Search PubMed⌕ Search

Biomedical subjects

K Hara

Publications and source records attributed to K Hara.

At least 361 records · Page 20Linked to original sources

Non-functional pituitary chromophobe adenoma in a calf.

A 5-month-old male calf showed neurological signs, including circling, in-co-ordination, depression, blindness and eventual recumbency. On necropsy, a mass measuring 3.5 x 4.5 x 5 cm was found at the base of the brain, at the level of the pituitary gland. The hypothalamus and optic nerves were compressed by the dorsally expanding mass. Non-functional pituitary chromophobe adenoma was diagnosed from histochemical, immunohistochemical and electron microscopical findings.

Adenoma, Chromophobe↗

Effects of competitive blood flow on arterial graft patency and diameter. Medium-term postoperative follow-up.

To identify predictors of arterial graft patency, we followed up 30 internal thoracic arterial grafts and 23 right gastroepiploic arterial grafts in situ with patency documented during postoperative angiography. After 24 months of follow-up on average, repeat angiography detected that one internal thoracic artery and two gastroepiploic arteries were anatomically occluded and that the other three gastroepiploic arteries were nonfunctioning. The logistic regression model identified a relationship between graft patency and competitive flow, which was detected as stenosis in the recipient coronary arteries (coefficients, p < 0.05; model, Hosmer-Lemeshow chi2 statistic 3.59, p = 0.89). The linear regression model demonstrated that changes in graft luminal diameter correlated with competitive flow (p < 0.01), smoking history (p < 0.05), and type of arterial grafts (p < 0.001) (R2 = 0.40, adjusted R2 = 0.36). The findings suggest a temporal relationship between competitive flow and prognosis of arterial graft.

Abdominal Muscles↗

Investigation of the mechanism of alcohol-induced bronchial asthma.

BACKGROUND: Many Japanese patients with asthma experience episodes or exacerbation of asthma after alcohol consumption. This phenomenon is not seen in Caucasians and is specific to Asians. This has been thought to be attributable to a difference in alcohol metabolism, in particular the metabolism of acetaldehyde, between Asians and Caucasians. METHODS: An oral ethanol challenge test, a leukocyte histamine release test, and an ELISA for detection of IgE specific to acetaldehyde-human serum albumin conjugate were carried out in 42 adults with bronchial asthma and nine healthy adults. RESULTS: Fifty-five percent of the patients with asthma responded to the ethanol challenge and showed a 20% or greater reduction in forced expiratory volume in 1 second. Blood acetaldehyde and plasma histamine levels were significantly higher in responders than in nonresponders. The leukocyte histamine release test revealed no ethanol-induced histamine release. Acetaldehyde, on the other hand, was found to induce histamine release in a volume-dependent manner. The histamine release was significantly higher in the asthma group (both responders and nonresponders) than in the healthy control group. ELISA did not detect any IgE specific to acetaldehyde-human serum albumin conjugate. CONCLUSION: Alcohol-induced bronchial asthma seems to develop as follows. Alcohol elevates blood acetaldehyde levels, which leads to degranulation of mast cells (or basophils). The resultant release of chemical mediators, such as histamine, induces asthma.

Acetaldehyde↗

Rapid detection and identification of mycobacteria by combined method of polymerase chain reaction and hybridization protection assay.

A new method for the rapid detection and identification of mycobacteria, combining polymerase chain reaction (PCR) with DNA probe, was developed. The mycobacterial 16S rRNA encoding gene was amplified by nested PCR, and the PCR product was identified by hybridization protection assay using acridinium ester labelled DNA probe. The optimum temperature for hybridization of PCR product and DNA probe was estimated as 55 degrees C. The specificity of the combined method was excellent in the detection and identification of Mycobacterium tuberculosis and Mycobacterium avium-intracellulare complex (MAC). The detection limit was 10 fg DNA for M. tuberculosis, and 100 fg DNA for MAC. Results of preliminary clinical investigation of this method using 207 clinical specimens demonstrated an efficient detection and identification of M. tuberculosis and MAC. These results indicate that the new combined method may be a useful test for the rapid detection and identification of M. tuberculosis and MAC in clinical specimens.

