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Biomedical subjects

K Chida

Publications and source records attributed to K Chida.

At least 19 recordsLinked to original sources

Cholesterol sulfate, a second messenger for the eta isoform of protein kinase C, inhibits promotional phase in mouse skin carcinogenesis.

Cholesterol sulfate is a second messenger for the eta isoform of protein kinase C mediating squamous differentiation. We found that cholesterol sulfate inhibited the promotional phase of skin carcinogenesis in female CD-1 mice, which was initiated by 100 micrograms 7,12-dimethylbenz[a]-anthracene and promoted by a single application of 10 micrograms 12-O-tetradecanoylphorbol-13-acetate, followed by repeated applications of 10 micrograms mezerein once a week for 19 weeks. Cholesterol sulfate, when applied topically at a dose of 400 micrograms (820 mumol) 10 min before treatment with the promoters, markedly suppressed tumor formation, resulting in decrease of 56% in the incidence of tumor-bearing mice, 81% in the number of tumors/mouse, and 60% in the size of tumors at 20 weeks of the promotion. This inhibition was not due to elimination of the initiated cells. Treatment with the parental cholesterol at a dose of 320 micrograms (820 mumol), which does not activate the eta isoform, did not inhibit tumor promotion. Repeated treatment with cholesterol sulfate induced scaling of skin at the site of application. Cholesterol sulfate, unlike most inhibitors of tumor promotion, did not inhibit induction of ornithine decarboxylase and hyperplasia in mouse epidermis caused by topical treatment with 12-O-tetradecanoylphorbol-13-acetate. These findings suggest that cholesterol sulfate inhibits tumor promotion by stimulating a differentiation pathway mediated by the eta isoform of protein kinase C.

9,10-Dimethyl-1,2-benzanthracene

Effects of chemical stimulation of the rostral and caudal ventrolateral medulla on cerebral and renal microcirculation in rats.

We investigated the effects of neurons in the rostral and caudal ventrolateral medulla (RVL and CVL) on cerebral and renal microcirculation in rats. Rats were anesthetized with chloralose, paralyzed with tubocurarine, and artificially ventilated. Cerebral and renal blood flows (CBF and RBF) were measured simultaneously using laser-Doppler flowmetry. Chemical stimulation of the RVL neurons by microinjection of the excitatory amino acid L-glutamate increased arterial pressure (AP), whereas that of the CVL neurons decreased AP. Stimulation of the RVL neurons also elicited a stimulus-locked increase in CBF and a decrease in RBF. The percent change in CBF and RBF was dose-dependent as stimulus intensity was increased. Cerebral and renal vascular resistance (CVR and RVR) levels were calculated from changes in CBF or RBF and changes in mean AP. The percent reduction in CVR and percent elevation in RVR were also dose-dependent. Chemical stimulation of the CVL neurons elicited a stimulus-locked decrease in CBF and an increase in RBF. The percent reduction in CBF and percent elevation in CVR were dose-dependent. The percent reduction in RVR was also dose-dependent, while the percent elevation in RBF was not significant. Blood withdrawal reduced AP by a similar degree to CVL stimulation, but did not significantly decrease CBF. The results suggest that RVL and CVL neurons integrate cerebral and systemic microcirculation.

Animals

Induction of MHC class II antigens on rat bronchial epithelial cells by interferon-gamma and its effect on antigen presentation.

