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Biomedical subjects

J Nakano

Publications and source records attributed to J Nakano.

At least 37 records · Page 2Linked to original sources

[Changes in intrapulmonary compression gas volume during measurement of the flow-volume curve].

Changes in intrapulmonary compression gas volume during flow-volume curve measurement were studied in 77 patients with bronchial asthma, 20 patients with emphysema, and 14 patients with pulmonary fibrosis. The peak point of intrapulmonary compression gas volume was observed at FEF 75 in the bronchial asthma and emphysema patients, and of FEF 25 in the pulmonary fibrosis patients. In the bronchial asthma patients, intrapulmonary compression gas volume increased significantly compared to the healthy control groups; that increase was especially obvious in cases where airway obstruction was severe, e.g. when FEV 1.0% was below 69% (p < 0.05). By contrast, the emphysema patients did not exhibit any significant increase in intrapulmonary compression gas volume compared to healthy control groups despite the existence of obstructive impairments. This study demonstrated that the intrapulmonary compression gas volume-curve is a useful index for the diagnosis of pulmonary diseases when combined with measurements of FVC and FEV 1.0%.

Adult↗

[Influential factors in elevation of serum creatine phosphokinase for the patients with Kanemi Yusho].

We studied the etiology of the elevation of serum creatin phosphokinase (CK) using the data from routine medical checkup of Kanemi Yusho patients during 1995 and 1997. We also studied the serum CK and blood urea nitrogen (BUN) in rats given the polychlolinated biphenyls as well as controls, and conducted optical microscopic observation of muscle tissue in rats given the polychlolinated biphenyls and control. The patients with elevation of serum creatine phosphokinase also showed the elevation of BUN and polychlolinated biphenyls in their serum. These are thought to be triggers of the elevation of CK in the serum. However, animal experiments failed to yield the same results as human. The rats given polycholorinated biphenyls showed atrophy of muscle fibers. Accordingly, we were unable to clarify the etiology of CK elevation in humans and muscle atrophy in rats.

Animals↗

[Benign clear cell tumor of the lung diagnosed by transbronchial biopsy].

A 26-year-old woman had an abnormal shadow on chest X-ray films during a general medical examination. A chest roentgenogram showed a nodular shadow 8 mm in diameter in the middle field of the right lung. Transbronchial biopsy specimens revealed that the coin lesion was a benign clear cell tumor. Benign clear cell tumors of the lung are rare; only 21 cases, including the present case, have been reported in Japan. Although the diagnosis in most of the cases reported required an open thoracotomy, for our patient the diagnosis was based solely on the findings of a transbronchial biopsy.

Adult↗

An unusual female melanoma patient with late metastases to both skin and ovaries.

We presented an unusual case of cutaneous and bilateral ovarian metastases of malignant melanoma. There was no previously identifiable cutaneous or mucous lesion or teratoid element. Past history revealed that the patient had undergone removal of a blackish, elevated, irregular shaped tumor from the right arm eleven years previously. This lesion was considered to be the primary melanoma; therefore, it was thought to be very unusual as metastasis occurred in both the skin and ovaries after an eleven year disease-free interval.

Adult↗

Pemphigus vegetans involving the esophagus.

A 44-year-old man with pemphigus vegetans had severe odynophagia. He received an endoscopic examination for esophageal involvement. Many white plaque-like lesions with an erythematous base were seen on the esophageal mucosa. Biopsy from the mucosal epithelial layer showed rounded epidermal cells with large nuclei and numerous inflammatory cells including eosinophils.

Adult↗

Synthesis and structure--antibacterial activity relationships of 7-(3-amino-1-propynyl and 3-amino-1-propenyl)quinolones.

7-(3-Amino-1-propynyl)-1-cyclopropyl-6,8-difluoro-1,4-dihydro-4- oxoquinoline-3-carboxylic acid (7a) and some related compounds (7b-f, 8a, b, 9) were prepared via palladium(0)-catalyzed cross-coupling reaction of 7-iodoquinolone 12 with acetylenic compounds and their antibacterial activity was tested. The methylene homologue (7d) and the N-methyl derivative (7e) of 7a showed essentially the same activity as that of 7a. Addition of methyl group(s) to C'-3 of 7a (giving 7b, c) reduced the activity. The hydrogenation of 7a to (Z)-3-amino-1-propenyl (8a), (E)-3-amino-1-propenyl (8b) and 3-amino-1-propyl (9) compounds retained or enhanced the activity of 7a. Among the compounds prepared, 8a was the most active, but was less active than ciprofloxacin (1). In order to get insight into structure-activity relationships, the spatial distribution of the amino groups of 7a, 8a, b, and 9 was examined by means of computer-aided molecular modeling.

