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Biomedical subjects

K Hara

Publications and source records attributed to K Hara.

At least 325 records · Page 18Linked to original sources

Cytokine messenger RNA expression in chronic inflammatory periodontal disease.

It has previously been reported that, in periodontitis lesions, T cells with a memory/activated phenotype and with a type 2 cytokine profile accumulate in an oligoclonal fashion. Delineation of the role of cytokines in periodontal inflammation has, however, been complicated because of cross-regulation and because of their overlapping and often redundant effects. The aim of this study was to examine messenger RNA levels for interferon gamma, interleukin 4 (IL-4), IL-10, IL-12 and IL-13 in gingival tissues and peripheral blood mononuclear cells of patients with adult periodontitis. Reverse transcription polymerase chain reaction and subsequent image analysis was used to determine the level of mRNA for each cytokine. The mean expression of interferon gamma mRNA was significantly higher in peripheral blood mononuclear cells than in gingival tissues. In contrast, the mean expression of IL-10 mRNA was higher in gingival tissues than in peripheral blood mononuclear cells. This high expression of IL-10 mRNA was, in fact, seen in only 7 gingival tissue samples with the majority of samples showing levels similar to peripheral blood mononuclear cells. There was no difference in the mean expression of IL-12 p35 mRNA between gingival tissues and peripheral blood mononuclear cells. However, IL-12 p40 mRNA was expressed higher in gingival tissues than in peripheral blood mononuclear cells in 6 out of 16 samples with significant difference of mean expression. Like IL-10, gingival tissue samples and peripheral blood mononuclear cells expressed similar levels of IL-12 p40 mRNA. There was no difference in the mean expression of IL-13 in gingival tissues and peripheral blood mononuclear cells. Nevertheless, more peripheral blood mononuclear cell samples demonstrated high IL-13 mRNA expression than gingival tissue samples. IL-4 mRNA was weak but detectable in 3 gingival tissue samples. These results support the concept that cytokines form complex networks in periodontitis lesions and that their overlapping and redundant effects should be taken into account when considering the pathology of inflammatory periodontal disease. Dichotomous expression of IL-10 and IL-12 p40 mRNA in the periodontal lesion may be associated with disease entity.

Adult↗

Clinicopathologic study of nasal T/NK-cell lymphoma among the Japanese.

A high prevalence of nasal lymphoma expressing a T- or natural killer (NK)-cell phenotype (NTCL) with frequent association of Epstein-Barr virus (EBV) has been indicated in Asians. To characterize NTCL among the Japanese, the clinicopathologic features of 32 cases were evaluated and the cases were also analyzed for EBV-RNA using an ISH method. Morphologically, 31 cases were identified by atypical pleomorphic lymphoid infiltrates with polymorphous, angicentric, and necrotic features. Their lymphoma cells ranged in size from small to large and were mixed in varying proportion from case to case. The other one case showed a monomorphic 'blastic' appearance. EBV-encoded small RNA (EBER) was detected in the neoplastic cells of 27 of the 32 cases examined. In the five EBV-negative cases, one was the 'blastic' type. Clonal T-cell receptor gene rearrangement was detected in none of seven cases examined. The patients had a median follow-up of 9 months (range, 1 month to 14 years and 11 months). The Kaplan-Meier estimate of overall survival was 49% at 5 years, correlating with clinical stage. These data support the concept that most cases of NTCL are identified as tumors with T/NK-cell characteristics and EBV association, distinctly different from other peripheral T-cell lymphomas. Furthermore, the one case of an EBV-negative 'blastic' variant appears not to fit well into the pleomorphic category but more closely resembles the pathologic features of extranasal angiocentric lymphoma with lymphoblastoid appearance. This study also showed no clear difference in clinical aspects other than the original site or in prognosis, between NTCL and extranasal angiocentric lymphomas despite the higher incidence of EBV association and the tendency for that peculiar anatomical site to be restricted to the former group.

Adolescent↗

Thromboxane inhibition and monocrotaline-induced pulmonary hypertension in rats.

