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Biomedical subjects

N Kitamura

Publications and source records attributed to N Kitamura.

At least 127 records · Page 7Linked to original sources
PubMed2000

Effects of recombinant tissue-type plasminogen activator on life-threatening acute pulmonary thromboembolism in a canine model: a comparative study of e6010 and alteplase.

We compared the effects a novel recombinant tissue-type plasminogen activator (rt-PA) E6010 with the more conventional therapeutic agent alteplase in a new canine model of life-threatening acute pulmonary thromboembolism (APTE). Fifty milliliters of autologous blood was obtained from anesthetized, adult mongrel dogs and mixed with 10,000 units of thrombin. The left pulmonary artery, pulmonary vein, and bronchus were ligated, and previously prepared blood clots were injected via the femoral vein until the mean pulmonary artery pressure (mPA) increased to 2.5-3.0 times over baseline mPA (control). E6010 (0.4 mg/kg) or alteplase (1.33 mg/kg) was administered to other animals following inducement of APTE. In control animals, 60 min after embolization, mPA increased from 13+/-3 mm Hg to 31+/-3 mm Hg (p < 0.0001), cardiac output (CO) decreased from 1.47+/-0.35 l/min to 1.15+/-0.39 l/min (p < 0.0001), and PaO2 decreased from 101+/-31 mm Hg to 65+/-20 mm Hg (p < 0.001). E6010 significantly reduced mPA from 31+/-3 mm Hg to 25+/-4 mm Hg (p < 0.0001) 30 min after administration. In the alteplase group, however, mPA did not significantly change. At 180 min following drug administration, further reduction of mPA was significantly observed in both treatments. CO and PaO2 did not improve after either treatment. The present study indicated that E6010 more rapidly reduced pulmonary hypertension in our APTE model. Because of its rapid action, E6010 might be a promising thrombolytic agent for treatment of APTE.

Acute Disease↗
PubMed1999

Opposite changes in phosphoinositide-specific phospholipase C immunoreactivity in the left prefrontal and superior temporal cortex of patients with chronic schizophrenia.

BACKGROUND: Abnormalities in types of neurotransmitter signaling that are coupled with phosphoinositide-specific phospholipase C (PLC) have previously been reported in brains from patients with schizophrenia. PLC, a main component of this pathway, may be affected in schizophrenia. METHODS: We immunoquantified PLC beta 1, gamma 1 and delta 1 in the left prefrontal cortex and superior temporal cortex, nucleus accumbens and amygdala, and in the right superior temporal cortex of postmortem brains obtained from a total of 19 patients with schizophrenia and a total of 27 controls. RESULTS: PLC beta 1 immunoreactivities were increased in the particulate fraction from the prefrontal cortex (by 64%), although they were decreased in the particulate fraction from the left superior temporal cortex (by 28%), as compared with the values in controls. There was no difference in PLC beta 1 immunoreactivities in the nucleus accumbens, the amygdala or the right superior temporal cortex between schizophrenic patients and controls. PLC gamma 1 and delta 1 immunoreactivities did not differ between the two groups in any of the regions studied. CONCLUSIONS: Changes in PLC beta 1 immunoreactivities in the prefrontal and superior temporal cortex of patients with schizophrenia may reflect abnormalities in neurotransmissions via receptors that are coupled with the Gq alpha-PLC beta 1 cascade.

Amygdala↗
PubMed1999

A human homolog of Drosophila warts tumor suppressor, h-warts, localized to mitotic apparatus and specifically phosphorylated during mitosis.

We identified a human homolog of Drosophila warts tumor suppressor gene, termed h-warts, which was mapped at chromosome 6q24-25.1. The h-warts protein has a serine/threonine kinase domain and is localized to centrosomes in interphase cells. However, it becomes localized to the mitotic apparatus, including spindle pole bodies, mitotic spindle, and midbody, in a highly dynamic manner during mitosis. Furthermore, h-warts is specifically phosphorylated in cells at mitotic phase, most likely by Cdc2 kinase. These findings suggest that h-warts functions as a component of the mitotic apparatus and is involved in proper progression of mitosis.

Amino Acid Sequence↗
PubMed1999

Association study of a polymorphism of nonerythroid alpha-spectrin gene with schizophrenia.