Anti-Infective Agents↗

Synergistic actions of pentobarbital and dihydropyridine Ca2+ antagonists on guinea pig isolated thoracic aorta.

In order to elucidate the mechanism(s) behind the interactions between barbiturates and Ca2+ antagonists, the effects of pentobarbital combined with three structurally diverse types of Ca2+ antagonist on CaCl2-induced contractile responses of the guinea pig thoracic aorta in Ca(2+)-free and 40 mM K+ medium and the effects of pentobarbital on Ca2+ antagonist binding to guinea pig aortic membranes were investigated. The dihydropyridine derivatives isradipine (10(-10)-10(-8) M) and nifedipine (10(-10)-10(-8) M) inhibited CaCl2-induced contractions concentration-dependently. Treatment with both pentobarbital (10(-4) M) and dihydropyridine Ca2+ antagonists (10(-9) M) shifted the CaCl2 concentration-response curves to the right significantly compared with those after treatment with the Ca2+ antagonists and pentobarbital alone. However, no synergistic effects of pentobarbital (10(-4) M) with other types of Ca2+ antagonist (verapamil (10(-7) M) and diltiazem (10(-6) M)) were observed. The binding of [3H]isradipine (2 x 10(-9) M) to guinea pig aortic membranes was increased significantly by simultaneous pentobarbital treatment, but no such effect was observed with [3H]verapamil (10(-8) M) or [3H]diltiazem (2 x 10(-8) M). These findings suggest that the synergistic contractile effects of pentobarbital and dihydropyridines were, in part, due to enhancement of dihydropyridine binding to guinea pig aortic membranes (L-type Ca2+ channels) by pentobarbital and that the interactions between pentobarbital and Ca2+ antagonists may be structurally specific.

Animals↗

Ganglioside expression in melanomas from Japanese individuals: unusual pattern in two patients with metastatic lesions of acral lentiginous melanomas.

Melanoma among Japanese is rare, and differs in its clinical and histological characteristics from that found in Caucasians. In this study, the ganglioside expression of melanoma specimens obtained from Japanese was determined and compared with previously published data on Caucasians. The ganglioside composition of 25 biopsy melanoma specimens, including 13 primary and 12 metastatic lesions, was studied using thin layer chromatography. Four gangliosides (GM3, GD3, GM2, GD2) were most commonly expressed in melanomas in Japanese. The expression of gangliosides was quite variable in both primary and metastatic melanomas as seen in previous reports. No significant differences were observed between gangliosides from primary and metastatic sites. A new type of ganglioside expression, in which GM3 was nearly the only ganglioside (> 95%), was found in metastatic tumors from two Japanese patients with acral lentiginous melanoma (ALM), which is the most common clinical and histopathological type of melanoma among Japanese but is very unusual among Caucasians. The patterns of expression were similar to those in Caucasians except for the detection of a "new" pattern.

Adult↗

Human melanoma cell lines deficient in GD3 ganglioside expression exhibit altered growth and tumorigenic characteristics.

We have selected GD3-deficient human melanoma cell lines, in order to investigate the function of GD3 ganglioside. This was done by treating SK-MEL-28 cells with anti-GD3 antibody (R24) and rabbit complement and subsequent subcloning of the surviving cells, resulting in the derivation of two cell lines deficient in the cell surface expression of GD3. Neither cell line (designated SK-MEL-28-N1 and SK-MEL-28-N2) had detectable cell surface expression of GD3 as analyzed with monoclonal antibody R24, and no GD3 was detectable in either cell line by glycolipid isolation, thin-layer chromatography, or resorcinol-HC1 spray, but thin-layer chromatography immunostaining with monoclonal antibody R24 showed the presence of low amounts of GD3 in both N1 and N2 (1/40 of the amount in the parent cell line in N1 and 1/500 in N2). In SK-MEL-28-N1, the residual GD3 was shown by immunofluorescence assays on permeabilized cells to be present in discrete intracellular organelles, suggesting that these cells have a defect in the transport of GD3 as well as in its synthesis. Both SK-MEL-28-N1 and -N2 had an increase in detectable GM3 expression. The mutant cell lines had altered cell morphology in comparison to the parent cell line and both had slower growth rates in vitro and lower tumorgenicity in nu/nu mice. These results indicate that GD3 ganglioside plays an important role in proliferation and growth of melanoma cells.

Animals↗

5-Alkoxyimidazoquinolones as potential antibacterial agents. Synthesis and structure-activity relationships.

