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Biomedical subjects

K Hara

Publications and source records attributed to K Hara.

At least 577 records · Page 32Linked to original sources

Localization of interleukin-1 (IL-1) mRNA-expressing macrophages in human inflamed gingiva and IL-1 activity in gingival crevicular fluid.

The exact cell type and site(s) involved in interleukin-1 (IL-1) production during gingival inflammation was determined by combining immunohistochemistry and in situ hybridization. IL-1 messenger RNA (mRNA)-expressing cells in human inflamed gingiva were identified as macrophages. The rate of IL-alpha mRNA expression in these macrophages was the same as IL-1 beta mRNA expression. The rate of IL-1 mRNA expression was higher in connective tissue furthest from the pocket epithelium, although more macrophages were present at the connective tissue subjacent to the pocket epithelium. The IL-1 activity in gingival crevicular fluid (GCF) obtained from inflamed gingiva was higher than that from healthy gingiva and decreased after periodontal therapy. The IL-1 activity in GCF was almost completely abolished by the addition of anti-IL-1 alpha antibody but not by anti-IL-1 beta antibody, indicating that IL-1 alpha is the predominant form in GCF. However, the IL-1 activity in GCF was unrelated to the number of IL-1 mRNA-expressing macrophages in the same gingival site where the GCF was obtained at the same time. The results suggest that macrophages in the connective tissue subjacent to the oral epithelium contribute to the production of IL-1 but those in connective tissue subjacent to the pocket epithelium play a different role in the generation of gingival inflammation.

Adult↗

Immunohistological analysis of memory T lymphocytes and activated B lymphocytes in tissues with periodontal disease.

Memory T-cells and activated B-cells were identified in cryostat sections of adult periodontitis (AP) lesions and categorized in terms of frequency and distribution. Nineteen periodontitis biopsies were obtained at the time of periodontal surgery to remove residual periodontal pockets following the completion of initial preparation. Gingival tissues exhibited various degree of inflammation (GI of 0-2) but probing depths of > 4 mm and > 5 mm loss of attachment. As a control, 5 gingivitis specimens (GI of 1, probing depth and loss of attachment of < or = 3 mm) were obtained from premolar and third molar sites requiring extraction for either orthodontic treatment or pericoronitis. Serial cryostat sections (6 microns in thickness) were prepared from each biopsy, on which a double staining avidin-biotin immunoperoxidase and avidin-biotin alkaline phosphatase technique was used to identify CD4+, CD45RO+ memory T-cells and activated CD19+ B-cells expressing CD23 or CD25. In periodontitis lesions, the mean percentage of CD4+ cells expressing CD45RO was consistently high (65.9% in the crevicular (C) one-third (1/3), 61.2% in the middle (M) 1/3 and 62.5% in the oral (O) 1/3). This contrasts with the low mean percentage of CD4+, CD45RA+ naive T-cells (17.1% in the C 1/3, 14.8% in the M 1/3 and 12.4% in the O 1/3). In gingivitis specimens, the incidence of CD4+, CD45RO+ was 81.9% in the C 1/3, 81.1% in the M 1/3 and 89.0% in the O 1/3. This was higher than that of periodontitis biopsies. With CD4+, CD45RA+ the incidence was 10.0% in the C 1/3, 8.0% in the M 1/3, and 6.6% in the O 1/3 and the relationship to the periodontitis biopsies was reversed. However, the percentage of CD23+ and CD25+, CD19+ B-cells which were identified in 13 out of 19 samples from periodontitis varied significantly (0-100% for CD23, 0-36.2% for CD25) in spite of similar clinical status. The frequency of B-cells and activated B-cells in the gingivitis was much lower than that of periodontitis. These results indicate that both T-cells and B-cells were in active stage in periodontitis lesions. Differences of immunohistological features between gingivitis and periodontitis may be attributable to the heterogeneity of profiles of cytokine production by CD4+, CD45RO+ "memory' cells.

Adult↗

Expression of TIMP-1, TIMP-2 and collagenase mRNA in periodontitis-affected human gingival tissue.

