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Biomedical subjects

S Nakai

Publications and source records attributed to S Nakai.

At least 181 records · Page 10Linked to original sources

The importance of good endocardial reflow immediately after reperfusion for myocardial salvage in dogs.

We studied the importance of reflow after reperfusion for myocardial salvage. In 19 open-chest dogs, the left anterior descending coronary artery was occluded for 3h and then reperfused. Non-radioactive colored microspheres were injected into the left atrium to measure regional myocardial blood flow (RMBF). Immediately after occlusion, RMBF was reduced to 23 +/- 2% (of control) in the inner layer and 32 +/- 2% in the outer layer. Five minutes after reperfusion, RMBF was increased to 170 +/- 20% and 156 +/- 11% of control in the inner and outer layers, respectively. One week later, RMBF in the inner layer was reduced to 63 +/- 4% but it was not reduced (100 +/- 6%) in the outer layer. There was a roughly positive correlation between the inner/outer flow ratio measured 5 min after reperfusion and myocardial creatine kinase activity. Myocardial necrosis determined by triphenyl tetrazolium chloride stain varied inversely with the inner/outer flow ratio. These results indicate that good reflow in the inner layer 5 min after reperfusion is a favorable indicator for myocardial salvage.

Animals↗

[Immunohistochemical investigation on expression of cytokeratins in normal epithelium, precancerous lesions and carcinomas of the hypopharynx].

In order to obtain a more objective method to evaluate epithelial disorders and carcinomas of the hypopharynx, the expression pattern of cytokeratins (CKs) was investigated by ABC technique using several kinds of monoclonal antibodies that react monospecifically with each subclass of CKs. In normal epithelia, CK-19 was strongly positive in the basal layer but apparently reduced in suprabasal layers and completely negative in superficial layers, while CK-13 showed a striking contrast to CK-19, being expressed within the whole thickness of epithelia except only in the basal layer. These 2 subclasses were also observed in "abnormal" epithelia, and characteristic changes of their combination were demonstrated in proportion to the histological gradings. In invasive carcinomas, CK-19 was strongly positive in all carcinoma cells of poorly differentiated carcinomas. It was sporadically positive in moderately differentiated carcinomas, the more differentiated the more sporadic. It was completely negative in well differentiated carcinomas. CK-13, on the other hand, was negative in poorly differentiated carcinomas but positive in keratinized cells of moderately or well differentiated carcinomas. Strong expression of CK-1 was observed only in well keratinized cells of hyperkeratotic epithelia and well differentiated carcinomas. These characteristic findings are consistently observed in all samples and, then, may be useful in evaluating epithelial disorders and carcinomas of the hypopharynx, when used in conjunction with standard histological techniques. It seems most likely that these results play a part in investigating normal and abnormal processes of cell differentiation.

Carcinoma, Squamous Cell↗

Substance p-induced cutaneous and bronchial reactions in children with bronchial asthma.

We studied substance P-induced cutaneous and bronchial reactions in children with allergic disorders. Furthermore, inhibitory effects of lidocaine on these responses elicited by substance P were also studied. In the intradermal test, children with moderate or severe bronchial asthma showed significantly stronger reactions than controls. In bronchial challenge with substance P, children with bronchial asthma showed an increasing fall in FEV1 and V50 in proportion to the severity of their asthma. Concomitant use of lidocaine significantly inhibited not only substance P-induced intradermal erythema and wheal reactions but air flow limitations. It also inhibited histamine-induced erythema and house dust-induced wheal and erythema reactions. No adverse reactions to lidocaine were observed. These results suggest that substance P might play an important role in cutaneous and bronchial hypersensitivity reactions in humans and that lidocaine has an inhibitory effect on substance P-induced reactions.

Adolescent↗

[Clinical characteristics of precordial ST-segment depression in acute inferior myocardial infarction].

Assessments of the significance of precordial ST segment depression in acute inferior myocardial infarction (AIMI) have yielded conflicting results. Among 92 AIMI patients admitted within 6 hrs after the onset, 65 showed ST depression, and the remaining 27 showed no ST depression. These depressions were present in all of V1-4 (right type; 17), V2-5 (middle type; 10), V3-6 (left type; 13) and V1-6 (broad type; 25). The clinical severity was Forrester subset I in the majority (89%) of patients without ST change, while complications were prevalent in patients with ST depression, especially in the right type (44% were Forrester subset II-IV). Peak CK was 2,150 +/- 399 U/L in patients without ST depression, but it was elevated to 3,172 +/- 811 in patients with ST depression, especially in the right type (4,506 +/- 499). Wall motion evaluated by echocardiography and QRS scores on ECG also revealed greater abnormality in patients with ST change. The initial right coronary angiogram on admission revealed complete occlusion in 76% of these patients with ST depression of whom all of the right type had completely occluded artery. Abnormal motion of the anterior wall, which suggests remote ischemia associated with AIMI was proved neither by left ventriculography nor echocardiography. Hospital mortality in patients with ST depression (9.2%) was as twice as high as that in those without ST depression (4.6%). We concluded that ST depression in patients with acute inferior infarction may not be indicative of remote ischemia but manifests as a mirror image of a large infarction with a complicated clinical course.