Recent studies have found aberrant expression of class II antigens by bronchial epithelial cells (BECs), suggesting that these cells may also be involved in airway mucosal immunity. However, the regulation of class II antigen expression on BECs by cytokines and the functional capacity of such cells bearing class II molecules remain unknown. We investigated the effect of IFN-gamma on class II antigen expression by cultured rat BECs, as well as the ability of these cells to present intact protein antigens to specifically sensitized T cells. Although primary BECs did not express class II antigens, IFN-gamma readily induced their expression in a dose-dependent manner. More than 85% of the BECs treated with 1000 U/ml of IFN-gamma were positive for class II antigens. In addition, when IFN-treated BECs bearing class II molecules were pulsed with ovalbumin (OVA), they significantly stimulated the proliferation of OVA-sensitized T cells, whereas cells that were not treated with IFN-gamma but were pulsed with OVA did not do so. Our findings indicate that BECs bearing class II molecules are capable of presenting OVA to OVA-sensitized T cells. These results suggest that various pathological conditions causing the local production of IFN-gamma may increase class II antigen expression on BECs, which in turn may modulate the airway mucosal immune response by the presentation of antigens to T cells.

Animals

Clinicopathologic characteristics of elderly patients with persistent ST segment elevation and inverted T waves: evidence of insidious or healed myocarditis?

OBJECTIVES: We sought to clarify the clinicopathologic characteristics of insidious or healed myocarditis in the elderly. BACKGROUND: Myocarditis is the cause of unexplained congestive heart failure and dilated cardiomyopathy. However, acute myocarditis of the Fiedler type is rare, and the incidence and implication of insidious or healed myocarditis in the elderly are not yet known. METHODS: In an autopsy study of 3,000 patients aged > or = 60 years, there were 12 (0.4%) with insidious or healed myocarditis, showing extensive and circumferential fibrosis and scattered lymphocytic infiltration of both ventricular walls without acute necrosis of the myocardial fibers. RESULTS: Unexplained congestive heart failure was found in seven cases. In all cases, electrocardiography had demonstrated upward elevation of the ST segment and inverted T waves for durations ranging from 1 month to 12.7 years (mean 5.7 years). Mean (+/- SD) heart weight was 338 +/- 81 g (range 220 to 470). In nine cases, fibrous lesions, which were scattered but extensive and circumferential, were located in the subepicardial and middle layers of the left ventricle. In the remaining three cases, the fibrous lesions were located predominantly in the subepicardial and middle layers, but the subendocardial layer was also locally involved. Fibrous lesions of the right ventricle were predominant in the subepicardial layer and involved the subendocardial layer in four cases. Scattered lymphocytic infiltration was found in the fibrous lesions. CONCLUSIONS: In more than half of the aged cases with insidious or healed myocarditis, unexplained congestive heart failure was also present. Fibrous lesions due to myocarditis were located predominantly in the subepicardial and middle layers and led to persistent upward elevation of the ST segment and inverted T waves.

Aged

The cell cycle-dependent nuclear import of v-Jun is regulated by phosphorylation of a serine adjacent to the nuclear localization signal.

Cell cycle-dependent phosphorylation and nuclear import of the tumorigenic transcription factor viral Jun (v-Jun) were investigated in chicken embryo fibroblasts. Nuclear accumulation of v-Jun but not of cellular Jun (c-Jun) is cell cycle dependent, decreasing in G1 and increasing in G2. The cell cycle-dependent regulation of v-Jun was mapped to a single serine residue at position 248 (Ser248), adjacent to the nuclear localization signal (NLS). Ser248 of v-Jun represents an amino acid substitution, replacing cysteine of c-Jun. It was shown by peptidase digestion and immunoprecipitation with antibody to the NLS that v-Jun is phosphorylated at Ser248 in the cytoplasm but not in the nucleus. This phosphorylation is high in G1 and low in G2. Nuclear accumulation of v-Jun is correlated with underphosphorylation at Ser248. The regulation of nuclear import by phosphorylation was also examined using NLS peptides with Ser248 of v-Jun. Phosphorylation of the serine inhibited nuclear import mediated by the NLS peptide in vivo and in vitro. The protein kinase inhibitors staurosporine and H7 stimulated but the phosphatase inhibitor okadaic acid inhibited nuclear import mediated by the NLS peptide. The cytosolic activity of protein kinases phosphorylating Ser248 increased in G0 and decreased during cell cycle progression, reaching a minimum in G2, whereas phosphatase activity dephosphorylating Ser248 was not changed. These results show that nuclear import of v-Jun is negatively regulated by phosphorylation at Ser248 in the cytoplasm in a cell cycle-dependent manner.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine

The influence of ovarian hormones on the granulomatous inflammatory process in the rat lung.