Collagenolysis in periodontitis is thought to be modulated by the expression of three genes, collagenase, tissue inhibitors of metalloproteinases-1 and -2 (TIMP-1 and -2). We assessed the possible difference in TIMP-1, TIMP-2 and collagenase mRNA levels between gingival samples from patients with periodontitis and those from healthy subjects by reverse transcription-polymerase chain reaction (RT-PCR). This technique allows detection of transcripts from a very small sample quantity. The experiments showed that levels of TIMP-1 and collagenase transcripts relative to beta-actin are significantly higher in the diseased group than in healthy controls (8.11 +/- 0.83 versus 1.38 +/- 0.28% for TIMP-1 and 0.50 +/- 0.10 versus 0.0075 +/- 0.0024% for collagenase, respectively). The difference in TIMP-2 between the two groups (2.91 +/- 0.46 versus 1.84 +/- 0.87%) did not differ. Therefore, the host would have responded to the increase in collagenase level by preferentially producing TIMP-1 against tissue destruction. The differential gene expression of TIMP-1 and TIMP-2 in our study may account for a distinct genetic regulation of TIMP-1 and -2 in vivo.

Actins↗

Differential expression of CR3, Fc epsilon RII and Fc gamma RIII on polymorphonuclear leukocytes in gingival crevicular fluid.

Polymorphonuclear leukocytes (PMNLs) are the most numerous cell population among the cellular infiltrates in gingival crevicular fluid (GCF) and play important roles in the host-defensive system in the gingival crevices. We determined the percentage of neutrophils, eosinophils and basophils in total PMNLs by light microscopic observation using Randolph-methylene blue staining, then assessed flow cytometric differences in the expression of CR3, Fc gamma RIII, Fc epsilon RII, LFA-1 alpha, and LFA-1 beta on PMNL in GCF and peripheral blood (PB) from 21 patients with adult periodontitis (AP) and 13 healthy donors. Percentages of basophils and eosinophils were higher in GCF than in PB. In both AP patients and healthy subjects, expression of CR3 and Fc epsilon RII was higher while Fc gamma RIII was lower in GCF than in PB. The statistical analysis showed that the expressions of Fc gamma RIII and Fc epsilon RII on GCF PMNLs were lower in AP patients than in healthy subjects. Expressions of LFA-1 alpha and beta on GCF were similar to those on PB PMNLs. PB PMNLs stimulated in vitro with Porphyromonas gingivalis culture supernatant and fMLP displayed an expression pattern of CR3, Fc gamma RIII and Fc epsilon RII on GCF PMNLs. However, C5a and IL-1 failed to induce changes in Fc gamma RIII and Fc epsilon RII. The results indicate that GCF neutrophils are activated, present enhanced adhesion and a decreased IgG-binding ability which would reflect that they are at the terminal stage of activation, and that GCF contains a larger eosinophil fraction than in PB. Moreover, these GCF eosinophils appear to be activated.

Adult↗

[Detection of mecA gene of methicillin resistant staphylococci from oral swabs by polymerase chain reaction].

We evaluated the polymerase chain reaction method (PCR) for the rapid detection of methicillin resistant Staphylococcus aureus (MRSA), and compared it with the conventional culture method. Primers for amplification of mecA gene were synthesized by DNA synthesizer according to the published sequences of mecA gene. The results were as follows: Specificity of PCR was excellent, as there was no cross-reaction with any organism other than MRSA. Fifty colony forming units of MRSA were detected, indicating good sensitivity. We examined oral swabs from 13 bed-ridden patients (age range: 65-82 yrs) by PCR and the conventional culture method. The PCR elicited positive results in 6 out of 13 cases. MRSA or coagulase negative Staphylococci (CNS) in Mueller-Hinton agar containing 12.5 micrograms/ml methicillin were obtained from all of these PCR-positive specimens. Two of 7 PCR-negative specimens raised MRSA or CNS colonies, but the number of colonies from these specimens was below the sensitivity threshold of the PCR. The good specificity and sensitivity of the PCR method for the detection of mecA gene obtained in this study suggest the possibility of application of this method for detection of MRSA in clinical specimens.

Aged↗

[A case of Campylobacter fetus subspecies fetus meningitis].

