Biomedical subjects

Y Kawabata

Publications and source records attributed to Y Kawabata.

At least 163 records · Page 9Linked to original sources

PubMed1994

Tissue distribution of macromolecular conjugate, adriamycin linked to oxidized dextran, in rat and mouse bearing tumor cells.

Tissue distribution of the radioactivities after intravenous administration of [14C]adriamycin ([14C]ADM) or [14C]ADM linked to oxidized dextran ([14C]ADM-OXD) in mouse bearing Lewis lung carcinoma (LLC) and rat bearing Walker 256 carcinosarcoma was studied. ADM conjugated with OXD increased plasma half-life and gave high area under the plasma concentration-time curve (AUC). The AUC values were 13.0 and 5.8 times higher than those of the [14C]ADM group in mice and rats, respectively. In the tumor tissues, AUC values of the [14C]ADM-OXD group were also respectively 1.6 and 1.9 times higher than those of the [14C]ADM group. However, the AUC values in the heart of the [14C]ADM-OXD group were about half those of [14C]ADM group in both animals. Thus the distribution of ADM was changed by the conjugation with OXD. The excretion profile of ADM was also changed by the conjugation. During 6 h after administration, [14C]ADM-OXD was mainly excreted into rat urine at 45.2% of the original dose, but in the [14C]ADM group recovery in urinary excretion was 4.2%. Using [14C]ADM-OXD and ADM-[14C]OXD, the respective tissue distribution of ADM and OXD portions in the ADM-OXD was studied in rats bearing Walker 256. The radioactivities of both [14C]ADM-OXD and ADM-[14C]OXD groups increased in tumor and liver within 1 h after administration. In the liver, both radioactivities were retained for 24 h, which suggested that ADM and OXD were retained as conjugated form, however, different behavior was observed between the two groups in tumor tissues.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Stereoselective synthesis of regioisomers of aldobiouronic acid.

alpha-Glucuronidase is a very important enzyme for the complete hydrolysis of plant hemicellulose, but the substrate specificity of the enzyme has not previously been reported. In this connection, the three regioisomers of O-(alpha-D-glucopyranosyluronic acid)-D-xylose (aldobiouronic acid), 2-O-(alpha-D-glucopyranosyluronic acid)-D-xylose (13), 3-O-(alpha-D-glucopyranosyluronic acid)-D-xylose (14), and 4-O-(alpha-D-glucopyranosyluronic acid)-D-xylose (15), were stereoselectively synthesized to clarify the substrate specificity.

Carbohydrate Sequence↗

PubMed1994

Lymphoid interstitial pneumonia as a pulmonary lesion of idiopathic plasmacytic lymphadenopathy with hyperimmunoglobulinemia.

A case of idiopathic plasmacytic lymphadenopathy with hyperimmunoglobulinemia is reported. A 71-year-old man was admitted to the hospital because of the abnormal shadow on chest roentgenogram. Chest X-ray taken on admission showed remarkable diffuse infiltration and pleural thickening. Laboratory examinations revealed an elevated total protein level of 10.1 g/dl, and a gammaglobulin level of 7.0 g/dl including 6,790 mg/dl IgG. Mediastinal lymphadenopathy was observed on a chest CT. The patient underwent open lung biopsy. Heavy infiltration of lymphocytes and plasma cells were seen in the moderately fibrotic pulmonary interstitium. LIP was diagnosed. Lymph node biopsy was also performed. Follicular hyperplasia with prominent germinal centers and plasma cell proliferation in the interfollicular area were seen. Treatment with prednisolone resulted in an improvement in the chest X-ray findings, as well as a diminished polyclonal hypergammaglobulin level.

Aged↗

PubMed1994

[The 69th annual meeting symposium. II: Mechanism of necrotizing granuloma formation and its function].

