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Biomedical subjects

N Nagata

Publications and source records attributed to N Nagata.

At least 361 records · Page 20Linked to original sources

Effects of macrophage colony-stimulating factor on reduction of viable bacteria and survival of mice during Listeria monocytogenes infection: characteristics of monocyte subpopulations.

Mice could well tolerate infection with a lethal dose of Listeria monocytogenes after intraperitoneal preinjections with 250 micrograms of macrophage colony-stimulating factor (M-CSF) per kg of body weight for 5 days. The characteristic changes in the surface markers (Mac-1, LFA-1, and F4/80) of peripheral monocytes were also investigated in order to analyze the mechanism of protection by M-CSF. This investigation shows the excellent effect of intraperitoneal preinjections of M-CSF on the reduction of viable Listeria organisms and the improvement of survival after an intravenous Listeria infection.

Animals↗

Clinicopathological study of migratory lung infiltrates.

Clinical features and the histological appearances of transbronchial lung biopsy specimens were investigated in 11 patients with migratory infiltrates on the chest radiograph. Serum circulating immune complexes were increased at the time that infiltrates were present in all patients and the levels returned to normal as patients recovered clinically and radiologically. The Mantoux test response was negative in most patients. Fifty serial sections were obtained from each paraffin embedded biopsy specimen block and every 10th section was stained (step sectioning) with haematoxylin and eosin. Six patients (group 1) did not have eosinophilic infiltration; four of these had granulation tissue plugs within respiratory bronchioles when the tissue was examined by step sectioning. All had organising pneumonia and interstitial inflammation in the setting of a clinical picture consistent with bronchiolitis obliterans organising pneumonia. In two cases IgG had been deposited in intraalveolar macrophages. Biopsy specimens in five patients (group 2) showed eosinophilic infiltration; four patients had chronic eosinophilic pneumonia and one the Churg-Strauss syndrome. Step sectioning of transbronchial biopsy specimens in patients with migratory pulmonary infiltrates is useful and may support the diagnosis of bronchiolitis obliterans organising pneumonia.

Aged↗

Step section preparation of transbronchial lung biopsy. Significance in the diagnosis of diffuse lung disease.

We retrospectively prepared step sections of nondiagnostic TBLB materials obtained from patients with diffuse or multiple lung disease and evaluated the diagnostic significance of the step section method. Among 112 patients with nondiagnostic TBLB findings, the preparation of step sections resulted in specific findings in seven cases. Step sections were especially useful for the detection of epithelioid granulomas and tumor tissue in patients with sarcoidosis and lymphangiosis carcinomatosa, respectively, but their contribution to the diagnosis of hypersensitivity pneumonitis, collagen-vascular disease, Mycoplasma pneumonia and pneumoconiosis was relatively small. In addition, step sections were useful for the detection of bronchiolitis obliterans affecting respiratory bronchioles. Overall, the examination of step sections was considered to be clinically useful in 30 cases (26.8 percent). Accordingly, the examination of step sections can be recommended before a further diagnostic procedure is chosen, if a TBLB performed in patients with diffuse or multifocal lung disease is nondiagnostic.

Biopsy↗

Simultaneous occurrence of SIADH, secondary hypogonadism and alopecia universalis in a woman with IDDM.

Syndrome of inappropriate secretion of antidiuretic hormone (SIADH), hypothalamic hypogonadism and alopecia universalis occurred in a 31-year-old female with insulin-dependent diabetes mellitus (IDDM). Despite various clinical investigations and careful observation for 20 months, the cause and pathogenesis of SIADH and hypothalamic hypogonadism were not elucidated. The complex of these disorders had not been described. The presence of IDDM and alopecia universalis, in which an autoimmune process has been assumed to be involved, is interesting in considering the pathogenesis of the SIADH and hypothalamic hypogonadism.

Adrenocorticotropic Hormone↗

The in vitro effects of glycyrrhizin and the derivatives of glycyrrhetinic acid on the activity of cAMP-dependent protein kinase and phosphorylation of cellular polypeptide by the kinase from Ehrlich ascites tumor cells.

