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Biomedical subjects

K Yokota

Publications and source records attributed to K Yokota.

At least 91 records · Page 5Linked to original sources

Crystal structure of staphylococcal LukF delineates conformational changes accompanying formation of a transmembrane channel.

Staphylococcal LukF, LukS, HgammaII, and alpha-hemolysin are self-assembling, channel-forming proteins related in sequence and function. In the alpha-hemolysin heptamer, the channel-forming beta-strands and the amino latch make long excursions from the protomer core. Here we report the crystal structure of the water soluble form of LukF. In the LukF structure the channel-forming region folds into an amphipathic, three-strand beta-sheet and the amino latch forms a beta-strand extending a central beta-sheet. The LukF structure illustrates how a channel-forming toxin masks protein-protein and protein-membrane interfaces prior to cell binding and assembly, and together with the alpha-hemolysin heptamer structure, they define the end points on the pathway of toxin assembly.

Amino Acid Sequence↗

Genetic polymorphism of aldehyde dehydrogenase 2 in patients with upper aerodigestive tract cancer.

BACKGROUND: Alcohol consumption is one of the major risk factors of the upper aerodigestive tract (UADT) cancers, and combined cancers are frequently discovered in the patients with UADT cancer. The association between esophageal cancer and alcohol-related metabolizing enzymes is well studied, but only a few examinations about the association between head and neck cancer and the enzymes were performed. METHODS: Fifty-two patients with UADT cancer (head and neck cancer in 25, esophageal cancer in 19, and multiple cancers in 8) were examined in the alcohol habit and in the polymorphisms of aldehyde dehydrogenase 2 (ALDH2) and cytochrome P-4502E1. RESULTS: Patients with multiple cancers had significantly higher ethanol consumption than the other two groups (p < 0.001). The frequency of ALDH2*1/2*2 heterozygote was significantly lower (p = 0.009) in patients with head and neck cancer (5/25) than patients with esophageal cancer (11/19). The allele frequency of P-4502E1 did not show a significant difference between the groups (p = 0.700). CONCLUSIONS: These results demonstrated the difference in the frequency of ALDH2 heterozygote between the patients with esophageal cancer and patients with head and neck cancer.

Aged↗

Antibodies to human gastric epithelial cells and heat shock protein 60 in Helicobacter pylori positive mucosa associated lymphoid tissue lymphoma.

BACKGROUND: Development of gastric mucosa associated lymphoid tissue (MALT) lymphoma is thought to be closely associated with host immune reactions to Helicobacter pylori. AIM: To investigate humoral immune responses in patients with MALT lymphoma to antigens shared by H pylori and human gastric epithelial cells. METHODS: Sera were obtained from H pylori positive patients with MALT lymphoma (n = 11) or other gastroduodenal diseases (peptic ulcer, n = 40; non-ulcer dyspepsia, n = 20) and from H pylori negative healthy control subjects (n = 10). Antibodies to HGC-27 human gastric epithelial cells and human recombinant heat shock protein (Hsp) 60 were examined using an enzyme linked immunosorbent assay (ELISA) and immunoblotting. RESULTS: Antibody titres to HGC-27 cells were significantly elevated in H pylori positive patients with MALT lymphoma when compared with titres in patients with other gastroduodenal diseases and in healthy subjects. Immunoblotting of sera from patients with MALT lymphoma often detected a band with a molecular mass corresponding to Hsp60, and both ELISA and immunoblotting showed elevated antibody titres to the recombinant human Hsp60. Antigenic similarity between Hsp60 and H pylori HspB was documented by immunoblotting experiments. CONCLUSIONS: Autoantibodies reactive with host gastric epithelial cells are often increased in MALT lymphoma, and Hsp60 is a major target antigen. Immune responses induced by immunological cross reactivity between H pylori HspB and human Hsp60 in gastric epithelium may be involved in the development of MALT lymphoma.

Adult↗

Insulin resistance and angiotensin converting enzyme polymorphism in Japanese hypertensive subjects.