This study was initiated to clarify the relationship between ovarian hormones and the granulomatous inflammatory process in the lung. To assess whether ovarian dysfunction influences the granulomatous inflammatory process, we compared immunological alterations in ovariectomized rats and in sham-operated rats. After a heat-killed, bacilli Calmette-Guérin (BCG)-elicited granulomatous reaction, the lung-body weight ratios, the number of lymphocytes and activated T-cells, and the interferon-gamma levels in the bronchoalveolar lavage fluid from the ovariectomized rats were significantly higher than those of the sham-operated rats. Moreover, exogenous ovarian steroids supplemented in vivo suppressed not only the granulomatous inflammatory process in the lungs, but also the parameters measured in the bronchoalveolar fluid. These results indicate that ovarian dysfunction may adversely affect the formation of granulomas in the lung.

Animals

An autopsy case of incomplete left atrial rupture following left atrial infarction associated with left ventricular myocardial infarction.

We report a 78-year-old woman with incomplete left atrial rupture following left atrial infarction associated with left ventricular myocardial infarction. An autopsy revealed a hemopericardium. A large hematoma was observed in the posterior wall of the left atrium and a few small tears were found on the same wall. Near its origin, the left circumflex artery was severely sclerotic and completely occluded by fresh thrombus. Histologic examination revealed that large intramural hematoma longitudinally dissected the inner third of the posterior wall of the left atrium, and transversely dissected through the necrotic tissue to the pericardial sac to result in rupture. Coagulation necrosis and intramyocardial hemorrhage were also observed throughout the entire left atrium and the postseptolateral wall of the left ventricle.

Aged

Diagnostic and prognostic value of myocardial scintigraphy with thallium-201 and gallium-67 in cardiac sarcoidosis.

STUDY OBJECTIVE: To examine the diagnostic and prognostic value of myocardial scintigraphy using thallium-201 and gallium-67 in cardiac sarcoidosis. PATIENTS: Twenty-five patients with sarcoidosis. METHODS: All patients underwent myocardial thallium-201 scintigraphy. Six patients with myocardial thallium-201 defects were classified into group A and another 19 without defects were classified into group B. Between group A and B, we compared the results of other noninvasive examinations, including standard 12-lead ECG, 24 h ambulatory ECG, chest radiography, measurements of serum angiotensin-converting enzyme (ACE) and lysozyme levels, and gallium-67 scintigraphy. RESULTS: Proportions of subjects who had varying degrees of heart block, severe ventricular arrhythmias (more than or equal to third grade of Lown's classification), and high levels of serum ACE and lysozyme levels were not different between these two groups (p > 0.05). Although an enlarged cardiothoracic ratio was more frequent in group A (p < 0.05), bilateral hilar lymphadenopathy was more frequent in group B (p < 0.01). Four patients of group A and 15 of group B underwent gallium-67 scintigraphy. Although no subjects of group B had myocardial uptake of gallium-67, two of four group A patients showed cardiac uptake. These four group A patients were treated with corticosteroids. The therapy provided clinical and scintigraphic improvement in two patients with myocardial gallium-67 uptake, although it did no improvement in the other two patients without gallium-67 uptake. CONCLUSIONS: When cardiac sarcoidosis was diagnosed according to myocardial thallium-201 defects, other noninvasive examinations were not useful to detect this disease. However, gallium-67 uptake may predict the efficacy of corticosteroids. Thus, the combination of thallium-201 and gallium-67 scintigraphy may be useful not only in diagnosis of cardiac sarcoidosis but also in prediction of effects of corticosteroids.

Adrenal Cortex Hormones

Hypersensitivity pneumonitis associated with home ultrasonic humidifiers.

