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Biomedical subjects

S Kojima

Publications and source records attributed to S Kojima.

At least 1,189 records · Page 66Linked to original sources

Effect of dietary sodium on platelet alpha 2-adrenergic receptors in essential hypertension.

To study the aggregation, adhesion, and specific binding of an alpha 2-antagonist, [3H]rauwolscine, to the platelet membrane fractions, platelets were obtained from 30 patients with essential hypertension and nine normotensive subjects fed a high sodium diet (NaCl, 16-18 g/day) for 7 days and thereafter a low sodium diet (NaCl, 1-3 g/day) for 7 days. The patients with essential hypertension were classified as either salt responders (all those who had greater than 7% decrease in mean arterial pressure from the high to low sodium period) or salt nonresponders (all others). In salt responders, the number of alpha 2-adrenergic receptors on platelet membrane fraction was increased from 523.4 +/- 55.4 fmol/mg of protein in the high sodium period to 669.4 +/- 84.0 fmol/mg of protein in the low sodium period (p less than 0.01), whereas it did not change in salt nonresponders. In contrast, the epinephrine-induced platelet aggregation through alpha 2-adrenergic receptors was decreased in nonresponders, from 47.3 +/- 7.4% in the high sodium period to 24.5 +/- 9.3% in the low sodium period (p less than 0.05), while it did not change in responders. No significant change in the number of alpha 2-adrenergic receptors or epinephrine-induced platelet aggregation was observed in the normotensive subjects.

Blood Platelets↗

A collaborative study of stroke incidence in Japan: 1975-1979.

A Japan Collaborative Study of Stroke covering 20 regional and occupational population groups was conducted with the support of the Ministry of Health and Welfare. In this study 17,423 males and 16,856 females, aged 40 to 69, were followed up prospectively from 1975 to 1979. The average annual incidence of all types of stroke was 3.94 for men and 2.52 for women per 1,000 population. The incidence of cerebral hemorrhage for men and women stood at 1.26 and 0.59 and that of cerebral infarction at 1.87 and 1.10 respectively. The difference in incidence between the sexes was large particularly in the age range of 40-49. The incidence of all types of stroke, cerebral hemorrhage and cerebral infarction increased with age. The incidence of all strokes in Japan during the period 1975-1979 appears to have decreased in comparison with that in 1960-1969, but tended to be still higher than that in Western countries.

Adult↗

Muscle pathology in polymyalgia rheumatica: histochemical and immunohistochemical study.

Immunohistochemical studies were performed on muscle biopsy specimens of polymyalgia rheumatica (PMR) to evaluate the extent of muscle and peripheral nerve involvement. The routine histochemistry revealed a mild variation of fiber size, type 2 fiber atrophy and type 2A or 2B fiber deficiency. In 63% of the PMR cases small angular fibers, pyknotic nuclear clumps or target-targetoid fibers were observed, suggesting neurogenic changes, although abnormalities were mild in degree. In immunocytochemical studies, neither major histocompatibility complex (MHC) class 1 nor class 2 products were expressed on the muscle surface membrane of PMR. But regarding intramuscular vessels, MHC class 2 products were distinctly visualized. On serial sections, combined deposits of IgG and Clq in perimysial arteries were seen in 38% of PMR. These results suggest that arteries of small caliber might be involved in immunopathological processes, causing muscle and peripheral nerve damage.

Aged↗

[Botulinum toxin therapy for cricopharyngeal spasm].

A 36-year-old woman presented an inability to ingestion and mild hemiparesis with superficial and deep sensory disturbances on the left side for two months after a stroke. Dysphagia was originated from bilateral cricopharyngeal spasm, which was disclosed by videofluorography, manometry at the pharyngo-esophageal segment, and needle electromyography. Although no focal lesion of the brain was detected even with MRI, neurological and electrophysiological findings suggested that the lesion was localized to the lower pontine and mudullary tegmentum on the right side. Two months after the onset, botulinum toxin (10 units) was administered into the bilateral cricopharyngeal muscles, which resulted in restoration of the normal swallowing function in 5 days, and the normal function is lasting 5 years. Botulinum toxin therapy is non-invasive and effective for cricopharyngeal spasm. This non-invasive method will be the first choice for cricopharyngeal spasm replacing surgical intervention.

