Study of the effects of AM-1155 in a rat chronic respiratory tract infection model with Pseudomonas aeruginosa.
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Animals↗
Biomedical subjects
K Chida
Publications and source records attributed to K Chida.
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↗
[Two cases of intrapulmonary lymph node associated with either progressive systemic sclerosis or idiopathic pulmonary fibrosis].
We encountered 2 cases of intrapulmonary lymph node. Case 1 was in a 48-year-old woman who had been given a diagnosis of progressive systemic sclerosis. Case 2 was in a 49-year-old woman with idiopathic pulmonary fibrosis. In each patient, a follow-up chest CT scan showed a pulmonary nodule, which could not be seen on chest X-ray film. Each nodule has an irregular margin and a linear shadow resembling pleural indentation. Histological examination of the open biopsy specimens revealed that these nodules were intrapulmonary lymph nodes surrounded by interstitial pneumonia. Previous case reports and these 2 cases indicate that unless a thoracotomy is done intrapulmonary lymph nodes are difficult to distinguish from lung cancers.
Diagnosis, Differential↗
[A case of eosinophilic pneumonia mimicking hypereosinophilic syndrome, which improved spontaneously].
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Adult↗
[Effect of inhaled vancomycin hydrochloride on elimination of methicillin-resistant Staphylococcus aureus].
Vancomycin hydrochloride (VCM) is one of the most useful drugs in treating methicillin-resistant Staphylococcus aureus (MRSA) infections. Intravenous administration of the drug is, however, not appropriate in patients with impaired renal or liver function. Thus, we studied the effect of inhaled VCM on MRSA. Fifty-one patients with MRSA in their sputum (35 men and 16 women 21, in the "infected" group and 30 in the "colonized" group, mean age 76.4 years) were studied. MRSA was eliminated in 84.3% of the patients (43 of 51 patients), and the average time required for elimination was 14.7 days. MRSA colonization or infection recurred in 46.5% of the patients (20 of 43 patients), and the duration from elimination until recurrence of MRSA averaged 28 days. Eight patients in whom MRSA was not eliminated by inhaled VCM were not clinically distinguishable from other patients, but their performance status was worse. Two hours after VCM was inhaled, serum VCM concentrations were unmeasurable in 7 patients. The VCM level in sputum peaked at 262.5 micrograms/g just after inhalation, and then gradually decreased. No side effects of this treatment were observed. These results suggest that inhaled VCM can be used to eliminate MRSA.
Administration, Inhalation↗
[Meningeal seeding of spinal cord glioblastoma multiforme without any signs of myelopathy].
An autopsy case of meningeal spreading of glioblastoma multiforme (GBM) probably originating in the cervical cord was reported. In contrast to autopsy findings, main symptoms were similar to subacute meningitis, and any signs of myelopathy could not be detected during the clinical course. The patient was a 22-year-old man who was hospitalized because of a 2-week history of progressive headache following cough and slight fever. Vomiting and somnolence, developing 5 days before admission, were improved the day after a lumbar puncture performed at another hospital. On admission, meningeal signs, mild right abducens palsy, and depressed deep tendon reflexes were detected. There was no muscle weakness, sensory loss, or Babinski sign. Lumbar puncture yielded CSF with an opening pressure of 280 mmH2O, 21 mononuclear cells/mm3, a protein level of 645 mg/dl, and a glucose level of 7 mg/dl. Cytology for malignancy and multiple cultures were negative. Brain CT scan showed mild hydrocephalus and swelling of the brainstem and cerebellum. Intravenous administration of antimicrobial drugs was started and ventriculoperitoneal shunt surgery was performed. During the third hospital week, however, meningeal signs progressed and somnolence reappeared, followed by progressive multiple cranial neuropathy and polyradiculopathy characterized by flaccid tetraparesis, muscle atrophy, and sensory impairment without a level. Babinski sign could not be detected. MRI revealed an intramedullary lesion in the lower cervical cord, swelling of the brainstem, cerebellum, spinal cord and nerve roots, and a diffuse or nodular thickning of leptomeninges. Repeated CSF cytology disclosed atypical cells. Examinations for extraneural malignancies were negative. During the 9th hospital week, flaccid tetraplegia progressed and stupor developed, and the patient died 2 weeks later. The pathological study was limited to the brain. The brain showed a diffuse opalescent thickening of the leptomeninges, especially over the ventral aspect of the brainstem and cerebellum, where the blood vesseles and cranial nerves were obscured. Histological examination revealed the appearance of GBM. The malignant cells filled the subarachnoid space, and to a variable extent penetrated the brainstem and cerebellum along perivascular spaces. Hypertrophied optic tracts and trigeminal nerves were also infiltrated by the cells. However, there were no mass lesions assumed to be primary ones anywhere in the cerebral parenchyma. Therefore, it was thought that GBM primarily growing in cervical cord metastasized to intracranial subarachnoid space by way of the cerebrospinal fluid pathway. Spinal cord GBM usually presents signs of myelopathy from the early stage. The present case was characterized by no signs of myelopathy during the clinical course. It is speculated that the intramedullary GBM, originating near the surface of cervical cord, had been rapidly disseminated into the subarachnoid space up to the intracranial cavity before myelopathy appeared, and caused cranial and spinal nerve roots dysfunction, which covered signs of myelopathy. Cord GBM should be always considered as a differential diagnesis in a case of subacute meningitis.
