Biomedical subjects
O Wada
Publications and source records attributed to O Wada.
Serum pepsinogen as a new marker for gastric carcinoma among young adults. Research Group on Prevention of Gastric Carcinoma among Young Adults.
BACKGROUND: Gastric carcinoma is relatively uncommon in Japan among persons younger than 40 years of age, but its prognosis is not favorable and it affects young adults in their most productive years. This study was performed to evaluate the validity of serum pepsinogen as a new marker for gastric carcinoma among Japanese younger than 40 years of age. METHODS: Data and sera were collected from the patients (108 patients younger than 40 years of age with gastric carcinoma from nine hospitals in the Kanto-Shin'etsu area in Japan) and from the control subjects (108 hospital control subjects and 108 screening control subjects) whose sex and age (within 4 years) were matched. Pepsinogen I and pepsinogen II values were measured and compared between patients and control subjects by paired t test. Sensitivities and specificities when criteria were defined by pepsinogen I, pepsinogen II, and pepsinogen I/II ratio were calculated. RESULTS: The pepsinogen I and pepsinogen II levels among patients were higher and the pepsinogen I/II ratio among patients was lower than among control subjects. When a pepsinogen II level higher than 14.8 ng/ml was considered positive, the test showed high sensitivity (83.3% for total gastric carcinoma and 85.0% for early gastric carcinoma) and high specificity (76.9% for hospital control subjects and 75.0% for screening control subjects). Similar degrees of sensitivity and specificity were obtained with the pepsinogen I/II ratio. CONCLUSIONS: These results suggest that a high pepsinogen II level combined with a low pepsinogen I/II ratio may be a useful screening test for gastric carcinoma in a young population at high risk for gastric carcinoma. This impression should be confirmed by a more extensive field trial to determine whether performance of these assays promotes early diagnosis of gastric carcinoma.
Dietary protein restriction in isolated glomeruli from rats with bilateral ureteral obstruction.
Dietary protein restriction ameliorates the decrease in GFR and renal plasma flow that occurs 24 hours after the onset of bilateral ureteral obstruction (BUO). The vasoactive hormones, prostaglandins (PGs) and thromboxane (Tx), have a role in the changes in renal function described above. Thus, we evaluated the effect of dietary protein restriction on the production of PGE2. 6-keto PGF1 alpha and TxB2 and on the activities of cyclooxygenase and phospholipases A2 and C in glomeruli isolated from sham-operated control (SOC) and BUO rats fed a low (6% casein) or a normal protein (23% casein) diet for approximately four weeks. A normal protein diet compared to a low protein diet significantly increased the glomerular production of PGE2, 6-keto PGF1 alpha and TxB2 in SOC rats. Glomeruli of rats with BUO fed a normal protein diet had further increased production of eicosanoids when compared to glomeruli of SOC rats ingesting the same diet. The production rates of eicosanoids correlated well with the activity of cyclooxygenase in the two groups of rats. On the other hand, a low protein diet completely abolished the increase in glomerular eicosanoid production seen in rats with BUO. The synthetic levels of eicosanoids were comparable in low protein-fed SOC and BUO rats, indicating normalization of glomerular eicosanoid production in BUO rats fed a low protein diet. Moreover, there were no significant differences in the activities of cyclooxygenase and phospholipases A2 and C between the SOC and BUO rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Regional characterization of G-protein subunits in glomeruli, cortices and medullas of the rat kidney.
We examined the types of guanine nucleotide-binding regulatory (G) protein subunits in isolated glomeruli, cortices excluding glomeruli and medullas of rat kidneys using bacterial toxin-catalyzed adenosine 5'-diphosphate (ADP) ribosylation and specific immunoblots. ADP ribosylation catalyzed by cholera or pertussis toxin revealed the presence of stimulatory G (Gs) or inhibitory G (Gi) proteins in membranes of the 3 segments of the kidney. Immunoblots further demonstrated the existence of several G-protein subunits, two Gs-protein alpha-subunits (G alpha s: 45 and 52 kD), Gi-protein alpha 1, alpha 2 and alpha 3-subunits (G alpha i1, G alpha i2: 40-41 kD, G alpha i3: 40 kD), bacterial toxin-insensitive G-protein alpha q- and alpha 11-subunits (G alpha q/11: 42 kD) and G-protein beta-subunits (G beta: 35-36 kD), in membranes of the preparations. The predominant subspecies of G alpha s was a 52-kD protein in glomerular membranes and a 45-kD protein in membranes of cortices and medullas. All of the G-protein subunits examined, however, were not detected in cytosolic fractions of glomeruli, cortices and medullas. Thus, we conclude that detectable quantities of several G-protein subunits including the new G-protein subunit, G alpha q/11, are present in membranes of glomeruli, cortices not containing glomeruli and medullas from the rat kidney. Both the existence of G alpha i1 and/or G alpha i2 subunits in glomeruli and the presence of G alpha q/11 subunits in the 3 preparations are new evidence.(ABSTRACT TRUNCATED AT 250 WORDS)
Importance of total leg muscle mass for exercise intolerance in chronic heart failure.
