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Biomedical subjects

K Hara

Publications and source records attributed to K Hara.

At least 487 records · Page 27Linked to original sources

Expression of human T lymphotropic virus type 1 (HTLV-1) tax/rex gene in fresh bronchoalveolar lavage cells of HTLV-1-infected individuals.

Accumulating evidence has suggested the involvement of HTLV-1 in the inflammatory lesions of various organs, including the lung. However, the causal relationship between HTLV-1 and inflammatory responses in the organs remains to be elucidated. In order to evaluate the expression of HTLV-1 and its effects in the lung, we examined the expression of mRNA for the HTLV-1 tax/rex gene in fresh bronchoalveolar lavage cells (BALC) and peripheral blood mononuclear cells (PBMC) of 23 seropositive individuals, including six patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), by use of an improved method of reverse transcription-polymerase chain reaction (RT-PCR). The tax/rex mRNA was more frequently detected in BALC than in PBMC. All the HAM/TSP patients and eight of 17 carriers without neurological symptoms showed the expression of tax/rex mRNA in the BALC. IgM class antibodies to HTLV-1 were preferentially detected in sera of the tax/rex mRNA-positive individuals. The detection of tax/rex mRNA correlated closely with the presence of lymphocytosis accompanied by an elevated proportion of IL-2 receptor-bearing T cells in the BALC. Our findings indicate the crucial role of viral expression in the inflammatory response in the lung in HTLV-1-infected individuals.

Adolescent↗

Activation of macrophages and expansion of specific T lymphocytes in the lungs of mice intratracheally inoculated with Cryptococcus neoformans.

A quantitative and qualitative change in inflammatory cells in the lungs of mice after intratracheal inoculation of heat-killed Cryptococcus neoformans was examined by direct analysis of the pulmonary intraparenchymal leucocytes. Macrophages and T and B lymphocytes increased, peaked at day 7, and then gradually decreased to the basal level. Macrophages were activated 7 days after the inoculation, as indicated by the enhanced expression of MHC class II, intercellular adhesion molecule-1 (ICAM-1) and Fc receptor (FcR), which have been known as their activation markers. T cells were also activated, as indicated by the induction of IL-2 receptor (IL-2R) and the enhanced expression of leucocyte function-associated molecule-1 (LFA-1) and ICAM-1, a pair of adhesion molecules which have also been regarded as T cell activation markers. CD4+ T cells preferentially accumulated in lungs, and proliferated in vitro by stimulation with heat-killed whole yeast cells, suggesting that at least some of the infiltrated T cells expand locally in response to the organisms. These results demonstrate that the activation of macrophages and T cells reactive to C. neoformans is induced in lungs after intratracheal inoculation of heat-killed organisms, and suggest that these cells interact to eliminate organisms more efficiently from the host.

Animals↗

IL-4- and IL-6-producing cells in human periodontal disease tissue.

IL-4- and IL-6-producing cells in human periodontal disease tissues were investigated using immunohistochemical and in situ hybridization techniques. Immunohistochemical analysis demonstrated the presence of IL-4-producing cells within the CD45RO+ subset and the percentage of IL-4+ cells was significantly higher in periodontal lesions than in gingivitis tissues (p < 0.01). The percentage of IL-6-producing memory cells was higher in periodontal lesions compared with gingivitis tissues, although it was not statistically significant (p > 0.05). A reverse tendency in IL-4- and IL-6-positive cells was observed in a few individual cases. No IL-4 mRNA could be detected using the in situ hybridization technique. However, high levels of IL-6 mRNA were present in clinically healthy tissues, with a further increase in both epithelium and connective tissues affected by gingivitis, although only the former was significant (p < 0.025). There was a significant decrease in IL-6 mRNA in both the connective tissue (p < 0.025) and epithelium (p < 0.01) in periodontitis tissues compared with levels in gingivitis tissues. However, the levels of IL-6 mRNA in periodontal tissues were high compared with those of IL-1 mRNA, which was used in this study as a positive control. These results suggest that Th2-type cells may accumulate in periodontal lesions.

Adult↗

Evidence for the existence of intraepithelial nerve endings in the junctional epithelium of rat molars: an immunohistochemical study using protein gene product 9.5 (PGP 9.5) antibody.