Adult↗

Elevation of glutathione in RAW 264.7 cells by low-dose gamma-ray irradiation and its responsibility for the appearance of radioresistance.

We examined the relationship between the induction of glutathione (GSH) level in macrophage-like RAW 264.7 cells by a low (adapting) dose gamma-rays and the cell damage caused by a lethal dose of gamma-rays at various intervals after the adapting dose. The reduced glutathione (GSH) level increased soon after exposure of the cells to 25 cGy of gamma-rays, peaked between 3 hr and 6 hr, and returned almost to the zero time (0 hr) level by 24 hr post-irradiation. Cell damage was assessed by measuring the 3H-thymidine (3H-TdR) incorporation into cellular DNA. gamma-Ray irradiation produced a dose-dependent cell damage in RAW cells, causing about 40% and 60% inhibition of 3H-TdR incorporation into DNA at 1.0 Gy and 2.0 Gy, respectively, as compared with non-irradiated cells. Treatment with the adapting dose of 25 cGy at 1 hr or 24 hr before the lethal irradiation was ineffective. However, pre-irradiation with 25 cGy at 3 hr or 6 hr prior to lethal irradiation inhibited the decrease of 3H-TdR incorporation into DNA, indicating a protective effect. GSH exogenously added to the medium also inhibited the cell damage induced by lethal doses of gamma-Rays in a dose-dependent manner. These results indicate that the induction of endogenous GSH in living cells immediately following low-dose gamma-Ray irradiation is at least partially responsible for the appearance of radioresistance to a subsequent lethal dose of radiation, and may make it possible to use higher doses of radiation in radiotherapy for tumor patients.

Animals↗

Effect of pre-irradiation with low-dose gamma-rays on chemically induced hepatotoxicity and glutathione depletion.

We examined the elevation of glutathione (GSH) level in mouse liver and HepG2 cells after low-dose gamma-ray irradiation and its inhibitory effect on acetaminophen (AAP)- and cumene hydroperoxide (CHP)-induced hepatotoxicity. The liver GSH level in male ddY mice increased 2 hours after irradiation with 50 cGy of gamma-rays, reached a maximum at around 4 hours and returned almost to the control level by 12 hours. The effect of irradiation at 2 hours before AAP-treatment on the hepatotoxicity was then investigated in terms of glutamic pyruvic transaminase (GPT) activity in serum and lipid peroxide (malondialdehyde, MDA) content in the liver. GPT activity and MDA level were markedly increased at 24 hours post-treatment with AAP. Both increases were significantly suppressed by a single low-dose pre-irradiation with gamma-rays (50 cGy). The cellular GSH level of HepG2 cells increased about 3 hours after exposure to gamma-rays (50 cGy), peaked at 12 hours and returned almost to the time 0 value by 48 hours post-irradiation. Exposure of HepG2 cells to CHP induced time- and dose-dependent cytotoxicity, as judged from lactate dehydrogenase activity (LDH) released into the medium. Pre-irradiation with gamma-rays (50 cGy) at 6 hours before addition of 1 mM CHP to the cells significantly suppressed the elevation of LDH activity at 24 hours post-treatment. In both cases, the lowered GSH levels induced by AAP and CPH appeared to be restored to the control level by pre-irradiation with a low dose of gamma-rays. These results suggest that low-dose gamma-ray irradiation might be effective for the prevention of hepatotoxicity involving GSH deficiency.

Acetaminophen↗

Mechanisms involved in the elevation of glutathione in RAW 264.7 cells exposed to low doses of gamma-rays.