Histological features of tuberculosis are caseation necrosis and epithelioid cell granuloma formation. Both phenomena are interpreted as expression of cellular immunity. Caseation necrosis is thought to be immunopathology and epithelioid cell granuloma formation is considered to be expression of protective immunity. Recently roles of cytokines for granuloma formation are gradually elucidated. In this symposium, mechanisms and functions of necrosis and granuloma formation Dr. Akagawa reported differentiation of two types of phenotypically different macrophages from human monocytes by GM (granulocyte-macrophage)-CSF or M (macrophage)-CSF. Interestingly such a basic differentiation induced by CSF was affected by IL-4 (interleukin-4). Langerhans-like dendritic cells were generated by cooperation of GM-CSF and IL-4, and multinucleated cells were generated by cooperation of IL-4 and M-CSF. Dr. Fukuda reported human Langerhans cell granulomatosis (LCG) from the pathological and immunohistochemical standpoints. In situ proliferation of LCs in the LCG was demonstrated by immunohistochemistry using antibody to PCNA (proliferating cell nuclear antigen) which is used to detect proliferating cells. In the course of granuloma formation, damage and disruption of lung structure such as alveolar basement membrane and elastic tissue framework, and reactive intraluminar fibrosis was observed. Mechanism of cystic dilation was also reported. Cytokines might play important roles in these events. Dr. Ina demonstrated experimental epithelioid cell granuloma formation. Extract (granuloma inducing factor, GIF) from Schistosoma mansoni Egg-induced granuloma, TNF -alpha, or IL-1 beta were coated, individually on the surface of beads, then these beads were inoculated to rat's skins or cultured with rat's monocytes. Four weeks later, epithelioid cell granuloma was demonstrated histologically and electronmicroscopically around beads in vitro and in vivo. GIF-induced granuloma was more organized than cytokine-induced ones. In vitro using human monocytes, activated macrophages accumulated around beads of which cytokines or GIF were coated. It was suspected that many cytokines or other factors are needed to make epithelioid cell granuloma. Dr. Sakamoto showed the presence of acid fast bacilli and various inflammatory cells including lymphocytes and macrophages in the tuberculous caseous necrosis after exudative reaction (E-necrosis) by immunohistochemistry. But no acid fast bacilli or inflammatory cells were found in the caseous necrosis after productive reaction (P-necrosis). TNF-alpha (tumor necrosis factor-alpha) and IL-4 were stained in the E-necrosis and IL-4 and ICAM-1 (intercellular adhesion molecule-1) were positively stained in the cytoplasm of epithelioid cells by immunohistochemistry. It was suspected that many cells and cytokines were involved in epithelioid cell granuloma formation and caseous necrosis formation.(ABSTRACT TRUNCATED AT 400 WORDS)

Granuloma↗

PubMed1994

Mechanistic analysis of renal protection by angiotensin converting enzyme inhibitor in Dahl salt-sensitive rats.

OBJECTIVE: To investigate whether and how renin-angiotensin inhibition attenuates renal injury seen in salt-induced hypertension in Dahl salt-sensitive (Dahl-S) rats. METHODS: Dahl-S rats fed a high-salt (4% sodium chloride) diet for 6 weeks were treated with the angiotensin converting enzyme (ACE) inhibitor alacepril or the angiotensin receptor antagonist losartan for 4 weeks. Functional and morphological alterations in the kidney were investigated. RESULTS: Alacepril decreased systolic blood pressure (SBP). This SBP reduction was associated with the attenuation of cardiac and aortic wall hypertrophy and that of proteinuria and urinary N-acetyl-beta-D-glucosaminidase excretion. Kidney injuries, e.g. glomerular, arterial and tubular damage, were improved with alacepril treatment. Losartan decreased SBP to the same extent as alacepril, but neither renal function nor morphological structure was improved as was the case with alacepril. The response of the renal eicosanoid system to alacepril was inadequate, but cyclic GMP excretion, an indicator of nitric oxide formation, was significantly enhanced and lipid peroxidation in the kidney was decreased. CONCLUSIONS: The beneficial effects of ACE inhibition on the renal injury in Dahl-S rats outrange those induced by the receptor antagonism. This might be due to multiple factors including an increased vasodepressor eicosanoid system, enhanced nitric oxide formation and possible inhibition of oxygen radical generation in the injured renal tissues.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1994

[A case of pulmonary eosinophilic granuloma confirmed by transbronchial lung biopsy].

