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Biomedical subjects

N Kitamura

Publications and source records attributed to N Kitamura.

At least 235 records · Page 13Linked to original sources

[Pit fall of aprotinin administration during open heart surgery].

Aprotinin administration during open heart surgery has been attempted at various institutions to reduce hemorrhage and improve the rate of no-transfusion operations, and has been reported to be effective. The treatment has been effective also in the 45 patients operated on at our institution. However, we experienced LOS at weaning from extracorporeal circulation (8 cases) considered to be due to aprotinin administration, suggesting unexpected risk of the treatment. Evaluation was made by classifying the patients according to the aprotinin dose; A high-dose group administered aprotinin at 300 x 10(4) units (20 patients), a low-dose group administered aprotinin at 100 x 10(4) units (8 patients), and a control group not administered aprotinin (15 patients). The volume of postoperative hemorrhage increased with the dose of aprotinin, and was significantly lower in the high dose and medium-dose groups than in the control group, but was not significantly different in the low-dose group. The postoperative peak CPK and CPK-MB were not significantly differ but increased slightly with the aprotinin dose. Probably for this reason, IABP was needed in 8 (17.8%) of the 45 patients because of LOS at weaning from extracorporeal circuration. A diagnosis of perioperative myocardial infarction (PMI) was made in 7 of these patients. Factors other than aprotinin are unlikely to be the cause of LOS, and the condition is considered to have been induced by micro-embolism during extracorporeal circulation with aprotinin administration. We propose two points as basis for this speculation. The first is that the body temperature during extracorporeal circuration, which was 30-35 degrees C in the bladder, promoted antifibrinolytic activity of aprotinin. The second is poor control of ACT during extra corporeal circulation. Thus, we suggest the risk of the use of aprotinin without further reduction in the body temperature during extracorporeal circuration. At present avoidance of high body temperatures and strict control of ACT during extracorporeal circulation are important preventive measures against micro-embolism possibly caused by aprotinin.

Aprotinin↗

[Susceptibilities of bacteria isolated from patients with respiratory infectious diseases to antibiotics (1992)].