Humans↗

Inhibitory effect of thromboxane A2 synthetase inhibitor, DP-1904, on antigen-induced contraction of human lung parenchyma.

BACKGROUND: Several mediators are released from mast cells during allergic reactions. These substances cause contraction of airway smooth muscles, increase the permeability of blood vessels, and enhance mucous secretion. Among these mediators, thromboxane A2 (TXA2) has a particularly strong bronchoconstrictive effect. OBJECTIVES: We examined antigen-induced contraction of excised human lungs and the suppressive effects of TXA2 synthetase inhibitor on TXA2 release. METHODS: Human lung parenchymal strips were subjected to passive sensitization with sera of 5+ RAST titer to the mite. They were suspended in magnus baths, to which buffer and 10(-4) to 10(-8) M of DP-1904, an inhibitor of TXA2 synthetase, were added. Following the measurement of TXB2 and leukotriene (LT) concentrations in each bath, parenchymal contraction was induced by the addition of a mite antigen. The concentration of TXB2 and LT was measured after contraction. RESULTS: Antigen-induced release of TXB2 was significantly suppressed by DP-1904 in a concentration-dependent manner. DP-1904 did not inhibit parenchymal contraction and the release of LT. CONCLUSIONS: Antigen-induced parenchymal contraction was not suppressed by inhibition of TXA2 release, suggesting that DP-1904 may not be effective in asthma.

Aged↗

Cathepsin B and D expression in squamous cell carcinoma.

To elucidate involvement of proteinases in malignancy of keratinocytes, expression of cathepsin B, a cysteine proteinase, and cathepsin D, an aspartic proteinase, was ascertained in formalin-fixed paraffin-embedded specimens of normal skin, squamous cell carcinoma (SCC). Bowen's disease, seborrhoeic keratosis and basal cell carcinoma (BCC). Presence of procathepsin B and an intermediate form of cathepsin D was confirmed by Western blotting and enzyme activity analysis. Cathepsin B stained more intensely in SCC tumour cells than in normal epidermis; staining patterns were diffuse, granular or both. Diffuse and granular patterns (procathepsin B and mature enzyme, respectively) appeared in inner and outer parts of tumour islands, respectively. Five of 20 cases of Bowen's disease showed diffuse enhanced cathepsin B expression; 20 cases of seborrhoeic keratosis or BCC did not. Cathepsin D stained intensely in tumour cells of half the SCC cases. The staining manner and distribution of cathepsins B and D was similar in the cytoplasm of cancer cells. No enhanced staining of cathepsin D was seen in any cases of Bowen's disease, seborrhoeic keratosis, or BCC. Coexistence and localization of active mature forms of cathepsins B and D suggests that cooperation between the two enzymes may play an important part in invasion of SCC.

Blotting, Western↗

Biased expression of T cell receptor V beta genes in periodontitis patients.

The aim of the present study was to investigate the hypothesis that there is selective activation and expansion of a limited repertoire of T cell receptor (TCR)-bearing T cells in periodontitis tissue. We studied TCR V beta gene expression in gingival tissues of periodontitis lesions and compared these with peripheral blood mononuclear cells (PBMC) from the same patients using polymerase chain reaction (PCR) amplification with 22 V beta-specific sense primers in combination with a common antisense C beta-specific primer. After initial therapy, gingival tissue specimens were obtained from 14 periodontitis patients at the time of periodontal surgery, and PBMC were also obtained from the same patients by density gradient centrifugation. Total RNA was extracted and analysed by reverse transcription PCR. The PCR products were electrophoresed on a 2% agarose gel and stained with ethidium bromide. For each product, gingival tissue and the respective peripheral blood were compared. The TCR repertoire identified in the PBMC in general overlapped with that of the gingival tissue. However, V beta 6 appeared to be over-expressed in the gingival tissues compared with the PBMC, but V beta 16 appeared to be under-expressed in the gingival tissues. Although it is not known whether this is due to antigen-specific activation or superantigen activation, the data suggest that there may be as yet uncharacterized T cell subsets in periodontal disease tissue.

Adult↗

Autoimmune cholangitis syndrome with a bias towards primary biliary cirrhosis.