A case of pulmonary eosinophilic granuloma confirmed by transbronchial lung biopsy (TBLB) is reported. A 63-year-old man was admitted to our hospital complaining of productive cough and exertional dyspnea. Chest roentgenogram and computed tomography showed bilateral linear and reticular shadows predominantly in the upper and middle lung fields. TBLB was performed and the specimens showed granulomatous lesions consisting of histiocytes with infiltration of eosinophils. Histiocytes were positive for S-100 protein by immunohistochemistry. He was diagnosed as having pulmonary eosinophilic granuloma. In the diagnosis of pulmonary eosinophilic granuloma, open lung biopsy is useful, but TBLB is also useful for diagnosis in the active or early stage of this disease.

Biopsy↗

PubMed1994

[Hemophagocytic syndrome in a patient with immunoblastic lymphadenopathy-like T-cell lymphoma].

We report a 70-year-old male case of immunoblastic lymphadenopathy-like T-cell lymphoma (IBL-T) complicated by hemophagocytic syndrome (HPS) as a terminal event. The patient experienced fever and systemic lymphadenopathy after 22 months' remission of IBL-T. He developed acute hepatic failure and consumption coagulopathy rapidly, and died on the 7th hospital day. Serum levels of cytokines, including interferon-gamma and tumor necrosis factor-alpha, were elevated. Postmortem bone marrow aspirate showed a marked proliferation of benign-looking macrophages, some of which phagocytized erythrocytes and platelets. Because there were no preceding viral or bacterial infections, the HPS of this case was assumed to be associated with IBL-T at relapse.

Aged↗

PubMed1994

[A case of interstitial pneumonia antedating rheumatoid arthritis--differentiation from idiopathic BOOP].

A 49-year-old female presented with productive cough, fever and chest pain, and was admitted to Nagoya University Hospital. Her chest X-rays, taken previously and on admission, showed infiltrative shadows in both upper lung fields and left-sided pleural effusion. Rheumatoid factors were positive in serum and the pleural effusion. Antibiotics were ineffective. Transbronchial lung biopsy revealed intraalveolar fibrosis as well as interstitial inflammation. Idiopathic BOOP was suspected on the basis of clinical findings together with the histological features. However, open lung biopsy revealed lymphoid hyperplasia with germinal center formation. The patient was diagnosed as having lung involvement antedating rheumatoid arthritis, despite the absence of joint symptoms at present.

Arthritis, Rheumatoid↗

PubMed1994

[Immunohistochemical studies on mycobacteria in tuberculous necrotizing granulomas].

For the purpose to know the pathogenesis of caseous necrosis in tuberculous lesion, authors compared the presence and the number of mycobacteria in the pulmonary tubercles of various histological types. Forty pulmonary tubercles obtained from 16 patients (9 males, 7 females; mean age 51) were examined. By Ziehl-Neelsen (ZN) method, acid-fast bacilli were detected in 40% of 5 proliferative, in 12.5% of 24 productive and none of 11 sclerotic granulomas. By immunohistological staining with anti-BCG antiserum, positive staining was observed in 60%, 87.5% and 91% of each type of granuloma, respectively. Types of necrosis were classified by silver-staining as necrosis after exudative reactions (EN), necrosis after productive reactions (PN) and filled materials after softening and liquification of necrotic lesions (LN). EN was observed in 24 tubercles, and mycobacteria were stained in 8% of EN by ZN method and in 75% by immunohistological method. PN was observed in 21 tubercles, and mycobacteria were detected in none and 5% of such type of necrosis by respective method. LN was observed in 28 tubercles, and mycobacteria were detected in 11% and 71% of these lesions by respective method. So, positive ratio by immunochemical method was significantly higher in EN and LN than in PN. Further, mycobacteria were stained with anti-BCG antiserum as granules and the number of such granules were much more numerous in EN and LN than in PN (p < 0.01). From these results, it was suggested that necrosis might occur by different mechanisms in exudative reactions and in productive reactions.

Adult↗

PubMed1993

Pronounced direct inhibitory action mediated by adenosine A1 receptor and pertussis toxin-sensitive G protein on the ferret ventricular contraction.