Bacteria isolated from lower respiratory tract infections were collected in cooperation with institutions located throughout Japan since 1981, and Ikemoto et al. have been investigating susceptibilities of the isolates to various antibacterial agents and antibiotics, and the relationships between the isolates and characteristics of the patients and so forth each year. We discuss the results in detail. In 20 institutions around the entire Japan from October 1992 to September 1993, 690 strains of bacteria were isolated mainly from sputa of 549 patients with lower respiratory tract infections and presumed to be the etiological bacteria. MICs of various antibacterial agents and antibiotics were determined against 101 strains of Staphylococcus aureus, 121 strains of Streptococcus pneumoniae, 122 strains of Haemophilus influenzae, 92 strains of Pseudomonas aeruginosa (non-mucoid), 32 strains of Pseudomonas aeruginosa (mucoid), 52 strains of Moraxella subgenus Branhamella catarrhalis, 28 strains of Klebsiella pneumoniae etc., and the drug susceptibilities of these strains were measured except the strains which died during transportation. 1. S. aureus S. aureus strains for which MICs of methicillin were higher than 4 micrograms/ml (methicillin-resistant S. aureus) accounted for 61.4% and the frequency of the drug resistant bacteria was higher than the previous year's 58.3%. MICs values indicated that arbekacin was as active as vancomycin against all the strains on S. aureus. 2. S. pneumoniae Benzylpenicillin among the penicillins showed potent activities against S. pneumoniae. Cefuzonam, cefazolin, cefotaxime and cefmenoxime among the cephems showed excellent antimicrobial activities against S. pneumoniae. Imipenem; carbapenems, showed the most potent activity, and MIC80 was 0.015 microgram/ml. 3. H. influenzae All the drugs tested were potent against H. influenzae. Ampicillin among the penicillins showed MIC80 1 microgram/ml against H. influenzae. Cefotaxime, cefmenoxime, cefuzonam and cefixime showed the most potent activities, and MIC80s were 0.063 microgram/ml. The antimicrobial activity of ofloxacin was equivalent to those of cephems. 4. P. aeruginosa (mucoid) Ciprofloxacin showed the most potent activity against P. aeruginosa (mucoid), and MIC80 was 1 microgram/ml. Cefsulodin, aztreonam, carumonam and tobramycin showed the next most potent activities with an MIC80s of 2 micrograms/ml. 5. P. aeruginosa (non-mucoid) Tobramycin and ciprofloxacin showed the highest activities against P. aeruginosa (non-mucoid) with an MIC80s of 2 micrograms/ml. Norfloxacin also showed some activity, and MIC80 was 4 micrograms/ml. Comparing to activities against P. aeruginosa (mucoid), all the drugs tested showed lower activities against P. aeruginosa (non-mucoid). 6. K. pneumoniae The activities of all drugs except penicillins were high activities against K. pneumoniae. Carumonam showed the most potent activity with an MIC80 of 0.063 microgram/ml, followed by flomoxef, cefixime and cefozopran with their MIC80s of 0.125 microgram/ml. 7. M.(B.) catarrhalis Imipenem; carbapenems, showed the most potent activity against M.(B.) catarrhalis with an MIC80 0.063 microgram/ml. Minocycline and ofloxacin showed MIC80s 0.125 microgram/ml, respectively. We also investigated year to year changes in the background of patients, as well as types of respiratory infectious diseases, and the etiological bacteria. As for patients backgrounds, there were many infectious diseases found among patients in a high age bracket, and the patients over age 60 accounted for 60.8% of the diseases. The distribution by lower respiratory tract infections was as follows: bacterial pneumonia and chronic bronchitis accounted for the greatest numbers of cases with 30.4%, 29.5%, respectively, followed by bronchiectasis with 12.2%. As for frequencies of etiologic bacteria for respiratory tract infections, H. influenzae: 22.2%, and S. pneumoniae: 15.1% in chronic bronchitis; S. pneumoniae: 2

Anti-Bacterial Agents↗

[A case report of an infundibular ventricular septal defect with severe right ventricular outflow tract obstruction due to aneurysm of the aortic sinus of valsalva].

This paper describes the case of a 46-year-old female. Upon contacting infective endocarditis at the age of 39 years, she was diagnosed with a ventricular septal defect (VSD). Because dyspnea gradually worsened, she was later hospitalized. Cardiac catheterization was performed and angiograms were taken, revealing an infundibular VSD accompanied by severe right ventricular outflow tract obstruction (RVOTO) due to aneurysm of aortic sinus of valsalva and to mild aortic regurgitation caused by prolapsing aortic valve. The operative procedure consisted of the closure of the aortic sinus fistula by continuous suture after excision of the aneurysmal sac and patch closure of the VSD without treatment of the prolapsing aortic valve. After the operation, RVOTO improved and aortic regurgitation disappeared. The patient was discharged and has since been well.

Aortic Aneurysm↗

Hepatocyte growth factor remains as an inactive single chain after partial hepatectomy or unilateral nephrectomy.

Hepatocyte growth factor (HGF) is a potent mitogen for hepatocytes and renal tubular epithelial cells. HGF is proteolytically activated in the tissue injured by hepatotoxin or nephrotoxin, suggesting that HGF functions as a crucial growth factor for tissue regeneration following hepatotoxin- or nephrotoxin-induced injury. In this study, we analyzed the molecular form of HGF after partial hepatectomy or after unilateral nephrectomy. The active form of HGF was not detected under our experimental conditions after these operations. Thus, HGF may play little role in liver regeneration after partial hepatectomy and in compensatory renal enlargement after unilateral nephrectomy.

Animals↗

Activation of hepatocyte growth factor by two homologous proteases, blood-coagulation factor XIIa and hepatocyte growth factor activator.

