[Tumor neovascularization inhibiting and tumor proliferation and metastasis suppressing actions of 14-, 15-, and 16-member ring macrolides].
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Animals↗
Biomedical subjects
N Hara
Publications and source records attributed to N Hara.
[Talc pulmonary granulomatosis caused by intravenous administration of methylphenidate].
A 57-year-old man was admitted with fever and a dry cough in 1985. He had used methylphenidate intravenously for 3 years. A chest X-ray film on admission showed diffuse micronodular shadows and massive lesions in the lower lung fields bilaterally. Pulmonary granulomatosis was diagnosed histologically, but the etiology remained unclear. In 1993, the patient was readmitted because of symptom exacerbation. The micronodular shadows had extended and the bilateral, massive lesions had enlarged. Transbronchial lung biopsy revealed granulomas with crystallized foreign bodies. Electron microscopy confirmed that the foreign bodies consisted of magnesium and silicon, suggesting talc. Talc granulomatosis caused by intravenous administration of methylphenidate was subsequently diagnosed. The symptoms improved with conservative treatment, and no signs of reexacerbation have appeared.
Central Nervous System Stimulants↗
[A case of intrapulmonary lymphangioma].
We report an extremely rare case of intrapulmonary lymphangioma. A 41-year-old woman was admitted to our hospital for complete medical evaluation of a pulmonary nodule on chest X-ray, which was found during an annual check-up. Chest radiograph showed a well-circumscribed spherical mass adjacent to the right border of the heart in the right lower lung field. Although a cystic tumor of the lung was suspected based on computed tomogram and magnetic resonance imaging findings, a histologic diagnosis could not be made on transbronchial biopsy. In addition, the nodule had increased in size compared with a chest X-ray taken 1 year previously. Enucleation was performed. Histological examination revealed numerous cysts with thin walls lined by a single layer of cells in which immunoreactivity to von Willebrand factor was weakly positive. Intrapulmonary lymphangioma was subsequently diagnosed.
Adult↗
[T 0 N 2 M 0 small cell lung cancer in a patient with Lambert-Eaton myasthenic syndrome].
We report an unusual case of T 0 N 2 M 0 small cell lung cancer in a patient with Lambert-Eaton myasthenic syndrome (LEMS). A 52-year-old man began to notice muscle weakness in a left limb in January 1996, which was followed by muscle weakness in his left arm and fingers, appetite loss, and general fatigue. An electromyogram (EMG) showed the waxing phenomenon in response to high-frequency repetitive stimulation. Lambest-Eaton myasthenic syndrome was diagnosed, based on his symptoms and EMG findings. Chest computed tomography (CT) was done, and left paratracheal, tracheobronchial, subaortic, and hilar lymphadenopathy were found. No mass was seen in either lung field. Cytologic examination of the sputum and bronchial lavage fluid were done, but no malignant cells were found Small cell lung cancer was diagnosed after thoracoscopic resection of the subaortic lymph nodes. No metastases were detected by bone scintigraphy, abdominal CT, or magnetic resonance imaging of the brain. Complete response and resolution of symptoms were obtained by chemotherapy and irradiation.
Antineoplastic Combined Chemotherapy Protocols↗
Effect of horizontal vergence on the motor and sensory components of vertical fusion.
PURPOSE: To compare motor and sensory capabilities for fusion of vertical disparities at different angles of horizontal vergence in healthy humans. METHODS: Eye movements were recorded from both eyes of 12 healthy subjects using three-axis search coils. The stimulus was a cross (+) (3.4 x 3.2 degrees , vertically and horizontally, respectively) presented to each eye with a stereoscopic display. Vertical disparities were introduced by adjusting the vertical position of the cross in front of one eye. The disparity was increased in small increments (0.08 degrees ) every 8 seconds. Viewing was defined as "near" if there was a horizontal disparity that elicited 6 degrees to 15 degrees convergence, depending on the subject's capability for horizontal fusion; viewing was defined as "far" at 1 degrees convergence. Maximum motor (measured), sensory (stimulus minus motor), and total (motor plus sensory) vertical fusion were compared. RESULTS: In 9 (75%) of 12 subjects the maximum total vertical fusion was more in near than in far viewing. The three who did not show this effect had relatively weak horizontal fusion. For the entire group, the motor component differed significantly between far (mean, 1.42 degrees ) and near (mean, 2.13 degrees). Total vertical fusion capability (motor plus sensory) also differed significantly between far (mean, 1.68 degrees ) and near (mean, 2.39 degrees ). For the sensory component there was no difference between between far (mean, 0.268 degrees ) and near (mean, 0.270 degrees ). As vertical disparity increased in a single trial, however, there was a small gradual increase of the contribution of the sensory component to vertical fusion. CONCLUSIONS: Vertical fusion capability usually increases with convergence. This increase is caused primarily by an increase in the motor component. There is a gradual but small increase in the sensory component as target disparity slowly increases.
