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Biomedical subjects

M Nakano

Publications and source records attributed to M Nakano.

At least 613 records · Page 34Linked to original sources

Intracellular protein phosphorylation in murine peritoneal macrophages in response to bacterial lipopolysaccharide (LPS): effects of kinase-inhibitors and LPS-induced tolerance.

Intracellular protein phosphorylation is thought to be the initial step in cell activation. Bacterial lipopolysaccharide (LPS) induces a special set of the protein phosphorylation in the murine peritoneal macrophages, including p65 (molecular mass of 65 kDa) which is a substrate of serine kinase and the most dominant phosphorylated cytosolic protein. This article deals with the relation between the LPS-induced protein phosphorylation in the murine peritoneal macrophages and their productions of IL-1 beta and TNF-alpha. LPS-induced p65 phosphorylation seems to be dependent on protein kinase C (PKC) and calmodulin (CaM), because it diminishes in the presence of inhibitors to PKC or CaM. Tyrosine kinase inhibitors do not affect the p65 phosphorylation. The PKC inhibitors also affect the mRNA expressions and the productions of active molecules of IL-1 beta and TNF-alpha. Though the CaM inhibitor inhibits the mRNA expression and the active molecule production of IL-1 beta, it does not affect those of TNF-alpha. These results suggest that LPS-induced p65 phosphorylation is closely related to PKC and CaM, and that IL-1 beta production depends on PKC and CaM, while the TNF-alpha production is not dependent on CaM. These findings indicate the existence of multiple pathways and different regulatory mechanisms for transduction of LPS signal in the macrophages. Furthermore, LPS-induced phosphorylation is not observed in endotoxin tolerant macrophages after re-stimulation with LPS, suggesting that the LPS-stimulus signal is blocked at a site in the signal transduction-pathway before the point of phosphorylation of proteins in the tolerant macrophages.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Serial change of gastric mucosa after challenging with Helicobacter pylori in the cynomolgus monkey.

The aim of this study was to clarify the change of the gastric mucosa following inoculation with Helicobacter pylori (H. pylori). Two pairs of cynomolgus monkeys received either H. pylori of human origin (group A) or H. pylori of monkey origin (group B) by intragastric inoculation at a dose of 10(9) CFU. After inoculation, endoscopical observation and biopsies were done every 7 days for one month. The bacteria in the biopsy samples were cultured quantitatively. The content of intracellular PAS-AB positive substance was quantitatively analyzed with the image analyzing system. Results were as follows: 1) Before inoculation, the gastric mucosa was endoscopically normal and free from H. pylori. 2) The quantity of H. pylori varied from 0 to 10(3) CFU/0.1 g tissue in group A and from 10 to 10(6) CFU/0.1 g tissue in group B. 3) Severe erosion was seen in group B, while mild mucosal erythema and erosion were observed in group A. 4) There was a correlation between the quantity of H. pylori and histological activity (Rauws' gastritis score). 5) The PAS-AB positive substance in H. pylori-positive mucosa was less than that in H. pylori-negative mucosa. In conclusion, gastric mucosal changes of varying degrees were brought about after inoculation of H. pylori depending on the quantity of bacilli in the gastric tissue.

Animals↗

Myocardial atrial natriuretic factor gene expression after coronary ligation in rats.

The atrial natriuretic factor (ANF) messenger RNA (mRNA) content was determined in a rat model of acute myocardial infarction. Non-infarcted tissue of left and right ventricles were examined soon after ligation of the left descending anterior coronary artery. In the left ventricles, ANF mRNA/alpha-actin mRNA ratio increased to reach a maximum on day 7 and was sustained while in the right ventricle, the maximum was reached on day 1. The plasma ANF was significantly (p < 0.01) elevated from days 1 to 28 after coronary ligation. The primary compensatory response of ANF within the first 7 days may be attributed not only its synthesis in the left ventricle but also to its generation in the right ventricle in acute heart failure.

Actins↗

Frequency of reciprocal translocations and dicentrics induced in human blood lymphocytes by X-irradiation as determined by fluorescence in situ hybridization.

