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Biomedical subjects

M Kitamura

Publications and source records attributed to M Kitamura.

At least 253 records · Page 14Linked to original sources
PubMed1996

Diagnostic strategies of periodontitis based on the molecular mechanisms of periodontal tissue destruction.

OBJECTIVE: Periodontitis is a disease showing differences in disease progression between patients and between sites within a patient. Routine clinical examinations today are not useful enough to distinguish susceptible patients and active lesions from resistant patients and chronic lesions. Diagnostic markers should be pathogenic and inflammatory factors participating in periodontal tissue destruction. These are both local and systemic factors. MATERIALS AND METHODS: First of all, pathogenic factors and proinflammatory cytokines or mediators in gingival crevicular fluid (GCF) were examined and the difference was found between active and inactive periodontitis lesions distinguished by attachment loss. Active lesions were detected by discriminant-function analysis of these examinations, although the sensitivity of differential diagnosis was low. Then, we established a novel needle biopsy for understanding the pathophysiological conditions elicited in active and chronic inflammatory processes of periodontal tissue destruction. A variety of cytokines and mediators were detected in biopsied specimens by reversed transcription polymerase chain reactions (RT-PCR). Cytokine profiles were varied in inflammed periodontal biopsies. As IFN gamma mRNA expression was enhanced in inflamed gingiva, antigen-presenting-cell (APC) functions of human gingival fibroblasts (HGF) were examined. RESULTS: Despite the phenotypical resemblance of IFN gamma-treated HGF to so-called APC, HLA-DR positive HGF could not induce proliferation but suppressed proliferation of alloreactive peripheral blood T cells (PBT). However, HLA-DR positive HGF stimulated the proliferative responses of PBT which had been primed with allo-APC. Regulatory immune responses by IFN gamma were different in T cell conditions. CONCLUSIONS: Various kinds of cytokines participated in periodontal inflammation, and every cytokine is multi-functional. Complex and compound inflammatory processes can be clarified by examining cytokine networks and the precise effects of each cytokine on each of the cell types comprising periodontal tissue. It is, therefore, necessary for establishing diagnostic strategies to integrate pathogenic and inflammatory factors in periodontal tissue destruction.

Antibodies, Bacterial↗
PubMed1996

Dual regulation of IL-1 beta-mediated matrix metalloproteinase-9 expression in mesangial cells by NF-kappa B and AP-1.

Glomerular mesangial cells express matrix metalloproteinase-9 (MMP-9) in response to the proinflammatory cytokine interleukin-1 beta (IL-1 beta). To elucidate the signal transduction systems involved, we focused on the role of nuclear factor-kappa B (NF-kappa B) and activator protein-1 (AP-1), since the 5'-flanking region of MMP-9 gene contains binding sequences for these transacting molecules. In rat mesangial cells treated with an inhibitor of NF-kappa B, pyrrolidine dithiocarbamate, induction of MMP-9 by IL-1 beta was suppressed at both mRNA and protein levels. Mesangial cells stably transfected with a transdominant negative mutant of NF-kappa B also showed blunted induction of MMP-9. Transient transfection study with a kappa B reporter plasmid revealed that IL-1 beta indeed activated the kappa B site and that pyrrolidine dithiocarbamate abolished this activation. These results suggest that IL-1 beta induced MMP-9 via the stimulation of NF-kappa B pathway. to examine whether tyrosine kinase is involved in this pathway, mesangial cells were stimulated by IL-1 beta in the presence of a tyrosine kinase inhibitor genistein. This inhibitor dose dependently suppressed the expression of MMP-9, as well as the activation of the kappa B site by IL-1 beta, indicating the involvement of tyrosine kinase in the stimulation of NF-kappa B. Because mesangial cells stimulated by IL-1 beta transiently expressed c-fos and c-jun nRNAs prior to the expression of MMP-9, the role of these genes in mediating the IL-1 beta response was further examined. Transfection of mesangial cells with a c-jun antisense cDNA and treatment with a pharmacological inhibitor of c-Jun/ AP-1, curcumin, revealed that the induction of c-Jun/AP-1 is essential for the expression of MMP-9 by IL-1 beta. Although protein kinase C (PKC) is regarded as a potential inducer of AP-1, stimulation of mesangial cells with phorbol 12-myristate 13-acetate failed to induce MMP-9. Similarly, depletion of intracellular PKC did not obviously affect the induction of MMP-9 by IL-1 beta. These findings demonstrate that dual operation of tyrosine kinase-mediated NF-kappa B stimulation and c-Jun/AP-1 activation is essential to the induction of MMP-9 by IL-1 beta in cultured mesangial cells.