Patients with chronic heart failure symptoms tend to avoid voluntary effort and are thus subject to physical deconditioning. The presence of symptoms in daily life is thought to predispose to physical deconditioning and subsequent skeletal muscle loss. This study was designed to describe the relation among daily physical activities, skeletal muscle loss and exercise capacity in patients with chronic heart failure. We studied 14 patients with severe cardiac dysfunction (left ventricular ejection fraction < 40%) and 7 age-matched normal subjects. We measured total leg muscle mass by dual energy X-ray absorptiometry. The patients were divided into 7 asymptomatic and 7 symptomatic individuals using questionnaires for specific physical activities. Peak oxygen uptake and anaerobic threshold were significantly reduced in cardiac patients as compared with normal subjects. The reduction in exercise capacity was greater in the symptomatic patients than in asymptomatic patients. Leg muscle mass was significantly reduced (-17%) in the symptomatic patients, while it remained normal in the asymptomatic patients. Oxygen uptake in unit muscle mass at the level of anaerobic threshold and at peak exercise was decreased in both the asymptomatic (-21% and -21%, respectively) and symptomatic patients (-27% and -30%, respectively) but the difference between these two groups was not significant. In the asymptomatic patients, the reduced exercise capacity was accounted for primarily by muscle mass-independent factors such as an impaired nutritive blood flow to exercising muscles or metabolic abnormalities within the muscle cell. In the symptomatic patients, the marked reduction in exercise tolerance was attributable to a decrease in leg muscle mass and to hemodynamic or metabolic abnormalities. We conclude that the loss of leg muscle mass plays an important role in exercise intolerance in patients who are prone to physical deconditioning as a result of symptomatic heart failure.
Influence of propagermanium (SK-818) on chemically induced renal lesions in rats.
A histopathological study was performed to examine the influence of propagermanium and germanium dioxide (GeO2) on chemically induced renal lesions in rats. Animals were treated with adriamycin or mercuric chloride to induce glomerular or proximal tubular damage, and then given drinking water containing propagermanium (480 or 2,400 ppm solution) or GeO2 (300 or 1,500 ppm solution: equivalent to propagermanium in terms of germanium contents). The distal tubular epithelium after 8 weeks dosage with the 1,500 ppm solution of GeO2 was characterized by vacuolization and deposits of PAS-positive material not only in adriamycin-treated rats, but also in normal rats. In contrast, propagermanium administration was not associated with any alternation in the changes induced by adriamycin or mercuric chloride. We previously clarified that propagermanium had no biochemical influence on the renal function of these renal injured rats. The histological demonstration that this compound does not exert renal toxicity, even when given at a high dosage to renal injured rats, further indicates that it would not exacerbate renal dysfunction already present. This confirms that propagermanium may be a safe compound for use in individuals with compromised kidneys.
Effects of dietary protein on glomerular eicosanoid production in rats with bilateral ureteral obstruction.