The apparent coexistence of primary biliary cirrhosis (PBC) and autoimmune hepatitis in the same patient raises unresolved problems for nosology and therapy. These are exemplified by a 45-year-old Japanese woman with overlapping clinical, serological and histological features of autoimmune cholangitis and autoimmune hepatitis. The classical serological test for PBC, antimitochondrial antibody (AMA) by immunofluorescence, was atypical. By immunoblotting there was reactivity with one of the enzymes of the 2-oxo-acid dehydrogenase complex (2-OADC) family, now recognized as autoantigens responsible for AMA reactivity. Also there was reactivity by immunofluorescence for antinuclear antibodies (ANA), one showing the typical speckled pattern of anti-Sp-100 and the other the peripheral pattern of antinuclear membrane antibody, both with titres > 10(6). There was also a positive result to the lupus erythematosus (LE) cell test. Treatment with ursodeoxycholic acid was beneficial. Thus while the clinical presentation suggested the overlapping syndrome of autoimmune hepatitis and PBC, PBC eventually proved to be the likely diagnosis. We suggest that apparent cases of overlapping PBC-autoimmune cholangitis-hepatitis syndromes, after detailed testing, will mostly align with PBC.

Antibodies, Antinuclear↗

IL-1 beta mRNA as the predominant inflammatory cytokine transcript: correlation with inflammatory cell infiltration into human gingiva.

Expression of mRNA for IL-1 alpha, IL-1 beta, IL-2, IL-4, IL-5, IL-6 and TNF-alpha in inflamed gingiva was quantitatively examined by ribonuclease protection assay and in situ hybridization. The IL-1 beta mRNA expression level was statistically high (P < 0.05) in periodontitis-affected tissues compared with that in gingivitis-affected tissues. The densities of macrophages (identified as CD68-positive cells) and CD45RO-positive cells infiltrating in the inflamed gingiva correlated statistically with IL-1 beta transcript levels (macrophages, P < 0.001; CD45RO-positive cells, P < 0.002). In situ hybridization revealed IL-1 beta mRNA expression in infiltrating cells, presumed to be macrophages. The IL-1 alpha and IL-6 mRNA expression levels were much lower than the IL-1 beta transcript level, and mRNAs for IL-2, IL-4, IL-5 and TNF-alpha were negligible in these gingival tissues. The results indicate that IL-1 beta is a cytokine expressed predominantly in inflamed gingiva and reflects the density of infiltrating macrophages and other leukocytes.

Adolescent↗

Biased T cell receptor V gene usage in tissues with periodontal disease.

In an attempt to characterize TCR V gene usage in human periodontally diseased tissue, V alpha 2, V beta 5.2-3, V beta 5.3, V beta 5.1, V beta 6.7, V beta 6.7, V beta 8 and V beta 12.1 expressions were examined. Serial cryostat sections obtained from 20 periodontitis and 9 gingivitis biopsies were then reacted with monoclonal antibodies directed to each repertoire. The technique was combined with a sensitive alkaline phosphatase-anti-alkaline phosphatase method. Peripheral blood was obtained from 10 periodontitis and 2 gingivitis patients. TCR repertoire was also quantified by flow cytofluorography with FITC-conjugated antibodies. Cells displaying binding of each antibody were counted. The proportions to CD3-positive cells were then calculated. The pattern of each TCR V gene product expression in inflamed gingiva exhibited individual variation, nevertheless, a consistent pattern emerged. The V beta 5 subfamily and V beta 6.7 were frequently used repertoires in gingiva, whereas the V alpha 2 and V beta 8 subfamily were underexpressed in most cases. Furthermore, the TCR V gene product expression in gingival tissue was biased compared with autologous peripheral blood. Three of 10 periodontitis subjects showed 1 or 2 strikingly overrepresented repertoire comparatively with autologous blood. In these 3 subjects V beta 6.7 was overexpressed in two cases and 5.2-3, V beta 8 and V beta 12.1 were overexpressed in one case. These results suggest that gingival T-cells are not randomly mobilized from peripheral blood and that local events influence the TCR repertoire at the level of T-cell recruitment or T-cell expansion.