Adult↗
[The roles of apoptosis in lung injury and fibrosis].
Apoptosis serves important roles in organ development, cell differentiation, and the maintenance of homeostasis. Lung injury studies have underlined the role of fibroblast and endothelial cell apoptosis during lung repair from acute lung injuries, and demonstrated apoptosis of alveolar epithelial cells in association with diffuse alveolar damage. Pulmonary fibrosis is characterized by the loss of lung epithelial cells and the proliferation of fibroblasts. It is possible that p53, p21, Fas, Fas ligand, and other apoptosis-regulating proteins play an important role in the pathophysiology of lung injury and fibrosis.
Animals↗
[An autopsy case of adult onset glycogen storage disease type Ia].
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Aged↗
[Renal hemodynamic interactions of nitric oxide and angiotensin II].
We have already reported that decreased renal medullary blood flow and retention of sodium play an important role in the development of hypertension during chronic systemic L-NAME (NG-nitro-L-arginine methyl ester) administration, despite the absence of measurable changes in renal cortical blood flow as determined from fibers implanted for laser-Doppler flowmetry. In the present experiment, to investigate the interaction between nitric oxide and angiotensin II on renal hemodynamics, the effect of chronic intravenous infusion of L-NAME on blood pressure, sodium and water retention, and intrarenal blood flow distribution were studied in a separate group of rats pretreated with captopril and in which optical fiber for laser-Doppler flowmetry had been implanted. Captopril completely prevented sustained hypertension, sodium retention, and decreased medullary blood flow during chronic L-NAME infusion. These date indicated that angiotensin plays an important role in the regulation of renal medullary blood flow and sodium excretion by modulating the effects of nitric oxide in renal medullary blood flow.
Angiotensin II↗
[A case of malignant rheumatoid arthritis complicated by secondary amyloidosis and membranous nephropathy].
A 30-year-old man had been treated for malignant rheumatoid arthritis from 1989 with a non-steroidal anti-inflammatory drug, then bucillamine for six months and prednisolone. Mild proteinuria appeared in May 1994, 4 years after bucillamine therapy was conducted. The patient was admitted to our hospital for a renal biopsy in July 1994. The specimen revealed secondary amyloidosis and membranous nephropathy (MGN). These findings suggest that MGN unrelated to bucillamine therapy might have occurred with secondary amyloidosis in rheumatoid arthritis.
Adult↗
Interleukin-8 participates in angiogenesis in non-small cell, but not small cell carcinoma of the lung.
We examined interleukin-8 (IL-8) production in 17 lung cancer cell lines, IL-8 expression in tumor specimens and IL-8's contribution to tumor-induced angiogenesis in vivo. Eight of 13 non-small cell lung cancer cell lines constitutively produced high levels of IL-8. Four small cell lung cancer cell lines produced little or no IL-8. Immunohistochemical analysis of transbronchial biopsy specimens revealed IL-8 staining within adenocarcinomas (22/32), squamous cell carcinomas (12/21) and large cell carcinomas (2/3), but not within most small cell carcinomas (1/22). Anti-IL-8 antisera blocked tumor angiogenesis by two IL-8 producing cell lines in a mouse model.
Adenocarcinoma↗
The perturbed membrane of cells undergoing apoptosis is susceptible to type II secretory phospholipase A2 to liberate arachidonic acid.
Several lines of evidence have suggested that the plasma membranes of cells elicited by proinflammatory stimuli or microvesicles shed from activated cells are sensitive to extracellular type II secretory phospholipase A2 (sPLA2) that liberates fatty acids and lysophospholipids. Here we report that the membranes of cells undergoing apoptosis are highly susceptible to type II sPLA2. When neuronally differentiated rat pheochromocytoma PC12 cells deprived of nerve growth factor and serum, mouse mast cells deprived of hematopoietic cytokines or human monocytic U937 cells stimulated via Fas antigen (a receptor for the death factor Fas ligand), were exposed to type II sPLA2 at concentrations comparable to those detected at inflamed sites, the release of arachidonic acid was significantly accelerated in association with the process of programmed cell death. Arachidonic acid release by sPLA2 was dependent on the extracellular Ca2+ and was accompanied by preferential hydrolysis of phosphatidylethanolamine and phosphatidylserine in the membrane phospholipids. Association of sPLA2 with cell surface proteoglycan, which has been shown to be a prerequisite for endogenous sPLA2-dependent arachidonic acid release from the plasma membranes of live cells, was not essential for sPLA2-mediated hydrolysis of apoptotic cell membranes. Taking these results together, the apoptotic cell membrane is a potential target for extracellular type II sPLA2. The present findings may be relevant to events occurring at inflammatory or ischemic disease sites where apoptotic cells accumulate.
