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Biomedical subjects

S Yamaguchi

Publications and source records attributed to S Yamaguchi.

At least 703 records · Page 39Linked to original sources

Priming with murine recombinant interleukin-5 resulted in the augmentation of PAF-induced airway hyperresponsiveness to histamine in guinea pigs.

The effects of pretreatment with murine recombinant interleukin 5 (mrIL-5) on platelet activating factor (PAF)-induced bronchoconstriction and airway hyperreactivity were investigated in guinea pigs. The intratracheal administration of mrIL-5 (2.5-10 micrograms) augmented platelet activating factor (PAF; 50 ng/kg)-induced bronchoconstriction in guinea pigs. When IL-5 (2.5 micrograms) was injected intratracheally, PAF (25 ng/kg)-induced bronchoconstriction was not affected, but PAF-induced airway hyperresponsiveness to histamine was exacerbated. Airway inflammation, in terms of increased capillary permeability and the accumulation of leukocytes in bronchoalveolar lavage fluid, was not produced by pretreatment with PAF (25 ng/kg), mrIL-5 (2.5 micrograms), or by a combination of these agents. This mrIL-5-induced augmentation of airway hyperreactivity by PAF was clearly inhibited by the phosphodiesterase-type III inhibitors, SDZ-MKS-492 and AH 21-132, but not by aminophylline.

Aminophylline↗

Effect of anti-IL-5 monoclonal antibody on allergic bronchial eosinophilia and airway hyperresponsiveness in mice.

The effect of pretreatment with rat anti-murine interleukin-5 (IL-5) antibody on antigen-induced bronchial eosinophilia and bronchial reactivity to acetylcholine in mice were studied. Three inhalations of an antigen by actively sensitized animals resulted in an increase in airway reactivity to acetylcholine. Twenty-four hours after the final inhalation, the number of leukocytes (mononuclear cells and eosinophils) and the amount of IL-5 in BALF increased significantly. Anti-IL-5 monoclonal antibody inhibited the antigen-induced increase of eosinophils with little effect on bronchial hyperreactivity.

Animals↗

Affinity chromatographic purification of tetrodotoxin by use of tetrodotoxin-binding high molecular weight substances in the body fluid of shore crab (Hemigrapsus sanguineus) as ligands.

A purification method for tetrodotoxin (TTX), based on affinity chromatography using the TTX-binding high mol. wt substances in the body fluid of shore crab (Hemigrapsus sanguineus) as ligands, was developed. This method was particularly useful for analysis of TTX in biological samples with low concentrations of TTX. The affinity gel prepared was highly specific for TTX, having no ability to bind 4-epi-TTX and anhydro-TTX as well as saxitoxin.

Ammonium Sulfate↗

Anticonvulsant activity of AMPA/kainate antagonists: comparison of GYKI 52466 and NBOX in maximal electroshock and chemoconvulsant seizure models.

The anticonvulsant activities of a noncompetitive (GYKI 52466) and a competitive (NBQX) AMPA/kainate antagonist were compared in the maximal electroshock (MES) seizure test and various chemoconvulsant models. Both antagonists were protective in the MES and pentylenetetrazol tests. GYKI 52466 was also protective against seizures and lethality induced by 4-aminopyridine, kainate and AMPA, but not by NMDA, whereas NBQX was ineffective in these chemoconvulsant tests. Both GYKI 52466 and NBQX produced motor impairment at doses similar to those that were protective in the MES test. Under some circumstances, noncompetitive AMPA/kainate antagonists could offer advantages over competitive antagonists in seizure therapy. However, neurological toxicity is an obstacle to the potential clinical use of both classes of agents.

4-Aminopyridine↗

Pharmacological effects of ibudilast on cerebral circulation: a PET study.

To evaluate the pharmacological effects of ibudilast on cerebral circulation, we examined 5 ischaemic stroke patients, using positron emission tomography, and we measured cerebral blood flow (CBF). Ibudilast loading per os led to a remarkable increase in CBF after 30 min. This CBF elevation was observed in the lesion side as well as in the nonlesion hemisphere. Therefore, we can confirm that ibudilast ameliorates the chronic low perfusion state of CBF in the ischaemic stroke patient.

Aged↗

Severity of promotion by sodium salts of succinic acid in rat urinary bladder carcinogenesis correlates with sodium ion concentration under conditions of equal urinary pH.