4-Substituted 6-cyclopropyl-6, 9-dihydro-5-methoxy-9-oxo-1H-imidazo[4,5-f] quinoline-8-carboxylic acids (6) and 8-substituted 1,5,6,11-tetrahydro-5-methyl-1-oxo-imidazo[4,5-g]pyrido[1,2,3-de][1,4] benzoxazine-2-carboxylic acids (7) were prepared as potential antibacterial quinolone derivatives. The appendages at C-4 of -6 and at C-8 of -7 were selected from 1-piperazinyl, 4-methylpiperazinyl, 3-aminomethylpyrrolidinyl, and 3-aminomethylpyrrolidinyl groups. The 5-methoxyimidazoquinolones 6 were superior to the corresponding ofloxacin type analogues 7 in in vitro antibacterial activity. The activity of 6 was equipotent against S. aureus, but 2 to 16 times less potent against E. coli and P. aeruginosa compared to that of the 5-fluoro analogue 3.

Anti-Bacterial Agents↗

Imidazo- and triazoloquinolones as antibacterial agents. Synthesis and structure-activity relationships.

4,5-Disubstituted 6-cyclopropyl-6,9-dihydro-9-oxo-1H-imidazo (30-32) and triazolo[4,5-f]quinoline-8-carboxylic acids (33-35) were synthesized starting from 5,6-diaminoquinolones 25. The imidazoquinolones 30-32 were equal or superior to the corresponding triazoloquinolone analogues 33-35 in in vitro antibacterial activity. As for the C-5 substituents, a fluorine atom was the most favorable of the three groups, H, F, and Cl. Among the compounds prepared, 4-(cyclic amino)-5-fluoro-imidazoquinolones 31 a-d showed potent and well-balanced antibacterial activity against both gram-positive and gram-negative bacteria. Structure-activity relationships for the C-4 substituents (cyclic amino groups) were also examined in detail.

Animals↗

Immunohistological reaction mechanism of anti-monosialoganglioside monoclonal antibody, MAb 202, showing predominant cytotoxicity for malignant melanoma.

Mouse monoclonal IgM antibody (MAb 202) can cause melanoma cell necrosis in vivo. We analysed its immune mechanism in three melanoma patients to whom MAb 202 was administered. After the MAb 202 administration, histopathological analysis showed necrosis of melanoma cells expressing only GM3 in two patients. Another patient carrying both GM3 and GD3 showed infiltration of lymphocytes within the tumor nest but no tumor cells or nest necrosis. Immunohistological examination using anti-mouse IgM antibody revealed MAb 202 bound on the surface of melanoma cells in two patients but not in the third (positive for both GM3 and GD3). In vitro, MAb 202 reacted with the melanoma cells of the same two patients, but not with any other tissues of these individuals. We found no reaction of MAb 202 to non-melanoma cells including normal melanocytes and glia cells. Our trials suggest, 1) MAb 202 reacts directly to monosialogangliosides on the melanoma cell surface and then leads to the cytotoxicity reaction, or 2) MAb 202 induces lymphocyte infiltration and possibly then promotes the secretion of some cytokines.

Adult↗

Effects of ET antagonists (PD143296 and PD145065) on contractions in guinea pig hilar bronchus induced by endothelin-1 and its related peptide.

ETs-induced contractions were resistant to ET(A)-selective antagonists and believed to be mediated by activation of ETB receptors in guinea pig bronchus. In the present study, the effects of the ET antagonists, PD143296 (Ac-D-Phe-L-Leu-L-Phe-L-Ile-L-Ile-L-Trp.2Na) and PD145065 (Ac-[(R)-2-10, 11-dihydro-5H-dibenzo[a, d]cyclohepten-5-yl]Gly)-L-Leu-L-Asp-L-Ile-L-Ile- L-Trp.2Na), on contractions induced by ET-1, ET-3, sarafotoxin S6c (STXc), and IRL1620 in the isolated hilar bronchus of the guinea pig were investigated. An ETA/B nonselective antagonist, PD145065 antagonized contractions induced by ET-1, ET-3, STXc, and IRL1620. Its antagonistic activity against ET-1, with pKB of 5.77 +/- 0.02 (n = 16, 3-10 microM), was significantly lower than that against ET-3, with pKB of 6.18 +/- 0.02 (n = 12, 3-10 microM), STXc, with pKB of 5.97 +/- 0.01 (n = 14, 3-10 microM), and IRL1620, with pKB of 6.80 +/- 0.04 (n = 14, 0.3-1 microM). Conversely, although a putative ETB-selective antagonist, PD143296 (10 microM) slightly but significantly antagonized the concentration-response curve of IRL1620 (pKB = 5.28 +/- 0.14, n = 6), it had no effect on ET-1-,ET-3-, or STXc-induced contractions. These results suggest that ETs possibly activate ETB2 or an atypical ETB receptor subtype in guinea pig hilar bronchus.

Animals↗