This study was designed to test the scoring efficiency of reciprocal translocations and dicentrics induced by X-irradiation in vitro using the fluorescence in situ hybridization (FISH) technique. An excess was found in the frequencies of reciprocal translocations relative to those of dicentrics by measurement with FISH at the first cell division after irradiation (translocation:dicentric approximately 60:40). However, when the same metaphases were also evaluated sequentially by a conventional staining method, the ratio of about 50:50 was restored. This was due in part to misclassification of certain dicentrics as reciprocal translocations by the FISH technique.

Adult↗

The characteristics of alcoholics with HCV infection: histopathologic comparison with alcoholics without HCV infection and chronic type C hepatitis.

Out of 71 patients admitted to the National Kurihama Hospital and a related hospital for alcoholics or hepatic dysfunction, we studied the histopathology of alcoholics with HCV infection. Liver biopsies were divided into three groups depending on whether or not the patient was an alcoholic and anti-HCV antibody positive. The three groups were: (1) 30 HCV-antibody negative alcoholics, (2) 17 HCV-Ab positive alcoholics, and (3) 24 HCV-Ab positive non-alcoholics. Alcoholics developed specific hepatic fibrosis with a solid appearance, and the HCV-Ab negative alcoholics had relatively less lymphocytic infiltration. In contrast, patients with type C virus developed fibrosis with a loose appearance with more lymphocytic infiltrates including lymphfollicular accumulation. HCV-Ab positive alcoholics showed mixed features such as more fibrosis and less piecemeal necrosis and lymphocytic infiltration, especially in follicle formation, than HCV-Ab positive non-alcoholics. Changes of hepatocytes, such as hydropic swelling, fatty change and acidophilic body, increased in severity in the alcoholics compared with the non-alcoholics with viral hepatitis. These findings suggest that the combined exposure to both alcohol and HCV enhances hepatocellular damage, but suppresses inflammatory reactions such as lymphocyte infiltration and follicle formation seen in type C hepatitis.

Alcoholism↗

Characteristics of DNA and multiple rpoD homologs of Microcystis (Synechocystis) strains.

The base compositions of DNAs from nine Microcystis strains, as determined by high-performance liquid chromatography, were 41 to 42 mol% G+C. Chromosomal DNAs derived from these strains were found to be extremely resistant to many restriction endonucleases, and a restriction analysis revealed the presence of a dam-like methylase or both dam- and dcm-like methylases in all of the strains examined. Genomic Southern hybridization in which a synthetic oligonucleotide probe (rpoD probe) was used showed that members of the genus Microcystis might have multiple rpoD homologs, and the hybridization signal patterns observed with the DNAs of Microcystis aeruginosa strains were different from each other.

Bacterial Proteins↗

Antigen-specific proliferative response of peritoneal exudate lymphocytes primed with antigen and bacterial lipopolysaccharide: the roles of Ia+ accessory cells and IL-2.

In vitro antigen-specific proliferation was investigated in a lymphocyte population that had been taken from the peritoneal exudate cells (PEC) of C3H/HeN mice (Iak) primed in vivo with both bacterial lipopolysaccharide (LPS) and horse red blood cells (HRBC) and had been purified by passage through a nylon fiber column (Nfc). The proliferative response of the Nfc-passed lymphocytes primed with HRBC and LPS [T(HRBC+LPS) cells] depended on the dose of antigen in the cultures, and the response was higher than that of cells prepared from mice primed with HRBC alone [T(HRBC) cells]. No response was seen in the cells prepared from the LPS-primed mice [T(LPS) cells] or normal mice [T(N) cells]. The response of the T(HRBC) cells was abolished by previous treatment of the cells with anti-Iak antibody and complement (C), whereas the response of the T(HRBC+LPS) cells was retained after the same treatment, indicating that the Ia- T(HRBC+LPS) cells can proliferate in response to antigen in spite of Ia+ accessory cell-depletion. Supernatants from the cultures of Ia- T(HRBC+LPS) cells in the presence of HRBC showed abundant IL-2 activity, while those of Ia- T(HRBC) cells did not. The IL-2 should be produced by the L3T4 cell population in T(HRBC+LPS) cells in response to antigen, since the previous treatment of the cells with anti-L3T4 antibody and C abrogated the production.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Dermal patch anaesthesia: comparison of 10% lignocaine gel with absorption promoter and EMLA cream.