Monocrotaline (MCT)-induced pulmonary hypertension (PH) is a useful model for the investigation of this disorder in humans. The role of thrombocytes in the genesis of PH has already been addressed; however, the exact mechanism by which they induce PH remains to be elucidated. We investigated the effects of a thromboxane A2 (TXA2) synthase inhibitor (OKY-046) and a TXA2/prostaglandin H2 (PGH2) receptor antagonist (ONO-8809) on the development of MCT-induced PH. A single dose of MCT (60 mg/kg bodyweight; BW) was injected subcutaneously in Wistar rats 24 h after the administration of OKY-046 or ONO-8809. The TXA2 inhibitors were administered by gavage daily for 3 weeks. Urinary excretion of eicosanoids was determined by radioimmunoassay. At the end of the treatment period, the lungs, heart and kidneys were morphologically examined. The per cent medial thickness of the muscular pulmonary arteries (%MT) and the ratio of the right to the left ventricular mass including the septum (RV/LV + S) increased significantly in MCT-treated rats compared with the control rats. The %MT was attenuated by the administration of ONO-8809. Either OKY-046 or ONO-8809 attenuated the increase in RV/LV + S. In addition, both TXA2 inhibitors reduced urinary excretion of 11-dehydro-TXB2, particularly during the early phase of PH, suggesting that platelet aggregation was reduced. These findings suggest that the inhibition of TXA2 by synthase inhibition or receptor antagonism reduces or delays the development of MCT-induced PH in rats, probably by inhibiting platelet aggregation.

Animals↗

Dynamic distribution of basic fibroblast growth factor during epulis formation: an immunohistochemical study in an enhanced healing process of the gingiva.

Basic fibroblast growth factor (bFGF) is thought to play an important role in wound healing. However, its histological localization, both in normal and pathological conditions in the oral mucosa, has not been well documented. We have studied the immunolocalization of bFGF in normal gingiva and gingival epulis specimens corresponding to different organizing stages. In normal gingiva, bFGF was detected in subpopulations of macrophages, mast cells and most endothelial cells in the lamina propria. Granulation tissue in epulides was histopathologically classified into six organizing stages. In stages 1 and 2, a small number of bFGF-positive macrophages was seen at the periphery of ulcer bases. In stages 3 and 4, histologically characterized by prominent capillary proliferation, large numbers of bFGF-positive macrophages and mast cells were located within granulation tissue. A positive reaction for bFGF was also found in some endothelial cells and in myxoedematous stroma that was rich in heparan sulfate proteoglycan. In stages 5 and 6, when fibrosis was accelerated, bFGF-positive macrophages and mast cells decreased in number and were localized only at the periphery of the fibrous tissue. These findings suggest that maximum amounts of bFGF are synthesized and released from some macrophages and mast cells into the extracellular matrix during neovascularization of granulation tissue.

Endothelium, Vascular↗

Loss of Fc gamma receptor and impaired phagocytosis of polymorphonuclear leukocytes in gingival crevicular fluid.

Immunoglobulin G type II and III receptors (Fc gamma RII and Fc gamma RIII) are essential for polymorphonuclear leukocytic (PMNs) phagocytosis. Our previous study demonstrated a downregulation of Fc gamma RIII on PMNs in gingival crevicular fluid (GCF). To determine whether this receptor downregulation may contribute to the periodontal host defence borne by PMNs, we examined the correlation between Fc gamma RII and Fc gamma RIII expressions and the phagocytic capacity of GCF-PMNs. In order to verify at which level of cellular events the loss of Fc gamma R occurs, we quantified mRNA levels to assess a de novo synthesis of these receptors. GCF was collected from 21 patients with adult periodontitis by gingival crevicular washing. Autologous peripheral blood (PB) PMNs served as control. Surface expressions of Fc gamma Rs and phagocytic capacity via Fc gamma Rs were analysed by flow cytometry. The difference in Fc gamma R mRNA levels between GCF- and PB-PMNs was assessed by reverse transcription polymerase chain reaction (RT-PCR). The amplified products were visualized by agarose gel electrophoresis and the endproduct yields were quantified by computerized image-analysis. Both Fc gamma RII and Fc gamma RIII expressions and phagocytic capacity on GCF-PMNs were significantly lower than those on PB-PMNs (p < 0.001). The downregulation of Fc gamma Rs on GCF-PMNs significantly correlated with the phagocytic capacity (r = 0.66 for Fc gamma RIII, p < 0.01; r = 0.50 for Fc gamma RII, p < 0.05). The mRNA level of Fc gamma RIII of GCF-PMNs was significantly lower than that of PB-PMNs (p < 0.05). Thus, GCF-PMNs are characterized by the decreased surface expressions and mRNA levels of Fc gamma Rs, and the impaired phagocytosis.