A 40-year-old male with no history of underlying disease was admitted to Hokusho Central Hospital on May 25, 1991, complaining of high fever and headache. Physical examination on admission revealed a temperature of 38.5 degrees C, a pulse rate of 84 beat/min (relative bradycardia) and no abnormal findings for the chest or abdomen. Slight neck stiffness without Kernig's sign was observed at neurological examination. Laboratory data were: ESR 11 mm/lh, WBC 12000/mm3, C-reactive protein positive. Lumbar puncture showed an initial pressure of 230 mmH2O; CSF revealed a cell count of 2633/3 mm3 with mononuclear pleocytosis, total protein of 76 mg/dl and sugar of 54 mg/dl (CSF:blood glucose ratio 0.47). We initially suspected tuberculous or cryptococcal meningitis, but Campylobacter fetus subsp. fetus (C. fetus) was isolated from the CSF and venous blood on the 27th hospital day. IPM/CS 1 g/day, MINO 200 mg/day and FOM 4 g/day were intravenously administered. This antibiotic therapy was very effective: the patient was soon afebrile, and gradually all signs and symptoms were resolved. C. fetus was sensitive to IMP/CS, MINO, KM, GM, EM, OFLX, CP. The patient was discharged with no complication. He has eaten raw beef frequently before admission, but stool culture for C. fetus was negative.

Adult↗

Efficacy of intravenous itraconazole against experimental pulmonary aspergillosis.

The efficacy of intravenous itraconazole solubilized in hydroxypropyl-beta-cyclodextrin was assessed in a rat model of Aspergillus fumigatus pneumonia. Immunosuppressed rats were infected by intratracheal inoculation of A. fumigatus conidia. Intravenous administration of various doses of itraconazole was started immediately after infection and continued once a day for 7 days. A 10-mg dose of intravenous itraconazole per kg was as effective on survival as 1 mg of amphotericin B per kg daily (a survival rate of 100% in 28 days), while treatment with 1 mg/kg did not increase the survival rate. The 50% lethal dose of intravenous itraconazole given to immunosuppressed and uninfected rats for 7 days was 24.5 mg/kg/day. A microbiological assay to estimate accumulation in tissue after five daily intravenous administrations of itraconazole at 10 mg/kg showed that itraconazole and its active metabolites were present in the lungs for at least 6 h, reaching the MIC as previously described (B. Dupont and E. Drouchet, Rev. Infect. Dis. 9(Suppl. 1):71-76, 1987; A. Espinel-Ingroff, S. Shadomy, and R. J. Gebhart, Antimicrob. Agents Chemother. 26:5-9, 1984). Intravenous itraconazole was considered to be worth evaluating in clinical trials of aspergillosis.

Animals↗

Changes in complement and immunoglobulin G receptor expression on neutrophils associated with Porphyromonas gingivalis-induced inhibition of phagocytosis.

We examined the phagocytic capacity and receptor expression on neutrophils stimulated with Porphyromonas gingivalis soluble products. Stimulated neutrophils had decreased phagocytic capacities and altered expression of CR1, CR3, Fc gamma RII, and Fc gamma RIII. For cases in which TLCK (N-alpha-p-tosyl-L-lysine chloromethyl ketone) neutralized the effects of the stimuli, the P. gingivalis-derived factors causing the phenomena seem to be trypsin-like proteases.

Humans↗

Dietary diacylglycerol-dependent reduction in serum triacylglycerol concentration in rats.

The effects of dietary diacylglycerol consisting of 1,3 (65.2%) and 1,2 species (32.6%) and triacylglycerol (rapeseed oil) on the serum and hepatic lipid profiles were compared in the rat. The fatty acid composition was similar between these dietary lipids. The dietary acylglycerols were added to the experimental diets so as to provide the same amounts of fatty acids (9.39%). Dietary diacylglycerol compared with triacylglycerol significantly reduced concentrations of serum triacylglycerol at 17 and 34 days of the feeding periods without influencing those of phospholipid and cholesterol. There were no significant differences in the concentrations of hepatic triacylglycerol, cholesterol and phospholipid between the two groups of rats at 34 days of the feeding period. In the second trial, triacylglycerol in the experimental diet was replaced by varying amounts of diacylglycerol while maintaining the fatty acid contents (9.39%). After 14 days of the feeding period, significant reductions in serum triacylglycerol levels were confirmed in the groups of rats fed the diets in which diacylglycerol fatty acids supplied more than 50% (50, 75 and 100%) of total dietary fatty acids. Thus, it was confirmed that dietary diacylglycerol compared with triacylglycerol exerts a potent serum triacylglycerol-lowering effect in the rat.

Animals↗

Treatment of disseminated intravascular coagulation and its prodromal stage with gabaxate mesilate (FOY): a multi-center trial.