Elevation of urinary pH and Na ion concentration induced by feeding high doses of sodium salts plays a crucial role in promotion of urinary bladder carcinogenesis in male rats initially treated with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN). In the present study, urinary bladder carcinogenesis in male F344 rats was promoted by feeding the mono- and di-sodium salts of succinic acid, and the activity was enhanced by varying urinary sodium ion concentration under conditions of equally high pH. In Experiment 1, the rats were given 0.05% BBN in their drinking water for 4 weeks and then fed basal diet containing 5% succinic acid, 5% sodium succinate (Na-Suc) or 5% di-sodium succinate (2Na-Suc) for 32 weeks. The development of carcinomas in the urinary bladder was enhanced by treatment with Na-Suc and with 2Na-Suc. 2Na-Suc induced larger urinary bladder tumors than the Na-Suc. In Experiment 2, 5% Na-Suc and/or 5% 2Na-Suc were fed to the rats for 8 weeks without prior BBN treatment. Induction of simple hyperplasia as observed by light microscopy, was greater in rats fed 2Na-Suc than Na-Suc. Increased 5-bromo-2'-deoxyuridine labeling index and alterations of the urothelial surface observed by scanning electron microscopy of the urinary bladder were similarly greater in rats fed 2Na-Suc compared to Na-Suc. In addition, there was a tendency toward increased spermidine/spermine N1-acetyltransferase activity in the urinary bladder epithelium of rats fed 5% 2Na-Suc. The results of Experiment 2 corresponded to differences in promoting activity for the different chemicals in Experiment 1. Thus, tumor growth was associated with sodium ion concentration level under conditions of equal increase of urinary pH.

Animals↗

The left ventricle affects the duration of right ventricular ejection.

OBJECTIVE: The aim was to determine if rapid changes in left ventricular pressure can acutely alter right ventricular systolic pressure and thus influence the length of right ventricular ejection. METHODS: The experiments were performed in six open chest anaesthetised dogs, weight 18-25.5 kg. Left and right ventricular pressures and pulmonary blood flow were recorded continuously as left ventricular pressure was abruptly decreased by opening a shunt in systole. From these data, the pressure and flow changes and the duration of right ventricular ejection were determined. RESULTS: Opening the left ventricular shunt caused left ventricular pressure to fall from 94.1(SD 10.5) to 62.6(11.3) mm Hg (p < 0.01), right ventricular pressure to fall from 30.3(4.6) to 27.0(3.6) mm Hg (p < 0.01), and pulmonary flow to fall from 69.5(14.2) to 57.5(13.9) ml.s-1. The duration of right ventricular ejection, determined from pulmonary flow, also decreased from 192.7(22.7) to 157.2(18.7) ms (p < 0.05) and was significantly related to the length of left ventricular systole. Time between end diastole and peak negative dP/dt decreased for both left and right ventricle. Left and right ventricular time intervals were related before (r = 0.99) and after (r = 0.75) opening the shunt. CONCLUSIONS: The duration of right ventricular ejection was decreased by a sudden decrease in left ventricular afterload and was significantly related to the length of left ventricular systole. The duration of right ventricular ejection may be coupled with left ventricular contraction through ventricular interdependence.

Animals↗

Lung cancer mortality among a cohort of male chromate pigment workers in Japan.

In 1975, five manufacturers of chromate pigment in Japan were examined in a study of the carcinogenicity of chromates. These companies were producing lead chromate, zinc chromate, molybdate orange and/or strontium chromate. The current study covers a cohort of 666 workers involved in the manufacture of chromate pigment for at least 1 year between 1950 and 1975. The workers were followed up for 15-40 years, until 1989. Many previous reports have found an excess lung cancer risk among workers involved in the manufacture of chromate pigments and chromate chemicals. In the current study, subjects were classified on the basis of years worked, years of observation, characteristics of company, type of work engaged in for the longest period of time, and involvement in the manufacture of zinc chromate. Mortality was compared with that of all Japanese males by means of the person-year method. The route of exposure was primarily inhalation through the respiratory system. None of the results showed statistically significant differences that would suggest an excess risk for malignant neoplasms, particularly lung cancer, among workers engaged in the manufacture of chromate pigment in Japan.

Cause of Death↗

Flagellar growth in a filament-less Salmonella fliD mutant supplemented with purified hook-associated protein 2.

Bacterial flagellum consists of a basal body, a hook, HAP1 (hook-associated protein 1), HAP3, a long helical filament, and a cap (composed of HAP2), all connected in series. The mutant deficient in the HAP2 structural gene (fliD) of Salmonella typhimurium has flagella composed of only hook-HAP1-HAP3 and excretes flagellin monomers into the culture medium. However, when purified HAP2 was added to this mutant, the flagellin stopped leaking out and flagellar filaments grew. Turnover of HAP2 was not necessary for the growth of a filament. Therefore HAP2 facilitates the polymerization of endogenous flagellin, apparently without falling off the filament tip. This experimental system with exogenous HAP2 allowed us to synchronize filament growth; the average rate of filament growth can be estimated by measuring the length of grown filaments at various time periods in electron micrographs. The initial growth rate was about 30 nm/min, which corresponds to one flagellin per second.