Adult↗
[Clinical and immunological study of airway disease in collagen vascular disease].
We studied the clinical and immunological characteristics of patients with bronchiolar diseases associated with collagen vascular disease (15 patients with rheumatoid arthritis and 1 primary Sjögren's syndrome). Histological examinations showed that 9 patients had follicular bronchiolitis and 7 had bronchiolitis obliterans. Follicular bronchiolitis was characterized by hyperplasia of bronchus-associated lymphoid tissue, and immunohistochemical studies revealed that the pattern of distribution of T cells and B cells in bronchus-associated lymphoid tissue from patients with follicular bronchiolitis was similar to that in diffuse panbronchiolitis, which may be used as a representative model of chronic respiratory infection. In addition, bacterial cultures of sputum samples were positive in 44% of patients with follicular bronchiolitis and in 71% of patients with bronchiolitis obliterans. These results suggest that antigen stimulation is involved in the development of bronchiolar diseases associated with collagen vascular disease.
Aged↗
Overproduction of a Ca(2+)-independent protein kinase C isozyme, nPKC epsilon, increases the secretion of prolactin from thyrotropin-releasing hormone-stimulated rat pituitary GH4C1 cells.
Rat pituitary GH4C1 cells express protein kinase C (PKC) transcripts for cPKC alpha, cPKC beta II, nPKC delta, nPKC epsilon, nPKC eta, and aPKC zeta, but not for cPKC gamma or nPKC theta. Of the transcripts produced, the nPKC epsilon isoform is the most abundant. Transfection of GH4C1 cells with an expression plasmid containing nPKC epsilon cDNA leads to the transient overexpression of cellular nPKC epsilon and confers enhanced phorbol ester binding activity. Transient expression of an inactive point mutant (nPKC epsilon K-->R) of nPKC epsilon, where Lys436 at the putative ATP-binding site is replaced with Arg, also confers elevated binding activity. However, only overproduction of the wild type in transfected cells increases the basal levels and stimulates the secretion of prolactin (PRL) by 12-O-tetradecanoylphorbol-13-acetate or thyrotropin-releasing hormone (TRH). In stable clones overexpressing nPKC epsilon, immunocytofluorescence and immunoblot experiments indicated that TRH causes the rapid translocation and down-regulation of an appreciable fraction of nPKC epsilon. Both the basal and TRH-stimulated levels of PRL secretion are clearly correlated with the expression level of nPKC epsilon but not with the TRH receptor densities in these clones. The dose dependence of TRH-stimulated secretion were similar in all cells overexpressing cPKC alpha, cPKC beta II, nPKC epsilon, and nPKC delta, but the enhancement of PRL secretion was specific for the overproduction of nPKC epsilon, no effect was found when other isozymes were overproduced. These findings clearly demonstrate that the expression level of nPKC epsilon in GH4C1 cells is rate-limiting for basal and TRH-stimulated PRL secretion, and they provide the first direct evidence that nPKC epsilon plays a key role in hormonal secretory processes.
Animals↗
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↗
Origin of the low-energy component and isotope effect on dissociative recombinations of HeH+ and HeD+
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Journal Article↗
The eta isoform of protein kinase C is localized on rough endoplasmic reticulum.
The eta isoform of protein kinase C, isolated from a cDNA library of mouse skin, has unique tissue and cellular distributions. It is predominantly expressed in epithelia of the skin, digestive tract, and respiratory tract in close association with epithelial differentiation. We report here that this isoform is localized on the rough endoplasmic reticulum in transiently expressing COS1 cells and constitutively expressing keratinocytes. By the use of polyclonal antibodies raised against peptides of the diverse D1 and D2/D3 regions, we found that immunofluorescent signals were strongest in the cytoplasm around the nucleus and became weaker toward the peripheral cytoplasm. Under immunoelectron microscopic examination, electron-dense signals were located on the rough endoplasmic reticulum and on the outer nuclear membrane which is continuous with the endoplasmic reticulum membrane. However, no signals were detected in the nucleus, inner nuclear membrane, smooth endoplasmic reticulum, Golgi apparatus, mitochondria, or plasma membrane. Treatment of the cells in situ with detergents suggested association of the isoform of protein kinase C with intracellular structures. By immunoblotting, a distinct single band with an M(r) of 80,000 was detected in whole-cell lysate and in rough microsomal and crude nuclear fractions, all of which contain outer nuclear membrane and/or rough endoplasmic reticulum. We further demonstrated the absence of a nuclear localization signal in the pseudosubstrate sequence. The present observation is not consistent with the report of Greif et al. (H. Greif, J. Ben-Chaim, T. Shimon, E. Bechor, H. Eldar, and E. Livneh, Mol. Cell. Biol. 12:1304-1311, 1992).
Amino Acid Sequence↗