One hundred and ninety-one patients with disseminated intravascular coagulation syndrome (DIC) or its prodromal stage (preDIC) were treated with only gabaxate mesilate (FOY) (group G) or a combination of gabaxate and unfractionated heparin (group GH), and the efficacy of gabaxate was evaluated in a multicenter study. Following the treatment, the mean DIC score, which was evaluated on the basis of clinical symptoms and hemostatic parameters, decreased significantly to 5.58 +/- 3.48 from 6.75 +/- 3.14 in group G (p < 0.001) and to 6.34 +/- 3.33 from 7.31 +/- 3.00 in group GH (p < 0.05). In patients with overt DIC, the mean score decreased to 6.71 +/- 3.54 from 8.42 +/- 2.84 (p < 0.001). In DIC, the rate of overall efficacy was 46.2% in group G and 35.1% in group GH. In preDIC, it was 41.5% in group G and 27.3% in group GH. No side effects, including severe bleeding, were found in this study. The results indicate that gabaxate mesilate is clinically effective for patients with DIC and preDIC.

Adolescent↗

Importance of central nervous system involvement by neoplastic cells in a patient with Waldenström's macroglobulinemia developing neurologic abnormalities.

The clinicopathology of central nervous system (CNS) involvement with tumor formation in the brain of a patient with Waldenström's macroglobulinemia (WM) who developed neurologic abnormalities in the absence of blood hyperviscosity is reported. Extravascular infiltration by monoclonal lymphoplasmacytoid cells with considerable perivascular disruption of the brain and reactive gliosis was a conspicuous histopathologic picture. The tumor as well as the patient's neurologic symptoms were successfully controlled by local radiation to the brain. This case report illustrates the importance of CNS involvement by neoplastic cells in the differential diagnosis of a patient with WM developing neurologic abnormalities.

Aged↗

A mechanism of erythromycin treatment in patients with diffuse panbronchiolitis.

Recently, "low-dose and long-term" erythromycin treatment has been reported as effective on diffuse panbronchiolitis (DPB), but its mechanism is still obscure. Patients with DPB were found to have significantly higher percentages of neutrophils in the pre-erythromycin treatment bronchoalveolar lavage fluid (BALF) than healthy nonsmoking volunteers (p < 0.001). They showed a significant reduction in BALF neutrophil percentages after erythromycin treatment (p < 0.01). The neutrophil chemotactic activity (NCA) was significantly elevated in BALF obtained from 19 patients with DPB compared with that from healthy volunteers (p < 0.001). A significant reduction in the NCA was observed in post-erythromycin treatment BALF of 11 patients with DPB (p < 0.001). Additionally, there was a significant correlation between the reduction of NCA and neutrophil percentage in pre- and post-erythromycin treatment BALF (r = 0.726, p < 0.05). Finally, we investigated the effect of erythromycin on the intrapulmonary influx of neutrophils by intratracheal injection of lipopolysaccharide (LPS) and interleukin-8 (IL-8) in mice. The intrapulmonary influx of neutrophils was significantly suppressed (p < 0.001) in mice intraperitoneally injected with erythromycin at 5 mg per animal 2 h before intratracheal injection of LPS (control group: 6.5 +/- 1.6 x 10(5) versus erythromycin-treated group: 1.7 +/- 0.5 x 10(5)), but not 10 h before lung challenge. This inhibition was observed at 6 h after lung challenge and became maximal with 84% suppression at 24 h. Week-long administration of erythromycin did not alter the intrapulmonary influx of neutrophils. The number of neutrophils in the peripheral blood was not affected by erythromycin, indicating that the drug was not toxic.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Elevation of tumor-associated carbohydrate antigens in patients with diffuse panbronchiolitis.

We investigated the serum levels of the tumor-associated carbohydrate antigens sialyl SSEA-1 (SLX) and sialyl Lewis(a) (CA19-9) in patients with diffuse panbronchiolitis (DPB) and other nonmalignant lung diseases. Both antigens were high in the serum and bronchoalveolar lavage fluid (BALF) of patients with DPB, bronchiectasis (BE), idiopathic pulmonary fibrosis (IPF), and interstitial pneumonia associated with collagen vascular disease (CVD). Markedly high levels of the antigens were demonstrated in the serum and BALF from patients with DPB. An immunohistochemical study of open-lung biopsy specimens from patients with DPB indicated that these antigens were selectively expressed on the bronchiolar epithelial cells and mucinous exudates in airspaces. Low-dose, long-term erythromycin (EM) treatment was recently reported to be effective for DPB, and we investigated its influence on serum and BALF antigen levels in DPB patients. Antigen levels in both serum and BALF decreased after EM treatment, with improvement of symptoms and laboratory data, and there was a significant correlation between the reduction in the SLX level in serum and neutrophil percentage in BALF pre- and post-EM treatment. Our result suggests that secreted carbohydrate antigens from the bronchiolar epithelium in DPB may appear in the serum as a result of airway damage in the lower respiratory tract, and serum levels of the antigens may be decreased by a reduction in neutrophils in BALF after EM treatment.