Hepatocyte growth factor (HGF) is secreted as an inactive single-chain precursor from the producing cells, and normally remains in this form associated with the extracellular matrix. In response to tissue injury, the single-chain precursor is converted to a biologically active heterodimer by a serine protease, the activity of which is induced in the injured tissue. We have previously identified HGF activator, a serum serine protease that activates single-chain HGF. The sequence of HGF activator cDNA revealed that the HGF activator is homologous to blood-coagulation factor XIIa. In this study, we found that coagulation factor XIIa has an ability to activate single-chain HGF. Factor XIIa exhibited a significant level of HGF-converting activity in the presence of dextran sulfate, although the specific activity of factor XIIa was slightly lower than that of the HGF activator. Since factor XIIa is activated during the initiation of contact activation induced by tissue injury, factor XIIa may function as an HGF-converting enzyme together with HGF activator in the injured tissue. C1-inhibitor, antithrombin III and alpha 2-antiplasmin, that regulate the blood-clotting activity of factor XIIa, were also effective against the HGF-converting activity of factor XIIa. Furthermore, factor XIIa was not active in the HGF-converting activity in serum. Thus, the HGF-converting activity of factor XIIa may be regulated by these serum inhibitors.

Factor XIIa↗

Placental defect and embryonic lethality in mice lacking hepatocyte growth factor/scatter factor.

Hepatocyte growth factor/scatter factor (HGF/SF) functions as a mitogen, motogen and morphogen for a variety of cultured cells. The genes for HGF/SF and its receptor (the c-met proto-oncogene product) are expressed in many tissues during the embryonic periods and in the adult. HGF/SF is thought to mediate a signal exchange between the mesenchyme and epithelia during mouse development. To examine the physiological role of HGF/SF, we generated mutant mice with a targeted disruption of the HGF/SF gene. Here we report that homozygous mutant embryos have severely impaired placentas with markedly reduced numbers of labyrinthine trophoblast cells, and die before birth. The growth of trophoblast cells was stimulated by HGF/SF in vitro, and the HGF/SF activity was released by allantois in primary culture of normal but not mutant embryos. These findings suggest that HGF/SF is an essential mediator of allantoic mesenchyme-trophoblastic epithelia interaction required for placental organogenesis.

Allantois↗

Abdominal tuberculoma mimicking a pancreatic neoplasm: report of a case.

We report herein a case of clinically solitary abdominal tuberculoma. A 28-year-old woman was admitted to hospital for treatment of an abdominal tumor shown to be located in the head of the pancreas and compressing the superior mesenteric vein by echosonography and computed tomography (CT). There were no clinical signs or symptoms of tuberculosis in the lungs or abdomen. Thus, under the diagnosis of a neoplasm of the pancreas, an exploratory laparotomy was performed which revealed tuberculosis. The patient made an excellent recovery on anti-tuberculous treatment, and no evidence of a tumor was seen on a CT scan performed 6 months after the initiation of treatment. Abdominal tuberculoma is often mistaken for a malignant neoplasm and the nonsurgical diagnosis of this entity continues to be a challenge.

Abdomen↗

Purification of human blood eosinophils by a combination method using anti-CD16 monoclonal antibody, immunobeads, and Nycodenz density gradient.

A simple method is described for the procurement of human blood eosinophil phenotypes by combining an anti-CD16 monoclonal antibody, immunobeads, and a non-toxic and non-ionic density gradient medium, Nycodenz. The purification depends on the removal of mononuclear cells using a 1.076/1.102 g/ml Nycodenz density gradient, partial removal of neutrophils based on different binding to plastic dishes, interaction of residual neutrophils with immunobeads via an anti-CD16 monoclonal antibody and, finally, extraction of eosinophil phenotypes by sifting the immunobeads-loaded neutrophils through an 1.080/1.102 g/ml Nycodenz density gradient. This method permits simultaneous preparation of highly purified normodense (> 1.080 g/ml) and hypodense eosinophils (< 1.080 g/ml) with reasonable chemiluminescence responses to opsonized zymosans and helminthotoxic activity to opsonized schistosomula corresponding to their own immunocytological properties.

