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Biomedical subjects

T Nakai

Publications and source records attributed to T Nakai.

At least 181 records · Page 10Linked to original sources
PubMed1996

Effects of BIBR-277, an angiotensin II type 1 receptor antagonist, on stunned myocardium in dogs.

BACKGROUND: Angiotensin converting enzyme inhibitors can protect the myocardium from ischaemic damage. We examined the effect of BIBR-277, an angiotensin II receptor type 1 antagonist, on myocardial stunning in dogs. METHODS: Pentobarbital-anaesthetized open-chest dogs were subjected to 20 min ligation of the left anterior descending coronary artery, followed by reperfusion for 60 min. Saline or 0.3, 1 or 3 mg/kg body weight BIBR-277 was injected intravenously 10 min before coronary ligation. The myocardial contractile function was measured by ultrasonometry. The tissue levels of energy metabolites in the 60 min reperfused heart were determined. RESULTS: Myocardial contractile function assessed in terms of percentage segment-shortening in the saline-treated group decreased during ischaemia and returned towards the pre-ischaemic level during reperfusion but incompletely (myocardial stunning). A significant and dose-dependent improvement in the percentage segment-shortening during reperfusion was observed in the BIBR-277-treated groups. The levels of ATP, ADP and AMP in the reperfused heart were not modified by BIBR-277 treatment compared with those in the saline-treated group. CONCLUSION: BIBR-277 ameliorates the myocardial contractile dysfunction during reperfusion after ischaemia, although it did not bring about any improvement in the high-energy phosphate levels in the reperfused heart.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1996

Effects of long-term alcohol intake on ADP ribosylation in rat liver plasma membranes.

Mono-ADP-ribosylation, In which the ADP-ribosyl moiety is transferred from NAD to an acceptor protein, is one of the important posttranslational modifications of cellular proteins. Because mounting evidence suggests significant biological roles of this reaction in transmembrane signal transduction and other cell metabolic reactions, we assessed how long-term alcohol intake alters toxin catalyzed- and endogenous mono-ADP-ribosylation in the liver of a rat model. We first found that thiol-preactivated cholera toxin-catalyzed ADP-ribosylation of the alpha-subunit of the stimulatory GTP-binding protein was enhanced after long-term alcohol intake. Unexpectedly, but interestingly, this enhancement was not accompanied by a concomitant increase of cholera toxin-catalyzed stimulation of the adenylate cyclase activity. We also found that long-term alcohol intake remarkably enhanced endogenous mono-ADP-ribosylation of a 58 kDa protein in plasma membranes. Thus, long-term alcohol intake stimulated endogenous, as well as, toxin-catalyzed mono-ADP-ribosylations. Characterization of the 58 kDa protein may uncover pathophysiological roles of this interesting phenomenon in alcohol-induced liver damage.

ADP Ribose Transferases↗
PubMed1996

Adenine nucleotides via activation of ATP-sensitive K+ channels modulate hypoxic response in rat pulmonary artery.

We examined the role of ATP-sensitive K+ channels in hypoxic pulmonary vasoconstriction, using isolated rat pulmonary arterial rings. Isolated rat pulmonary arterial rings displayed a rapid contraction followed by relaxation under hypoxic conditions. The ATP-sensitive K+ channel blocker glibenclamide (concentration > 1 microM) or a hyperglycemic buffer (15 mM glucose) attenuated the hypoxic relaxation in a dose-dependent manner but did not affect the hypoxia-induced contraction. To examine the relationship between hypoxia, energy, and redox state, intracellular levels of adenine nucleotides and pyridine coenzymes were determined by high-performance liquid chromatography in freeze-dried isolated rat pulmonary arteries at three time points (0, 4, and 10 min) before and during hypoxia. Hypoxia time dependently decreased the ATP content and the ATP-to-ADP ratio and increased the ADP and the AMP content in association with a rapid increase in the NADH and the NADH-to-NAD+ ratio. Hyperglycemic buffer (15 mM glucose) suppressed the hypoxia-induced changes of the adenine nucleotides (the decrease of the ATP content and the ATP-to-ADP ratio) but did not affect the hypoxia-induced changes of the NADH and the NADH-to-NAD+ ratio. Hypoxia did not affect the NADP+ or the NADPH content of pulmonary arteries. These findings indicate that an ATP-sensitive K+ channel regulates the tone of rat pulmonary arteries. Furthermore, an imbalance of the energy state may be involved in ATP-sensitive K+ channel activation during hypoxic vasorelaxation.