Adult↗

In situ hybridization study on tissue inhibitors of metalloproteinases (TIMPs) mRNA-expressing cells in human inflamed gingival tissue.

This study presents the exact cell types and localization of tissue inhibitors of metalloproteinases (TIMPs) production sites in periodontal diseased gingiva by means of in situ hybridization. Gingival tissue specimens were fixed, embedded and hybridized in situ with specific digoxigenin-labeled cRNA probes (386 and 496 bp). TIMP-1 and -2 mRNAs were expressed on macrophages, mononuclear cells, capillary endothelial cells and some fibroblasts throughout the gingival tissue. In periodontitis, TIMP-1 and -2 mRNA-expressing cells showed significantly different localization. TIMP-1 mRNA was broadly observed in the gingival connective tissue while TIMP-2 mRNA was predominantly expressed in the connective tissue adjacent to the pocket epithelium (p < 0.01). Fewer TIMPs mRNA were observed in minimal gingivitis than in periodontitis, especially in the middle zone of gingival tissue. Thus, TIMP-1 and TIMP-2 mRNA was detected differentially and site-specifically in periodontal diseased gingival tissue.

Aged↗

[A case of bacterial meningitis induced by strongyloidiasis].

A 75-year-old female with diabetes mellitus, who was born and lived in West north Kyusyu, was admitted to our hospital, because of unconsciousness and loss of appetite. The physical examination showed neck stiffness and a high fever. The laboratory data showed accentuation of inflammatory reaction and azotemia and positive HTLV-1 antibody. The spinal fluid showed increase of cell count and amount of protein. A stool and sputum smear revealed rhabditis form larvae of the nematode. Antibiotics and ivermectin were administered for the bacterial meningitis and hyperinfection of the strongyloides, respectively. Consequently, meningitis and strongyloidiasis improved. It was considered that the patient was infected with strongyloides from her husband who serve in the army during World-War II, and hyperinfection of strongyloides resulted from the immunosuppressive state of diabetes mellitus. Ivermectin, and anti-strongyloides agent, was effective, and no side effects were seen. However, the therapeutic resistance in this case was associated with the positive HTLV-1 antibody.

Aged↗

Relevance of immunoglobulin G Fc receptor polymorphism to recurrence of adult periodontitis in Japanese patients.

Polymorphonuclear neutrophil (PMN) phagocytic function has been shown to be impaired in some patients with periodontitis. PMN constitutively express members of two immunoglobulin G receptor (Fc gammaR) classes: Fc gammaRIIa (CD32) and Fc gammaRIIIb (CD16). Both receptors exhibit genetically determined structural and functional biallelic polymorphisms, which have been shown to influence PMN phagocytic function. In this study, we assessed the relevance of these Fc gammaR polymorphisms to susceptibility to adult periodontitis and recurrence rate. The distribution of Fc gammaRIIa and Fc gammaRIIIb genotypes of 100 Japanese patients with adult periodontitis during follow-up was compared to the distribution of genotypes in 105 race-matched healthy controls. No significant skewing of distributions of Fc gammaRIIa and Fc gammaRIIIb genotypes was observed between patients and controls. Notably, however, a significant overrepresentation of the Fc gammaRIIIb-NA2 allotype was found in patients with disease recurrence (P < 0.05; odds ratio, 4.29; 95% confidence interval, 1.19 to 16.24). Moreover, the annual rate of recurrence was significantly higher in patients with the Fc gammaRIIIb-NA2/NA2 and Fc gammaRIIIb-NA1/NA2 genotypes than in Fc gammaRIIIb-NA1/NA1 individuals (P < 0.05). Fc gammaRIIa-R/R131 individuals also exhibited higher recurrence rates, though the difference was not statistically significant (P = 0.06). These results suggest that the Fc gammaRIIIb-NA2 allotype represents a risk factor for recurrence of adult periodontitis.