Renin-angiotensin system activity has been shown to affect insulin sensitivity. However, the relationship between I/D polymorphism and insulin resistance is controversial. Therefore, we examined the relationship between the ACE genotype and insulin sensitivity in 51 Japanese hypertensive patients using the glucose clamp technique. The ACE genotype distribution in the hypertensive subjects was: 7 subjects with DD, 20 subjects with ID, and 24 subjects with II. Insulin sensitivity in terms of the glucose disposal rate was not significantly different among the three ACE genotypes, although there was a tendency for insulin sensitivity to decrease in the order of II, ID and DD, DD being the lowest. These findings are contrary to previous reports that insulin sensitivity was increased in normotensive subjects with the DD genotype who were Caucasian or African-American. There might be a difference due to race and whether the subjects are hypertensive or obese. We concluded that insulin sensitivity was not different among the ACE genotypes in the Japanese hypertensive subjects, supporting a previous report on the Chinese population. To date, insulin sensitivity has not been found to differ with ACE genotypes in the oriental population.

Adult↗

Morphological features of the spermatic cord in the musk shrew (Suncus murinus) with special reference to extratesticular Leydig cells.

Morphological features of the testicular artery and vein in the spermatic cord of the musk shrew (Suncus murinus) were evaluated by light microscopy, transmission electron microscopy, corrosion cast technique combined with scanning electron microscopy and immunohistochemistry. The vascular architecture in the spermatic cord of the musk shrew was simple. The testicular artery in the musk shrew was straight and accompanied by 1 to 3 branches of testicular vein. The testicular vein was also straight and anastomosed with each other in some points along its length, but it did not form a delicate pampiniform plexus. In the middle and distal portions of the spermatic cord, the tunica adventitia of the artery and vein was joined together to form a single connective tissue septum. Clusters of cells were found in this connective tissue septum in the middle portion of the cord. These cells were located close to the arterial wall and nerve endings, but they did not appear inside of neurium. They showed several typical characteristics similar to Leydig cells, and they were positive for 3beta hydroxysteroid dehydrogenase (HSD) antibody. Ultrastructural and immunohistochemical studies also indicated that the cells in cluster found in the vascular wall of the musk shrew spermatic cord may be equivalent to Leydig cells in testes. These extratesticular Leydig cells had characteristics of the active steroid-producing cell and seemed to be another source of testosterone.

3-Hydroxysteroid Dehydrogenases↗

Molecular typing of enterohemorrhagic Escherichia coli O157:H7 isolated in Okayama Prefecture using pulsed field gel electrophoresis and random amplification of polymorphic DNA.

Three outbreaks and many isolated cases of enterohemorrhagic Escherichia coli O157:H7 occurred in 1996 and 1997 in Okayama Prefecture, Japan. In an attempt to investigate the route of these infections, the strains isolated from the 3 outbreaks (total 33 strains) and 15 isolated cases (total 15 strains) were investigated using random amplification of polymorphic DNA (RAPD) and pulsed-field gel electrophoresis (PFGE). In addition, 10 strains from an outbreak in Tojo Cho, Hiroshima Prefecture (June 1996), 2 strains from the particular types of meat in Kochi Prefecture, and 42 strains isolated from bovine feces in a farm in Okayama Prefecture were also investigated in the same manner. PFGE was much more useful than RAPD for molecular typing of the clinical isolates, in that it allowed us to classify them into 10 PFGE groups. We noted that the strains differed according to the time and place of the outbreaks (or isolated cases). This indicates that O157:H7 infections in Okayama Prefecture were caused by different strains (although some cases were aggravated by the same strains as were found in other areas). The isolates from bovine feces were classified into 5 groups by PFGE profiles, but none of them were identical to those of the clinical isolates.

Animals↗

Hypercalcemia accompanied by hypothalamic hypopituitarism, central diabetes inspidus and hyperthyroidism.