Animals↗
PubMed1996

Differentiated phenotype of glomerular mesangial cells in nodular culture.

Prolonged culture of glomerular mesangial cells forms nodular structures composed of cells and surrounding extracellular matrix (ECM), which may mimic the situation in the glomerular mesangium of the kidney. The aim of this study was to investigate whether nodule-associated cells (NAC) exhibit a different phenotype to nodule-unassociated cells (NUC) in vitro. As phenotypic markers for rat mesangial cells, we examined mitogenic activity, expression of alpha-smooth muscle actin, and production of ECM constituents. Autoradiographic and immunohistochemical analyses revealed that NAC showed far less mitogenesis that NUC, like mesangial cells in the normal glomerulus. Immunofluorescence study and Northern blot analysis showed that alpha-smooth muscle actin, a marker of mesangial cell activation/dedifferentiation, was strongly expressed in NUC but faint in NAC. When nodules were dissolved by trypsinization, the dispersed NAC regained both active mitogenesis and alpha-smooth muscle actin expression, suggesting that the altered phenotype was reversible. Northern blot analysis revealed that the ratio of type IV collagen versus type I collagen expression, a marker of mesangial cell differentiation, was elevated in NAC compared with NUC. This phenotypic shift toward differentiation was associated with upregulation of transforming growth factor-beta 1. These findings demonstrate that mesangial cells in nodules exhibit a phenotype which is distinct from that of cells in two-dimensional cultures. We hypothesize that, as a differentiated feature, cultured mesangial cells have the ability to create an appropriate three-dimensional cyto-architecture that resembles the glomerular mesangium.

Actins↗
PubMed1996

Antioxidant PDTC induces stromelysin expression in mesangial cells via a tyrosine kinase-AP-1 pathway.

We found that pyrrolidine dithiocarbamate (PDTC) induces the matrix metalloproteinase stromelysin in cultured glomerular mesangial cells. Although PDTC is a well-known inhibitor of nuclear factor-kappa B (NF-kappa B), this effect was independent of the NF-kappa B activity, since overexpression of a dominant negative mutant of p50 NF-kappa B subunit repressed activity of the kappa B site, whereas it failed to induce stromelysin. To elucidate the intracellular mechanisms involved, we focused on the role of activator protein 1 (AP-1), since its binding site, the 12-O-tetradecanoylphorbol 13-acetate (TPA) response element (TRE), is located in the 5'-flanking region of the stromelysin gene. Northern blot analysis revealed that PDTC upregulated expression of c-jun and c-fos before the expression of stromelysin. Transient transfection studies using a TRE-LacZ reporter plasmid elucidated that activity of AP-1 was significantly increased by PDTC. Stable transfection with a c-jun antisense cDNA or pretreatment with curcumin, a pharmacological inhibitor of c-Jun/AP-1, revealed that inactivation of AP-1 diminished the induction of stromelysin by PDTC. To identify the machinery involved upstream of AP-1 activation, the role of tyrosine kinases was investigated. Western blot analysis showed that PDTC induced phosphorylation of tyrosine kinases. Treatment of mesangial cells with tyrosine kinase inhibitors suppressed activation of AP-1 as well as induction of stromelysin by PDTC. These findings demonstrate that the antioxidant PDTC induces stromelysin expression via stimulation of the tyrosine kinase-AP-1 pathway independent of its suppressive action on NF-kappa B.

Animals↗
PubMed1996

Expression of CD44 splice variants in human transitional cell carcinoma.