The specificity of cytoarchitectural abnormalities in limbic structures of patients with schizophrenia and their contributions towards the etiology of schizophrenia remain unknown. We have recently reported an increased breakdown of nonerythroid alpha-spectrin (fodrin), a major component of neuronal cytoskeletal proteins, in schizophrenic left superior temporal cortices [Kitamura et al., 1998: Biol Psychiatry 43:254-262], suggesting that polymorphisms of the alpha-spectrin gene might contribute to the vulnerability to schizophrenia. We screened for genetic variations associated with schizophrenia through the C-terminus sequences of the human nonerythroid alpha-spectrin gene (SPTAN1) spanning two EF-hands and also tested a possible contribution of the polymorphism to the development of schizophrenia by an association study. We found a polymorphic region of an intron located in the second EF-hand of SPTAN1 gene. There was no significant difference between patients with schizophrenia and controls in allele frequencies or genotype distribution. There is evidence that the Psh BI SPTAN1 gene polymorphism does not play a major role in the genetic component of schizophrenia.

Adult↗
PubMed1999

Hepatocyte growth factor activator inhibitor type 2 lacking the first Kunitz-type serine proteinase inhibitor domain is a predominant product in mouse but not in human.

Hepatocyte growth factor activator inhibitor type 2 (HAI-2) is a new Kunitz-type serine protease inhibitor, which is purified and cloned from human stomach cancer cell line MKN45. The mature HAI-2 protein contains two Kunitz domains and the first domain is mainly responsible for the inhibitory activity against hepatocyte growth factor activator (HGFA). In this study, we identified the mouse homolog of HAI-2 (mHAI-2) by screening the data base of public expressed sequence tag (dbEST). In addition to a full-length cDNA corresponding to human HAI-2, a shorter size of mHAI-2 cDNA was obtained from mouse kidney by reverse-transcription polymerase chain reaction (RT-PCR). Sequence analysis of this shorter cDNA revealed that the region encoding the first Kunitz domain was completely deleted. Analysis of mouse genomic DNA showed that the deleted cDNA was generated by an alternative splicing mechanism. Surprisingly, the spliced form lacking the first Kunitz domain was a predominant transcript in all tissues of mice tested but not in those of human as assessed by RT-PCR analysis. This phenomenon is also confirmed by Western blot analysis using the specific antiserum against human HAI-2 protein. These results suggest that most of HAI-2 expressed in various tissues of mice may be unable to inhibit HGFA efficiently.

Alternative Splicing↗
PubMed1999

The effects of cardiopulmonary bypass on postoperative oxygen metabolism.

The relationships between oxygen delivery (DO2), oxygen consumption (VO2), and the extraction rate (ER = VO2/DO2 x 100) in patients undergoing cardiopulmonary bypass (CPB) may differ from the normal physiologic state due to the oxygen debt acquired during CPB. Blood gas analysis and hemodynamic parameters were repeatedly measured for the determination of DO2 and VO2 in 40 patients undergoing CPB, every 8 h during the first 48 h postoperatively. As a control, 20 patients who had suffered acute myocardial infarction (AMI) were also studied using the same protocol. In the CPB group, a regression analysis showed that VO2 was significantly dependent on DO2, even within the physiologic range of DO2 (>500 ml/min per m2); VO2 = 121.4 + 0.0844 x DO2 (r = 0.254, P = 0.023). Conversely, in the AMI group, no such supply-dependent consumption was observed within the same range of DO2. At an ER of 30%, which is the optimal value in general, the DO2 of the CPB group was 575 ml/min per m2 and that of the AMI group was 493 ml/min per m2. All these results suggest that patients undergoing CPB need a much higher oxygen supply to recover from the oxygen debt acquired during open heart surgery.

Aged↗
PubMed1999

Does neoadjuvant chemotherapy for carcinoma in the thoracic esophagus increase postoperative morbidity?