We examined the mechanisms of the elevation of glutathione level induced in macrophage-like RAW 264.7 cells by low doses of gamma-rays. The level increased soon after exposure of the cells to 50 cGy of gamma-rays, peaked between 3 hours and 6 hours and returned almost to the time 0 value by 24 hours post-irradiation. Doses between 25 and 100 cGy significantly increased the glutathione level at 4 hours post-irradiation. However, there was no significant elevation at doses of more than 100 cGy or less than 25 cGy. When the effect of dose rate was examined at a constant absorbed dose of 50 cGy, dose rates of more than 50 cGy/minute significantly increased the GSH level at 4 hours post-irradiation. It was also shown that the elevation of glutathione level in cells irradiated with low doses of gamma-rays followed the induction of mRNA coding for gamma-glutamylcysteine synthetase (gamma-GCS), a rate-limiting enzyme of the de novo glutathione synthesis pathway. When the cells were exposed to the radiation in the presence of genistein, calphostin C or nifedipine, the elevations of glutathione and gamma-GCS mRNA expression were both mostly blocked. EGTA also strongly inhibited these elevations. These results suggest that the tyrosine kinase, calcium channel and protein kinase C activities play an essential role in the low-dose-radiation-induced elevation of cellular glutathione.

Animals↗

Quantitative in vitro bioassay for recombinant human interleukin-11.

A cell culture-based in vitro bioassay was developed to measure the biological activity of recombinant human interleukin-11 (rhIL-11). The bioassay measures induced proliferation of T10 cells, derived from the T1165 murine plasmacytoma line. A colorimetrically detectable formazan product, obtained by cellular reduction of the tetrazolium compound, 4-[3-(4-iodophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzene disulfonate (WST-1), was used as an endpoint for response of clone T10 to added rhIL-11. Positions of the samples and the standards in 96-well microplates affected the precision of this bioassay, which was improved by using 2 microplates where serially diluted sample and standard lines were interleaved and their positions were alternated. The coefficient of variation for this bioassay was less than 8%. This method is suitable for quality control of rhIL-11 because of its simplicity, reproducibility, and accuracy.

Animals↗

Comparison of motor reactivity of the human colon cold-stored in different preservative solutions to carbachol and noradrenaline in vitro.

We have compared the reactivity to carbachol and noradrenaline of circular smooth muscle isolated from the human colon which was cold-stored at 4 degrees C in three different preservative solutions: Krebs bicarbonate solution (KBS), phosphate buffer solution (PBS) or minimum essential medium (MEM). Concentration-dependent contractions in response to carbachol were reduced in terms of both their sensitivity (pEC50) and reactivity (Emax), depending on the period of cold storage. The reduction was more marked when the tissue was cold-stored in either MEM or KBS than in PBS. Similar reduction of the relaxation response to noradrenaline was also observed after cold storage. It is concluded that the cold storage of surgically resected human colon in PBS for two to three days best preserved smooth muscle functions for pharmacological examinations.

Adult↗

Highly symptom-aware children were heavily infected with urinary schistosomiasis in southern Ghana.

OBJECTIVES: To assess the relationship between the infection status of children and their knowledge, attitudes, beliefs, and practices (KABP) related to urinary schistosomiasis. DESIGN: Questionnaire survey. SETTING: Nine schools in eight rural communities (total population: 4,636) in Ga and South Akuapem Districts, Ghana. SUBJECTS: Four hundred and six children attending primary and secondary schools. MAIN OUTCOME MEASURE: Schistosoma haematobium infection status of children and their KABP. RESULTS: Of 354 children who responded and also submitted their urine samples, 297 (83.9%) tested positive for S. haematobium and the intensity of infection was 90 (95% CI: 74 to 110) eggs per 10 ml urine. General knowledge variables such as the knowledge of symptoms (p < 0.001), and knowledge of swimming or bathing in the river as a transmission route (p < 0.001) showed significant association for higher prevalence and intensity of infection. Treatment-seeking behaviour was not associated with the lower prevalence or intensity of infection. Practice variables such as washing clothes in the stream (p < 0.001) and fishing in the stream (p < 0.01) were significantly associated with both higher prevalence and higher intensity of infection. Children who knew of contact with river water as a transmission route reported more water contact activities (p < 0.001). CONCLUSION: This study showed that highly symptom-aware people were heavily infected, and people frequently exposed to infested water were heavily infected. Moreover, highly symptom-aware people never constituted a group whose exposure was slight. Why was awareness of disease symptoms and general knowledge of the disease not linked to low infectivity? Why didn't awareness result in avoidance of infested water sources? This report highlights the urgent need to address these important questions in future research.

Adolescent↗

Differentiation of benign and malignant lymph nodes with contrast-enhanced echolymphography using endoscopic ultrasound-guided puncture.