Innervation of the junctional epithelium was investigated in rat molars by means of immunohistochemistry for protein gene product 9.5 (PGP 9.5) at light and electron microscopic levels. In comparison with our previous study on same tissues using neurofilament protein (NFP)-antibody, the PGP 9.5-immunostaining further disclosed numerous nerve fibers in the gingiva of rat molars and revealed the existence of a well-developed plexus of PGP 9.5-positive nerve fibers. The interproximal portion also contained numerous nerve fibers. Observation of horizontal sections revealed a denser innervation toward the inner junctional gingival epithelium than the outer marginal epithelium. The nerve fibers, beaded in appearance and extending from the nerve bundles in the lamina propria, penetrated into the junctional epithelial layer and were distributed throughout the junctional epithelium, with some nerves being located near the epithelial surface. Non-neuronal cells showing PGP 9.5-immunoreactivity were absent in the junctional epithelium. In immunoelectron microscopy, the axoplasm of nerves in the gingiva was filled with electron-dense reaction products of PGP 9.5, except for the cell organellae. The nerve fibers were devoid of Schwann cell investment and terminated among the epithelial cells in the junctional epithelium, frequently beneath the epithelial surface. The intraepithelial nerve endings contained various kinds of vesicles including large-cored ones, supporting the presence of peptidergic innervation shown by previous studies. These findings confirmed the usefulness of PGP 9.5-immunohistochemistry for the identification of delicated nerve fibers in dental tissue, and suggested the dense network of nerve fibers that may serve as sensory receptor and other functions in the junctional epithelium.

Animals↗

[Five cases of tsutsugamushi disease].

We experienced 5 cases of tsutusgamushi disease from October to November 1993 at Hokusyo Central Hospital. All patients showed high fever, skin rash and eschar and four patients showed lymph node swelling. All cases were diagnosed serologically by indirect-immunofluorescence technique and treated with minocycline. In a survey of anti-Karp, Kato, Gilliam, Kawasaki, Kuroki antibodies, all patients showed the highest antibody titers against the Kawasaki strain and they were considered Kawasaki type. In Nagasaki Prefecture, the number of patients with tsutsugamushi disease has been increasing since 1982. We carried out immunologic and epidemiologic studies about this disease in Nagasaki Prefecture.

Adult↗

Epidemiology studies of clinical isolates of Cryptococcus neoformans of Japan by restriction fragment length polymorphism.

Previous epidemiological studies of Cryptococcus neoformans infection in Japan showed that only C. neoformans var. neoformans is present and serotype A is the most common with frequencies in excess of 95%. A DNA fingerprinting method, using a genomic DNA probe (UT-4p), has become available recently which discriminates between individual isolates in a population that are morphologically and serologically indistinguishable. Fifty-two serotype A isolates of C. neoformans were obtained from three different institutions (in Nagasaki, Chiba, and Tokyo) in Japan. Only two of these strains were isolated from AIDS patients and one from pigeon excreta. Of the nine reported finger-printing patterns in serotype A, only three types (IV, V and VII) were observed in Japanese isolates. Pattern IV was almost exclusively observed in Nagasaki isolates (21/22) with only one of pattern VII. In Chiba, however, patterns VII and IV appeared to be equally distributed. In Tokyo, patterns IV and V (which included two isolates from AIDS patients) were observed at similar frequencies. Restriction fragment length polymorphism analysis of four isolates of serotype AD showed a typical serotype A pattern which also contained a serotype D-specific band. This finding suggests the independence of serotype AD. These data could enhance the survey of the epidemiology of cryptococcosis.

Cryptococcosis↗

[A case of brain abscess associated with enterococcal endocarditis].

Enterococcal infections involving the central nervous system are uncommon clinical entities. A 74-year-old male was admitted to our hospital on November 3, 1991 for high fever. Nuchal rigidity was observed at neurological examination. All four blood cultures yielded E. faecalis. The MIC value of ABPC against the isolated E. faecalis was 0.25 microgram/ml. Vegetation on the mitral valve and mitral regurgitation were revealed by an echocardiogram. Enhanced CT scan showed low density area with ring enhancement in the right basal ganglia and a CSF examination suggested bacterial meningitis. He became better after ABPC 8 g/day was intravenously administered. Then the vegetation on the mitral valve and the brain abscess disappeared. He was discharged with no complications. We reported a rare case of brain abscess associated with enterococcal endocarditis.