Adult↗

Acyclic monoterpene primary alcohol:NADP+ oxidoreductase of Rauwolfia serpentina cells: the key enzyme in biosynthesis of monoterpene alcohols.

Acyclic monoterpene primary alcohol:NADP+ oxidoreductase, a key enzyme in the biosynthesis of monoterpene alcohols in plants, is unstable and has been only poorly characterized. However we have established conditions which stabilize the enzyme from Rauwolfia serpentina cells, and then purified it to homogeneity. It is a monomer with a molecular weight of about 44,000 and contains zinc ions. Various branched-chain allylic primary alcohols such as nerol, geraniol, and 10-hydroxygeraniol were substrates, but ethanol was inert. The enzyme exclusively requires NADP+ or NADPH as the cofactor. Steady-state kinetic studies showed that the nerol dehydrogenation proceeds by an ordered Bi-Bi mechanism. NADP+ binds the enzyme first and then NADPH is the second product released from it. Gas chromatography-mass spectrometric analysis of the reaction products showed that 10-hydroxygeraniol undergoes a reversible dehydrogenation to produce 10-oxogeraniol or 10-hydroxygeranial, which are oxidized further to give 10-oxogeranial, the direct precursor of iridodial. The enzyme has been found to exclusively transfer the pro-R hydrogen of NADPH to neral. The N-terminal sequence of the first 21 amino acids revealed no significant homology with those of various other proteins including the NAD(P)(+)-dependent alcohol dehydrogenases registered in a protein data bank.

Alcohol Oxidoreductases↗

Convulsants induce interleukin-1 beta messenger RNA in rat brain.

The effects of systemic administration of kainic acid and pentylenetetrazol on interleukin-1 beta gene expression in the rat brain was studied. After the administration of kainic acid in a convulsive dose (10 mg/kg i.p.), Interleukin-1 beta mRNA was induced intensely in the cerebral cortex, thalamus and hypothalamus, moderately in the hippocampus and weakly in the striatum, but not in the midbrain, pons-medulla and cerebellum. Pentylenetetrazol induced Interleukin-1 beta mRNA in the cerebral cortex, hypothalamus, and hippocampus with a faster time-course than kainic acid. Diazepam suppressed both the convulsion and the induction of Interleukin-1 beta mRNA produced by kainic acid. Dexamethasone suppressed the induction of Interleukin-1 beta mRNA, but did neither the convulsion nor the induction of c-fos mRNA following the injection of kainic acid. These results provide the first evidence that intensive neuronal excitation induces Interleukin-1 beta mRNA in particular regions of the brain.

Animals↗

Isolation of a gene for a regulatory 15-kDa subunit of mitochondrial F1F0-ATPase and construction of mutant yeast lacking the protein.

A gene coding for yeast 15-kDa protein, a regulatory factor of mitochondrial F1F0-ATPase, was isolated. The cloned gene was disrupted in vitro and mutant strains that did not contain the 15-kDa protein were constructed by transformation of yeast cells with the disrupted gene. The ATP-synthesizing activity of the mutant mitochondria was the same as that of wild-type cells, suggesting that the 15-kDa protein is not required for mitochondrial oxidative phosphorylation. Collapse of the membrane potential induced ATP-hydrolyzing activity of F1F0-ATPase of the mutant mitochondria but not of normal mitochondria. Activation of the enzyme was also observed during incubation of submitochondrial particles from mutant cells, but not of those from wild-type cells. Thus, it is inferred that the 15-kDa protein supports the action of an intrinsic ATPase inhibitor of the ATP-hydrolyzing activity of the enzyme upon de-energization of mitochondrial membranes.

Amino Acid Sequence↗

Interleukin-1 beta inhibits long-term potentiation in the CA3 region of mouse hippocampal slices.

The effect of recombinant human interleukin 1-beta (IL-1 beta) on long-term potentiation (LTP) in the mossy fiber-CA3 pathway of mouse hippocampal slice preparations was investigated. IL-1 beta significantly inhibited LTP in concentrations as low as 2.9 pM (50 pg/ml). This effect of IL-1 beta was blocked by concurrent application of 100 nM Lys-D-Pro-Thr, a tripeptide analogue of IL-1 beta. This is the first evidence that IL-1 beta can regulate LTP of synaptic transmission in the hippocampus.

Animals↗

A mutant protein of human interleukin-1 beta with immunostimulatory but not pyrogenic potency.