BACKGROUND/AIMS: Although endoscopic ultrasonography is considered the most useful diagnostic modality for the regional staging, the capability of diagnosing lymph node metastasis based on endoscopic ultrasonography images alone is not sufficient. To improve the capability of differential diagnosis of lymph node enlargement, contrast-enhanced echolymphography was performed using endoscopic ultrasonography-guided puncture. METHODOLOGY: Contrast-enhanced echolymphography was performed in 8 metastatic lymph nodes surgically resected from patients with gastrointestinal cancers (in vitro study) and also in 55 patients in whom abdominal lymph node swelling was indicated by endoscopic ultrasonography (in vivo study). Lymph nodes were punctured under real-time endoscopic ultrasonography guidance, and carbon dioxide microbubbles were injected to evaluate echo features before and after microbubbles injection. RESULTS: Contrast-enhanced echolymphography of freshly resected metastatic lymph nodes showed nonhomogeneous echo patterns. In regions demonstrating filling defects detected by contrast-enhanced echolymphography, neoplastic infiltration was pathologically observed. In almost all of the malignant lymph nodes studied in vivo, filling defects and heterogeneous enhancements were observed by contrast-enhanced echolymphography. However, contrast-enhanced echolymphography demonstrated uniform patterns in most of the benign group. The sensitivity, specificity, positive and negative predictive value, and accuracy of differential diagnosis by contrast-enhanced echolymphography were 95.8%, 90.3%, 88.5%, 96.6%, and 92.7%, respectively. CONCLUSIONS: Contrast-enhanced echolymphography is a useful method for help in the differentiation between reactive and malignant alterations of lymph nodes.

Adult↗

The immunomodulatory beta-galactoside-specific lectin from mistletoe: partial sequence analysis, cell and tissue binding, and impact on intracellular biosignalling of monocytic leukemia cells.

Nanogram quantities of the beta-galactoside-specific lectin from mistletoe (ML-I) that is composed of two different types of subunits exhibit immunomodulatory potency and enhance cytokine secretion in vitro and in vivo. Partial sequence analysis of the carbohydrate-binding B chain revealed a ragged N-terminus and overall homologies to the B subunit of Ricin D and Ricin E. Two evolutionarily neutral substitutions were apparent in the otherwise identical N-terminal sequences of the two toxic chains within the lectin preparation. On the basis of the influence of chemical modification by group-specific reagents on ligand binding, the lectin was biotinylated with biotinyl-N-hydroxysuccinimide ester to allow monitoring of cell binding. Monocytic leukemia cells (THP-1) specifically bound the lectin with positive cooperativity at low lectin concentrations. Radiolabelled lectin could be found in several organs and in an experimental solid tumor in biodistribution in mice. Its presence in a notable amount in spleens is especially noteworthy with respect to the already reported immunomodulation. To determine intracellular responses that precede the lectin-dependent augmentation of cytokine secretion, phosphorylation of proteins and phospholipids as well as Ca(2+)-mobilization were assessed in THP-1 cells. Quantitative increases of [32P]-phosphate incorporation were determined for a 28 kDa protein and for phosphatidylinositol-4,5-biphosphate. Similarly, the fluorescence activity of the intracellular Ca(2+)-indicator fluo-3 is elevated by approximately 25% after lectin treatment. Apparently, cell binding of the lectin is followed by modulation of biosignalling processes.

Amino Acid Sequence↗

Effect of nafamostat mesilate on bradykinin generation during low-density lipoprotein apheresis using a dextran sulfate cellulose column.

The dextran sulfate (DS) cellulose column usually used for low-density lipoprotein (LDL) apheresis, is an activator of the contact phase of intrinsic coagulation pathway. Hageman factor (factor XII), high-molecular-weight kininogen (HMWK) and prekallikrein (PK) form a complex on the surface of this activator, and bradykinin is released from HMWK by the action of kallikrein converted from PK. Heparin, a frequently used anticoagulant, has no effect on this process, whereas a protease inhibitor, nafamostat mesilate (FUT-175) is thought to inhibit the process. Five patients with severe hypercholesterolemia were treated with LDL apheresis using heparin or FUT-175, each on a different day. During treatment with heparin, factor XII, HMWK, and PK were markedly decreased by passing through the DS column. A distinct generation of bradykinin was observed by passing through the DS column, which led to an increase of blood bradykinin levels from 12.5 +/- 5.3(Mean +/- SEM) pg/ml to 127.3 +/- 67.1 pg/ml after 1000 ml plasma treatment. FUT-175 almost completely suppressed this bradykinin generation. Because bradykinin generated during LDL apheresis seems to have some vasodilative effect, FUT-175 might be preferred in cases with unstable hemodynamics, although this presumption remains to be demonstrated.

