Thoracic↗

[Susceptibilities of bacteria isolated from patients with lower respiratory infectious diseases to antibiotics (1997)].

The bacteria isolated from the patients with lower respiratory tract infections were collected by institutions located throughout Japan, since 1981. Ikemoto et al. have been investigating susceptibilities of these isolates to various antibacterial agents and antibiotics, and analyzed some characteristics of the patients and isolates from them each year. Results obtained from these investigations are discussed. In these 17 institutions around the entire Japan, 512 strains of presumably etiological bacteria were isolated mainly from the sputa of 440 patients with lower respiratory tract infections during the period from October in 1997 to September in 1998. MICs of various antibacterial agents and antibiotics were determined against 100 strains of Staphylococcus aureus, 81 strains of Streptococcus pneumoniae, 85 strains of Haemophilus influenzae. 71 strains of Pseudomonas aeruginosa (non-mucoid strains), 27 strains of Pseudomonas aeruginosa (mucoid strains), 33 strains of Moraxella subgenus Branhamella catarrhalis, 17 strains of Klebsiella pneumoniae etc., and the susceptibilities of these strains were assessed except for those strains that died during transportation. S. aureus strains for which MICs of oxacillin (MPIPC) were higher than 4 micrograms/ml (methicillin-resistant S. aureus: MRSA) accounted for 55.0%. The frequency of the drug resistant bacteria decreased comparing to the previous year's 67.3%. Arbekacin (ABK) and vancomycin (VCM) showed the most potent activities against MRSA. Imipenem (IPM) and panipenem (PAPM) of carbapenems showed the most potent activities with MIC80S of 0.063 microgram/ml against S. pneumoniae. The frequency of penicillin (PC)-intermediate S. pneumoniae (PISP)+PC-resistant S. pneumoniae (PRSP) had decreased gradually, that is, in 1995 the frequency of it was 40.3%, but that was 30.9% in 1997. Against H. influenzae and M.(B.) catarrhalis, all the drugs showed good activities. But the sensitive strains of them against ceftazidime (CAZ) had decreased in 1997, compared those in 1995 and 1996. Meropenem (MEPM), IPM and tobramycin (TOB) showed the most potent activity against P. aeruginosa (mucoid strains). And TOB and ciprofloxacin (CPFX) showed the most potent activities against P. aeruginosa (non-mucoid strains). All drugs except ampicillin (ABPC) were more active against K. pneumoniae in 1997 than that in 1996. Also, we investigated year to year changes in the characteristics of patients, their respiratory infectious diseases, and the etiology. The examination of age distribution indicated that the proportion of patients with ages over 70 years was 45.5% of all the patients showing a slight increase year by year. About the proportion of diagnosed diseases, not so particular changes were recognized as follows: Bacterial pneumonia and chronic bronchitis were the most frequent with 33.6% and 29.1%, respectively. Number of strains isolated from patients before administration of antibiotics were more than those after administration of them in chronic bronchitis, but these had reversed in bacterial pneumonia. The tendency in bacterial pneumonia had been acknowledged since 1995. The increase of S. aureus and P. aeruginosa (both mucoid and non-mucoid strains) isolated after administration of antibiotics, has suggested the decrease of the susceptibility of these strains against antibiotics. Administration of antibiotics has changed the results of the frequency of isolation of bacterial species. Bacterial isolations before administration of antibiotics were as follows: S. pneumoniae 24.5%, H. influenzae 21.4%, S. aureus 18.4% and P. aeruginosa 12.2%. The frequencies of S. aureus decreased after antibiotics administration over 15 days, but the frequencies of P. aeruginosa was not affected. The frequencies of P. aeruginosa was 47.8% after administration over 15 days. From patients administered antibiotics of penicillins and cephems. S. aureus was mainly detected with 31.7-58.3%, and from patients administere

Adult↗

[Genome analysis of adenovirus type 7 and adenovirus type 11].