An adenosine A1 receptor agonist R-N6-phenylisopropyladenosine (R-PIA) elicited a pronounced negative inotropic effect with the EC50 value of 0.69 mumol/l in the presence of a beta-adrenoceptor blocking agent bupranolol (0.3 mumol/l) in the isolated ferret papillary muscle. The negative inotropic effect of R-PIA was not associated with changes in cyclic AMP level. Adenosine and other A1 receptor agonists also elicited a negative inotropic effect. DPCPX (1,3-dipropyl-8-cyclopentyl xanthine) antagonized the negative inotropic effect of R-PIA in a competitive manner (pA2 value = 8.4). The inhibitory action of R-PIA was markedly attenuated in the ventricular muscle preparation isolated from ferrets pretreated with pertussis toxin that caused ADP-ribosylation of 39 kDa proteins in the membrane fraction. In the membrane fraction derived from the ferret ventricle, [3H]-DPCPX bound to a single binding site in a saturable and reversible manner with high affinity (Kd value = 1.21 +/- 0.41 nmol/l; Bmax = 12.8 +/- 3.02 fmol/mg protein; n = 7). The binding characteristics of [3H]-DPCPX in the rat ventricle (Kd value = 1.51 +/- 0.09 nmol/l; Bmax = 12.7 +/- 1.47 fmol/mg protein; n = 5) were similar to those in the ferret. On the other hand, the content of G(o), a major pertussis toxin-sensitive G protein in the ferret heart, was much higher in the ferret than in the rat ventricle. The present results indicate that adenosine receptors may play an important role in the inhibitory regulation of ventricular contractility in the ferret in contrast to other mammalian species. The signal transduction process subsequent to agonist binding to A1 receptors including the pertussis toxin-sensitive G protein and ion channels may be responsible for the unique inhibitory action of adenosine in this species.

Adenosine Diphosphate Ribose↗

PubMed1993

De novo synthesis of phospholipase A2 and prostacyclin production by proliferating rat smooth muscle cells.

We investigated the role of phospholipase A2 (PLA2) in cell cycle-dependent alterations of endogenous prostacyclin (PGI2) synthesis in aortic smooth muscle cells in culture (VSMC) from Wistar Kyoto rats. Randomly cycling VSMC generated more PGI2 than the stationary cells. Cell cycle analysis showed that PGI2 production capacity was increased from the G0/G1 through the early DNA synthetic (S) phases. Enzyme analysis revealed that, although there were different mechanisms underlying this increase in the PGI2 production during the G0/G1, the peak at 4 hours coincided with a sharp increase in PLA2 activity. This increase in PLA2 activity was preceded by an increased expression of functional PLA2 messenger RNA, and protein synthesis inhibition prevented most of the increase in PGI2 production at 4 hours. These data indicate that endogenous PGI2 generation is mainly increased during the G0/G1 period and that this event is secondary to de novo synthesis of PLA2 and probably, at least in part, to cyclooxygenase induction. This mechanism provides a negative feedback regulating VSMC proliferation.

Animals↗

PubMed1993

Possible radical scavenging properties of cicletanine and renal protection in Dahl salt sensitive rats.

Much interest in cicletanine, a novel antihypertensive drug, has grown because it uniquely stimulates prostacyclin (PGI2) production and may, thereby, provide further cardiovascular protection. We postulated that cicletanine may be an antioxidant, and assessed its ability to protect the kidney in Dahl salt-sensitive (Dahl S) rats on a high salt diet. Cicletanine eradicated in vitro a stable radical, DPPH, and decreased the lipid peroxidation both in rat brain homogenate and in a xanthine-xanthine oxidase (X-XOD) superoxide generating system. Furthermore, cicletanine attenuated the inhibition of PGI2 synthase activity by 15HPETE. However, cicletanine did not exhibit superoxide dismutase-like activity in X-XOD system, suggesting that it behaves primarily as a hydroxy radical scavenger. A 6 week cicletanine treatment reduced blood pressure in Dahl S rats fed a high salt diet, and ameliorated functional and morphological injury to the kidney. This attenuation of glomerular sclerosis correlated with the attenuation of lipid peroxidation in the kidney homogenate. These data indicate that cicletanine is an antioxidant that protects the kidney from salt-induced hypertension in Dahl salt-sensitive strain rats.

Animals↗

PubMed1993

Inhibition of protein synthesis and antiproliferative effect of the angiotensin converting enzyme inhibitor trandolaprilat in rat vascular smooth muscle cells.