The CD44 cell adhesion molecule is a surface glycoprotein mainly expressed in lymphoid tissues. Recently, abnormal variants of CD44 including alternatively-spliced large molecular variants, have been reported in many neoplastic tissues. We studied the variation in the size of CD44 molecules in 25 transitional cell carcinomas and 11 normal transitional epithelial tissues, using the reverse transcriptase-polymerase chain reaction (RT-PCR) followed by electrophoresis and Southern blot hybridization. Whereas 23 of 25 (92.0%) tumor tissues expressed CD44 splice variants with large molecular size, only 1 of 11 (9.1%) normal tissues expressed the abnormal variants. Urine sediments from 5 of 7 (71.4%) patients also was positive for the CD44 splice variants. CD44 splice variants are increased markedly in human transitional cell carcinoma. In conclusion, detection of CD44 splice variants using the RT-PCR, which is a convenient molecular biological technique, may be useful in combination with other diagnostic methods such as cytology, flow cytometry, and tumor antigens.

Alternative Splicing↗
PubMed1996

A new haemocompatible phospholipid polyurethane based on hydrogenated poly(isoprene) soft segment.

A new haemocompatible phospholipid polyurethane based on hydrogenated poly(isoprene) glycol (HPIP) and 4,4'-methylendiphenyl diisocyanate (MDI) was synthesized using 2-[bis(2-hydroxyethyl)methyl-ammonio]ethylstearylphosphate (BESP) and 1,4-butanediol (BD) as chain extender. The bulk and surface characteristics of this material was investigated by differential scanning calorimetry (DSC), dynamic viscoelasticity and tensile property measurements, attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), and contact angle measurement. This polymer possessed a hydrophobic surface revealed by contact angle measurement. The haemocompatibility of this polyurethane was evaluated by platelet rich plasma (PRP) contacting studies and scanning electron microscopy (SEM) observation using medical grade poly(vinyl chloride) (PVC) as the reference. The results show that this new polyurethane had relatively lower platelet adhesion and limited shape change for the attached platelets compared to PVC. The clotting time of the materials in contact with platelet poor plasma (PPP) was 99, 75, and 62 s and in contact with PRP was more than 240, 100, and 86 s for new polyurethane, PVC, and glass, respectively. This new phospholipid polyurethane is expected to have wide applications as coating or structural material for blood-contacting medical equipment due to its outstanding haemocompatibility and excellent mechanical strength.

Biocompatible Materials↗
PubMed1996

Soluble egg shell membrane protein as a regulating material for collagen matrix reconstruction.

Soluble egg shell membrane protein (SEP) was prepared from egg shell membrane by the combined treatment of performic acid oxidation (4 or 25 degrees C for 24 h) and pepsin digestion (25 degrees C for 24-72 h) before dialyzing against water and lyophilizing. The yield of SEP was about 16-39%. SEP had high contents of acidic amino acids (320-340 residues/1000 residues) containing cysteic acid (101-108 residues) converted from cystine, a small amount of saccharides, a main molecular weight of 12,000-22,000 and pI 4.2-4.8. SEP accelerated the reconstruction of collagen matrix with ordered molecular rearrangement and reduced redissolution of the collagen matrix under several solvent conditions. SEP elevated the denaturation temperature of the matrix.

Amino Acids↗
PubMed1996

Familial occurrence of electrocardiographic abnormalities of the Brugada-type.

Electrocardiographic abnormalities were pointed out in a 51-year-old Japanese male whose major complaint was dizziness. His electrocardiogram showed a complete right bundle branch block, and a prolonged His bundle-ventricle (HV) interval of 100 msec. Two members of his family died of heart disease and 3 members, including a case of sudden death, presented an abnormal electrocardiogram of the Brugada-type with persistent ST segment elevation in the right precordial leads and right bundle branch block. The signal-averaged examination was made in the children of cases that died with the diagnosis of sudden death. Four cases showed a tendency of delay in the HV interval and a positive finding in the late potential. Further studies are necessary to clarify the relationship between electrocardiographic abnormalities of the Brugada-type and atrioventricular conduction disorder as well as to clarify the genetic basis of this disorder.