Interleukin-1 (IL-1) mediates a variety of immune and inflammatory responses. In order to understand the mechanisms involved in multiple biological functions, it is important to define the active sites of IL-1. Using the technique for site-specific mutagenesis, we tested whether the arginine residue at the 4th position in human IL-1 beta is essential for multiple biological activities. In our experiments, the fourth position is replaced by a non-basic amino acid--either glycine or aspartic acid. The resulting mutant protein shows both immunostimulatory activity and the ability to induce hematopoietic growth factors similar to native IL-1 beta, but has a markedly reduced pyrogenic potency. Therefore, the mutant protein of IL-1 beta may represent a good candidate for use in vivo as an adjuvant for poor immunogenic vaccines.

Adjuvants, Immunologic↗

Induction of interferon after administration of a traditional Chinese medicine, xiao-chai-hu-tang (shosaiko-to).

We examined the ability of a traditional chinese herbal medicine, xiao-chai-hu-tang (Japanese name: shosaiko-to) to induce IFN in mice. A maximum activity (105 units/ml) of interferon (IFN) appeared in the serum of mice 16 h after intraperitoneal (i.p.) treatment with 250 mg/kg of shosaiko-to. Addition of polymyxin B did not abrogate the ability of shosaiko-to to induced serum IFN. The IFN was identified as IFN-alpha/beta by neutralizing test using anti-IFN alpha/beta antibodies. Pretreatment of mice with carrageenan suppressed the IFN induction by shosaiko-to, whereas the IFN induction by shosaiko-to was impaired neither in mice treated with anti-asialo-GM1 antibody nor in T-cell-deficient athymic nude mice. IFN was produced in vitro by spleen cells obtained from shosaiko-to treated mice. Moreover, spleen cells from untreated mice could also produce IFN when they were cultured with shosaiko-to. Additionally, serum IFN was also induced by the adoptive transfer of spleen cells from shosaiko-to treated mice to normal mice. On the other hand, peroral administration of shosaiko-to also induced IFN-alpha/beta in the serum. While IFN activity induced by i.p. administration of shosaiko-to declined after repeated treatments, the activity induced by its peroral administration did not decline during a long term treatment. These results showed that shosaiko-to is an IFN-alpha/beta inducer capable of repeated peroral administration.

Administration, Oral↗

[Correlation of proliferation index with submucosal invasion of hypopharyngeal cancer].

Proliferation index of biopsied specimens from 11 cases of hypopharyngeal carcinoma was studied immunohistochemically using anti-BrDU monoclonal antibody. S-phase cell labelling index (SLI) was measured and compared with the extent of submucosal invasion that was evaluated histologically in each extirpated specimen by means of continuous large section technique. Conclusions were as follows: 1. The largest SLI was obtained in a moderately differentiated carcinoma, and calculated up to 56, while the smallest was encountered in a well differentiated carcinoma as 18. Mean value in these 11 cases was 35. 2. It seemed likely that moderately or poorly differentiated carcinomas show larger SLI, but its statistical significance could not be delineated in these materials. 3. Submucosal invasion was much longer in the oral direction than in the anal. The longest invasion was observed in a case that showed the largest SLI, and measured up to 22 mm. The shortest invasion, on the contrary, was seen in a case with the smallest SLI, and was only 9 mm. Mean value in these 11 cases was 14.4 mm. 4. SLI correlates well in every case to the extent of submucosal invasion toward the oropharynx. 5. SLI evaluated preoperatively in biopsied specimen may help to indicate an ample safety margin at the surgery.

Carcinoma, Squamous Cell↗

[Histological and histochemical changes in the neck muscles of spontaneously occurring scoliosis in a special strain of Japanese quail, SQOHM].

A strain of Japanese quail, SQOHM, is known as a model of idiopathic scoliosis in humans. It shows hereditary scoliotic deformities occurring in the cervical region. Histological, histochemical and serological studies were performed in 51 scoliotic and 109 non-scoliotic quail. Histological study revealed internal nuclei and tiny groups of small fibers in the neck muscles. The incidence of these, however, was only 19% in the scoliotic and 7% in the non-scoliotic quail. Histochemical observation with adenosine triphosphatase, phosphorylase and succinic dehydrogenase stains was made on the dorsal neck muscles. An increase in the number of beta-fibers, and a decrease in the number and hyperplasia of alpha-fibers were observed on the concave side of the scoliosis. The increase in number of beta-fibers on the concave side can play a role in promoting the deformity was suggested.

Adenosine Triphosphatases↗

[Epidemiological studies of air pollution and health effects in areas near roadways with heavy traffic in Tokyo].