The analgesic effects of transdermally applied 10% lignocaine aquagel containing 3% glycyrrhetinic acid monohemiphthalate disodium (as an absorption enhancer) and EMLA cream were compared on the forearms of 34 adult volunteers in a double-blind fashion. The mean pinprick pain scores (graded by noting the number of painful pinpricks out of five) at 30, 60 and 90 min after application and 30 min after removal of the anaesthetics were 3.3 (0.3) (mean SE), 1.2 (0.3), 0.3 (0.1) and 0.3 (0.1) respectively, in the lignocaine gel group. Corresponding scores were 3.5 (0.3), 1.5 (0.3), 0.7 (0.2) and 0.1 (0.1) respectively, in the EMLA group. Insertion of a 26-gauge needle into the treated skin to a depth of 1 mm at 90 min after application was not painful in 91% of the volunteers in the lignocaine gel group and 88% of those in the EMLA group. There was no significant difference in any of the corresponding pain scores between the two groups.

Administration, Cutaneous↗

The measurement of a new antimicrobial quinolone in hair as an index of drug exposure.

1. Scalp hair samples were obtained at 1 month intervals up to 5 months from healthy male volunteers participating in a phase I study of a new antimicrobial quinolone, OPC-17116. 2. Hair was sectioned into 1 cm lengths from the scalp end. Corresponding portions from five pieces of hair were dissolved in 1 N NaOH and assayed for OPC-17116 by h.p.l.c. 3. In all subjects taking a single dose (400 mg, n = 5) or repeated doses (400 mg day-1, twice daily, for 6.5 days, n = 6), the drug was detected in the portions of hair corresponding to the administration period, assuming a hair growth rate of 1 cm/month. 4. OPC-17116 (300 mg day-1, three times daily, for 2 days) was given to four healthy male volunteers, from whom hair samples were obtained at 1 month and 3 months. The drug was detected in 1 to 4 consecutive 2.5-mm long portions of a single hair and there was no significant axial diffusion of the agent along the hair shaft with time. 5. These findings indicate the utility of measuring this quinolone derivative in hair as an index of exposure, and as a time-marker for the hair analysis of other drugs.

Adult↗

Pediatric and MCH training in Japan: JICA training program in the National Children's Hospital.

The experience of the training program for overseas doctors in the National Children's Hospital during 8 years is described. The program was supported by the Japan International Cooperation Agency (JICA) and the objectives of the training course are to provide doctors from developing countries with a better understanding of diagnosis and treatment as specialized pediatricians and pediatric surgeons and to introduce recent medical techniques and equipment for child care. From 1984 to 1993, 37 doctors from 22 developing countries of Asia, Middle and South America and Africa have attended this program. There were 22 pediatricians, 14 pediatric surgeons and one dentist. The outline of this group training program and problems with the course are discussed.

Child↗

[A study on acid resistance of Helicobacter pylori].

Physiological saline solutions, each adjusted to pH 1.0, pH 2.0 and pH 7.2, and added urea and urease inhibitor (Acetohydroxamic acid), were inoculated with a culture solution of Helicobacter pylori NCTC11637 strain derived from man, and allowed to react for 10, 30, 60 and 120 minutes. After five days of incubation on a blood agar medium, remaining viable H. pylori was counted. Survival of H. pylori was inadequate under the conditions of pH 1.0 and pH 2.0, but survival up to 120 min was observed on addition of urea. Further, on addition of urease inhibitor the survival time was reduced. H. pylori survived under the condition of pH 7.2 independent of addition of urea and urease inhibitor. Urea is essential for survival of H. pylori under strongly acidic conditions, and utility of urease inhibitor was observed for inhibition of survival of H. pylori.

Acids↗

A possible mechanism of iron neurotoxicity.