Bacterial Proteins↗

Establishment of a human small cell lung carcinoma cell line carrying amplification of c-myc gene and chromosomal translocation of t(3p;6p) and t(12q;17p).

A transplantable tumor and an in vitro culture cell line (GK-T3) were established from metastatic liver tissue of human small cell lung carcinoma (SCLC). Southern blot analysis revealed about 30-fold amplification of c-myc gene in the tumor cells in liver, xenografts, and in vitro cell line. The degree of c-myc amplification was essentially conserved through serial passages in nude mice and cultivation in vitro. The level of c-myc mRNA was significantly increased in these cells. Cytogenetically, numerical and complex structural abnormalities were observed in GK-T3 cells, including t(3p;6p), t(12q;17p), two homogeneously staining regions (hsrs) and several double minutes (dmins). These results suggest that activation of c-myc gene and alteration of gene(s) around these chromosomal breakpoints may play a role in tumorigenesis of GK-T3 SCLC.

Aged↗

Number of simultaneously expressed enzyme alterations correlates with progression of N-ethyl-N-hydroxyethylnitrosamine-induced hepatocarcinogenesis in rats.

Preneoplastic and neoplastic liver cell lesions, induced by EHEN (N-ethyl-N-hydroxyethylnitrosamine) in rats, were investigated to establish the numbers of simultaneously expressed altered enzyme phenotypes within the lesion cells. The lesions were divided into 5 classes on the basis of altered expression in one or more of the following 5 enzymes: glutathione S-transferase placental form, glucose-6-phosphate dehydrogenase, glucose-6-phosphatase, adenosine triphosphatase, and gamma-glutamyl transpeptidase. Class 1 lesions contained cells expressing one altered enzyme. Similarly, class 2, 3, 4 and 5 lesions had cells simultaneously expressing 2, 3, 4, and 5 enzyme alterations, respectively. Four histopathological categories of lesions, ACF (altered cell foci) (274 lesions), HN (hyperplastic nodules) (47 lesions), HCC (hepatocellular carcinomas) (99 lesions) and THC (transplanted hepatocellular carcinomas) (5 lesions) were studied. Proliferation potential was assessed in terms of 5-bromo-2'-deoxyuridine (BrdU) incorporation. The distribution profiles of classes 1 to 5 showed a clear reciprocal change from low class (1 to 2 enzymes) predominance in ACF to high class (4 to 5 enzymes) predominance in HN. Increase of BrdU labeling indices was clearly correlated with progression from HN to HCC. Only a small population of class 5 ACF showed a high BrdU labeling index, indicating particular potential for further development. Thus, the stages of EHEN-induced neoplasia were found to be characterized by gradual increase in the number of altered enzyme phenotypes, with acquisition of proliferative potential being associated with further progression towards malignant conversion.

Adenosine Triphosphatases↗

Influence of ionic strength on crystal adsorption and inhibitory activity of macromolecules.

We investigated the influence of ionic strength on both the binding ability of macromolecules onto calcium oxalate crystals and the inhibitory activity of macromolecules related to calcium oxalate crystal growth and aggregation in vitro. The amount of heparin sodium salt adsorbed onto calcium oxalate crystals was studied in both a seed and a non-seed crystal system at various ionic strengths with the aid of radiolabelled heparin. In both adsorption models, adsorption of heparin was greater in the buffered solutions of lower ionic strength, and significantly so in the range of physiological ionic strength. The inhibitory activity of heparin in the non-seed crystal system, which was determined using a Coulter Multisizer, increased as the adsorbed dose increased. The naturally existing urinary macromolecules showed a similar change in their inhibitory activity on calcium oxalate crystal growth and/or aggregation in accordance with changes in ionic strength. These results indicate that macromolecular inhibitory activity seems to be enhanced in urine of lower ionic strength as a result of an increased adsorption of macromolecules on the surface of calcium oxalate crystals.

Adsorption↗

Salmonella typhimurium fliG and fliN mutations causing defects in assembly, rotation, and switching of the flagellar motor.

FliG, FliM, and FliN are three proteins of Salmonella typhimurium that affect the rotation and switching of direction of the flagellar motor. An analysis of mutant alleles of FliM has been described recently (H. Sockett, S. Yamaguchi, M. Kihara, V. M. Irikura, and R. M. Macnab, J. Bacteriol. 174:793-806, 1992). We have now analyzed a large number of mutations in the fliG and fliN genes that are responsible for four different types of defects: failure to assembly flagella (nonflagellate phenotype), failure to rotate flagella (paralyzed phenotype), and failure to display normal chemotaxis as a result of an abnormally high bias to clockwise (CW) or counterclockwise (CCW) rotation (CW-bias and CCW-bias phenotypes, respectively). The null phenotype for fliG, caused by nonsense or frameshift mutations, was nonflagellate. However, a considerable part of the FliG amino acid sequence was not needed for flagellation, with several substantial in-frame deletions preventing motor rotation but not flagellar assembly. Missense mutations in fliG causing paralysis or abnormal switching occurred at a number of positions, almost all within the middle one-third of the gene. CW-bias and CCW-bias mutations tended to segregate into separate subclusters. The null phenotype of fliN is uncertain, since frameshift and nonsense mutations gave in some cases the nonflagellate phenotype and in other cases the paralyzed phenotype; in none of these cases was the phenotype a consequence of polar effects on downstream flagellar genes. Few positions in FliN were found to affect switching: only one gave rise to the CW mutant bias and only four gave rise to the CCW mutant bias. The different properties of the FliM, FliG, and FliN proteins with respect to the processes of assembly, rotation, and switching are discussed.