Recent concern regarding health effects of air pollution in Japan has concentrated mainly on traffic-induced air pollution and its health effects in large cities. In Japan, where many people in large cities have been living near major roadways, the increase of automobile exhaust due to heavy traffic congestion will predictably cause a greater impact on people living near major roadways. We surveyed the characterization of residential suspended particulate matter (SPM) and nitrogen dioxide (NO2) concentrations along the major roadways in Tokyo, along with a health survey on the respiratory conditions of residents living in the same area, to examine the relationships between indoor pollutant levels, prevalence of respiratory symptoms and distance from roadways. The environmental monitoring was conducted in five phases. Using a newly developed SPM sampler and NO2 filter badge, continuous 4 day (96 hours) measurements were conducted in two hundred residential homes for four weeks. NO2 was measured in the living room, kitchen and outside of each home, while SPM was monitored in the living room. Health information was collected in October 1987 using ATS-DLD self-administered questionnaires. Of the 1,093 homes investigated, responses from 805 homes were received. The following results were obtained. SPM and NO2 concentrations showed large variations. Indoor pollution levels mostly depended on indoor sources, i.e. cigarette smoking and unventilated space heaters, and the effects of those indoor sources were influenced by the building structure with respect to air tightness. An association between increase in pollutant levels and the distance from the roadway was observed. However its effect is small compared to indoor source effects. The prevalence rate of respiratory symptoms was higher in those areas nearest roadways with heavy traffic both in children and adults. These results suggest the presence of a relationship between automobile exhaust and health effects.

Adult↗

[Significance of HDL cholesterol/apolipoprotein A-I ratio].

HDL cholesterol (HDL-Ch)/apolipoprotein A-I (A-I) ratio was studied in fourteen healthy students, fifteen male habitual drinkers, five male patients with chronic hepatitis (CH) and seven controls. HDL-Ch/A-I ratio in male students, female students, male drinkers, CH and control were 0.36 +/- 0.029, 0.39 +/- 0.03, 0.41 +/- 0.065, 0.40 +/- 0.02, and 0.36 +/- 0.039, respectively. Elevation of HDL-Ch/A-I ratio in female students, male drinkers and CH were statistically significant compared with control, while there was no significant change in HDL-Ch or A-I in female students but the elevations of both in male drinkers or the reduction of A-I in CH. Positive correlations were found between HDL-Ch/A-I ratio and HDL2-Ch, and HDL2-Ch/HDL3-Ch ratio in students and CH. The elevation of HDL-Ch/A-I ratio in CH appeared to be related to the reduction of HDL3-Ch. It is suggested that HDL-Ch/A-I ratio could indicate HDL2-Ch/HDL3-Ch ratio and is useful parameter for analysis of HDL metabolism.

Adult↗

[Lipoprotein metabolism analysis in arteriosclerotic diseases].

Lipoprotein metabolism was studied by analyses of apolipoproteins, cholesterol content in lipoproteins and electrophoresis. The findings obtained suggested that the apolipoprotein levels such as A1 and B are related with particle number of lipoproteins such as HDL and LDL, while cholesterol content in lipoproteins is affected by qualitative change in particles as well. In patients with diabetes mellitus (NIDDM), LDL cholesterol correlated with HbA1c, and cholesterol and apolipoprotein B in the beta-area on electrophoresis showed accelerated mobilities, which were mimicked by in vitro glycation of LDL. In coronary heart diseases, elevation of apolipoprotein B and a low level of HDL cholesterol were general findings. The B/A1 ratio could be a sensitive indicator for these diseases. Hyper HDL cholesterolemias, excluding the patients with prostatic cancer who had undergone estrogen-treatment, showed elevated levels of apolipoprotein E in alpha 2-area on electrophoresis. Heterogeneity in Hyper HDL cholesterolemia was implicated. Qualitative analysis of lipoproteins by our method is believed to be useful.

Adult↗

Hypelcin A, an alpha-aminoisobutyric acid containing antibiotic peptide, induced permeability change of phosphatidylcholine bilayers.

Interactions of hypelcin A, an alpha-aminoisobutyric acid containing antibiotic peptide, with phosphatidylcholine vesicles were investigated to obtain information on its bioactive mechanism. The peptide induced the leakage of a fluorescent dye, calcein, entrapped in sonicated vesicles. The leakage rate depended on both the peptide and the lipid concentrations. Analysis of this dependency indicated that the leakage was due to the monomeric peptide and that the membrane-perturbing activity of the monomer was higher for solid distearoylphosphatidylcholine vesicles than for fluid egg yolk phosphatidylcholine vesicles. Hypelcin A also affected the gel to liquid-crystalline phase transition of dipalmitoylphosphatidylcholine multilamellar vesicles. The transition was broadened with a reduced transition enthalpy, suggesting the peptide strongly binds the surrounding lipids to perturb the bilayer lipid packing. A circular dichroism study revealed that the helical content of hypelcin A increases upon membrane binding. We concluded that the monomeric peptide with an increased helical content, complexed with the lipids, perturbs the lipid organization and induces the increased permeability.

Alamethicin↗