Aged↗

[Roxithromycin treatment in patients with chronic lower respiratory tract disease--its clinical efficacy and effect on cytokine].

We demonstrated the efficacy of "long term" roxithromycin (RXM) treatment in 15 patients with chronic lower respiratory tract disease (11 with diffuse panbronchiolitis and 4 with sinobronchial syndrome). (1) Fourteen (93.3%) of the 15 patients showed improvement when assessed by the comprehensive improvement score, and they showed significant improvements in PaO2 (74.2 +/- 10.4 Torr to 84.3 +/- 10.9 Torr, p < 0.01), %VC (86.9 +/- 20.2% to 96.0 +/- 21.9%, p < 0.001) and FEV1 (1.81 +/- 0.87 L to 2.14 +/- 1.08 L, p < 0.01) after RXM treatment. (2) Neutrophils accumulated in the pre-RXM treatment bronchoalveolar lavage (BAL) fluid and decreased in BAL fluid of patients responding to RXM treatment (49.8 +/- 28.3% to 17.1 +/- 15.7%, p < 0.01). Additionally, the levels of interleukin 1 beta and interleukin 8 were significantly higher in BAL fluid of these patients than those in the healthy volunteers (p < 0.025, p < 0.01 respectively), and correlated with the neutrophil accumulation (r = 0.619, p < 0.05). These cytokines showed a decrease after RXM treatment. These results indicated that RXM acts by reducing pulmonary inflammation through reduction of neutrophil migration to inflammatory sites, and is effective on chronic lower respiratory tract disease.

Adult↗

[Anaerobic respiratory infection--evaluation of methods of obtaining specimens].

Anaerobic cultures were performed on various kinds of specimens obtained from 67 patients with respiratory infections. The infections consisted of 33 cases of pneumonia, 14 cases of lung abscess, 6 cases of pyothorax, 9 cases of chronic lower respiratory tract infection, and 5 cases of infection of pulmonary cyst. Specimens included bronchoscopic specimens obtained using a single tube or protected catheter brush (PCB), transtracheal aspirate, percutaneous lung aspirate, aspirate using a suction tube through the tracheostomy or intubation tube, and pleural fluid. Anaerobes were isolated in 80% of pyothorax, 43% of lung abscess, and 15% of pneumonia (42% of aspiration pneumonia), respectively. Anaerobes isolated frequently in respiratory infections included Prevotella spp., Fusobacterium spp., and Peptostreptococcus spp. In regard to the type of specimen, bronchial aspirate obtained by bronchoscopy was useful in examination of pneumonia, and was useful as percutaneous lung aspirate in examination of lung abscess. But there was discrepancy of culture results between specimens obtained by different methods in the same patient. To confirm anaerobes as pathogens in respiratory infections, it is necessary to select an appropriate method to obtain specimens and to interpret the culture results comprehensively.

Adult↗

[Clinical investigation of obstructive pneumonia with lung cancer].

Nineteen episodes (18 patients) of obstructive pneumonia occurring in 247 patients with lung cancer were clinically examined, and the following findings were obtained. 1) All 18 patients were male smokers, with an average of 64 years. 2) Body temperatures stood above 37 degrees C in 95% of the 19 episodes. Leukocytosis was detected in 41%, and neutrophilia was observed in 69%. CRP values were positive in all episodes. 3) The frequency of obstructive pneumonia according to the site of lung cancer was 13.2% in proximal tumors and 1.7% in peripheral tumors. Pathologically, the frequency was 5.2% in adenocarcinomas 7.6% in squamous cell carcinomas, 15.6% in small cell carcinomas and 9.1% in large cell carcinomas. Squamous cell carcinomas even in Stage I led to obstructive pneumonia at the rate of 13.0%. In contrast, higher frequency was observed in adenocarcinomas in Stage II or later and small cell carcinomas in Stage IIIB or later. 4) Obstructive pneumonia was detected at the time of discovery of lung cancer in 48% of the 18 patients, and during treatment and in the terminal stage in 26% respectively. 5) Chest X-ray examinations showed that 42% of the pneumonia cases were lobar pneumonia and 11% had pleural effusion. 6) In expectorated sputum, 50% of bacteria isolated were gram-negative, 10% were gram-positive and 40% were unknown. 7) Most of the bacteria isolated from expectorated sputum showed a good susceptibility to antimicrobial agents, but those proved clinically ineffective. 8) The prognosis of obstructive pneumonia was significantly affected by performance status and levels of total protein and choline-esterase.