Adenine Nucleotides↗
PubMed1996

Protective effects of BQ-123, an ETA receptor antagonist, against leukotoxin-induced injury in rat lungs.

We tested the hypothesis that BQ-123, a novel endothelin type A (ETA) receptor antagonist, protects the lung against leukotoxin 9,10-epoxy-12-octadecenoate (Lx), which causes acute lung injury in animals. In isolated rat lungs perfused with Earle's balanced salt solution, BQ-123 suppressed the Lx-induced increase in wet lung weight, wet lung weight/dry lung weight, the effluent perfusate lactic dehydrogenase activity, and effluent perfusate and lung tissue ET-1 levels. BQ-123 also significantly attenuated the Lx-induced increase of the pulmonary capillary filtration coefficient. Thus our experimental results indicate that the ETA receptor antagonist, BQ-123, protects against Lx-induced experimental lung vascular injury.

Animals↗
PubMed1996

Pneumonitis during interferon and/or herbal drug therapy in patients with chronic active hepatitis.

We report four cases of acute pneumonitis due either to interferon, or a herbal drug, "Sho-saiko-to", or both in combination, in patients with chronic active hepatitis, focusing on its pathogenesis and response to prednisolone therapy. These cases shared common clinical features: fever, dry cough, dyspnoea, hypoxaemia, diffuse infiltrates both on chest radiography and chest computed tomography, restrictive pulmonary functional impairment, and alveolitis on examination of transbronchial lung biopsy, all of which suggest acute interstitial pneumonia. Furthermore, lymphocytosis was observed in association with the dominant CD8+ T-cell subset in bronchoalveolar lavage fluid. A lymphocyte stimulation test using peripheral blood was positive to interferon in one case and to Sho-saiko-to in another. All patients responded to oral prednisolone therapy. Peripheral soluble interleukin-2 receptor levels decreased in parallel with improvement in the clinical course. All patients were free of symptoms with a follow-up of 1-3 yrs. We conclude that interferon- and/or Sho-saiko-to-induced acute pneumonitis may be due to allergic-immunological mechanisms rather than toxicity, and that peripheral levels of soluble interleukin-2 receptor appear to be good markers of disease activity.

Adult↗
PubMed1996

Determination of serum des-gamma-carboxy prothrombin levels in patients with small-sized hepatocellular carcinoma: comparison of the conventional enzyme immunoassay and two modified methods.

OBJECTIVES: Currently available enzyme immunoassays for des-gamma-carboxy prothrombin (DCP) are not sensitive enough to detect hepatocellular carcinoma (HCC) at an early stage. Therefore, the objectives of this study were to enhance the sensitivity of the currently available enzyme immunoassay (EIA) for DCP and to assess the diagnostic values of the new methods compared with those of alpha-fetoprotein (AFP) in patients with small-sized HCC. METHODS: Coded serum samples obtained from a total of 128 patients with chronic liver diseases, including 27 patients with small-sized HCC, were analyzed. DCP levels were determined in three different ways: 1) conventional EIA, 2) the overnight method, similar to the conventional EIA but the first reaction (immunoreaction of DCP with the monoclonal antibody) was proceeded overnight, and 3) the avidin-biotin complex (ABC) method. RESULTS: In 27 patients with HCC ( < or = 3 cm in diameter), the rates of abnormal values obtained by the conventional, the overnight, and the ABC methods were 14.8, 25.9, and 29.6%, respectively. The overnight and the ABC methods comparably increased the sensitivity, whereas the ABC method gave the highest false-positive value in patients with chronic liver diseases (cirrhosis and chronic hepatitis) without HCC. The negative predictive value was 84.9% when AFP and the overnight DCP assays were combined, whereas the true positive rate by the combination assay of the ABC method for DCP and AFP (cut-off level at 200 ng/ml) was 33.3%. CONCLUSIONS: Two modifications of the conventional EIA for DCP comparably increased the sensitivity, but the overnight method may be of more practical value in terms of specificity and ease. The rate of detection of small-sized HCC by tumor markers alone, however, is not satisfactory even when the modified DCP and AFP measurements are combined.