We present here a case of prominent hypercalcemia accompanied by hypothalamic tumor and Graves' disease. A 24-year-old man with hypothalamic tumor showed hypopituitarism, central diabetes inspidus (DI) and hyperthyroidism. Nausea, loss of thirst and appetite, and general fatigue were found with the unveiling of hypercalcemia and hypernatremia. Parathyroid hormone (PTH) and 1alpha-dihydroxyvitamin D levels were suppressed with a normal range of PTH-related protein values. One-desamino-(8-D-arginine)-vasopressin (DDAVP) and half-saline administration normalized hypernatremia, while hypercalcemia was still sustained. Administration of cortisone acetate and thiamazole reduced the elevated serum Ca level. In the present case, concurrent hyperthyroidism was assumed to accelerate skeletal mobilization of calcium into the circulation. Hypocortisolism and central DI was also considered to contribute, to some extent, to the hypercalcemia through renal handling of Ca.

Adult↗

Prevention of occupational allergy caused by exposure to acid anhydrides.

This paper focuses on the prevention of IgE-mediated symptoms of the eyes and airways caused by exposure to acid anhydrides in the workplace. Acid anhydrides are widely used in the production of alkyd resins and as curing agents for epoxy resins. Heavy exposure to acid anhydrides causes severe irritation. However, reports of direct irritation of mucous membranes or skin are rare in recent years, since a package of multiple engineering controls has been introduced to reduce exposure. On the other hand, acid anhydrides are well-known industrial inhalant sensitizers and can cause occupational allergy even at very low exposure intensities. Therefore, safe use in industry demands both control of the level of exposure causing allergic diseases in the workshop and programmes for prevention of occupational allergy.

Anhydrides↗

Determination of methyltetrahydrophthalic anhydride in air using gas chromatography with electron-capture detection.

Methyltetrahydrophthalic anhydride (MTHPA) stimulates the production of specific IgE antibodies which can cause occupational allergy even at extremely low levels of exposure (15-22 micrograms/m3). Safe use in industry demands control of the levels of exposure causing allergic diseases. Thus, the air monitoring of MTHPA is very important, and sensitive methods are required to measure low air concentrations or short-time peak exposures. This paper outlines the use of silica-gel tubes for sampling airborne MTHPA vapour, followed by analysis using gas chromatography with electron-capture detection. No breakthrough was observed at 113, 217, 673 and 830 micrograms/m3 (sampling volume 30, 60, 60 and 20 l, respectively; relative humidity 40-55%). Concentrations > 1.0 microgram/m3 could be quantified at 20-min sampling with a sampling rate of 1 l/min. The present method can also be applied to measurements of exposure to hexahydrophthalic and methylhexahydrophthalic anhydride. The risk of MTHPA exposure in two condenser plants was also assessed by determining MTHPA levels in air of the workplace. In conclusion, our method was found to be reliable and sensitive, and can be applied to the evaluation of MTHPA exposure.

Air Pollution, Indoor↗

Cytotoxic activity and cytokine gene induction of Asp-hemolysin to murine macrophages.

We examined the effects of Asp-hemolysin from Aspergillus fumigatus Fresenius-Muramatsu strain on the viability and cytokine gene expression of mouse peritoneal macrophages. The cytotoxic activity of Asp-hemolysin to macrophages cultured in FCS-RPMI medium was increased in a dose-dependent manner. Treatment of Asp-hemolysin with N-ethylmaleimide or sulfo-N-hydroxy-sulfosuccinimide-acetate caused a remarkable loss of the cytotoxic activity, however, the cytotoxic activity of Asp-hemolysin to macrophages cultured in serum-free medium was significantly increased as compared with that in FCS-RPMI medium. As other biological activities of Asp-hemolysin, tumor necrosis factor-alfa (TNF-alfa), interleukin-1 beta(IL-l beta) and interleukin-1 alfa (IL-l alfa) mRNA expression were observed in macrophages cultured with 1 micro g/ml of Asp-hemolysin.

Animals↗

[The so-called megaureter-megacystis syndrome: a case report].