Animals↗
ADP-ribosylation of tuftsin suppresses its receptor-binding capacity and phagocytosis-stimulating activity to murine peritoneal macrophages.
Arginine-specific ADP-ribosyltransferase present in granules of chicken polymorphonuclear leukocytes (so-called heterophils) is released into the extracellular space by stimulus of calcium ionophore A23187 or opsonized zymosan [Terashima et al. (1996) J. Biochem. 120, 1209-1215]. In the present work, we examined extracellular targets of the released transferase and identified tuftsin, a phagocytosis-stimulating tetrapeptide derived from leukokinin, as a preferential substrate of the enzyme in chicken plasma. Specific binding of FITC-tuftsin to murine peritoneal macrophages, observed under a fluorescent microscope, was impaired by ADP-ribosylation of the labelled peptide. Phagocytic assay analyzed by flow cytometry revealed that ADP-ribosylation of tuftsin decreased its phagocytosis-stimulating activity towards the macrophages. Thus, the ADP-ribosylation of tuftsin apparently decreases its biological activity and ADP-ribosylation may possibly be involved in inflammatory processes through alterations in tuftsin activity.
Adenosine Diphosphate Ribose↗
Molecular cloning and characterization of arginine-specific ADP-ribosyltransferases from chicken bone marrow cells.
Among a number of tissues and peripheral blood cells in chicken, leukocytes, bone marrow cells, liver and spleen showed high ADP-ribosyltransferase activity, with leukocytes having the highest. Density gradient centrifugation of the leukocytes revealed that the leukocyte ADP-ribosyltransferase originates in the polymorphonuclear cells, so called heterophils. Subcellular distribution of the cells showed the localization of the enzyme in the granule fraction. Based on the obtained amino acid sequences of arginine-specific ADP-ribosyltransferase purified from chicken peripheral heterophils, two arginine-specific ADP-ribosyltransferase cDNAs (designated AT1 and AT2) were obtained from chicken bone marrow cells. Each cDNA encodes a different peptide of 312 amino acid residues. Homology of the deduced amino acid sequences between AT1 and AT2 was 78.3%. Arginine-specific ADP-ribosyltransferase activity was detected in culture medium of COS 7 cells transiently transfected with AT1 cDNA, while activity from the cells transfected with AT2 cDNA was found in both culture medium and cell lysate. AT1 transferase required 2-mercaptoethanol (MSH) for the activity and in the presence of NaCl, the activity was inhibited while the AT2 enzyme was activated by either agent. Highly conserved regions were observed among the deduced amino acid sequences of AT1, AT2, chicken erythroblast and rabbit and human skeletal muscle ADP-ribosyltransferases, and rodent T-cell surface antigen RT6. Two forms of the transferase with much the same properties as AT1 and AT2 proteins, regarding the effect of NaCl and MSH, were detected in bone marrow cells. Based on these results it seems that AT1 and AT2 cDNAs encode the two forms of arginine-specific ADP-ribosyltransferase detected in chicken bone marrow cells.
ADP Ribose Transferases↗
Characterization and molecular cloning of mouse type II phospholipase A2.
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Amino Acid Sequence↗
Detection of group C adenovirus DNA in small-cell lung cancer with the nested polymerase chain reaction.
Group C adenovirus is latent in human tissues and can malignantly transform cells. The purpose of this study was to investigate the association between this virus and lung cancer. We investigated latent adenoviral infection using the nested polymerase chain reaction and in situ hybridization in transbronchial biopsy specimens from patients with small-cell lung cancer and non-small-cell lung cancer. The polymerase chain reaction was performed on DNA extracts with two sets of primers directed at a 261-base-pair target sequence of the E1A region of the adenoviral genome. In situ hybridization was performed on histological sections using DNA representing the entire adenovirus type 5 genome. E1A target DNA was present in 11 (31%) of 35 cases of small-cell lung cancer but in none of the 40 cases of non-small-cell lung cancer (P < 0.01). Of the 11 cases found positive by PCR, 8 were positive for adenovirus DNA by in situ hybridization. Adenovirus was prominent in tumor cells in 5 of the 8 cases, and in normal epithelial cells in the 3 remaining cases. Adenovirus DNA was not detected by in situ hybridization in specimens in which E1A DNA was not detected by the polymerase chain reaction. Small-cell lung cancer has mutations or deletions in the p53 and retinoblastoma genes more frequently than are found in non-small-cell lung cancer. Therefore, we speculate that adenovirus infection might participate in the pathogenesis of SCLC by producing mutation in these genes, rather than by inhibiting the function of these proteins.