Iron-dependent microsomal lipid peroxidation and catechol-iron (copper)-induced lipid peroxidation have been studied to prove possible nigrostriatal cell damage. Iron-dependent microsomal lipid peroxidation could be initiated by reduced irons coordinated with phosphate moieties in the membranes and significantly inhibited by copper salicylate (hydrophobic and permeable O2-scavenger) and desferrioxamine (a powerful iron-chelating agent), but not by SOD. Ferric or cupric ion significantly promoted a peroxidative cleavage in liposomes (model membranes) after coordinating with dopa or dopamine. Either alpha-tocopherol or desferrioxamine completely abolished the dopa-Fe3+ complex-induced phospholipid peroxidation, while SOD, catalase or sodium benzoate did not. A ferroxidase, ceruloplasmin, significantly inhibited the lipid peroxidation induced by the dopa-Fe3+ complex, indicating the importance of the reduction of iron moiety in the complex for the lipid peroxidation. On the basis of the results obtained with these model systems, nigrostriatal damage by iron had been discussed.

Animals↗

Cu-Zn superoxide dismutase activities in platelets from stable bronchial asthmatic patients.

Cu-Zn superoxide dismutase (SOD) activities in platelets from stable bronchial asthmatic patients were measured using 2-methyl-6-[p-methoxyphenyl]-3,7- dihydroimidazo[1,2-a]pyrazin-3-one as a chemiluminescence probe. Cu-Zn SOD activities in platelets from the asthmatics were significantly higher than those from normal healthy subjects. Platelet Cu-Zn SOD activities were significantly higher in atopic than in non-atopic asthmatics. There were no significant differences in platelet Cu-Zn SOD activities between aspirin-sensitive and aspirin-tolerant patients. These results suggest that an oxidant-to-antioxidant imbalance may play a role in the inflammatory situations in the airways of asthmatics.

Adult↗

Co-activation of sternocleidomastoid muscles during maximum clenching.

In an attempt to determine the degree of co-activation present in selected cervical muscles during clenching, we instructed 12 male subjects to produce four brief maximum voluntary contraction (MVC) efforts (clenching) in a position of maximum intercuspation. Surface EMG activity was recorded bilaterally from the masseter and sternocleidomastoid (SCM) muscles. The contraction level for the SCM during clenching was reported as a percentage of the SCM's maximum activity achieved during maximum neck flexion against resistance. All EMG signals for the masseter and SCM were converted to a true RMS voltage signal and digitized at a 100-Hz sampling rate. Mean peak EMG voltage levels were determined for the activity recorded during each brief MVC task. All subjects demonstrated co-activation of the SCM during strong abrupt clenching efforts. The mean levels (+/- S.D.) of SCM activity were 11.8 +/- 9.6% (right) and 14.2 +/- 9.4% (left) of the MVC capacity. Fifty percent of masseter activity was required to achieve 5% activity of the SCM bilaterally, and there was a progressive development of the SCM co-activation which paralleled the masseter activation.

Adult↗

Sternocleidomastoid muscle inhibition induced by trigeminal stimulation.

Among numerous reports of anatomical and functional coupling between the trigeminal and cervical systems is the demonstration that the sternocleidomastoid (SCM) muscles may become activated along with the masseter muscles during forceful abrupt biting maneuvers. Whether the co-activated SCM is also inhibited by stimuli that produce masseter inhibition is not known. This study evaluated the SCM for the presence of inhibition during mechanically-elicited (chin or forehead tap) and electrically-elicited (anterior maxillary gingiva stimulation) inhibition of the masseter muscle in ten healthy men. Surface EMG data were recorded bilaterally from the masseter and SCM muscles. The data for each muscle were converted to ratios of the pre-stimulus maximum voluntary contraction activity for each subject and averaged across subjects. Means of these percentages were determined at several defined pre- and post-stimulus intervals. The results indicate that masseter inhibition was clearly elicited by the electrical and both forms of mechanical stimulation. SCM co-inhibition could be evoked by electrical and chin tap stimulation but not by forehead tap. The responses to these stimuli varied among subjects, from trial to trial, and within subjects depending on the experimental condition. The fact that it was possible for this co-inhibition to be evoked is presented as further indication of the functional coupling of the trigeminal and cervical systems.

Adult↗

Disposition of enantiomers of sultopride in a human, rats and rabbits.

Pharmacokinetics of sultopride enantiomers was examined following a single dose in a human, rabbits and rats. Pharmacokinetic profiles were similar between (+)- and (-)-enantiomers of sultopride in human, whereas the serum concentrations of (-)-sultopride were slightly higher than those of (+)-sultopride after i.v. administration of 50 mg/kg of racemic sultopride to rats and rabbits.

Amisulpride↗