We encountered a patient with megaureter-megacystis syndrome showing a giant bladder and dilated ureters with marked reflux, which is very rare; to our knowledge, only 2 patients have been reported in Japan. The patient was a 4-year-old boy, who showed inborn polyposia and polyuria, and proteinuria at the age of 1 year. He visited the pediatric department in our hospital complaining of cold-like symptoms, stomachache and diarrhea. Urinary infection and kidney dysfunction were observed, and the patient was hospitalized for close examination. Bilateral pyelocaliceal hydronephrosis was detected by ultrasonography, and the patient was referred to our department. CT revealed bilateral hydronephrosis (right atrophic kidney), hydroureters and megacystis. Bilateral grade V vesicoureteral reflux, an increase in the bladder volume (> 300 ml), and urination without residual urine were noted by voiding cystourethrography. Uroflowmetry revealed that maximum flow rate was 21.6 ml/sec, voided volume was 110 ml, and residual volume was 24 ml. From these examinations, the patient was diagnosed as having megaureter-megacystis syndrome, and underwent antireflux operation of the bilateral ureters using Cohen's procedures.

Child, Preschool↗

[Postoperative prophylactic intravesical instillation of tetrahydropyranyl-adriamycin (THP) for superficial bladder cancer].

Intravesical instillation of tetrahydropyranyl-adriamycin (THP) was performed on 51 patients with superficial bladder cancer after transurethral resection (TUR) for prophylaxis of recurrence. The instillation was carried out with 20 mg of THP dissolved in 40 ml of distilled normal saline. Instillation was performed once 24 hours postoperatively, 9 times every 2 weeks, and 8 times every 4 weeks. These drugs were instilled for 30 to 60 minutes. The recurrence-free survival at 1, 2 and 3 years was 74.5%, 64.6% and 58.0%, respectively. Side effects of THP instillation were observed in only 4 cases (7.8%) as slight urinary frequency or micturition pain. Cases involving 5 or more tumors, or tumors measuring 3 cm or larger, more frequently demonstrated recurrence. The cases that did not respond to preoperative intravesical instillation of THP demonstrated a high frequency of recurrence. Intravesical instillation of THP as a prophylaxis against recurrence of superficial bladder cancer was effective in selected patients.

Administration, Intravesical↗

[Changes in 24-hour urinary excretion of sodium and potassium in a community-based heath education program on salt reduction].

PURPOSE: To examine changes in urinary excretion of sodium, potassium and sodium/potassium ratio in a community-based health education program on salt reduction. SUBJECTS AND METHODS: The surveyed community was Kyowa town (census population in 1985 = 16,792) where we have conducted a community-based blood pressure control program since 1981 and health education on reduction of salt intake since 1983 for primary prevention of hypertension. A 24-hour urine collection was conducted for systematically selected samples of the participants aged 40-69 in cardiovascular risk surveys in 1982-86 (early period) and in 1990-94 (later period) to estimate changes in urine excretion of sodium, potassium, and sodium/potassium ratio. RESULTS: A 24-hour urine collection was available for 565 persons (410 men and 155 women) in 1982-86 and 1,461 persons (571 men and 890 women) in 1990-94. A decline in mean sodium excretion was larger in ages 40-49 than in other age groups, and for ages 40-69 combined, the decline was 0.9-1.1 g per day for men and women. Mean sodium excretion declined to 10 g or less per day for men and women aged 60-69. Mean potassium excretion did not change except for men aged 60-69 with an increase in potassium. Sodium/potassium ratio tended to decline for women aged 40-49, and declined significantly for other sex-age groups. A larger reduction in sodium excretion was seen among persons with a history of hypertension compared to those without it. CONCLUSIONS: A significant reduction in urinary excretion of sodium and sodium/potassium ratio was observed in a community-based health education program. Men and women aged 60-69 reached a recommended level of 10 g or less in sodium intake.

Adult↗

Association of Helicobacter pylori with gastroduodenal diseases.