Adenoviridae↗
A deletion in the sapA homologue cluster is responsible for the loss of the S-layer in Campylobacter fetus strain TK.
The surface array protein (SAP) of Campylobacter fetus strain TK is encoded by seven homologous sapA genes clustered on the chromosomal DNA. The spontaneously arising variant strain TK(SAP-) produces no SAP and carries an approximately 10-kb chromosomal deletion. To elucidate the mechanism underlying the loss of SAP synthesis, we analyzed the region containing the sapA homologues and the deletion. We constructed a physical map of the sapA cluster region by aligning the clones that contain sapA homologues. These analyses demonstrated that all sapA homologues were located within a limited region of about 50 kb of chromosomal DNA of strain TK. The TK(SAP-) deletion was located within this cluster and was 13.3 kb in size. The deletion occurred between two sapA homologues and resulted in the formation of a chimeric sapA homologue in the variant strain. Sequence analysis of the upstream regions and the conserved regions of all sapA homologues revealed a high degree of similarity. However, only one sapA homologue contained a putative promoter sequence. This promoter sequence was located in the deleted region. Thus, the deletion of the promoter appears to be responsible for the loss of SAP expression in TK(SAP-).
Bacterial Outer Membrane Proteins↗
Clarithromycin is a potent inhibitor of tumor-induced angiogenesis.
We investigated the inhibitory effect of clarithromycin, a 14-membered ring macrolide antibiotic, on tumor-induced angiogenesis in vivo using a mouse dorsal air sac model. The inhibitory effect of clarithromycin was dose-dependent, and 100 mg/kg of clarithromycin administered intraperitoneally twice a day reduced the area of dense capillary network to about 30% that of the control. However, in concentrations up to 50 microM clarithromycin had no effect on lung cancer cells and human vascular endothelial cell growth, endothelial cell migration, or lung cancer cell production of the angiogenesis-inducing factors interleukin-8 and vascular endothelial growth factor. Clarithromycin in concentrations greater than 10 microM inhibited endothelial cell tube formation on Matrigel in a dose-dependent manner. These data suggest clarithromycin is a potent inhibitor of tumor-induced angiogenesis that exerts its effect by inhibiting endothelial cell tube formation, and may be a possible candidate for therapeutic application.
Animals↗
Immunohistochemical study of endothelin-1 in preeclamptic nephropathy.
Whether the serum levels of endothelin, a vasoconstrictive peptide produced in the endothelial cell, increase in preeclamptic patients is still controversial. We performed immunohistochemical studies to observe the changes in endothelin-1 (ET-1) in preeclamptic kidney tissues. The monoclonal anti-human ET-1 antibody (Yamasa, Japan) and anti-von Willebrand factor (vWF, Dako, Denmark), a marker of endothelial cells, were used for the studies by the strepto-avidin-biotin peroxidase method (ABC-POD Kit, Wako, Japan). Twenty-nine patients and 12 normal controls were divided into four groups. The preeclamptic group included 14 patients diagnosed with preeclampsia by clinical symptoms of hypertension, proteinuria, and edema occurring in late pregnancy and as having preeclamptic nephropathy. They underwent renal biopsy 16.7 +/- 1.0 (mean +/- SEM) days after delivery. The nephrotic group comprised 10 normotensive nonpregnant patients with nephrotic-range proteinuria examined through biopsy before treatment (six cases of minimal change, two of focal segmental glomerulosclerosis, one of membranous nephropathy, and one of IgA nephropathy). The pregnant women with preexisting glomerular disease group included five pregnant women with normal renal function who were normotensive and had no increase in the amount of proteinuria throughout pregnancy. They underwent renal biopsy 10.8 +/- 2.9 days after delivery (two cases of membranous nephropathy, one of focal segmental glomerulosclerosis, one of thin basement membrane disease, and one of non-IgA mesangioproliferative glomerulonephritis). The normal kidney group comprised 12 healthy tissue samples taken from nephrectomized kidneys (five cases of renal cell carcinoma, one case of lipofibrosarcoma, and six cases of kidney transplant donors). In these four groups, ET-1 and vWF showed equally positive staining in small arteries. VWF also showed positive staining in arterioles and peritubular capillaries in all groups. Although the glomeruli showed positive staining with ET-1 along the capillary walls in the normal group and the nonpregnant nephrotic group, they showed very weak or negative results in the preeclamptic group. Moreover, gravida with underlying glomerular disease without superimposed preeclampsia also showed negative findings of ET-1 in the glomeruli. The glomeruli in the four groups showed positive findings, with vWF readings the same as in the controls. These results indicate that the production of ET-1 in the glomerular endothelial cells decreases in cases of both preeclampsia and normal pregnancy, and the condition may be caused by pregnancy itself.
Adult↗