OBJECTIVES: The aims of this study were to examine whether neoadjuvant chemotherapy for a carcinoma in the thoracic esophagus increased the incidence of postoperative complications, and which clinicopathological factors may affect postoperative complications after esophagectomy. SUBJECTS AND METHODS: One hundred and forty-four patients who underwent neoadjuvant chemotherapy followed by esophagectomy for a carcinoma in the thoracic esophagus were reviewed in a retrospective study. Ninety-six patients received neoadjuvant chemotherapy and 48 did not. The postoperative complications were grouped either general complications (Complications A) or surgery-related complications (Complications B). Complications A consisted of pulmonary, cardiac, hepatic, renal, and neurological complications, and catheter sepsis. Complications B consisted of a gastrointestinal tract leak, gastrointestinal tract necrosis, an intrathoracic or intraabdominal abscess, hemorrhage, ileus, and vocal cord palsy. In these two categories of complications, 17 factors obtained from subjects were compared between patients with complications and those without by univariate and multivariate analyses. RESULTS: The patient characteristics did not differ between patients who received neoadjuvant chemotherapy and those without. The preoperative serum albumin level was higher in patients without complication than in those with complication in both two categories of complications (Complications A: p = 0.001, Complications B: p = 0.05). The proportion of patients who received neoadjuvant chemotherapy did not differ between patients with complication and those without complication in either category of complications. Multivariate analysis showed that preoperative Onodera's Prognostic Nutritional Index was the only factor reducing the incidence of complications A (p = 0.02, Odds ratio: 0.63). CONCLUSION: Neoadjuvant chemotherapy was well tolerated and was not associated with any increased morbidity or mortality after esophagectomy for a carcinoma in the thoracic esophagus.

Chemotherapy, Adjuvant↗
PubMed1999

Role of macrophage scavenger receptors in hepatic granuloma formation in mice.

In mice homozygous for the gene mutation for type I and type II macrophage scavenger receptors (MSR-A), MSR-A-/-, the formation of hepatic granulomas caused by a single intravenous injection of heat-killed Corynebacterium parvum was delayed significantly for 10 days after injection, compared with granuloma formation in wild-type (MSR-A+/+) mice. In the early stage of granuloma formation, numbers of macrophages and their precursor cells were significantly reduced in MSR-A-/- mice compared with MSR-A+/+ mice. In contrast to MSR-A+/+ mice, no expression of monocyte chemoattractant protein-1, tumor necrosis factor-alpha, and interferon-gamma mRNA was observed in MSR-A-/- mice by 3 days after injection. Also in MSR-A-/- mice, uptake of C. parvum by Kupffer cells and monocyte-derived macrophages in the early stage of granuloma formation was lower and elimination of C. parvum from the liver was slower than in MSR-A+/+ mice. In the livers of MSR-A+/+ mice, macrophages and sinusoidal endothelial cells possessed MSR-A, but this was not seen in the livers of MSR-A-/- mice. In both MSR-A-/- and MSR-A+/+ mice, expression of other scavenger receptors was demonstrated. These data suggest that MSR-A deficiency impairs the uptake and elimination of C. parvum by macrophages and delays hepatic granuloma formation, particularly in the early stage.

Animals↗
PubMed1999

Transient dysfunction of the freestyle stentless xenograft.

After replacement of a bicuspid aortic valve with a Freestyle stentless xenograft, right coronary leaflet dysfunction and an elevated pressure gradient developed. Attempts to match the right and left ostia of the prosthesis, which were located at an angle of less than 120 degrees, to the native right and left ostia, which were located at 180 degrees, may have resulted in the leaflet distension. This is a suggestive finding about its implantation technique.

Aortic Valve↗
PubMed1999

Indications for three-field dissection followed by esophagectomy for advanced carcinoma of the thoracic esophagus.

OBJECTIVE: The aim of this study was to evaluate the indication for 3-field lymphadenectomy (3-field dissection) followed by esophagectomy for locally advanced carcinoma of the thoracic esophagus in the presence of lymph node metastasis. METHODS: From January 1983 to December 1995, 86 patients with thoracic esophageal carcinoma invading muscularis propria or adventitia underwent radical subtotal esophagectomy after preoperative chemotherapy. Forty-six of the 86 patients underwent a 2-field dissection (mediastinal and abdominal nodes, group A), and 40 patients underwent a 3-field dissection (bilateral cervical, mediastinal, and abdominal nodes, group B). Survival curves were compared between the 2 groups after stratification according to the degree of lymph node involvement (number of positive nodes and involvement of intrathoracic or intrathoracic recurrent nerve chain nodes). Potential prognostic factors of these 86 patients were evaluated by means of Cox regression analysis. RESULTS: There were no significant differences in age, sex ratio, depth of tumor invasion, pTNM classification, or number of positive nodes between the 2 groups. Among patients with positive intrathoracic nodes, the 5-year survival of group B (42%) was significantly longer than that of group A (13%, generalized Wilcoxon test P =.02). Among patients with 1 to 4 positive nodes, the 5-year survival of group B (54%) was significantly higher than that of group A (22%, P =.01). Multivariate analysis revealed the number of positive nodes, age, and pT4 stage to be significant predictors of survival in patients with thoracic esophageal carcinoma. CONCLUSIONS: Three-field dissection for advanced carcinoma of the thoracic esophagus is effective in patients with 1 to 4 positive nodes.