We describe five patients with hypersensitivity pneumonitis (HP) that was related to using home ultrasonic humidifiers. All patients had micronodular infiltrates on their chest radiograph, and their lung biopsy specimens revealed alveolitis with or without epithelioid cell granulomas. Challenge tests were performed on two patients with the humidifier water and three patients using the humidifier. All patients tested exhibited a positive response. Tests for precipitating antibodies against an extract of the humidifier water gave strongly positive reactions in all patients tested. Precipitins to Cephalosporium acremonium and Candida albicans were also present in all cases, whereas precipitins to thermophilic actinomycetes were not detected. Although cultures of the water grew a variety of fungal and bacterial organisms, thermophilic actinomycetes could not be detected. These findings suggest that thermophilic organisms may not be the causative antigens of HP associated with ultrasonic humidifiers. All five patients had an increase in the bronchoalveolar lavage (BAL) lymphocytes that were predominantly CD4+ lymphocytes. The T helper cell count (CD4) to suppressor T cell count (CD8) ratio was significantly higher than that observed in summer-type HP, and lower than that observed in bird fancier's lung, indicating that the phenotypes of the BAL lymphocytes may vary with the type of HP.

Adolescent

Effect of 14-membered ring macrolide therapy on chronic respiratory tract infections and polymorphonuclear leukocyte activity.

We studied the efficacy of the long-term administration of 14-membered ring macrolides in treating patients with diffuse panbronchiolitis (DPB) (34 patients) and bronchiectasis (BE) (40 patients). Oral administration of erythromycin (400 or 600 mg), roxithromycin (150 or 300 mg) or clarithromycin (200 or 400 mg) given daily for at least 2 months, was evaluated. The efficacy of erythromycin, roxithromycin, and clarithromycin in DPB was 19/24 (79%), 6/7 (86%), and 2/3 (67%), respectively. Efficacy of these agents in BE exceeded 50%. We determined the effect of these macrolides on the activity of polymophonuclear leukocytes (PMNs) obtained from healthy volunteers. There were no significant differences between the effects of these 14-membered ring macrolides and josamycin, a 16-membered ring macrolide which was previously found to be ineffective in treating DPB. Thus, the effectiveness of the 14-membered ring macrolides in treating DPB appears to depend on mechanism(s) other than alterations in PMN activity.

Adult

Enzyme cytochemical study of alkaline phosphatase in rat hepatocytes--change of location after colchicine administration or bile duct ligation.

Changes in location of alkaline phosphatase (ALP) in rat hepatocytes after two different treatments were examined by the enzyme cytochemical technique. Although reaction deposits which indicate ALP activity were observed mainly in the bile canalicular membranes until 6 hr after colchicine administration, they were present not only in the bile canalicular membranes but also in the sinusoidal and lateral membranes 12 hr after drug administration. Eighteen and 24 hr after colchicine administration, a large number of reaction deposits were seen in the sinusoidal membranes and in the mutual membranes between adjacent hepatocytes, where the bile canaliculi were completely deformed and complex interdigitations appeared. On the other hand, after bile duct ligation, reaction deposits appeared in every domain of the plasma membranes. Twenty-four hr after colchicine administration to bile-duct-ligated rats, an increase in the number of the reaction deposits was observed, but the location of ALP remained unchanged. The present study suggests that intracellular transport and location of ALP in hepatocytes may be controlled by a common mechanism in colchicine-treated and bile-duct-ligated rats.

Alkaline Phosphatase

[Serum phospholipase A2 activity in patients with aspirin-induced asthma].