PURPOSE: To study the epidemiology of adenovirus type 7 (Ad 7) conjunctivitis and adenovirus type 11 (Ad 11) conjunctivitis by determining genome types and subgenome types. MATERIALS AND METHODS: For Ad 7 I used twelve strains from patients with acute viral conjunctivitis and one strain from a patient with pneumonia. For Ad 11 I used seventeen strains from patients with acute viral conjunctivitis and three strains from patients with cystitis. For Ad 7 genome typing, I used eleven DNA restriction endonucleases (REs) recognizing 6- or 7-base pair sequences and for Ad 11 genome typing, I used seven. For Ad 7 and for Ad 11 subgenome typing, I used Taq I and Hinf I which recognize 4- or 5-base pair sequences. RESULTS: The thirteen Ad 7 strains all belonged to the same genome type and subgenome type. Ad 11 strains showed six genome types. Ad 11 p was the most frequent strain. Fifteen Ad 11 p strains showed three subgenome types, but none of them was the same as the prototype. CONCLUSION: Ad 7 seems quite stable and the Ad 7 epidemic may recur again. On the other hand Ad 11 showed several different types. Ad 11 was probably not epidemic in the first half of the 1990's.

Adenoviruses, Human↗

Significance of three-field lymphadenectomy for carcinoma of the thoracic esophagus based on depth of tumor infiltration, lymph nodal involvement and survival rate.

BACKGROUND: Significance of three-field lymhpadenectomy for carcinoma of the thoracic esophagus was examined retrospectively based on depth of tumor infiltration, lymph nodal involvements and long-term survival. METHODS: One hundred and fifty-two consecutive patients who underwent curative esophagectomy for thoracic carcinoma invading to submucosa (pT1) or deeper layers of the esophageal wall from 1983 to 1996 were examined. Sixty-six patients underwent three-field lymphadenectomy (3F) and 86 underwent two-field lymphadenectomy (2F). Survival curves were compared between 3F and 2F after stratifications according to depth of tumor infiltration, the number of positive nodes (0, 1 to 4, 5 or more), and positive intrathoracic recurrent nerve-chain nodes. RESULTS: Overall 5-year survival rate for 3F was 43.8%, while it was 30.2% for 2F (p = 0.07). In 41 patients with pT1 cancers, the 5-year survival rate for 3F was 55.7%, while it was 41.4% for 2F (p = NS). In patients with cancers invading to muscularis propria (pT2), the 5-year survival rate for 3F was 49.4%, while it was 30.7% for 2F (p = 0.06). In patients with tumors invading to adventitia, there was no significant difference. In patients with one to four positive nodes, the 5-year survival rates for 3F was 50.1%, while it was 24.1% for 2F (p = 0.01). There was no significant difference in the subgroups with no positive nodes and five or more. In subgroups with positive recurrent nerve-chain nodes, the 5-year survival rate for 3F was 27.9%, while it was 0% for 2F (p = 0.01). CONCLUSIONS: Significance of three-field lymphadenectomy was found in patients with one to four positive nodes or positive intrathoracic recurrent nerve-chain nodes.

Adenocarcinoma↗

Effects of various 5-HT3 receptor antagonists, granisetron, ondansetron, ramosetron and azasetron on serotonin (5-HT) release from the ferret isolated ileum.

The object of this study was to evaluate the involvement of 5-HT3 receptors in the regulation of 5-HT release from the small intestine using ferrets, an animal model of emesis. 2-Methyl-5-HT, a 5-HT3 receptor agonist, produced a concentration-dependent increase of 5-HT from the ferret ileum. This increase in 5-HT release was significantly inhibited by granisetron (10(-7) and 10(-6) M) or azasetron (10(-7) and 10(-6) M) in a concentration-dependent manner. Ondansetron (10(-7) M) and ramosetron (10(-6) M) also significantly inhibited the 2-methyl-5-HT-induced increase in 5-HT release. When the concentration of ondansetron was increased from 10(-7) M to 10(-6) M, inhibition of 5-HT release was reduced. Ramosetron, for which 5-HT3 receptor binding of the rat brain is remarkably stronger than for any other 5-HT3 receptor antagonists, inhibited the 5-HT release at only the highest concentration of 10(-6) M. Based on these observations that the mode of action on the 2-methyl-5-HT induced 5-HT release is different among 5-HT3 receptor antagonists, it is suggested that there is a possibility that the neuronal 5-HT3 receptors and the 5-HT3 receptors on the EC cells may represent two distinct subtypes.

Animals↗

Molecular cloning and characterization of a novel protein serine/threonine kinase highly expressed in mouse embryo.