Adult↗

Patency of intermediate size side branches after Palmaz-Schatz stent implantation.

The immediate and long-term patency of intermediate size side branches was assessed by serial coronary angiography in 47 patients with 48 lesions to determine whether the presence of these side branches (1-2 mm in diameter) is unsuitable for Palmaz-Schatz stent implantation. Coronary angiography was performed at baseline, after conventional balloon angioplasty, immediately after stent implantation, at 1 week, and at 6-month follow-up. Sixty-eight lesion-associated side branches that were 1-2 mm in diameter, 11 with branch ostial stenosis (Group A) and 57 without ostial stenosis (Group B) were studied. After stent implantation, 9 (13%) branches became totally occluded and coronary flow deteriorated in 13 branches (19%). The incidence of side branch occlusion during the procedure in group A was greater than in group B (55% vs. 12%; p < 0.005). One (2%) patient suffered persistent chest pain, but no procedure was complicated by Q-wave myocardial infarction or significant elevation of creatine kinase concentration. Flow improved in 82% of the occluded side branches after 1 week and in 90% after 6 months. These results suggest that the presence of intermediate size side branches is not a contra-indication to Palmaz-Schatz stent implantation.

Angioplasty, Balloon, Coronary↗

Involvement of IL-4 in human glomerulonephritis: an in situ hybridization study of IL-4 mRNA and IL-4 receptor mRNA.

Interleukin-4 (IL-4) has been recently implicated in the pathogenesis of glomerulonephritis. However, the expression of IL-4 and IL-4 receptor (IL-4R) in human kidney has not been fully determined. Nonradioactive in situ hybridization was used to examine the expression of IL-4 mRNA and IL-4R mRNA in tissues from normal kidneys and specimens from a variety of human kidney diseases. In normal glomeruli, a few mesangial cells and cells of the Bowman's capsule weakly expressed IL-4 and IL-4R mRNA, whereas in diseased glomeruli both mRNA types were strongly expressed in resident glomerular cells, including mesangial cells, glomerular epithelial cells, and cells of the Bowman's capsule. The relationship between the expression of these mRNA and the degree of glomerular injury was different in different types of glomerulonephritis. In IgA nephropathy and non-IgA mesangial proliferative glomerulonephritis, IL-4 expression correlated positively with the degree of mesangial hypercellularity and extracellular matrix expansion. However, IL-4R expression was relatively constant. In contrast, the expression of IL-4 and IL-4R mRNA correlated negatively with the degree of glomerular injury in lupus nephritis. Coexpression and discordant expression of these mRNA forms were observed in individual cells. In tubulointerstitium with severe lesions, IL-4 mRNA and IL-4R mRNA were observed in atrophic tubules and some of the infiltrating cells and fibroblasts. The interstitial expression of these mRNA forms was similar in IgA nephropathy, non-IGA mesangial proliferative glomerulonephritis, and lupus nephritis and correlated positively with the degree of tubulo-interstitial changes. These results suggest that an autocrine and/or paracrine pathway of IL-4 is present in human diseased kidneys and that IL-4 may be involved in tissue injury in glomerulonephritis.

Adult↗

Apical ectodermal ridge-dependent expression of the chick 67 kDa laminin binding protein gene (cLbp) in developing limb bud.

Apical ectodermal ridge (AER)-mesoderm interaction is important for morphogenesis in the developing chick limb bud. Genes whose expression is dependent upon the presence of AER, are likely to play important roles in the AER-mesoderm interaction. We report here the gene expression pattern of the chick homolog of the 67 kDa laminin binding protein (LBP), which is a non-integrin laminin receptor whose function relates to cell attachment, spreading, and polarization. Northern analysis showed that a single 1.4 kb transcript exists in stage 20 limb buds and which is dramatically reduced 24 hr after removal of AER. In situ hybridization analysis revealed that the chick 67 kDa laminin binding protein gene (cLbp) was expressed in the mesodermal region overlapping the Msx1-expressing domain and in the AER in early stage limb buds. Expression in the mesoderm was gradually restricted to the distal region underneath the AER as development proceeds. The expression in the limb mesoderm could be induced by local application of FGF-2 which could thus mimic the AER functions. These results indicated that the expression of cLbp depends on AER signals and that the 67 kDa non-integrin receptor binding to laminin plays a role in the AER-mesoderm interaction.