Animals↗

Association of p120, a tyrosine kinase substrate, with E-cadherin/catenin complexes.

p120 was originally identified as a substrate of pp60src and several receptor tyrosine kinases, but its function is not known. Recent studies revealed that this protein shows homology to a group of proteins, beta-catenin/Armadillo and plakoglobin (gamma-catenin), which are associated with the cell adhesion molecules cadherins. In this study, we examined whether p120 is associated with E-cadherin using the human carcinoma cell line HT29, as well as other cell lines, which express both of these proteins. When proteins that copurified with E-cadherin were analyzed, not only alpha-catenin, beta-catenin, and plakoglobin but also p120 were detected. Conversely, immunoprecipitates of p120 contained E-cadherin and all the catenins, although a large subpopulation of p120 was not associated with E-cadherin. Analysis of these immunoprecipitates suggests that 20% or less of the extractable E-cadherin is associated with p120. When p120 immunoprecipitation was performed with cell lysates depleted of E-cadherin, beta-catenin was no longer coprecipitated, and the amount of plakoglobin copurified was greatly reduced. This finding suggests that there are various forms of p120 complexes, including p120/E-cadherin/beta-catenin and p120/E-cadherin/plakoglobin complexes; this association profile contrasts with the mutually exclusive association of beta-catenin and plakoglobin with cadherins. When the COOH-terminal catenin binding site was truncated from E-cadherin, not only beta-catenin but also p120 did not coprecipitate with this mutated E-cadherin. Immunocytological studies showed that p120 colocalized with E-cadherin at cell-cell contact sites, even after non-ionic detergent extraction. Treatment of cells with hepatocyte growth factor/scatter factor altered the level of tyrosine phosphorylation of p120 as well as of beta-catenin and plakoglobin. These results suggest that p120 associates with E-cadherin at its COOH-terminal region, but the mechanism for this association differs from that for the association of beta-catenin and plakoglobin with E-cadherin, and thus, that p120, whose function could be modulated by growth factors, may play a unique role in regulation of the cadherin-catenin adhesion system.

Binding Sites↗

Interaction of the cell-binding domain of fibronectin with VLA-5 integrin induces monokine production in cultured human monocytes.

The effect of fibronectin on IL-1 alpha, IL-1 beta, tumour necrosis factor-alpha (TNF-alpha), and IL-6 production was investigated with cultured monocytes isolated from human peripheral blood. Monokine concentrations were determined by both ELISA and bioassay. Fibronectin markedly stimulated the secretion of IL-1 alpha, IL-1 beta, TNF-alpha and IL-6 from cultured monocytes in a dose-dependent manner, with the maximal effect apparent within 24 h. Northern blot analysis revealed a marked increase in the abundance of mRNA specific for each monokine on exposure of monocytes to fibronectin. Monoclonal antibodies to the alpha chain of very late antigen (VLA)-5, the beta 1 integrin, the alpha chain of Mac-1, and the beta 2 integrin, as well as the synthetic peptide of GRGDSP (which corresponds to the cell-binding domain of fibronectin), inhibited (> 50%) fibronectin-induced monokine production. Monoclonal antibodies to the alpha chain of VLA-4, and the alpha chain of LFA-1, as well as the synthetic peptide CS-1 (which corresponds to the alternatively spliced connecting segment of fibronectin) and the control peptide GRADSP, had no inhibitory effect on monokine production. A MoAb, R60, that recognizes an epitope of the fibronectin molecule that includes the RGD sequence, inhibited monokine production, whereas the MoAb Y16, which recognizes another epitope of fibronectin not including RGD, did not. These results indicate that fibronectin-induced production of IL-1 alpha, IL-1 beta, TNF-alpha and IL-6 from cultured monocytes is mediated predominantly by interaction of the cell-binding domain of fibronectin with VLA-5, although Mac-1 also may contribute to this effect of fibronectin. Our results indicate that the interaction of fibronectin with integrins may contribute to the cytokine network in inflammatory response.