The effects of glycyrrhizin (GL) and the derivatives of glycyrrhetinic acid (GA) on the activity of cAMP-dependent protein kinase (A-kinase) and the phosphorylation of cellular polypeptides by the kinase purified from Ehrlich ascites tumor cells had been investigated in vitro. It was found that (i) the derivatives [3 beta-hydroxy-olean-11,13 (18)-diene-30-oic acid Na, olean-9(11), 12 diene-3 beta, 30-diol-3 beta, 30-di-o-hemiphthalate 2Na and olean-12-ene-3 beta, 30-diol 3 beta, 30-di-o-phosphate 2Na] of GA inhibited the activity of A-kinase at the concentrations higher than 25 microM; (ii), at 10 microM, these derivatives and native GL stimulated the activity of the kinase significantly; and (iii) the inhibitory and stimulatory effects of some GA derivatives were clearly correlated with their chemical structures. Moreover, sodium dodecyl sulfate polyacrylamide gel electrophoresis and two dimensional gel electrophoresis followed by autoradiography detected several acidic polypeptides, including polypeptides with approximate molecular weights of 35,000 (pI 4.3), 27,000 (pI 4.5) and 18,000-21,000 (pI 4.5), phosphorylated by A-kinase, to be functioning as mediators in response to these drugs. This observation suggests that the GL-induced inhibition of phosphorylation of these cellular polypeptides by A-kinase may be physiologically implicated in the biochemical mechanisms involved in the anti-inflammatory effect of the drug.

Animals↗

[Protective effect of urinastatin on ischemic renal injury in rabbits].

Protective effect of urinastatin on ischemic renal injury in rabbits was investigated by urinary enzymes and renal function tests. Ten rabbits were divided into two groups: the control group and urinastatin group administered 50,000 units/kg of urinastatin. The ischemic renal injury model was made by occluding the left renal artery for 60 minutes. Urinary excretions of N-acetyl-beta-D-glucosaminidase (NAG) and gamma-glutamyl transpeptidase (gamma-GTP) (U-NAG and U-gamma-GTP), creatinine clearance (Ccr), free water clearance (CH2O), fractional excretion of sodium (FENa) and urine volume (UV) were measured before occlusion of the left renal artery and after reflow. There were no significant differences in the values before occlusion (baseline values) for U-NAG, U-gamma-GTP, Ccr, CH2O, FENa, and UV between the two groups. U-NAG after reflow was increased in the two groups compared with baseline values, and the increase was significantly lower in the urinastatin group than control group. U-gamma-GTP after reflow was also increased in the two groups compared with baseline values, but the change was not significant between the two groups. Ccr and CH2O after reflow were significantly decreased, and FENa and UV were increased in the two groups compared with baseline values. However, no significant differences were observed between the two groups in these four parameters. These results suggest that urinastatin is effective for the protection of the kidney against ischemic damage, especially of the renal tubular cells.

Acetylglucosaminidase↗

[Multiple pulmonary metastasis from histologically benign giant cell tumor of the right radial olecranon].

An unusual case of a benign giant cell tumor of bone with pulmonary metastasis is reported. A 23-year-old man had a painful tumor in the right radial olecranon that proved to be a histologically benign giant cell tumor. Curettage and bone-grafting were performed, but the tumor recurred twice, 8 months and 20 months after initial treatment. Histological examination of biopsy materials from the recurring tumor showed typical benign giant cell tumors. Five years later, wedge resections were performed for bilateral pulmonary nodules, which had been detected by chance. The pulmonary nodules turned out to be histologically similar to the primary tumor of the olecranon. Almost 7 years later, he was asymptomatic and the chest radiograph was clear, and there was no local recurrence of the lesion.

Adult↗

[A case of broncho-bronchiolitis obliterans associated with rheumatoid arthritis and Sjögren's syndrome].