OBJECTIVE: To investigate the effect of the angiotensin converting enzyme (ACE) inhibitor trandolaprilat on vascular smooth muscle cell growth, and to analyse its mechanism of action. DESIGN: Aortic vascular smooth muscle cells (VSMC) from Wistar-Kyoto rats were cultured, and cell proliferation was analysed using a cell synchrony technique. METHODS: Proliferative activity was assessed by [3H]-thymidine uptake and doubling time. Protein synthesis was assessed by [3H]-leucine incorporation. Actin formation was measured using sodium dodecylsulphate-polyacrylamide slab gel electrophoresis and a densitometric assay. The effect of trandolaprilat on translational protein synthesis was also examined using the cell-free protein synthesis system of reticulocyte lysate and messenger RNA from VSMC. RESULTS: Trandolaprilat decreased [3H]-thymidine uptake and increased the doubling time of randomly cycling VSMC. The cell synchrony study revealed that this antiproliferative effect was due to increased transition time from S to G2-M. Decreased cell cycle progression during G2-M was reflected by inhibition of cellular protein synthesis during this period. Cellular protein in randomly cycling VSMC was also decreased by trandolaprilat. This decreased protein synthesis was probably produced by inhibition of RNA translation. CONCLUSIONS: The ACE inhibitor trandolaprilat reduces VSMC proliferation by lengthening the G2-M phase of the cell cycle, and produces a decrease in cellular protein content. This effect is probably mediated by inhibition of protein synthesis at the translational level.

Actins↗

PubMed1993

Cytokine induction by extracellular products of oral viridans group streptococci.

During an etiological study of Kawasaki disease (mucocutaneous lymph node syndrome [MCLS]), we found that dominant viridans streptococcal strains on tooth surfaces and in the throat of both MCLS patients and non-MCLS control children formed erythrogenic and biologically active, extracellular products. In this study, we demonstrated that erythrogenic culture supernatant concentrates of representative strains (two Streptococcus mitis and two Streptococcus oralis), when injected intravenously, induced serum tumor necrosis factor alpha, interleukin-6 (IL-6), and gamma interferon in muramyldipeptide- or Propionibacterium acnes-primed C3H/HeN mice. The concentrates also induced tumor necrosis factor alpha, IL-6, and thymocyte-activating factor (essentially IL-1) in murine peritoneal macrophage, human monocyte, and human whole-blood cultures. An erythrogenic, heat-labile extracellular protein fraction (F-1) that was concentrated from the culture supernatants of a representative S. mitis strain exhibited the above-mentioned cytokine-inducing activity. This partially purified F-1 fraction also induced thymocyte-activating factor and IL-6 in human umbilical vascular endothelial cell and gingival fibroblast cultures.

Animals↗

PubMed1993

Effects of the positive inotropic agent Org 30029 on developed force and aequorin light transients in intact canine ventricular myocardium.

The action of a novel cardiotonic agent N-hydroxy-5,6-dimethoxy-benzo[b]thiophene-2-carboximide hydrochloride (Org 30029) on intracellular aequorin light transients and isometric contractions was investigated in isolated canine ventricular trabeculae. The positive inotropic effect of Org 30029 (30 microM-3 mM) was consistently associated with prolongation of the duration of contraction and an increase in the amplitude of the intracellular Ca2+ transients. The maximum inotropic response to Org 30029 was approximately 150% of the maximum response to isoproterenol, whereas the maximum increase in the amplitude of Ca2+ transients produced by Org 30029 was only 20% of the isoproterenol-induced maximum. The duration of isometric contractions was prolonged by Org 30029, with no change in the duration of the light transients. The concentration-response curve for the positive inotropic effect of Org 30029 was shifted by carbamylcholine chloride (carbachol, 3 microM) to the right and downward, but the maximum response to Org 30029 was greater than that to isoproterenol even in the presence of carbachol. Carbachol abolished the increase in light transients and cAMP accumulation induced by Org 30029 (1 mM), whereas it only partially attenuated the positive inotropic effect of Org 30029. In the presence of carbachol (3 microM), Org 30029 increased the force of contraction in a concentration-dependent manner without augmenting the aequorin light transients. These results are compatible with the hypothesis that Org 30029 increases cardiac contractility by increasing myofilament Ca2+ responsiveness.