Adolescent↗
PubMed1996

[Quality control of surgery in multicenter study--interinstitutional and individual differences].

UNLABELLED: In a prospective randomized controlled trial (PRCT) of adjuvant chemotherapy for gastric cancer patients participated by 6 cancer center hospitals, inter-institutional and inter-individual differences about several factors related to the surgery and remote survivals were analyzed. From 1988 to 1992, 1,049 evaluable patients were enrolled and stratified to 6 groups according to the grade of the serosal invasion and curability, and analyzed statistically. RESULTS: 1) There were no inter-institutional differences about postoperative survival rate, but there were slight differences about patient's background factors and entry policy of each institution. 2) There were no inter-institutional differences about several factors related to the surgery such as operative time, bleeding volume during operation, and the length of the administration periods. 3) There were no inter-individual differences about the length of the administration periods, but there were a little differences about operative time and the volume of hemorrhage. When the PRCT of adjuvant chemotherapy of which the end point is survival would be designed, no inter-institutional differences about remote survival and surgical operation in each institution should be confirmed before starting the trial.

Chemotherapy, Adjuvant↗
PubMed1996

[Analysis of specificity of resected esophageal cancer patients with a history of apoplexy].

We studied 15 resected cases with a history of apoplexy (2.5%) among 599 cases of esophageal cancer admitted between 1972 and 1993. Fourteen were male, and female, aged 48 to 77 years. Twelve had suffered from cerebral infarction, 2 intracerebral hemorrhage, and one subarachnoid hemorrhage. Duration from apoplexy to operation was between 2 months and 19 years in the cerebral infarction cases, between 8 and 10 years in the intracerebral hemorrhage cases and 4 years in the subarachnoid hemorrhage case. Preoperative neurological disturbance was found in 7 of the 12 cerebral infarction cases, and in both intracerebral hemorrhage cases. Four cases showed hemiplegia, and the other 5 cases showed partial paralysis of limbs. Preoperative complications were found in 7 of the 15 cases, and consisted of diabetes mellitus in 5, hypertension in 4, bronchial asthma in one, and renal dysfunction in one case. Intra- and postoperative complications were found in 11 of the 15 cases, and consisted of anastomotic leakage in 5, delirium in 3, apoplexy in 2, peritonitis in one, ARDS in one, intraoperative cardiac arrest in one, and wound infection in one. Postoperative disorders of consciousness were found in 5 cases, consisting of delirium in 3, and excitation at awakening of anethesia in 2 cases. Rate of direct operative death was 6.7% in preoperative apoplectic patients, and 8.5% in non-apoplectic patients, and there was no significant difference between the 2 groups. On the other hand, rate of postoperative apoplexy was 13.3% in the preoperative apoplectic patients, and 0.4% in non-apoplectic patients. There was a significant difference between them (p < 0.01). But they were cured of it, and left our hospital. It is concluded that active surgical treatment can be indicated for esophageal cancer patients with a history of apoplexy, if more attention is given to the management of diabetes mellitus or hypertension.

Aged↗
PubMed1996

[Clinico-pathological studies and problems on para-aortic lymph node dissection--D4 dissection].

The advantage or disadvantage of para-aortic lymph node dissection was studied from the viewpoint of clinicopathological findings and their prognosis. No 16 lymph node dissection was performed in 427 cases, and metastasis was observed in 100 (23%). The metastatic rate increased with the depth of cancer. High metastatic rates were seen in type 3 and 4, and in the histologically undifferentiated type. Five year survival rate of patients with No. 16 metastasis (PoHo) was 14%. The n3 (-) group among cases with n4 showed a significantly better outcome than the n3 (+) group. Concerning total gastrectomy with pancreato-splenectomy procedure, blood loss was greater and length of surgery was longer in the D4 group than D2 group. The exudate volume was much higher in D4 and serum albumin significantly decreased in D4 than D2. Almost the same findings were seen in D4 with subtotal gastrectomy. Postoperative complications in D4 group were the same as D2 excluding abscess around pancreatic stump which was higher in D4. In conclusion, D4 dissection does not have an obvious disadvantage for the patients. Randomized clinical trials between D4 and D2 should be done in order to clarify an efficacy of the D4 dissection.