A 45-year-old female patient with rheumatoid arthritis and Sjögren's syndrome was admitted because of progressive exertional dyspnea and palpitation. The chest X-ray film was normal except for slight overinflation. Pulmonary function tests indicated severe mixed-type impairment, and arterial blood gas analysis revealed hypoxemia. 99mTc-MAA lung perfusion scintigraphy and 81mKr lung ventilation scintigraphy showed multiple nonsegmental defects in both lungs. During six months of observation, the perfusion defect increased in size and intensity, although the chest radiography remained unchanged. The diagnosis of bronchobronchiolitis obliterans (BBO) was confirmed by open lung biopsy. Glucocorticoid therapy was ineffective, and she died of respiratory failure a month after discharge. It is noteworthy that perfusion scintigram demonstrated the progression of the disease much better than chest radiography, which showed no apparent change during the observation period.

Arthritis, Rheumatoid↗

[A case of whole visual field visuomotor ataxia of bilateral hands associated with bilateral parietooccipital lesions in the white matter].

A 29-year-old male with visuomotor ataxia was reported. Visuomotor ataxia of bilateral upper extremities was noted in whole visual field including central visual field (optische Ataxie). Neither contraction nor depression of visual field was detected by the test using kinetic or static perimeter, respectively. Magnetic resonance imaging and computed tomography of the brain revealed bilateral parietooccipital lesions in the white matter, and pathological examination of brain biopsy specimen demonstrated demyelination. We considered that bilateral parietooccipital lesions in the white matter were responsible for visuomotor ataxia in this case.

Adult↗

[Step section of the TBLB specimens in the diagnosis of sarcoidosis].

The authors analyzed a total of 132 cases clinically diagnosed as sarcoidosis from 1979 to 1990. Routine TBLB sections revealed sarcoid granulomas in 57 cases (Stage 0; 5%, Stage 1; 40%, Stage 2; 57%). In 75 cases in whom routine sections did not show granuloma, we prepared additional sections from paraffin-embedded blocks as step sections. When examined with step sections in addition to routine specimens, the detection rate of sarcoid granuloma increased to 47% in Stage 1 and 82% in Stage 2. We concluded that making step sections of TBLB specimens is a useful diagnostic method in cases suspected of sarcoidosis, especially in Stage 2 cases.

Adolescent↗

Anatomic pathway of pulmonary fluid leakage in endotoxemia induced in rats. The red blood cell packing method and its application.

The anatomic site of pulmonary fluid leakage in endotoxemia in rats was investigated using the red blood cell packing method and low-dose horseradish peroxidase as a tracer. To differentiate between arterioles and venules in a given section by light and electron microscopy, human red blood cells fixed with 4% paraformaldehyde were administered to the rat pulmonary arterial trunk at a pressure of 40 cm water. Fixed red blood cells were packed in the lumina of arteries, arterioles, and a few capillaries surrounding arterioles, while veins, venules, and almost all capillaries were void of red blood cells in the lumina. Fifteen minutes after the intravenous administration of 3 and 30 mg/kg of Escherichia coli endotoxin, extravascular leakage of horseradish peroxidase from venules (nonmuscular veins) was evident. Two hours after the intravenous injection of the same doses of endotoxin, some arterioles (nonmuscular arteries) and venules (non-muscular veins) showed extravascular leakage of horseradish peroxidase, while few capillaries showed this leakage. These results suggest that pulmonary fluid leakage occurs predominantly through venules in the early phase of endotoxemia (at 15 minutes), while the arterioles contribute to fluid leakage in addition to venules in the late phase of endotoxemia (at 2 hours).

Animals↗

Enhanced leukotriene C4 synthase activity in thioglycollate-elicited peritoneal macrophages.

The utilization of LTA4 by peritoneal macrophages (MO) obtained from untreated rats (control) as well as by those elicited from rats was investigated at designated intervals (on days 3, 7, and 14) following the intraperitoneal injection of thioglycollate (TG). On day 7 following the injection the elicited MO converted LTA4 to LTC4 at the highest rate while the resident MO showed the lowest rate. The conversion of LTA4 to LTC4 and LTB4 was next examined by using each MO lysate. The apparent LTC4 synthase activity was significantly higher in the MO lysate both on day 3 and day 7, with the latter being the highest value obtained. The GSH S-transferase activity in each lysate using as the substrate, DNCB was significantly lower on day 3 but significantly higher on day 7 as compared to control values. However, this elevated activity was less variable than that observed with LTC4 synthase. The possible implication for these observations is discussed.