Urinary excretion of leukotrienes is greater in patients with aspirin-induced asthma (AIA) than in other patients with asthma in remission, and is greater still during an aspirin-induced attack. We therefore hypothesized that increased phospholipase A2 (PLA2) activity leads to increased leukotriene synthesis when non-steroidal antiinflammatory drugs inhibit cyclooxygenase in patients with AIA, and that PLA2 activity increases further during an aspirin induced attack. To test this hypothesis, we measured the serum PLA2 activity in adult asthmatic patients, and compared the activity in those with AIA to the activity in those without AIA. The subjects were 43 patients with asthma in remission, 17 with AIA and 26 without AIA. Serum PLA2 activity was also measured before and after intravenous administration of lysine-aspirin in three patients with AIA and in one without AIA. Serum PLA2 activity was measured by radioimmunoassay. Serum PLA2 activity in patients with AIA, in those without AIA, and in healthy controls was 300.9 +/- 52.9, 294.4 +/- 65.3 and 171.7 +/- 41.8 pmol/ml/min, respectively. Serum PLA2 activity in asthmatic patients was significantly higher than in healthy controls (p < 0.01), but there was no difference between patients with and without AIA. Intravenous lysine-aspirin provoked asthmatic attacks in three patients with AIA. However, intravenous lysine-aspirin did not significantly change serum PLA2 activity in the three patients with AIA or in the patient without AIA. These results indicate that although PLA2 may be involved in the pathogenesis of bronchial asthma, it is not specific to AIA. Thus, the pathophysiology of AIA remains unclear and further investigation is needed.

Adult

[Efficacy of video thoracoscopic lung biopsy in diffuse lung diseases: comparison with open lung biopsy].

The efficacy and safety of video thoracoscopic lung biopsy (VTLB) and of open lung biopsy (OLB) were compared in patients with diffuse lung diseases. Thirty-three patients who had undergone VTLB were retrospectively studied and compared with 67 patients who had undergone OLB. There were no significant differences in age (52.8 +/- 10.9 vs 53.4 +/- 10.3), in the number of biopsies per patient (2.6 +/- 0.6 vs 2.7 +/- 0.6), or in the rate of diagnosis (94% vs 93%) between the two groups. However, the rate of diagnosis was low when the number of VTLB or OLB performed per patient was low. The patients undergoing VTLB had significantly shorter operative times (VTLB, 100.2 +/- 27.2 min. vs OLB, 119.8 +/- 42.6 min; p < 0.01) and less blood loss (VTLB, 4.7 +/- 14.6 ml vs OLB, 65.7 +/- 77.0 ml; p < 0.001). Complications occurred in 3 of the 33 who underwent VTLB, and in 18 of the 67 who underwent OLB. These results indicate that VTLB is an effective and safe alternative in the diagnosis of diffuse lung diseases.

Adult

Lipoxygenase inhibitor-provoked acute asthma in a patient with asthma relieved by aspirin.

BACKGROUND: A very small number of patients with asthma show symptomatic improvement after administration of aspirin and other cyclooxygenase inhibitors. The clinical features of such patients with so-called aspirin-relieved asthma are similar to those with aspirin-induced asthma, but the pathogenesis is unclear. METHODS: We encountered one confirmed aspirin-relieved asthma patient and investigated the effects of cyclooxygenase and lipoxygenase inhibitors on his condition. RESULTS: Our patient showed a marked improvement of the forced expiratory volume in one second (FEV1) after administration of aspirin and three other cyclooxygenase inhibitors (indomethacin, mefenamic acid, and ketoprofen). A 5-lipoxygenase inhibitor (AA861, Takeda, Japan), however, evoked acute asthma, and repeated administration of this drug resulted in some desensitization, but not complete tolerance. CONCLUSIONS: These results suggest an altered balance of arachidonic acid metabolism may play a critical role in the pathophysiology of aspirin-relieved asthma.

Acute Disease

[Augmentation of immune defense mechanisms of the lung by romurtide].