Greater protein intake increases glomerular eicosanoid production in rats. Bilateral ureteral obstruction (BUO) also enhances glomerular eicosanoid production in experimental animals. To examine the effects of dietary protein intake on glomerular eicosanoid production in ureteral obstruction, we measured the in vitro production of the vasodilatory prostaglandins, PGE2, and 6-keto PGF1 alpha, and the vasoconstrictor, TxB2, and the mass of cyclooxygenase in glomeruli of sham-operated control (SOC) rats and rats with BUO of 24 hr duration fed a low- (6% casein) or a high- (40% casein) protein diet for approximately 4 weeks. The animals were pretreated or not with the angiotensin converting enzyme inhibitor, enalaprilat, prior to sham-operation or ureteral obstruction. Glomeruli from SOC rats fed a high-protein diet produced significantly greater amounts of PGE2, 6-keto PGF1 alpha, and TxB2, and had substantially increased mass of cyclooxygenase when compared with glomeruli from SOC rats fed a low-protein diet. Pretreatment of animals with enalaprilat prior to sham operation prevented the increase in glomerular eicosanoid production and cyclooxygenase content in SOC rats fed a high-protein diet and the levels observed were similar to those in SOC rats fed a low-protein diet. Both eicosanoid production and cyclooxygenase mass were further increased in glomeruli from rats with BUO fed a high-protein diet when compared with glomeruli of SOC rats fed the same diet. The increased levels of these measurements in BUO rats fed a high-protein diet fell markedly when the rats were pretreated with enalaprilat in vivo. The values were essentially comparable to those of SOC rats fed a low-protein diet. By contrast, there was no substantial increase in the production of PGE2, 6-keto PGF1 alpha, and TxB2 and in the mass of cycloxygenase in glomeruli of BUO versus SOC rats fed a low-protein diet. Enalaprilat did not affect glomerular eicosanoid production or cyclooxygenase content in SOC and BUO rats fed a low-protein diet. Taken together, the present study indicates that dietary protein affects BUO-induced increases in glomerular eicosanoid production by altering the activity of the cyclooxygenase pathway mainly via the reninangiotensin system. Thus, protein content in a diet may modify an alteration in renal hemodynamics caused by BUO by changing the glomerular production of eicosanoids and the activity of the renin-angiotensin system.
[Pulmonary diseases due to toxic gases, irritant gases and fumes].
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Optical properties of a high-quality (311)-oriented GaAs/Al0.33Ga0.67As single quantum well.
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In-plane orientation of Bi2Sr2CaCu2Ox thin films on (110) SrTiO3 vicinal surfaces.
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A fluorescent carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in human lens.
A fluorescent carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) has been identified in both human normal lenses and cataractous lenses. The total amounts of PhIP in normal lenses were 50.7 +/- 36.0 pg (n = 7) while those of PhIP in senile and diabetic cataractous lenses were 143 +/- 29.2 pg (n = 10) and 148 +/- 55.0 pg (n = 10), respectively. Although it was not possible to strictly compare the contents of PhIP among normal, senile and diabetic lenses, due to the limited numbers of normal lenses available, the mean total amounts of PhIP in normal lenses were the lowest among normal, senile and cataractous lenses when allowing for differences in age. Furthermore, there was a significant correlation between total amounts of PhIP in human lenses, and age of the lens, suggesting that the content of PhIP in human lens is increased with age. In all types of lenses, the concentrations of PhIP in the insoluble-protein fraction (pg mg-1 protein) were significantly higher than those in the water-soluble protein fraction. In addition, PhIP was formed when bovine lens was incubated at 37 degrees C under the presence of creatinine and glucose for various time periods, and the yield of PhIP during incubation was found to be time-dependent. The results from our study suggest that PhIP may be one of the age-related fluorogens in the human lens.
Importance of abnormal lung perfusion in excessive exercise ventilation in chronic heart failure.
Whether excessive ventilatory response to exercise is related to the maldistribution of pulmonary blood flow was examined in 23 patients with chronic heart failure and nine age-matched normal subjects. With the use of technetium 99m macroaggregated albumin, the resting distribution of pulmonary blood flow was assessed by the scintigraphic counts ratio of upper to lower lung fields. The ventilatory response to exercise was assessed by the slope of the relationship between minute ventilation and carbon dioxide production during exercise. Eight patients (group A) had slope less than 33, the upper limit of the normal range, and 15 patients had slope of 33 or greater (group B). In group B pulmonary blood flow was distributed more to the upper lung, which made the counts ratio (60%) higher than in normal subjects (34%) or in patients in group A (38%). There was no significant difference in pulmonary flow distribution between normal subjects and patients in group A. In group B tidal volume did not increase during exercise as much as it did in normal subjects and in patients in group A; therefore, the respiratory pattern was rapid and shallow. Although the ratio of physiologic dead space to tidal volume fell by 20% during exercise in normal subjects and by 23% in patients in group A, it failed to decrease in patients in group B (-1%), which indicates a relative increase in dead space respiration during exercise. These data indicate that decreased lung compliance and regional ventilation-perfusion mismatch caused by pulmonary vascular and parenchymal abnormalities would play an important role in the excessive exercise ventilation in chronic heart failure.