Actin Cytoskeleton↗

PubMed1993

Acute exacerbation in idiopathic pulmonary fibrosis. Analysis of clinical and pathologic findings in three cases.

We treated three patients with idiopathic pulmonary fibrosis who had an acute clinical exacerbation. We analyzed their clinical, radiographic, therapeutic, and pathologic findings. Their initial symptoms were influenza-like illness or cough with fever, and all had leukocytosis and elevation of C-reactive protein. Infectious events were ruled out by extensive bacteriologic and serologic examination. The patients' lung injury scores progressed rapidly to severe lung injury compatible with adult respiratory distress syndrome. Findings from bronchoalveolar lavage fluid showed marked neutrophilia and elevation of albumin concentrations. All patients showed various degrees of improvement following corticosteroid therapy. Histologic findings from open lung biopsy specimens showed both usual interstitial pneumonia (UIP) and organizing acute lung injury pattern. Whether these two forms of interstitial pneumonia (UIP and acute lung injury pattern) are variants of one disease or are unrelated and also the effectiveness of corticosteroid therapy on such conditions remain to be determined by further studies.

Acute Disease↗

PubMed1993

Oxygen radical scavengers and renal protection by indapamide diuretic in salt-induced hypertension of Dahl strain rats.

In addition to the hemodynamic components, the roles of various humoral factors have been emphasized in the progression of vascular and renal injury in hypertension. Radical scavenging properties have attracted much attention in this field. This article discusses the implication of antioxidant properties of the antihypertensive diuretic indapamide on renal injury in Dahl salt-sensitive (Dahl S) rats. Hydroxyl radicals, oxygen radicals toxic to cellular membranes, are eradicated by indapamide in different assay systems, e.g., reduction of alpha-alpha-diphenyl-beta-picrylhydrazyl, rat brain homogenate, or xanthine-xanthine oxidase systems. Such antioxidant effects of indapamide are primarily due to inhibition of lipid peroxidation induced by hydroxyl radicals, and this mechanism may stimulate prostacyclin generation through activation of prostacyclin synthase. In fact, the antioxidant properties of indapamide are well expressed in vivo as well; indapamide treatment reduced oxygen radicals in the kidney of Dahl S rats with hypertension. This was accompanied by a functional improvement of the kidney; decreases in urinary protein and n-acetylglucosaminidase excretion and an increase in glomerular filtration rate were observed. In addition, indapamide morphologically ameliorated the renal injury, and decreased glomerular sclerosis score, arterial injury, and renal tubular injury. Trichloromethiazide reduces blood pressure similar to that produced by indapamide. However, trichloromethiazide did not lead to reduction of oxygen radicals in the kidney, and did not improve the functional disturbance or morphological injury seen in Dahl S rats. These results indicate that indapamide has antioxidant properties, and in addition to blood pressure reduction, such radical scavenging effects may contribute to its beneficial effects on renal function in vivo.

Animals↗

PubMed1993

[Two cases of M. avium complex infection presenting as solitary pulmonary nodule].

Case 1 was a 75-year-old woman. Her chest X-ray showed a 3 cm solitary nodule in the right S4, and biopsy obtained by fiberoptic bronchoscopy revealed epithelioid cell granuloma. Four weeks later, Mycobacterium avium complex (MAC) was detected on culture of the bronchial lavage fluid. She was treated with INH, RFP and EB for 12 months and recovered with no relapse. Case 2 was a 75-year-old man with mild diabetes mellitus and hypertension. Chest X-ray showed a 4 cm solitary nodule in the right S9. Percutaneous pulmonary aspiration revealed numerous acid-fast bacilli on smear, and he was treated with INH, RFP and EB. Culture proved M. avium complex. The patient was unable to continue his medications because of gastrointestinal side effects, so right lower lobectomy was performed. Cases of M. avium complex infection presenting as solitary pulmonary nodule are very rare. We found only 12 reported cases in Japan and in other countries. The most usual site of cavitary lesions in M. avium complex infections is both upper lobes, in contrast to the relatively even distribution of solitary pulmonary nodules of the 14 cases (12 reported cases and our 2 cases).

Aged↗