Aged↗

Effects of antifungal agent combinations administered simultaneously and sequentially against Aspergillus fumigatus.

The in vitro effects of antifungal agent combinations administered simultaneously and sequentially against 15 strains of Aspergillus fumigatus were tested by the yeast-malt broth method. The synergistic effect of the combination of amphotericin B (AMPH) and miconazole was observed in nine strains (60%). However, the combinations of AMPH and fluconazole, AMPH and ketoconazole, and AMPH and itraconazole administered simultaneously showed antagonistic effects against three (20%), five (34%), and four (26%) strains, respectively. The effects of combinations of azole antifungal agents administered simultaneously were indifferent or antagonistic against A. fumigatus. In experiments measuring the effects of sequentially administered antifungal agents, however, pretreatment with AMPH and then azole antifungal agents exhibited better in vitro efficacy than that found in experiments measuring the effects of simultaneously administered AMPH and azole compounds.

Antifungal Agents↗

Pneumonia caused by Stenotrophomonas maltophilia with a mucoid phenotype.

We describe the first known case of pneumonia caused by a mucoid Stenotrophomonas maltophilia (Xanthomonas maltophilia) strain in a patient with bronchiectasis. The patient was admitted because of mild hemoptysis and productive cough with infiltrative shadow in the right lower lung field on chest X ray. The clinical symptoms were mild, and treatment with minocycline was effective.

Female↗

Effect of bis (tributyl tin) oxide on permeability of the blood-brain barrier: a transient increase.

OBJECTIVES: To study the effect of bis (tributyl tin) oxide (TBTO) on permeability of the blood-brain barrier. METHODS: Electron microscopy and an x ray microanalyser with lanthanum chloride as a tracer were used, and blood tin concentrations were determined with an atomic absorption spectrophotometer. Adult male wistar rats received 0.05 ml/kg body weight of TBTO orally. RESULTS: A transient increase in paracellular permeability at the blood-brain barrier was found 2 h after the dose of TBTO. Electron dense lanthanum deposits penetrated tight junctions of the endothelia and permeated the subendothelial space. The x ray microprobe data showed an accumulation of TBTO at the tight junctions at 2 h. Leakage of tracer did not occur at 4 h, but oedematous changes in the surrounding glial cells were prominent between 4 and 8 h and had almost returned to normal by 24 h. By atomic absorption analysis, it was seen that blood tin concentrations rapidly increased at 1 h and rose to a maximum peak at 8 h, then gradually decreased to reach zero at 24 h. CONCLUSIONS: Accumulated TBTO at tight junctions could have caused the temporary replacement of calcium ion by tin, which induces a transient increase in paracellular permeability throughout the blood-brain barrier.

Animals↗

Endothelium-dependent relaxation by angiotensin-converting enzyme inhibitors in canine femoral arteries.

The effects of angiotensin-converting enzyme (ACE) inhibitors on vascular reactivity were investigated using isolated canine femoral arteries with and without endothelium. N-N-(S)-1-carboxy-3-phenylpropyl-L-alanyl-N-(indan-2-yl)glycine (M-1; an active metabolite of delapril, a nonsulfhydryl ACE inhibitor) and captopril (a sulfhydryl ACE inhibitor, 10(-8) to 10(-5) M) relaxed in a dose-dependent manner canine femoral arterial rings precontracted with prostaglandin F2 alpha in the presence of endothelium only. The endothelium-dependent relaxations by M-1 and captopril were completely blocked by methylene blue, an inhibitor of soluble guanylate cyclase; NG-monomethyl-L-arginine (L-NMMA), an inhibitor of nitric oxide synthesis; and oxyhemoglobin, an inactivator of nitric oxide; they were partially blocked by aspirin, an inhibitor of cyclooxygenase and were enhanced by superoxide dismutase, a radical scavenger. The inhibitory effect of L-NMMA on the relaxations by M-1 and captopril were reversed by a high dose of L-arginine. Moreover, a bradykinin antagonist partially inhibited these relaxations. These results suggest that endothelium-dependent relaxations by M-1 and captopril in canine femoral arteries are mediated through the release of both prostanoids and endothelium-derived nitric oxide via endogenous bradykinin.