Helicobacter pylori was first cultured in vitro in 1982. This bacterium is a spiral gram-negative rod which grows under microaerophilic conditions. The ecological niche is the mucosa of the human stomach which had been thought to be aseptic before the discovery of this bacterium. This organism causes a long-lasting infection throughout a person's life if there is no medical intervention. Numerous persons are infected with the organism around the world, and the rate of infection in Japan is nearly 50% of the population. However, the route of infection remains unclear because the organism has not been isolated from any environment other than several animals. H. pylori is now recognized as a causative agent of gastritis and peptic ulcers. Though gastritis, and especially chronic active gastritis, is observed at least histologically in all persons with H. pylori, peptic ulcers develop in only some infected persons. Specific factors in the host and/or the bacteria are needed for the development of peptic ulcer disease. Furthermore, H. pylori is considered to be related to the development of gastric mucosa-associated lymphoid tissue (MALT) lymphoma, especially those of low grade. Also, H. pylori infection is a major determinant for initiating the sequence of events leading to gastric cancer. In some patients with low-grade gastric MALT lymphoma, the eradication of H. pylori led to a regression of lesion. Gastric cancer has been induced in Mongolian gerbils with long-term H. pylori infection. The combinations of drugs, which consist of an antisecretory agent (acid-suppressing agent) and antimicrobial agents, are used for the eradication of the organism. Eradication therapy is recommended at least for patients with peptic ulcers.

Animals↗

Oxidized low density lipoprotein inhibits the hemolytic activity of Asp-hemolysin from Aspergillus fumigatus.

We have examined the effect of chemically modified human low density lipoproteins (LDLs), acetylated LDL and oxidized LDL, on the hemolytic activity of Asp-hemolysin. Oxidized LDL, but not acetylated LDL, inhibited the hemolytic activity of this toxin. The inhibitory effects of oxidized LDL increased with the time of Cu(2+)-induced LDL oxidation. Similar inhibition was observed in the filtrate which was separated from the incubation mixture of Asp-hemolysin with oxidized LDL (for 2 h of oxidation) following ultrafiltration through a membrane with a molecular mass cutoff of 100,000. However, at longer LDL oxidation times, the inhibition by the filtrates was less than the control mixture without ultrafiltration. We suggest that the inhibition by oxidized LDL was due to the binding of oxidized LDL to Asp-hemolysin at shorter LDL oxidation times.

Acetylation↗

The effect of danaparoid sodium (danaparoid) on endotoxin-induced experimental disseminated intravascular coagulation (DIC) in rats.

Danaparoid sodium (danaparoid) is a low molecular weight heparinoid with anticoagulation properties, which mainly consists of heparan sulfate. Compared with heparin sodium (heparin), danaparoid has a much higher anti-Xa/anti-thrombin ratio. We compared the effect of danaparoid on endotoxin-induced experimental disseminated intravascular coagulation (DIC) in rats with heparin. A bolus injection of endotoxin (10 mg/kg) induced gradual decreases in the platelet count, and the plasma fibrinogen, antithrombin III (AT-III) and heparin cofactor II levels, as well as an increase in the fibrinogen/fibrin degradation products level from 1 to 6 hours after the injection, indicating that both coagulation and fibrinolysis were activated. The intravenous administration of danaparoid or heparin 3 hours after the endotoxin injection inhibited the endotoxin-induced decreases in the platelet count and plasma fibrinogen level and also inhibited the endotoxin-induced increase in glomerular fibrin deposition in the kidney. Differences between danaparoid and heparin were observed in their effects on the plasma AT-III level and clotting time. Danaparoid significantly inhibited both the decrease in the plasma AT-III level and the prolongation of the prothrombin time induced by endotoxin, where as heparin showed no effect on those responses. Moreover, danaparoid enhanced the prolongation of the activated partial thromboplast in time induced by endotoxin to a lesser degree than heparin. These findings suggest that the effects of danaparoid on the endotoxin-induced decrease of the plasma AT-III level and the prolongation of the clotting time are more advantageous than those of heparin. The results may have been due to a higher anti-Xa/anti-thrombin ratio of danaparoid than that of heparin, indicating that danaparoid may be useful in the treatment of DIC.

Animals↗

Development of obstructive hypertrophic cardiomyopathy from nonobstructive hypertrophic cardiomyopathy.

A rare case of obstructive hypertrophic cardiomyopathy (HC) with mitral regurgitation (MR) is reported, which developed over 7 years from nonobstructive HC in an elderly woman. Systolic anterior motion of the anterior mitral leaflet was the most likely cause of the outflow obstruction and mitral valve replacement combined with septal myectomy resulted in complete abolition of the outflow tract gradient and MR.

Aged↗