Adult↗

Characterization of 5-hydroxytryptamine-induced relaxations of guinea-pig proximal colon.

The 5-hydroxytryptamine (5-HT) receptor by which 5-HT can evoke nonadrenergic noncholinergic (NANC) relaxations in isolated guinea-pig proximal colon was characterized using a variety of 5-HT receptor agonists and antagonists. In the presence of atropine (0.2 microM), guanethidine (5 microM) and ketanserin (10 microM), a concentration-dependent relaxation was obtained with 5-HT (apparent mean pEC50 value 6.43), 5-CT (5.64) and 5-CH3-T (5.02); 8-OH-DPAT, TFMPP, GR43175 and 5-OCH3-N,N-DMT (up to 100 microM) did not relax the guinea-pig proximal colon. The nonselective 5-HT receptor antagonist, metitepine (0.1 microM), the 5-HT1C/5-HT2 receptor antagonists, mianserin (1 microM) and pizotifen (0.1 microM), and the 5-HT1A/5-HT2 receptor antagonists spiperone (3 microM) shifted the concentration-response curves for 5-HT to the right. The 5-HT1A/5-HT1B receptor antagonist, cyanopindolol (0.3 microM) and a selective 5-HT3 receptor antagonist, ICS205-930 (1 microM) failed to block the 5-HT-induced NANC relaxation. In conclusion, the experiments with agonists and antagonists are compatible with the view that a 5-HT1-like receptor is involved in 5-HT-induced NANC relaxations of the guinea-pig proximal colon.

Animals↗

Identification of urinary metabolites of 2-isopropylnaphthalene in rats.

Metabolism of 2-isopropylnaphthalene in rats was found to proceed through the oxidation of the isopropyl chain of the molecule. Four unconjugated metabolites were isolated from the urine and identified: 2-(2-naphthyl)propionic acid, 2-(2-naphthyl)-2-propanol, 2-(2-naphthyl)-1,2-propanediol, and 2-(2-naphthyl)-2-hydroxypropionic acid, together with a small amount of the unchanged compound. Identification was made by means of mass, infrared, and nuclear magnetic resonance spectroscopy. The presence of glucuronides of four metabolites described above was also suggested by thin-layer and gas-liquid chromatography of the extract that was obtained after enzymatic hydrolysis.

Animals↗

Urinary metabolites of 2,6-diisopropylnaphthalene in rats.

Metabolism of 2,6-diisopropylnaphthalene (2,6-DIPN) in rats was found to proceed exclusively through oxidation of the isopropyl chain of the molecule. Five unconjugated metabolites were isolated from the urine and identified: 2,6-naphthalenedi(2-propan)-2-ol, 2-[6-(1-hydroxy-1-methyl)ethylnaphthalen-2-yl]-2-propionic acid, 2,6-naphthalenedi-2-propionic acid, 2-[6-(1-hydroxy-1-methyl)ethylnaphthalen-2-yl]-2-hydroxypropionic acid, and 2-[6-(1-hydroxy-1-methyl)ethylnaphthalen-2-yl]-1,2-propanediol, together with a small amount of the unchanged compound. The identification of these metabolites was made by means of mass, infrared, and nuclear magnetic resonance spectrometry. The presence of glucuronides of five metabolites described above was also suggested by thin-layer and gas-liquid chromatography of the extract that was obtained after hydrolysis by beta-glucuronidase. In addition, the quantitative determination of metabolites indicated that these five were the major urinary metabolites of 2,6-DIPN, and that the total urinary excretion of these metabolites in 24 hr after administration was about 23% of the dose.

Animals↗