Alleles↗

Resetting of regional preload due to ventricular shape change alters diastolic and systolic performance.

The diastolic and systolic pressure of one ventricle is increased by an increase in volume and/or pressure of the opposite ventricle; however, a mechanism for the ventricular interaction remains unclear. We hypothesized that the shape change of one ventricle elicited by the opposite ventricle would lead to resetting of the regional length, which may explain the ventricular interaction. We used 15 cross-circulated isovolumically contracting canine hearts in which both ventricular volumes were independently controlled. Diastolic regional segment area was calculated by multiplying circumferential and longitudinal lengths on right ventricular free wall (RVFW; n = 6), interventricular septum (IVS; n = 11), and left ventricular (LV) FW (n = 12). The regional area at relatively small volumes of both ventricles were expressed as 100%. With constant RV volume, increasing LV from 7 to 19 ml increased RV diastolic and systolic pressures by 2.7 and 5.5 mmHg, respectively. Conversely, increasing RV volume increased LV diastolic and systolic pressures by 2.3 and 7.5 mmHg, respectively. Increasing LV volume increased RVFW regional area from 121.0 to 124.6% (P < 0.01) and increased IVS regional area from 103.3 to 108.7% (P < 0.01), whereas the RV volume was held constant. Increasing RV volume also increased LVFW and IVS regional areas from 109.9 to 111.6% (P < 0.01) and from 106.8 to 108.9% (P < 0.05), respectively. Ventricular shape change elicited by ventricular interaction will increase the regional wall area, even though the volume of the chamber is unchanged. The increase in the regional area alters the position of the tissue on its resting and active length-tension relations and, thus, leads to enhancement of the chamber pressure.

Animals↗

Secondary mucinous adenocarcinoma of the prostate in a patient with ulcerative colitis.

Herein we report a rare case of prostatic invasion of rectal carcinoma in a patient with ulcerative colitis. Malignant transformation is a well-known complication of long-standing ulcerative colitis. Mucinous adenocarcinoma, with positive carcinoembryonic antigen and negative prostate-specific antigen, strongly suggested the rectal origin of the tumor.

Adenocarcinoma, Mucinous↗

Biochemical and immunochemical study of seven families with 3-ketothiolase deficiency: diagnosis of heterozygotes using immunochemical determination of the ratio of mitochondrial acetoacetyl-CoA thiolase and 3-ketoacyl-CoA thiolase proteins.

The possibility of identifying heterozygotes of 3-ketothiolase deficiency, an inborn error of metabolism caused by a defect of mitochondrial acetoacetyl-CoA thiolase (T2), was tested in seven unrelated families by using enzymatic assay of thiolase activity and immunoblot analysis. The ratio of acetoacetyl-CoA thiolase activities, in the presence and absence of K+ ion (+K/-K ratio), in fibroblasts from 15 normal controls was around 2.0 (1.8 to 2.4), whereas the +K/-K ratio in eight patients was always 1.0. The ratio for the 13 obligate carriers ranged from 1.4 to 1.9, causing a minor overlap with control. Identification of heterozygote cells by immunoblot analysis, using anti-T2 antibody alone as a probe, was difficult, as previously reported. We therefore carried out immunoblot analysis, using as probes a mixture of anti-T2 antibody and the antibody against mitochondrial 3-ketoacyl-CoA thiolase (T1), another mitochondrial thiolase, and determined the ratio of the intensities of the T2 and T1 bands (T2/T1 ratio) using a densitometer. When the T2/T1 ratio was calculated, there was no overlap between the heterozygotes and normal controls. Hence, the heterozygotes can be unambiguously identified using this method. The thiolase activities and T2/T1 proteins in immunoblotting were detectable in peripheral lymphocytes, rectal mucosa, amniocytes, and liver. Thus, the postnatal diagnosis of 3-ketothiolase deficiency can be readily made using lymphocytes or rectal mucosa. The applicability of these methods in amniocytes indicates that prenatal diagnosis of this disease should be possible.

Acetyl-CoA C-Acetyltransferase↗