Animals↗

Vasodepressor effects of exercise are accompanied by reduced circulating ouabainlike immunoreactivity and normalization of nitric oxide synthesis.

Our object was to evaluate the effects of regular mild exercise on blood pressure and on circulating level of ouabainlike factors (OLF) and of nitrate anion, an endproduct of nitric oxide (NO) in humans. We measured plasma ouabainlike immunoreactivity (OLI) and nitrate ions (NO3.) before and after mild exercise for 3 months' duration in 16 patients with essential hypertension, diabetes mellitus, obesity, or hyperlipidemia. Plasma OLI was measured using an amplified ELISA system with anti-ouabain antibody and biotinyl-tyramide. Serum NO3. was measured with high-performance liquid chromatography (HPLC) with an anion-exchange column. With the reverse phase HPLC system with an octa decylsilyl silicagel column, the elution volume of plasma OLI of a healthy volunteer matched that of authentic ouabain in a gradient elution system of acetonitrile/H2O. Plasma OLI levels decreased significantly by about 34% after mild exercise, and NO3. levels tended to be within the reference interval in normal volunteers. Body weight, diastolic and systolic blood pressure, serum triglyceride and acetylcholine esterase (a marker of the fatty liver) were significantly decreased (p < 0.01) after 3 months of regular mild exercise. The plasma OLI level was significantly correlated with plasma NO3., there was a trend toward a correlation with diastolic blood pressure (p = 0.06) before and after regular exercise. Regular mild exercise led to a decrease in plasma levels of OLI, and acetylcholine esterase activity and blood pressure in adult patients. Results suggest that changes in OLF production contribute to the blood pressure regulation seen in patients who exercise regularly.

Adult↗

[Evaluation of various somatosensory stimulations for functional MRI].

The aim of this functional magnetic resonance imaging (fMRI) study was to test detectability of activated area using various somatosensory stimulations. The following stimulations were performed in normal volunteers: regular or irregular electrical median nerve stimulation (n = 5, each), tactile stimulation to the palm and fingers (n = 8), pain stimulation to the index finger (n = 5) or to the palm and fingers (n = 5). fMRI was acquired with a spoiled gradient echo sequence at 1.5 T. Detectability of activated area was the highest when the pain stimulation was applied to the palm and fingers (80%). A successful rate for the tactile stimulation was 25%, and the other stimulations failed to demonstrate any activation. When successful, the highest signal activation on fMRI was seen on a sulcus, which presumably arose from a vein. The sulcus was defined as the central sulcus by somatosensory evoked field using a median nerve stimulation. Our study indicates that the pain stimulation to the palm and fingers may be a choice for the sensory fMRI.

Adult↗

[The clinical study of clarithromycin for pulmonary Mycobacterium avium-intracellulare complex infection].

A nationwide study was conducted to investigate the efficacy of Clarithromycin (CAM) on pulmonary atypical mycobacteriosis caused by the Mycobacterium avium-Mycobacterium intracellulare complex, including intractable cases. Out of total 97 patients examined, the analysis for bacteriological efficacy was possible in 69 cases. The negative conversion of bacilli was observed in 18 cases (26.1%), and 5 out of 12 cases in which the follow-up was conducted turned out continued negative status. The efficacy of CAM was relatively high in the following cases: the duration of the disease was less than 6 months the extent of pulmonary lesions on chest roentogenograms was limited or moderate; and antituberculous agents which were previously unused were applied in combination with CAM. Also, the efficacy was high in cases where the dose of CAM was 600 mg/day or higher. Major side effect was mill to moderate digestive symptoms. In conclusion, at daily dose of 600 mg or higher, CAM was effective in the elimination or reduction of M avium M. intracellulare complex that caused atypical mycobacteriosis, without developing serious side effect. Treatment with this drug should be attempted in intractable cases.