Animals↗

Inhibition of estradiol uptake and transforming growth factor alpha secretion in human breast cancer cell line MCF-7 by an alkyl-lysophospholipid.

We investigated the effect of 1-O-octadecyl-2-O-methyl-sn-glycero-3-phosphocholine (ET-18-OCH3), an alkyl-lysophospholipid, on the uptake of estrogen, the secretion of transforming growth factor (TGF) alpha and the content of progesterone receptors (PRs) in the hormone-dependent breast cancer cell line, MCF-7. The uptake of labeled estradiol by MCF-7 was dose dependently decreased by 12 h pretreatment with 10-25 micrograms/ml ET-18-OCH3, and this suppression occurred prior to the onset of the inhibitory action of ET-18-OCH3 on MCF-7 growth. Scatchard analysis demonstrated that ET-18-OCH3 reduced the number of estrogen receptors in MCF-7 without affecting their affinity. Both the secretion of TGF-alpha from MCF-7 into the conditioned medium and the PR content of MCF-7 were decreased by 48 h treatment with 10 micrograms/ml ET-18-OCH3. The estradiol uptake, the TGF-alpha secretion, and the PR content were not affected by platelet-activating factor, lyso-PAF, and palmitoyl-lysophosphatidylcholine, all at 10 micrograms/ml. These results suggest that the reduction of estrogen receptor level induced by ET-18-OCH3 resulted in decreases in both the secretion of TGF-alpha and the content of PR in MCF-7, and these effects are specific to ET-18-OCH3. We concluded that these effects of ET-18-OCH3 may lead, at least partly, to its antitumor action in hormone-dependent breast cancer cell lines.

Antineoplastic Agents↗

Inhibition of renal membrane adenylate cyclase by extract of pancreatic cancer associated with humoral hypercalcemia of malignancy.

The parathyroid hormone (PTH)-like activity, defined by the stimulation of cAMP production in MC3T3E1 cells, in the extract of a pancreatic cancer associated with humoral hypercalcemia of malignancy (HHM) was eluted in two peaks (I and II) by reverse phase HPLC. Both peaks dose-dependently inhibited the binding of human (h) PTH(1-34) to canine renal membrane in an essentially similar fashion to hPTH(1-34) or PTH-related protein (rP). In the renal membrane, neither of these peaks stimulated adenylate cyclase (AC) but rather dose-dependently inhibited AC activity stimulated by hPTH(1-34), PTH-rP(1-34) or forskolin. In rat renal cortical slices, however, both peaks could exhibit their own stimulatory effect and did not inhibit PTH or forskolin-stimulated cAMP production. It has been concluded that a factor which inhibits AC activity, probably reflecting the direct action at catalytic site, can occasionally be produced with PTH-like factor. Although PTH-like and AC-inhibiting activities were very close on reverse phase HPLC, currently the interrelation between these two activities is not clear. It may be important to be aware of the presence of such a factor in the evaluation of the bioassay data employing a broken cell preparation, which is often used to assess the PTH-like activity of tumor products.

Adenylyl Cyclase Inhibitors↗

Enhanced superoxide anion generation but reduced leukotriene B4 productivity in thioglycollate-elicited peritoneal macrophages.