Adult↗

Responses of periodontal nerve terminals to experimentally induced occlusal trauma in rat molars: an immunohistochemical study using PGP 9.5 antibody.

The response of periodontal nerves to experimentally induced occlusal trauma in rat molars was assessed by immunohistochemistry for protein gene product 9.5 (PGP 9.5) at light and electron microscopic levels, and by computerized image analysis. The occlusal surface on the left upper first molar of 8-wk-old male Wistar rats was raised approximately 1 mm under ether anaesthesia. The rats were perfusion-fixed on d 1, 2, 3, 4, and 7 after bite-raising and then decalcified for 2-3 wk. Frozen sagittal cryostat sections were stained by the avidin-biotin complex method. By the second day after bite-raising many Ruffini endings were swollen and their outline unclear at the light microscopic level. Transmission electron microscopy disclosed PGP 9.5 reaction products within Ruffini endings that had unusually long cytoplasmic projections extending through enlarged slits of the Schwann sheaths and also diffuse extracellular PGP 9.5-immunoreactivity near the Ruffini endings. From d 2 to 4, thin nerve fibres on the pressure side of the periodontal ligament were orientated irregularly and had a prominent beaded appearance. An increase in beaded nerve terminals occurred at d 2-4 post elevation, and decreased later. These results suggest that occlusal trauma indices specific changes in the distribution and shape of nerve terminals in the periodontal ligament.

Animals↗

Cellular immunity and hypersensitivity as components of periodontal destruction.

BACKGROUND: Cellular immunity has been implicated in periodontal destruction for over 25 years. Studies in the 1970s used lymphocyte transformation and lymphokine assays to establish a role for cell-mediated mechanisms in periodontal disease. Immunohistological studies subsequently showed that the formation of gingivitis followed a similar pattern to the formation of a delayed type hypersensitivity reaction. Further functional studies suggested that a T cell/macrophage immunoregulatory imbalance may exist locally in the periodontitis lesion and that this imbalance may be antigen specific. RECENT EVIDENCE: More recently, T cell subsets have been dichotomised on the basis of their cytokine profiles. In general, ThI cells produce IL-2 and IFN-gamma while Th2 cells produce IL-4, IL-5 and IL-6. The major function of Th1 cells is to mediate delayed type hypersensitivity. In contrast the major function of Th2 cells is to provide B cell help. HYPOTHESIS: A model for periodontal disease has now been developed based on this functional dichotomy which provides a framework for the study of cytokine profiles in periodontal disease. Early studies in this context have demonstrated a higher proportion of IL-4 producing cells in periodontitis tissues suggesting a role for Th2 cells in the progressive lesion. Clonal studies have shown that the selection of a particular cytokine profile is not antigen dependent and that differences may be due to the host susceptibility although this remains to be determined. CONCLUSION: These emerging data clearly establish a role for cell-mediated mechanisms in the control of periodontal destruction and raise the possibility that in the future cytokine therapy for the treatment of periodontal disease in susceptible subjects may become a viable option.

Animals↗

Relationship between rifampin MICs for and rpoB mutations of Mycobacterium tuberculosis strains isolated in Japan.

We analyzed the relationship between rifampin MICs and rpoB mutations of 40 clinical isolates of Mycobacterium tuberculosis. A point mutation in either codon 516, 526, or 531 was found in 13 strains requiring MICs of > or = 64 micrograms/ml, while 21 strains requiring MICs of < or = 1 microgram/ml showed no alteration in these codons. However, 3 of these 21 strains contained a point mutation in either codon 515 or 533. Of the other six strains requiring MICs between 2 and 32 micrograms/ml, three contained a point mutation in codon 516 or 526, while no alteration was detected in the other three. Our results indicate that the sequencing analysis of a 69-bp fragment in the rpoB gene is useful in predicting rifampin-resistant phenotypes.

Amino Acid Sequence↗

New drug susceptibility test for Mycobacterium tuberculosis using the hybridization protection assay.

We developed a novel method for early detection of drug-resistant strains of Mycobacterium tuberculosis by using the hybridization protection assay (HPA). The number of viable bacteria during the incubation period correlated well with the number of relative light units measured by the HPA. In addition, the relative light unit values of susceptible strains on the first, third and fifth days of incubation were significantly different from those of resistant strains for both isoniazid and rifampin. Our results suggest that after isolation of the organism from clinical specimens, drug-resistant strains of M. tuberculosis are accurately detected by the HPA even after 1 day of incubation with the drug.