Anti-Bacterial Agents↗

[Seasonal changes of laboratory data in patients with Japanese cedar pollinosis].

Japanese cedar pollen (JCP) causes a significant seasonal allergic rhinitis in Japan during the early spring. Blood samples were collected monthly from October 1993 through October 1994 from 11 patients with Japanese cedar pollinosis. The patients were segregated into two categories based on specific IgE (RAST): single positive RAST to JCP only and multiple positive RAST to JCP, house dust (H1) and mite (D1). These two populations differed in levels of total serum IgE, numbers of eosinophils, basophils and neutrophils in peripheral blood and clinical symptoms. Seasonal increase of JCP-specific IgE was observed after pollen season in both groups. In the single positive group, but not in the multiple positive group, seasonal increase of the number of eosinophils in peripheral blood was observed with post seasonal fall and the level of total serum IgE was increased in the same manner as that of the JCP specific IgE. Although it was not significant, there was a broad seasonal increase of serum nitrate anion, a metabolite of nitric oxide.

Adult↗

Evaluation of plasma (1-->3)-beta-D-glucan measurement by the kinetic turbidimetric Limulus test, for the clinical diagnosis of mycotic infections.

The present multicentre clinical study was conducted to assess the clinical utility of a new diagnostic method for deep mycosis in which (1-->3)-beta-D-glucan, a fungal cell wall component existing in plasma, was quantitatively measured by the kinetic turbidimetric Limulus test (WB003). Plasma (1-->3)-beta-D-glucan concentrations were 0.57 +/- 0.10 microgram/l in 92 healthy subjects and 0.62 +/- 0.32 microgram/l in 26 patients with non-mycotic diseases (disease control group). In comparison with these healthy subjects and patients with non-mycotic diseases, patients with mycosis had significantly higher plasma (1-->3)-beta-D-glucan concentrations: 19.63 +/- 73.28 micrograms/l in 12 patients with candidaemia, 11.28 +/- 21.42 micrograms/l in 7 patients with urinary Candida infection, 4.84 +/- 12.71 micrograms/l in 5 patients with pulmonary candidiasis, and 12.21 +/- 31.31 micrograms/l in 4 patients with invasive pulmonary aspergillosis. On the statistical analysis of these data, a cut-off value was set at 1.0 microgram/l. Using this cut-off value, 3 patients with pulmonary cryptococcosis and 4 patients (4/6) with pulmonary aspergilloma were all negative with low plasma (1-->3-beta-D-glucan levels. The test WB003 provided equivalent or higher efficiency of diagnosis of candidiasis and aspergillosis, in comparison with commercially available antigen detection kits, demonstrating its utility as a diagnostic reagent. It may also be useful in assessing therapeutic effectiveness when used periodically after treatment.

Adolescent↗

[Transient hyperphosphatasemia observed in a boy with acute lymphoblastic leukemia].

A detailed time course of alkaline phosphatase (ALP; EC3.1.3.1) activity of transient hyperphosphatasemia (TH) in a 9-year-old boy with acute lymphoblastic leukemia (ALL) is described. The patient's serum ALP activity rose transiently to 49 times the upper limit of normal adult, without any evidences of hepatic and bone disease. The half-life of ALP activity was calculated about 10 days. We characterized ALP isoenzymes by usual electrophoresis using cellulose acetate membrane (Titan III iso-vis) and polyacrylamide disc gel (AlkPhor), and isoelectric focusing using polyacrylamide slab gel. The former two methods showed typical two bands (fast-alpha 2 and alpha 2 beta bands) and the latter one method revealed more basic bands of liver and bone, suggesting the extensive sialylation. The patient complained fever and diarrhea. Enterococcus faecium was detected from his stool. Etiologically, two more patients in the same ward showed TH in the same period. It suggested TH would be occurred by infectious states. Awareness of such benign forms of hyperphosphatasemia not related to malignancy will aid the physician in the differential diagnosis of elevated ALP activity.

Alkaline Phosphatase↗