Binding Sites↗

Growth factor-induced tyrosine phosphorylation of Hrs, a novel 115-kilodalton protein with a structurally conserved putative zinc finger domain.

The activation of growth factor receptor tyrosine kinases leads to tyrosine phosphorylation of many intracellular proteins which are thought to play crucial roles in growth factor signaling pathways. We previously showed that tyrosine phosphorylation of a 115-kDa protein is rapidly induced in cells treated with hepatocyte growth factor. To clarify the structure and possible function of the 115-kDa protein (designated Hrs for hepatocyte growth factor-regulated tyrosine kinase substrate), we purified this protein from B16-F1 mouse melanoma cells by anti-phosphotyrosine immunoaffinity chromatography and determined its partial amino acid sequences. On the basis of the amino acid sequences, we molecularly cloned the cDNA for mouse Hrs. The nucleotide sequence of the cDNA revealed that Hrs is a novel 775-amino-acid protein with a putative zinc finger domain that is structurally conserved in several other proteins. This protein also contained a proline-rich region and a proline- and glutamine-rich region. The expression of Hrs mRNA was detected in all adult mouse tissues tested and also in embryos. To analyze the Hrs cDNA product, we prepared a polyclonal antibody against bacterially expressed Hrs. Using this antibody, we showed by subcellular fractionation that Hrs is localized to the cytoplasm; we also showed that that tyrosine phosphorylation of Hrs is induced in cells treated with epidermal growth factor or platelet-derived growth factor. These results suggest that Hrs plays a unique and important role in the signaling pathway of growth factors.

Amino Acid Sequence↗

Urinary trehalase activity is a useful marker of renal proximal tubular damage in newborn infants.

To clarify the reliability of urinary trehalase activity as a marker of cellular proliferation and/or damage of renal proximal tubules, the activity was examined in healthy newborn infants or infants treated with tobramycin, a drug known as causing tubular cell damage. Eighty-one newborn infants (56 mature infants and 25 premature infants) were enrolled in the study. Urinary trehalase was examined using a spot urine sample during the first 7 days of age and on the 10th day of age. A good positive correlation was observed between urinary trehalase activity/creatinine ratio (T/Cr) on the 10th day of age and conceptional age or body weight (n = 46, r = 0.58, p < 0.001). Urinary trehalase of 29 healthy mature infants was higher during the first few days of age, after which it decreased to an almost steady level. Urinary trehalase of 6 premature infants during the first few days of age was significantly lower than that of mature infants, after which it increased and became equal to that of the mature infants on the 7th day of age. Treatment with ampicillin (100 mg/kg) and tobramycin (5 mg/kg) of 6 mature infants with pneumonia for 6 days resulted in a significant elevation of the urinary T/Cr. The extent of this elevation was greater than that of the urinary N-acetyl-beta-D-glucosaminidase (NAG) activity/creatinine ratio (NAG/Cr). A significant correlation was observed between the urinary T/Cr and the urinary NAG/Cr (r = 0.67, p < 0.01) or gamma-glutamyl transpeptidase/creatinine ratio (r = 0.48, p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Spontaneous diabetes mellitus associated with persistent bovine viral diarrhea (BVD) virus infection in young cattle.