Adult↗
PubMed1996

[Determination of PIVKA-II levels in patients with small hepatocellular carcinoma--comparison of new sensitive methods].

Current EIA for PIVKA-II is not sensitive enough to detect small Hepatocellular Carcinoma (HCC). In an attempt to increase the diagnostic threshold, the current EIA was modified in two different ways: 1) immunoreaction of PIVKA-II in the sample with its monoclonal antibody was carried out overnight at 5 degrees C instead of for two hours at room temperature (the overnight method), 2) Avidin-Biotin technique was used for the second reaction(the ABC method);and their diagnostic values were determined as compared with the current EIA(2hr method) in a total of 138 patients including 36 patients with HCC. In 27 patients with HCC(< 3 cm in diameter), the rates of abnormal values obtained by the 2hr-, the overnight- and the ABC method were 14.8, 25.9 and 29.6% respectively. False positive rates of these three methods in 69 patients with liver cirrhosis were 1.4, 8.6 and 22.9% respectively. Thus, these two modifications improved the sensitivity of the current EIA and the overnight method appears to be superior to the ABC method in terms of specificity and simplicity. This conclusion was confirmed by ROC analysis.

Biomarkers↗
PubMed1996

[Immunodeficiency with thymoma (Good's syndrome) similar to sino-bronchial syndrome].

A 58-year-old man was admitted to our hospital because of recurrent pulmonary infections that began three years previously. Laboratory data showed hypogammaglobulinemia and a chest computed tomogram showed diffuse bilateral micronodular shadows and an anterior mediastinal tumor. Immunodeficiency with thymoma (Good's syndrome) was diagnosed. After undergoing a thymectomy, he received intravenous gamma-globulin injections once a month for prophylaxis. Good's syndrome occurs rarely in Japan. A solid tumor-like shadow is not necessarily observed in routine chest X-ray studies, and hypogammaglobulinemia is one sign of this syndrome. The hypogammaglobulinemia of Good's syndrome should be carefully differentiated from that of other immunodeficiency diseases such as common variable immunodeficiency, the acquired immunodeficiency syndrome, chronic lymphocytic leukemia, non-Hodgkin's lymphoma, and multiple myeloma (non-secretory type).

Agammaglobulinemia↗
PubMed1996

[Mitochondrial dysfunction in acute lung injury caused by endothelial-1 and leukotoxin].

We studied whether endothelin-1 (ET-1) and leukotoxin (Lx), which have a different effects on vascular tone in isolated perfused rat lungs, also have different effects on mitochondrial function in edematous lung injury. Lung mitochondria were extracted from isolated perfused rat lungs exposed to each mediator. In lungs exposed to 0.5 nmol of ET-1, lung wet weight increased with a markedly elevated perfusion pressure but with no increase in the release of lactate dehydrogenase (LDH), an index of cell damage, into the perfusate. Neither mitochondrial respiration rate no ATP content in the lung tissue differed from those of untreated lungs. In contrast, in lungs treated with 30 mumol of Lx, lung wet weight markedly increased despite a small elevation of perfusion pressure; release of LDH into the perfusate increased, and the mitochondrial respiration rate in state 3 adn 4 significantly decreased while the ATP content in the lung tissue was less than in untreated lungs. We also examined cellular and mitochondrial damage in hydrostatic lung edema caused by raising an outflow reservoir. Mitochondrial respiration was not suppressed, and perfusate LDH activity was not increased, although lung wet weight increased as much as it did after the treatment described above. These results indicate that lung mitochondrial function is differentially affected by ET-1 and Lx, and they suggest that abnormalities in energy production by lung mitochondria are related to permeability edema.