Lipoxygenase metabolism of arachidonic acid was compared between peritoneal macrophages from untreated rats and those from rats on day 7 after intraperitoneal injection of thioglycollate broth (TG). Resident macrophages (M phi) from untreated rats produced mainly LTB4 (303 +/- 25 pmol/5 x 10(6) cells) and 5-HETE (431 +/- 56 pmol/5 x 10(6) cells) when stimulated with 5 micrograms/ml calcium ionophore A23187 for 20 min at 37 degrees C. On the other hand, TG-elicited M phi generated less amounts of lipoxygenase metabolites (157 +/- 10 pmol LTB4 and 319 +/- 19 pmol 5-HETE/5 x 10(6) cells) with the same stimulus. Then, leukotriene productivity was examined by using subcellular fractions of each M phi lysate and an unstable epoxide intermediate, leukotriene A4. LTA4 hydrolase activity was mainly contained in soluble fractions from the both groups of M phi. The cytosol fraction from the resident M phi exhibited the following specific and total activity; 2.2 +/- 0.1 nmol LTB4/mg protein/5 min and 12.2 +/- 0.5 nmol LTB4/5 min per 10(8) cells. On the contrary, the cytosol fraction from the TG-elicited M phi showed 1.9 +/- 0.1 nmol LTB4/mg protein/5 min and 9.6 +/- 0.3 nmol LTB4/5 min per 10(8) cells. The resident M phi, however, generated 0.14 +/- 0.04 nmol O2-/min/4 x 10(5) cells whereas the TG-elicited M phi did 0.49 +/- 0.13 nmol O2-/min/4 x 10(5) cells when stimulated with wheat germ lectin. These results suggest that the TG-elicited macrophages show enhanced superoxide production but generate less lipoxygenase metabolites.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Auto-MHC class II-reactive T cell line obtained from MRL/+mice suffering from "lpr-GVHD". I. Characterization of surface phenotypes, specificities and functions in vitro.

When MRL/Mp-(+)/+ (MRL/+) mice are lethally irradiated and then reconstituted with bone marrow or spleen cells from MRL/Mp-lpr/lpr (MRL/lpr) mice, they develop a graft-versus-host disease (GVHD)-like syndrome, colloquially known as "lpr-GVHD". To analyze the roles of the MRL/lpr T cells in the development of "lpr-GVHD" and autoimmune diseases, several T cell lines were established from the spleen cells of MRL/+ mice suffering from "lpr-GVHD". The surface phenotypes, specificities, and functions of a representative clone (l/+T1) of the cloned T cell lines were characterized. The l/+T1 cells showed Thy-1.2+, L3T4+ and T3+, but Lyt-2- and B220- phenotypes. Proliferative response was observed by co-culturing the cells with spleen cells from MRL/+, MRL/lpr, AKR/J, and C3H/HeN mice, but not from BALB/c or C57BL/6 mice. Furthermore, the l/+ T1 cells responded to spleen cells of B10.BR and B10.A but not B10.D2 mice. The proliferative response of l/+ T1 cells to MRL/+ spleen cells was inhibited by anti-I-Ek (but not anti-I-Ak or anti-Kk) antibodies, suggesting that the specificity of l/+T1 cell culture enhanced the proliferative response only in the presence of appropriate stimulators. Treatment of stimulator cells with J11d.2 + C (but not anti-Thy-1.2 + C or 33D1 + C) abolished the stimulatory effect, indicating that B cells are effective stimulator cells for auto-MHC class II-reactive l/+T1 cells. When MRL/+ splenic B cells were co-cultured with l/+T1 cells, both B cell proliferation and IgM production were observed. In addition, IgM-class rheumatoid factor and anti-ssDNA antibody activities were found in the supernatants of MRL/+ splenic B cells co-cultured with l/+T1 cells. These results are discussed in relation to "lpr-GVHD" and autoimmunity in MRL/lpr mice.

Animals↗

Pulmonary aspergillosis with bronchocentric granulomas.

A 56-year-old Japanese man without asthma was admitted with cough, excessive sputum, and abnormalities on the chest X-ray film. The lung biopsy material showed necrotizing granulomas centered upon bronchioles. Serial sections of the material revealed a mass of well-oriented, uniform, viable-appearing aspergillus hyphae in the center of the granulomas. There was no evidence of blood eosinophilia, tissue infiltration of eosinophils, or deposition of immunoglobulins or complement in the granulomatous lesion. Thus, we obtained no direct evidence of an allergic reaction. After treatment with the antifungal drug, 5-flucytosine, the patient is in good health. This may be the first documentation of pulmonary aspergillosis showing predominantly bronchocentric granulomas in a nonasthmatic patient who was not immunocompromised.

Aspergillosis, Allergic Bronchopulmonary↗