Aged↗
PubMed1999

On-line measurement of adenosine triphosphate and catecholamine released from adrenal chromaffin cells.

Adenosine triphosphate (ATP) and catecholamine (CA) released from cultured porcine adrenal chromaffin cells were continuously measured with an ATP photometer (luciferin-luciferase method) and electrochemical detector, respectively. Application of acetylcholine (ACh, 0.1 mM) or high K+ (60 mM) caused increases of ATP and CA in perfused effluent with the same time course. The peak molar ratio of CA to ATP in the effluent was about 10 for ACh and high K+ stimulation. The high-performance liquid chromatographic (HPLC) analysis of adenine nucleotides in the collected effluent revealed that the relative amounts of ATP, ADP and AMP were almost the same throughout the period of stimulation, suggesting that ATP breakdown in the effluent was constant. Changes in the peak molar ratio of CA to ATP appearing in the effluent did not occur with repetitive high K+ or sustained Ba2+ stimulation (5 mM). The similarity between the time courses of ATP and CA appearing in the effluent suggests that releasable chromaffin granules have a constant molar ratio of CA to ATP. The on-line system developed is a simple and rapid method for examining ATP and CA secretion, simultaneously.

Acetylcholine↗
PubMed1999

An immunohistochemical survey of catecholamine-synthesizing enzyme-immunoreactive nerves and endocrine cells in the bovine pancreas.

The distribution of catecholamine-synthesizing enzyme-immunoreactive nerves and endocrine cells in the pancreas of the calf and cow was studied immunohistochemically using antisera against tyrosine hydroxylase (TH) and dopamine beta-hydroxylase (DBH). TH- and DBH-immunoreactive nerve fibres were abundant both within and around the islet of Langerhans. A few TH- and DBH-immunoreactive nerve fibres were seen around the large islets characteristic of calf pancreas, but the majority of cells in the large islets, and some in islets of Langerhans, showed TH immunoreactivity. In the exocrine pancreas, both TH- and DBH-immunoreactive nerve fibres were distributed randomly among the acini, with the DBH-immunoreactive fibres being more numerous. Abundant TH- and DBH-immunoreactive nerve fibres were seen in close association with blood vessels and in the connective tissue around the interlobular duct. Immunoreactivity for both enzymes was also observed in the nerve cell bodies and fibres of the intrapancreatic ganglia. The findings suggest an important role for catecholamines in the regulation of bovine pancreatic function.

Animals↗
PubMed1999

The prognostic significance of cell cycle markers in esophageal cancer after neoadjuvant chemotherapy.

Proliferating cell nuclear antigen (PCNA), p27 and cyclin A were analyzed by immunohistochemistry in 89 patients (untreated control n = 40, neoadjuvant chemotherapy n = 49) with esophageal cancer invading the submucosal lesion. The mitotic index (MI) was calculated as the percentage of mitotic cells. In control subjects, the mean PCNA, p27, cyclin A and MI were, respectively, 60.4%, 18.0%, 19.9% and 1.7%; in the chemotherapy group, these values were 46.8%, 15.1%, 18.0% and 1.2% respectively. Neoadjuvant chemotherapy decreased PCNA and the MI significantly. As prognostic indicators, PCNA and the MI were significant in control subjects and p27 and cyclin A were significant in the chemotherapy group. Using multivariate analysis, p27 was a prognostic factor in both groups and cyclin A was prognostic only in the chemotherapy group. Although PCNA and the MI were useful growth and prognostic markers in untreated control subjects, their significance was lost after neoadjuvant chemotherapy. p27 and cyclin A were determined to be significant markers in the neoadjuvant chemotherapy group, especially p27, which was independent in both groups.

Aged↗
PubMed1999

An immunohistochemical study of interstitial cells of Cajal (ICC) in the equine gastrointestinal tract.