Acute Disease↗
PubMed1995

Four Cases of Familial Breast Cancer.

We report 4 families with a remarkable history of cancer, including bilateral breast cancer, early onset breast cancer under age 40, and one or more cancers at other sites. We detected a second malignancy in 4 probands during follow-up after the first operation(families 1, 2, 3 and 4), and could salvage 3 of them (families 2, 3 and 4). We also found 2 family members with cancer by surveillance of family 4 and they underwent suitable treatment (elder sister and elder brother). In conclusion, a knowledge of the natural history of familial breast cancer with particular attention to age at onset and bilaterality may allow for the development of more accurately targeted surveillance, genetic counseling, and management strategies.

Journal Article↗
PubMed1995

Enhancement of the binding of triglyceride-rich lipoproteins to the very low density lipoprotein receptor by apolipoprotein E and lipoprotein lipase.

The low-density lipoprotein (LDL) receptor plays a crucial role in cholesterol metabolism. A related protein, designated the very low density lipoprotein (VLDL) receptor, that specifically binds apolipoprotein (apo) E has recently been characterized and shown to be expressed in heart, muscle and adipose tissue and the human monocyte-macrophage cell line THP-1. The VLDL receptor binds and internalizes VLDL and intermediate density lipoprotein from Watanabe heritable hyperlipidemic (WHHL) rabbits as well as beta-migrating VLDL from cholesterol-fed rabbits but not LDL from WHHL rabbits. Chinese hamster ovary (CHO) cells transfected with the rabbit VLDL receptor cDNA have now been shown to bind or internalize VLDL (d < 1.006 g/ml) isolated from fasted normolipidemic human subjects with lower affinity than WHHL-VLDL or rabbit beta-VLDL. However, binding and internalization were markedly enhanced when fasted human VLDL was preincubated with either recombinant human apoE (3/3) or lipoprotein lipase (LPL) in CHO cells overexpressing the rabbit or human VLDL receptor. CHO cells transfected with both the rabbit VLDL receptor cDNA and the human LPL cDNA effectively bound, internalized, and degraded fasted human VLDL without pretreatment. Treatment of heparinase reduced the effect of LPL-mediated binding at 4 degrees C, but the inhibitory effect was lower at 37 degrees C. Pseudomonas LPL also enhanced the binding of human fasted VLDL to the VLDL receptor at 37 degrees C in CHO cells overexpressing the human VLDL receptor. Taken together, LPL causes the enhancement of triglyceride-rich lipoproteins binding to the VLDL receptor via both the formation of bridge between lipoproteins and heparan sulfate proteoglycans and its lipolytic effect. Ligand blot analysis showed that the apparent molecular mass of the VLDL receptor is 118 kDa, which is smaller than that of the LDL receptor. These results indicate that the VLDL receptor recognizes both triglyceride-rich lipoproteins that are also relatively rich in apoE, as well as the remnants of triglyceride-rich lipoproteins after catabolism and the interaction with heparan sulfate proteoglycans by LPL. The VLDL receptor may thus function as a receptor for remnants of triglyceride-rich lipoproteins in extrahepatic tissues.

Apolipoproteins E↗
PubMed1995

Increased nitric oxide biosynthesis in leukotoxin,9,10-epoxy-12-octadecenoate injured lung.

We measured effluent nitric oxide levels using a chemiluminescence method from leukotoxin (Lx, a linoleate epoxide) injured isolated rat lungs perfused with physiological salt solution. Nitric oxide production from Lx-injured lung promptly increased and lasted for 20 min. Pretreatment with NG-monomethyl-L-arginine (LNMMA) significantly suppressed Lx-induced production of nitric oxide. Effluent from control lungs showed trace levels of nitric oxide. The wet to dry lung weight (WLW/DLW) after termination of the experiments was significantly elevated in Lx-treated lungs compared with that of LNMMA pretreated lungs or control lungs. There was a correlation between nitric oxide levels (at 10 min) and lung edema (WLW/DLW). Thus, nitric oxide plays a role in the pathogenesis of Lx-induced lung injury.

Animals↗