Aorta↗
PubMed1996

[Hemodynamic plus series of St. Jude medical valve prosthesis in aortic position: early clinical outcome and reconsideration of its application].

St. Jude Medical Hemodynamic plus bileaflet valve prosthesis (HP) was employed in 7 cases undergoing aortic valve replacement since December 1993. Echocardiographic evaluation of left ventricular dimension and transvalvular pressure gradient was performed in 5 cases with 19 HP before and after operation. Each data was compared with those of 21 cases having undergone aortic valve replacement with 19 mm Standard model (19 SD). There was no significant postoperative change in left ventricular end-diastolic dimension (50 +/- 4 mm to 44 +/- 8 mm; p = NS) and left ventricular end-systolic dimension (34 +/- 4 mm to 34 +/- 9 mm; p = NS) in 19 HP cases. However, left ventricular end-diastolic dimension (51 +/- 11 mm to 41 +/- 8 mm; p < 0.05) and left ventricular end-systolic dimension (35 +/- 12 mm to 28 +/- 9 mm; p < 0.05) decreased in 19 SD cases. Transvalvular systolic peak pressure gradient was reduced significantly in both groups (19 HP: 94 +/- 38 mmHg to 43 +/- 19 mmHg; p < 0.05, 19 SD: 73 +/- 49 mmHg to 33 +/- 14 mmHg; p < 0.05). Poor reduction of left ventricular volume and high residual systolic pressure gradient in patients with 19 HP might be due to relatively high incidence of stenotic lesion in original aortic valve disease. In some cases with these critical aortic stenosis, radical annular enlargement procedure would provide more fundamental release of left ventricular outflow tract stenosis rather than one size increase of effective orifice area by employing HPs. Structural examination demonstrated that 19 HP had the same outer diameter of sewing flange with identical orifice ring as 21 SD (24 mm) did, and 17 HP had that of 19 SD (22 mm). Therefore, precise attention is needed for application of SJM-19 HP in patients with small aortic annuli.

Adolescent↗
PubMed1996

[Long-term results and special issues of operation for infective endocarditis].

Between 1977 and June 1996, 183 patients underwent operation for infective endocarditis (IE) at our institution. Long-term mortality and morbidity were analyzed according to the STS/AATS guidelines (1988). Operative mortality including hospital deaths was 4.9% in all patients. Actuarial survival (including all deaths) at 10 postoperative years was 79.6% after AVR (n = 91), 87.9% after MVR (n = 40) and 90.0% after DVR (n = 46). There was no significant difference among 3 groups. Reoperation free and freedom from all valve-related mortality and morbidity at 10 years were 94.0% and 70.4% after AVR, 90.9% and 83.7% after MVR and 93.4% and 79.7% after DVR, respectively. And the differences among 3 groups were not significant in both freedom proportions. Overall results in this series of patients were acceptable. However, several patients with active IE and extensive perivalvular abscess were not saved even if translocation method and/or other advanced surgical procedures were applied. Introduction of aortic valve homografts might be a key factor for successful treatment for patients with extensive IE lesion.

Adolescent↗
PubMed1996

[A case of saccular aneurysm of the coronary artery].

A 42-year-old man with chest oppression was diagnosed as having a saccular aneurysm of the coronary artery by cardiac catheterization. At the time of operation on April 26, 1993, the aneurysm, measured 15 mm in diamer, and arose from the proximal segment of the first septal branch of the left anterior descending coronary artery. Several coronary arteriovenous fistulae from the aneurysm to the pulmonary artery were also noted. The stem of the aneurysm and the coronary arteriovenous fistulae were ligated and the aneurysm was resected. We considered the etiology to be mainly arteriosclerosis on the basis of the aneurysm pathology. And this aneurysm was also considered to have congenital factors because of the existence of arteriovenous fistulae. There were no symptoms after the operation and he was discharged at 24th postoperative day. Now he continues to do well.

Adult↗