The interstitial cells of Cajal (ICC) are c-kit immunoreactive cells of the gastrointestinal tract which are suggested to have a role in the control of intestinal motility. Cells with c-kit immunoreactivity have not been previously described in the gastrointestinal tract of the horse. Immunoreactivity for c-kit was revealed using immunohistochemical labelling with an anti-c-kit polyclonal antibody. Sections of normal gastrointestinal tissue were examined from 13 anatomically defined sites from stomach to small colon taken from horses free from gastrointestinal disease. Three types of c-kit immunoreactive cells were identified: spindle-shaped cells in the region of the myenteric plexus, stellate or bipolar cells in the circular muscle layer, and round cells in the submucosa. The round cells were shown to be mast cells with the use of toluidine blue staining, whereas the other c-kit immunoreactive cells did not exhibit metachromasia and were classified as ICC. This study will serve as a basis for future pathological studies in the horse.

Animals↗
PubMed1999

Multiple sites of proteolytic cleavage to release soluble forms of hepatocyte growth factor activator inhibitor type 1 from a transmembrane form.

Hepatocyte growth factor activator inhibitor type 1 (HAI-1) is a Kunitz-type serine protease inhibitor, which was identified as a potent inhibitor of hepatocyte growth factor (HGF) activator from the conditioned medium of a human carcinoma cell line. HGF activator is a blood coagulation factor XII-like serine protease that is responsible for proteolytic activation of the inactive single chain precursor of HGF in injured tissues. The predicted sequence of the primary translation product of HAI-1, which has a hydrophobic sequence in its COOH-terminal region, suggested that HAI-1 is first produced in a membrane-associated form. In this study, we identified a transmembrane form of HAI-1 integrated in the plasma membrane of cultured cells using a monoclonal antibody against HAI-1. We also identified several soluble forms of HAI-1 in the conditioned medium of the cells, indicating that multiple sites are present in the transmembrane form of HAI-1 at which proteolytic cleavage releases the extracellular domain. At least two proteases, one of which is a metalloprotease, appear to be responsible for the release. Further, the soluble forms of HAI-1 have different inhibitory activity against HGF activator. These findings suggest that proteolytic processing plays important roles in regulation of the inhibitory activity of HAI-1.

Base Sequence↗
PubMed1999

Evaluation of oxygen consumption and resting energy expenditure in critically ill patients with systemic inflammatory response syndrome.

OBJECTIVE: To determine whether oxygen consumption VO2), CO2 production, and resting energy expenditure (REE) in critically ill patients differ in varying grades of systemic inflammatory response syndrome (SIRS). DESIGN: Prospective, clinical study. SETTING: Intensive care unit at a university hospital. PATIENTS: Twenty-six critically ill patients requiring mechanical ventilation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 100 metabolic measurements were performed. The grade of SIRS and the Acute Physiology and Chronic Health Evaluation II score were evaluated at the time of the metabolic cart study. VO2 and REE differed among the groups inadequate for SIRS (non-SIRS), with SIRS without infection (nonseptic SIRS), and with SIRS with infection (septic SIRS) (125 +/- 37 mL/min/m2 and 855 +/- 204 kcal/day/m2, 135 +/- 33 mL/min/m2 and 948 +/- 214 kcal/day/m2, and 166 +/- 55 mL/min/m2 and 1149 +/- 339 kcal/day/m2, respectively; p < .005). Patients with septic SIRS had higher VO2 and REE than patients with non-SIRS and nonseptic SIRS. CONCLUSION: VO2 and REE differ among groups of patients with non-SIRS, nonseptic SIRS, and septic SIRS. Patients with septic SIRS have higher VO2 and REE than patients with non-SIRS or nonseptic SIRS. The present study shows that classifying patients into three grades (non-SIRS, nonseptic SIRS, and septic SIRS) is a valid predictor of metabolic stress in critically ill patients.

APACHE↗
PubMed1999

Adenovirus strains of subgenus D associated with nosocomial infection as new etiological agents of epidemic keratoconjunctivitis in Japan.

Adenovirus strains of a new type were isolated from patients with epidemic keratoconjunctivitis. They were not completely neutralized by any antiserum against adenovirus prototypes. PCR followed by restriction endonuclease analysis demonstrated that they were type 8. PCR followed by sequencing revealed a high homology rate between them and type 9.

Adenoviridae↗