By a PCR-based screen for cDNA clones of protein kinases, we have isolated a cDNA clone encoding a novel protein kinase (referred to as EDPK) of 305 amino acids. EDPK has a catalytic domain of 271 amino acids that contains all conserved subdomains characteristic of the protein kinase family. Only short sequences are present at the N- and C-terminal ends outside the catalytic domain. EDPK expressed in Escherichia coli and in mammalian cells phosphorylated serine and threonine, but not tyrosine, residues in an exogenous substrate. The amino acid sequence similarity between EDPK and known serine/threonine kinases was less than 35%. Thus, the newly isolated protein kinase EDPK is a novel member of the serine/threonine kinase family. Northern blot analysis showed that the EDPK mRNA was highly expressed in various stages of mouse embryo development. The expression of the mRNA was also found in a variety of mouse adult tissues. These results suggest that EDPK plays a crucial role in intracellular signaling not only during mouse development but also in adult tissues.

Amino Acid Sequence↗

Hepatocyte growth factor activator: a possible regulator of morphogenesis during fetal development of the rat gastrointestinal tract.

The role played by the hepatocyte growth factor activator (HGFA) during morphogenesis of the gastrointestinal tract was investigated in fetal rats between days 16 and 21 of gestation. By our recently established method using chelation and dissecting microscope, samples could be separated into epithelium and mesenchyme, essentially without cross-contamination. The expression of the gene for HGFA together with those for hepatocyte growth factor (HGF) and its receptor, c-met, was investigated in each tissue element by RT-PCR. In the fetal rat gastrointestinal tract, mRNA signals for the HGFA gene were observed only in epithelia expressing c-met mRNA. In contrast, expression of HGF mRNA was limited to the mesenchymal elements, indicating the presence of a local HGF system in the gastrointestinal tract; an inactive form of HGF (proHGF) is secreted from the mesenchyme and then cleaved into the active form by HGFA secreted by the target epithelia. During the period of morphogenesis and histodifferentiation in the gastrointestinal tract, enhanced expression of the genes for HGF and its receptor/c-met was evident, with elevated HGFA mRNA level observed throughout the gastrointestinal tract except in the forestomach, where mRNA expression was barely detectable. These results strongly suggest the possibility that morphogenesis of the gastrointestinal tract is regulated not only by a local increase in production of HGF, but also by enhanced proteolytic activation of proHGF. Thus, it is probable that locally synthesized HGFA plays a significant role as a regulator of the morphogenic action of HGF during gastrointestinal tract development.

Animals↗

Structural organization and chromosomal localization of the human hepatocyte growth factor activator gene--phylogenetic and functional relationship with blood coagulation factor XII, urokinase, and tissue-type plasminogen activator.

The organization and structure of the gene coding for hepatocyte growth factor activator (HGFA) have been determined by isolation of unique clones from a human genomic library. These clones were characterized by restriction mapping, Southern blotting and DNA sequencing. The complete sequence of the gene was determined and found to span about 7.5 kilobases of DNA and consist of 14 exons separated by 13 introns. The coding region of HGFA consists of multiple putative domains that are homologous to those observed in blood coagulation factor XII (FXII). These regions were found as separate exons in the gene, and the exon/intron arrangement was similar to that of FXII, suggesting that the genes for HGFA and FXII have arisen through gene duplication events from a common ancestral gene. The major transcription initiation site is located 75 bp upstream of the translational start codon. The gene was mapped to chromosome 4p16, using spot-blot hybridization on sorted chromosomes and fluorescence in situ hybridization on metaphase chromosome spreads. The phylogenetic and functional relationships between HGFA and FXII as well as urokinase and tissue-type plasminogen activator are discussed.

Base Sequence↗

Inhibition of post-ischemic reperfusion injury of the kidney by diamine oxidase.

To elucidate the role of histamine in the pathogenesis of post-ischemic reperfusion injury of tissues, the effect of diamine oxidase (DAO) was studied on the changes in renal functions induced by 30 min occlusion followed by reperfusion of the renal vessels of unilaterally nephrectomized rats. Kinetic analysis using radiolabeled albumin revealed that vascular permeability of the kidney increased markedly after reperfusion. Although the intensity of neutrophil-dependent chemiluminescence of the blood remained unchanged during the occlusion, it increased significantly after reperfusion. Histological examination revealed a marked degeneration of glomeruli and proximal tubules in the reperfused kidney. Transtubular transport of phenolsulfophthalein (PSP) decreased markedly after reperfusion with concomitant increase in plasma levels of creatinine. Intravenously administered DAO markedly inhibited the reperfusion-induced increase in vascular permeability, preserved the structure of the kidney and normalized the rate of clearance of PSP and creatinine. Combined use of diphenylhydramine and ranitidine also inhibited the reperfusion injury of the kidney. These results suggested that histamine and its receptors might play critical roles in post-ischemic reperfusion injury of the kidney.

Amine Oxidase (Copper-Containing)↗