Detection of a carcinogen, 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine, in airborne particles and diesel-exhaust particles.
A carcinogen, 2-amino-1-methyl-6-phenylimidazo [4,5-b]-pyridine (PhIP), has been measured in airborne particles, diesel-exhaust particles, and incineration ash from garbage-burning plants. PhIP was found in all kinds of samples. In the light of the present results, together with the previous findings that PhIP was present in cooked foods and cigarette smoke, PhIP is likely to be an ubiquitous environmental pollutant. These observations also suggest that PhIP may be formed through the combustion process.
Production of polyclonal antibodies against 1,1'-ethyliden bis[L-tryptophan] (EBT), a potential contaminant causing eosinophilia-myalgia syndrome (EMS).
Eosinophilia-myalgia syndrome (EMS) is thought to be caused by the intake of contaminated L-tryptophan products. 1,1'-Ethyliden bis[L-tryptophan] (EBT) is one of the contaminants in the L-tryptophan products and is thought to be a possible cause of EMS. In the present study we report that anti-EBT antibodies are generated by immunizing rabbits with the low molecular weight substance, EBT (molecular weight 434). These antibodies may be available tools for elucidating the mechanisms responsible for the outbreak and/or development of EMS.
Detection of the carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in beer and wine.
A carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), was measured in beer and wine by HPLC. PhIP was found to be present in all brands of beer and wine analyzed. The concentrations of PhIP in beer and wine were 14.1 +/- 6.18 ng/l (mean +/- SD, n = 11) and 30.4 +/- 16.4 ng/l (n = 10) respectively.
Nucleic acids induce the formation of a carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in a model system.
Effects of nucleic acids on the formation of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) were studied in a model system. When a mixture of a certain amount of DNA or RNA, creatinine (1 mmol) and phenylalanine (1 mmol) in 10 ml of 50 mM phosphate buffer, pH 7.4, was heated at 60 degrees C for 4 weeks in a screw-capped vial, PhIP was produced, and the yield of PhIP was dependent on the heating time as well as the dose of nucleic acid added to the mixture. However, PhIP was not detectable in the mixtures without the presence of nucleic acids. Both deoxyribonucleotides and ribonucleotides tested induced the formation of PhIP under the presence of phenylalanine and creatinine, although bases of nucleic acids such as adenine and guanine did not induce PhIP formation. Moreover, we confirmed that 2-deoxy-D-ribose as well as D-ribose induced the formation of PhIP in the presence of creatinine and phenylalanine. These results indicate that nucleic acids can induce the formation of PhIP in the presence of creatinine and phenylalanine in the model system. Our data also suggest that pentose in nucleic acids may participate in PhIP forming reactions.
Increases in glomerular eicosanoid production in rats with bilateral ureteral obstruction are mediated by enhanced enzyme activities of both the cyclooxygenase and 5-lipoxygenase pathways.
Glomeruli isolated from rats with bilateral ureteral obstruction (BUO) of 24 hr duration produced significantly greater amounts of prostaglandin (PG) E2, 6-keto-PGF1 alpha, thromboxane B2, and leukotriene B4 than glomeruli isolated from sham-operated control (SOC) rats. To examine the mechanisms underlying the greater production of eicosanoids by glomeruli isolated from rats with BUO, we measured the activities of enzymes related to eicosanoid formation such as cyclooxygenase, 5-lipoxygenase, PGE2 isomerase, and PGI2 and thromboxane synthase in glomeruli isolated from SOC rats and rats with BUO. Glomeruli isolated from rats with BUO had a significantly increased activity of cyclooxygenase with de novo synthesis of this enzyme and a markedly augmented activities of PGE2 isomerase and both PGI2 and thromboxane synthases relative to glomeruli isolated from SOC rats. Similarly, the activity of membrane-bound 5-lipoxygenase, the active location of this enzyme, was significantly greater in glomeruli isolated from rats with BUO than in glomeruli isolated from SOC rats. Thus, BUO of 24 hr duration enhances the glomerular production of eicosanoids via the activation of enzymes in both the cyclooxygenase and 5-lipoxygenase pathways.