Adult↗

[Effects of terguride, an ergot alkaloid derivative, on the central nervous system: biochemical and behavioral studies].

Effects of terguride, a 9,10-dihydrogenated derivative of lisuride, on the central nervous system were investigated in rodents in comparison with those of lisuride. In vitro binding studies in rat brains showed that terguride, similar to lisuride, had a high affinity for D2-, 5-HT1A-, 5-HT2-, alpha 1- and alpha 2-receptors. Terguride, as does lisuride, induced hypomotility and yawning at low doses in rats, suggesting its presynaptic D2-agonist action. Terguride, unlike the postsynaptic D2-agonist lisuride, induced neither hypermotility nor stereotypy in rats and guinea pigs, but suppressed the hypermotility and stereotypy induced by apomorphine. Terguride suppressed haloperidol-induced catalepsy in rats and induced contralateral rotations in unilaterally 6-OHDA-lesioned rats, as does lisuride. These effects may be due to the postsynaptic D2 partial agonist action. Terguride, unlike lisuride, neither induced the serotonin syndrome nor generalized to the discriminative stimuli of the 5-HT1A- agonist 8-OH-DPAT in rats. Terguride did not induce head twitch in mice. Terguride blocked noradrenaline-induced lethality and clonidine-induced hypothermia at high doses in mice. Repeated administration of terguride did not affect the behavioral actions in rats. Thus, the effects of terguride on the central nervous system seems to be produced by mediation of the agonist and partial agonist actions at presynaptic and postsynaptic D2- receptors, respectively.

Animals↗

Effects of menatetrenone on bone loss induced by ovariectomy in rats.

The effects of menatetrenone, a vitamin K2 homologue, on bone loss induced by ovariectomy in rats were studied in 3 experiments. Menatetrenone was given as a dietary supplement. In experiment 1, at 2 weeks postovariectomy, menatetrenone (10 mg/kg/day given for 2 weeks) inhibited the decrease in bone density of the femoral metaphysis induced by the ovariectomy. In experiment 2, menatetrenone (3 or 30 mg/kg/day given for 6 months) inhibited the decrease in bone strength of the femur and the decrease in calcium and hydroxyproline content of the femoral diaphysis at 6 months postovariectomy. In experiment 3, menatetrenone treatment, at 30 or 100 mg/kg/day for 6 months, protected against the decrease in bone strength and calcium and hydroxyproline content in the bone loss model induced by ovariectomy and calcium-deficient diet. These findings suggest that menatetrenone protects against the bone loss induced by ovariectomy.

Animals↗

Effect of lactosucrose (4G-beta-D-galactosylsucrose) on fecal flora and fecal putrefactive products of cats.

The effects of lactosucrose (4G-beta-D-galactosylsucrose) on fecal flora and fecal putrefactive products were studied in 3 Himalayan and 5 Persian cats fed 175 mg of lactosucrose/each/day for 2 weeks. During lactosucrose administration, the counts of lactobacilli increased significantly (p < 0.05), whereas the counts of clostridia, including Clostridium perfringens and Enterobacteriaceace decreased significantly (p < 0.05). The levels of fusobacteria and staphylococci were decreased significantly (p < 0.01) on day 7 of lactosucrose administration, while the counts of bacteroides increased significantly (p < 0.05) and day 14 of lactosucrose administration compared to pre-administration. In frequency of occurrence, bifidobacteria increased significantly (p < 0.001) during lactosucrose administration, while Spirochaetaceae and lecithinase-negative clostridia decreased significantly (p < 0.05) on day 14 of lactosucrose administration compared to pre-administration. No detectable change occurred in the counts of other organisms throughout the experimental periods. Fecal concentrations of ammonia, indole, ethylphenol, and urinary ammonia were reduced significantly (p < 0.05) on day 14 of lactosucrose administration. The water content and weight of the feces increased slightly during lactosucrose administration, but the pH values decreased slightly. The environmental ammonia and the fecal odor also decreased remarkably (p < 0.01) during administration.

Animals↗