Angiotensin-Converting Enzyme Inhibitors↗

Suppressive effects of the anti-allergic drugs, tranilast and azelastine, on the lysophosphatidylserine-dependent activation of rat mast cells.

Anti-allergic drugs, tranilast and azelastine, were examined for their effects on lysophosphatidylserine (lysoPS)-dependent histamine release from rat mast cells. Although both compounds suppressed the histamine release in a dose-dependent manner, the inhibition was affected by lysoPS concentration differently. In the presence of an increasing concentration of lysoPS, the suppressive effect of tranilast decreased. The inhibition by azelastine, however, was independent of the concentration of lysoPS. The findings suggest that these two drugs inhibit lysoPS-depedent histamine release through essentially different routes.

Animals↗

[Influence of vitamin D3 on inhibitory effect of vitamin K2 on bone loss in ovariectomized rats].

To evaluate whether the vitamin D3 level in the plasma influences the inhibitory effect of vitamin K2 on bone loss, vitamin K2 (25 mg/kg/day) was administered to ovariectomized (OVX) rats fed a diet containing vitamin D3 (V.D.(+)) or a diet deficient in vitamin D3 (V.D.(-)). After 3 months of treatment, the plasma 25-OH-vitamin D3 (25-OH-D3) level in the V.D(-)-sham group was about 1/3 of that in the V.D(+)-sham group. The plasma calcium level and alkaline phosphatase activity were also significantly lower in the V.D(-)-sham group than in the V.D(+)-sham group. In the V.D(+) group, the plasma 25-OH-D3 level in the vitamin K2 group was about 1.5 times higher than that in the OVX-control group. Ovariectomy resulted in a significant decrease in bone density, bone mineral content (BMC) and bone mineral density (BMD) of femurs in both the V.D(+) and V.D(-) groups. In the V.D(-) group, vitamin K2 had no marked effect on the bone loss. In the V.D(+) group, the bone density and BMD in the mid portion of the femur were significantly increased by vitamin K2 treatment. These findings suggest that the effect of vitamin K2 on bone loss is affected by the vitamin D3 level in the plasma.

Animals↗

Effects of menatetrenone on the decrease in calcium balance induced by vitamin K-deficient diet and sodium loading in rats.

The effects of menatetrenone (2-methyl-3-tetraprenyl-1,4-naphthoquinone, MK-4) on calcium balance were studied in male Sprague-Dawley rats. Experiment 1: Rats in metabolic cages that were fed a vitamin K-deficient diet and injected daily with latamoxef (100 mg/kg, i.p.) were either treated or untreated with MK-4 for 7 days. Daily food intake, urine volume and feces weight were determined, and calcium concentration in these samples was measured. Calcium balance was calculated as the difference between calcium intake and urinary and fecal calcium excretion. Cumulative calcium balance in the vitamin K-deficient group treated with latamoxef was lower than that in normal rats; this balance was significantly improved by MK-4 (1 and 10 mg/kg, s.c.) administered for 7 days. Experiment 2: Rats were fed a vitamin K-deficient diet containing 4.6% sodium chloride for 6 weeks. MK-4 was administered as a dietary supplement. Forty-eight-hour calcium balance, determined once a week, was significantly reduced compared with that of normal rats after 3 and 5 weeks; the balance was restored dose-dependently by MK-4 administration (1 and 10 mg/kg). Experiment 3: Rats were subjected to the same experimental conditions as experiment 2 for 6 weeks, and intestinal calcium transport was determined using an everted gut-sac technique. Calcium transport was reduced by the high sodium, vitamin K-deficient diet, and this reduction was restored by MK-4 administration (10 mg/kg). These results suggest that MK-4 improves the reduced calcium balance by increasing intestinal calcium absorption in these rats.

Alkaline Phosphatase↗