Histologic and immunohistochemical studies were carried out on four young cattle with diabetes mellitus associated with persistent bovine viral diarrhea (BVD) virus infection. Clinical findings included persistent hyperglycemia, decreased glucose tolerance, glycosuria, polydipsia, and severe emaciation. Macroscopically, multiple erosions and ulcers in the mucosa of upper and lower alimentary tracts and swollen lymph nodes were commonly observed. Erosions and ulcers in the mucosa of tongue, esophagus, and forestomach were represented histologically by necrosis of squamous epithelium with neutrophilic infiltration. In the small and large intestines, villous atrophy and suppurative cryptitis were often observed, along with diffuse infiltration of lymphocytes and macrophages and fibroplasia in the lamina propria. In the pancreas of all cattle, there was a reduction in the number of islet cells, and most of the residual islet cells had hydropic degeneration and a decreased number of secretory granules. Immunohistochemical examination confirmed that these cells were severely degranulated beta-cells. In addition, many islets containing necrotic islet cells were observed. These islet cells had increased eosinophilia and shrinkage of cytoplasm, as well as pyknotic nuclei. Inflammation of the islets with mild infiltration of lymphocytes was observed in all pancreatic lobes. In addition, bovine IgG-immunoreactive cells were identified immunohistochemically in the affected pancreatic islets. The BVD virus antigen was not identified in the cytoplasm of the islet cells by immunohistochemical study, although it was identified in the epithelial cells of the small intestine. The histologic and immunohistochemical studies demonstrated that the pancreatic lesions in these animals were similar to those caused by acute insulin-dependent diabetes mellitus (IDDM) in human beings.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Young female patient with testosterone-producing adrenocortical adenoma also showing signs of subclinical Cushing's syndrome.

A 28-year old female patient with virilization due to left adrenocortical adenoma was studied. The patient had clinical features of hyperandrogenism such as hirsutism and a low pitched voice, but not of hypercorticoidism. Plasma testosterone and dehydroepiandrosterone-sulfate (DHEA-S) were high. Although the basal plasma cortisol concentration and urinary excretion of 17-hydroxycorticosteroids (17-OHCS) were within the normal range, the absence of diurnal variation in plasma cortisol and loss of suppressibility by dexamethasone suggested constitutive secretion of cortisol by the tumor. Inappropriate cortisol secretion was also supported by blunted ACTH response to provocative stimuli. After successful removal of the left adrenal tumor, such endocrinological abnormalities were all normalized. Immunohistochemical analysis revealed that tumor cells were positively stained for C21 hydroxylase cytochrome P-450 (P-450C21) and P-450(11) beta which convert 17-hydroxy (OH) progesterone to cortisol as well as P-450SCC, 3 beta-hydroxysteroid dehydrogenase and P-450(17) alpha which are involved in testosterone biosynthesis. These findings suggest that adrenocortical adenoma secretes predominantly testosterone and constitutively cortisol in a young woman patient with virilization.

17-Hydroxycorticosteroids↗

[Cultured human monocytes activated by cytokines or lipopolysaccharide induce fibronectin].

We studied the effects of cytokines such as IL-1 alpha, IL-6 and TNF alpha, and lipopolysaccharide (LPS) on cultured human monocytes. Increased fibronectin (FN) production, as a indicator of the activation of monocytes, was observed with any cytokines or LPS stimulation those were added in the culture medium. These increased FN production by cytokines showed a dose dependent fashion, and 4 hours culture with these cytokines was enough to obtain the amount of FN measured with radioimmunoassay. The combination of sub-optimal dose of cytokines (IL-1 alpha + IL-6, IL-1 alpha, IL-6 + TNF alpha), that could not induce substantial amount of FN with any single cytokine, also could induce FN by cultured monocytes. The specificity of cytokines for the FN production by cultured monocytes was confirmed by the neutralization using monoclonal antibodies specific for each monokines. Northern blot analysis with cDNA specific for FN confirmed the expression of FN mRNA in cultured monocytes stimulated with cytokines or LPS. Cytokine network plays an essential role for immune and inflammatory reaction, and FN has been shown to induce monokines through VLA-5 receptor on cultured monocytes. Our data suggests that monocytes may not always require high concentration of cytokines for the activation of monocytes in vitro, and that the synergistic action of low concentration of cytokines for the activation was enough for the progression of immune or inflammatory reaction.

Cells, Cultured↗