Antibiotics, Antitubercular↗

After-effects of exercise on haemodynamics and muscle sympathetic nerve activity in young patients with dilated cardiomyopathy.

OBJECTIVE: To determine the after-effects on sympathetic nerve activity and calf and systemic haemodynamics of symptom-limited exercise in young patients with dilated cardiomyopathy. PATIENTS: 14 young patients with dilated cardiomyopathy (mean (SEM) age 35 (2) yr) and 17 healthy controls (age 29 (2) yr). METHODS: Blood pressure, muscle sympathetic nerve activity, calf blood flow, plasma noradrenaline, and stroke volume were recorded during baseline rest and an hour after symptom-limited treadmill exercise (up to 45 min) at 70% of resting heart rate reserve. RESULTS: Before exercise, sympathetic nerve activity (45 (6) v 21 (2) bursts.min-1; P = 0.001) and calf vascular resistance (55 (5) v 31 (3) units; P < 0.0005) were higher in the dilated cardiomyopathy group, and there was a significant correlation between these two variables (r = +0.64; P < 0.001). Patients with ventricular dysfunction exercised for 31 (3) min. In both groups there were significant and similar reductions in diastolic blood pressure, total peripheral resistance, and calf vascular resistance after exercise. Sympathetic nerve activity and plasma noradrenaline were unchanged and there was no longer any relation between muscle sympathetic nerve activity and calf vascular resistance. Cardiac output increased in both groups but, in contrast to healthy controls, mean values for systolic blood pressure and stroke volume (P < 0.005) did not decrease in the cardiomyopathy group. For similar reductions in total peripheral resistance, there were two to three fold greater increases in stroke volume after exercise in patients with left ventricular dysfunction (P < 0.03). There was no relation between exercise duration and the magnitude of these after-effects of exercise in these patients. CONCLUSIONS: In young patients with dilated cardiomyopathy the haemodynamic after-effects of submaximal symptom-limited exercise resemble responses to pharmacological afterload reduction but are not accompanied by reflex sympathetic activation. Sustained calf and systemic vasodilation after exercise were not attenuated, as compared with healthy controls. These cardiac, peripheral, and sympathoneural after-effects provide further support for exercise training as a non-pharmacological adjunct to the management of chronic stable heart failure.

Adult↗

Interleukin 1 beta, tumor necrosis factor alpha, and interleukin 8 in bronchoalveolar lavage fluid of patients with diffuse panbronchiolitis: a potential mechanism of macrolide therapy.

We measured the levels of interleukin (IL) 1 beta, tumor necrosis factor alpha, and IL-8 in bronchoalveolar lavage fluid (BALF) and sera of patients with diffuse panbronchiolitis (DPB) before and after administration of erythromycin or roxithromycin. The pretreatment levels of IL-1 beta and IL-8 were significantly higher in the BALF of patients with DPB than in the BALF of patients with sarcoidosis and controls. The tumor necrosis factor alpha level was also higher than in controls, but not statistically significant. There was a significant correlation between percentage of neutrophils and IL-8 level in the BALF of DPB patients (r = 0.509; p < 0.05) on the one hand and between IL-1 beta and IL-8 on the other (r = 0.476; p < 0.04). Treatment for 1-24 months significantly reduced BALF levels of IL-1 beta and IL-8 of DPB patients in parallel with a reduction in BALF neutrophils. The serum level of IL-8 of DPB patients was higher, albeit insignificant, than that of controls and significantly lower than that in the BALF of the same patients (p = 0.0088). Serum IL-1 beta was below the detection limit. In addition, the concentration of IL-8 in alveolar macrophages obtained from 2 volunteers before and after oral erythromycin administration also decreased ex vivo. Our results indicate that IL-8 induces the migration of neutrophils to inflammatory sites. It is possible that the macrolides impair production and/or secretion of these cytokines, ultimately reducing neutrophil accumulation in the airway.

Adult↗