Muramyl dipeptide (MDP), derived from the major constituent of bacterial cell walls, can augment host defense mechanisms, and romurtide [MDP-Lys (L18)], a synthetic MDP derivative, is thought to be more potent than other MDP derivatives. Therefore, we evaluated whether romurtide can bolster the immune defense mechanisms of the lung. We compared the functions of peripheral blood leukocytes with those of broncho alveolar lavage fluid cells (BALF cell) in DA rats and in patients with lung cancer who were treated with radiation. The results indicate that romurtide can increase the antibacterial activity of BALF cells preferentially and that this adjuvant therapy can help to prevent respiratory infections.

Acetylmuramyl-Alanyl-Isoglutamine

[Analysis of T cell receptor V beta gene expression in bronchoalveolar lavage fluid lymphocytes from patients with idiopathic interstitial pneumonia].

T lymphocytes in bronchoalveolar lavage (BAL) from idiopathic interstitial pneumonia (IIP) patients are considered to recognize unknown antigens, such as dust, fume, virus or degenerated autoantigens. To analyse the nature of these T lymphocytes, we investigated T cell receptor (TCR) V beta gene usage (22 kinds) in BAL Lymphocytes and Peripheral blood lymphocytes from 10 11P patients and 9 normal controls, using reverse transcriptase-polymerase chain reaction method. In BAL lymphocytes, predominant usage of V beta genes (> 15% of the sum of all V beta transcripts) was recognized in 7 of 10 IIP patients, which appeared to vary in individuals (Case 1: V beta 14, case 2: V beta 3, V beta 5.1, case 5: V beta 2, case 6: V beta 6, case 7: V beta 8, case 8: V beta 7, V beta 20, case 9: V beta 6), whereas no predominant V beta usage was demonstrated in normal controls. It remains to be elucidated whether the BAL lymphocytes expressing predominant V beta genes are involved in the activation of alveolar macrophages, fibroblasts, thereby inducing the production of autoantibodies.

Base Sequence

[Restricted T cell receptor V beta gene expression in bronchoalveolar lavage lymphocytes of patients with sarcoidosis].

T lymphocytes in bronchoalveolar lavage (BAL) fluid from patients with sarcoidosis are activated. They are thought to recognize as yet unknown antigens and to play an important role in the pathogenesis of the disease. We studied the use of the T cell receptor V beta gene of lymphocytes obtained by BAL and lymphocytes obtained from peripheral blood of 11 patients with sarcoidosis and 9 normal controls, using the reverse transcriptase-polymerase chain reaction. As compared to the normal controls, V beta 2 and V beta 6 genes were predominantly expressed (> 15% of the sum of all V beta transcripts) on lymphocytes obtained from BAL fluid in 4 and 7 of 11 patients with sarcoidosis, respectively, but no specific V beta gene was predominantly expressed on lymphocytes obtained from peripheral blood. These results imply that those lymphocytes that are obtained from BAL fluid and that express V beta 2 and V beta 6 genes are involved in the pathogenesis of sarcoidosis.

Adult

Phospholipid analysis of alveolar macrophages and bronchoalveolar lavage fluid following bleomycin administration to rabbits.

Changes in the lipid metabolism of the lung during pulmonary injury were investigated by quantitative and qualitative analysis of phospholipids in pulmonary surfactant and alveolar macrophages (AM) obtained from rabbits that had been given a single transtracheal injection of bleomycin hydrochloride (BLM) 0, 7, 14, 21, and 28 days previously. BLM treatment increased the phospholipid content of both bronchoalveolar lavage (BAL) supernatant fluids and BAL cells. Furthermore, the proportion of phosphatidylcholine (PC) showed an increase in BAL cells during the development of pulmonary injury, and BLM treatment appeared to cause transformation of AM to foamy AM. Lipid analyses of the foamy AM revealed that their phospholipid content was increased, and that the percentage of PC with palmitic acid was elevated. Thus it appears that accumulation of phospholipids derived from pulmonary surfactant contributes to the increase in phospholipids and PC in BAL cells. These findings indicate that BLM treatment produces an alteration in the amount and composition of AM phospholipids, and also in BAL supernatant fluids.

Animals