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Biomedical subjects

K Yasuda

Publications and source records attributed to K Yasuda.

At least 19 recordsLinked to original sources
PubMed1992

Cloning of a novel somatostatin receptor, SSTR3, coupled to adenylylcyclase.

The gene encoding a novel mouse somatostatin receptor termed mSSTR3 was isolated and characterized. The sequence of mSSTR3 shows 46 and 47% identity with mSSTR1 and mSSTR2, respectively. mSSTR3 binds somatostatin-14 and somatostatin-28 with high affinity, but shows very low affinity for the somatostatin analogs MK-678 and SMS-201-995. In addition, mSSTR3 is coupled to pertussis toxin-sensitive G proteins and mediates somatostatin inhibition of forskolin-stimulated and dopamine D1 receptor-stimulated cAMP formation, indicating that it is coupled to adenylylcyclase. The pharmacological properties of mSSTR3 and its ability to couple with adenylylcyclase distinguish SSTR3 from the other cloned somatostatin receptors and indicates that it mediates biological functions different from SSTR1 or SSTR2. In situ hybridization indicates that SSTR3 mRNA is widely distributed in the mouse brain, and its expression in the nucleus of the lateral olfactory tract and in the piriform cortex, the primary olfactory cortex in the rodent brain, suggests that SSTR3 may participate in the processing and modulation of primary sensory information.

Adenylyl Cyclases↗
PubMed1992

The cooperative interaction between two motifs of an enhancer element of the chicken alpha A-crystallin gene, alpha CE1 and alpha CE2, confers lens-specific expression.

An 84 bp element located between nucleotides -162 and -79 of the chicken alpha A-crystallin gene exhibits lens-specific enhancer activity. Transient transfection experiments using 5' deletion and linker scanner mutants has indicated that the 84 bp enhancer element is composed of three motifs, alpha CE1 (-162 to -134), alpha CE3 (-135 to -121) and alpha CE2 (-119 to -99). Neither alpha CE1 or alpha CE3 motif alone can exhibit enhancer activity even when trimerized, whereas together they can direct some degree of lens-specific expression. alpha CE2 alone shows low transcriptional activity when trimerized. A combination of alpha CE1 with alpha CE2 exerts full lens-specific enhancer activity comparable with that of the 84 bp enhancer element, indicating that alpha CE1 and alpha CE2 motifs are sufficient to confer lens-specific expression. Transcriptional activation by these two motifs from a distance required the additional presence of either or both motifs adjacent to the beta-actin basal promoter. Gel shift experiments indicated that the alpha CE1, alpha CE2 and alpha CE3 motifs specifically bind nuclear proteins. alpha CE1 binds a protein predominantly present in lens cells, whereas alpha CE2- and alpha CE3-binding proteins differ between lens and lung cells. Mutations within the alpha CE1 and alpha CE2 motifs that failed to bind nuclear factors in vitro resulted in loss of transcriptional activation, indicating that these nuclear factors play a key role in controlling lens-specific expression.

Animals↗
PubMed1992

Localization of pancreatic endocrine tumors by endoscopic ultrasonography.

BACKGROUND: After a pancreatic endocrine tumor has been diagnosed on the basis of clinical signs and the results of laboratory tests, localization of the tumor by the usual imaging procedures fails in as many as 40 to 60 percent of patients. Endoscopic ultrasonography, a sensitive test for small carcinomas of the pancreas, might also be useful in patients with endocrine tumors of the pancreas that cannot be localized by conventional methods. METHODS: We studied 37 patients later shown to have 39 endocrine tumors of the pancreas who had negative results on transabdominal ultrasonography and CT. All the patients underwent endoscopic ultrasonography, and 22 also underwent selective angiography. All the tumors were confirmed by surgical excision and immunohistologic examination; they consisted of 31 insulinomas, 7 gastrinomas, and 1 glucagonoma, 0.5 to 2.5 cm (mean, 1.4 cm) in diameter. All but one of the patients were cured of their disease, as ascertained by at least six months of clinical and laboratory follow-up. RESULTS: Using endoscopic ultrasonography, we were able to localize 32 of the 39 tumors (sensitivity, 82 percent); no tumor was incorrectly localized. The size of the tumors was very similar (within 2 mm) to that predicted by endoscopic ultrasonography. Among the 22 patients who underwent both angiography and endoscopic ultrasonography, ultrasonography was significantly more sensitive than angiography for tumor localization (sensitivity, 82 percent vs. 27 percent). Among 19 control patients without pancreatic endocrine tumors, endoscopic ultrasonography was negative in 18 (specificity, 95 percent). CONCLUSIONS: Endoscopic ultrasonography is a highly sensitive and specific procedure for the localization of pancreatic endocrine tumors. It should be considered for the preoperative localization of such tumors once the clinical and laboratory diagnosis has been established.

Adenoma, Islet Cell↗
PubMed1992

Gly145 to Arg substitution in HBs antigen of immune escape mutant of hepatitis B virus.

A Japanese child born to an HBeAg-positive carrier mother received anti-HBs immunoglobulins and a plasma-derived HBs vaccine with a poor anti-HBs-antibody response. The child, who is now 3 years old, is presently suffering from chronic hepatitis with unusual serological findings that are positive for HBsAg, anti-HBs and HBeAg, since being infected with a measles virus at 12 months of age. The nucleotide sequences of the S region of HBV DNA obtained from the patient, the mother and an HBeAg-positive brother were completely identical except for one nucleotide at position 587 (mother and brother: guanosine, patient: adenosine), giving an amino acid change: Gly - greater than Arg at position 145 of the major HBs protein.

Amino Acid Sequence↗
PubMed1992

Nonsense mutation in the glucokinase gene causes early-onset non-insulin-dependent diabetes mellitus.

Maturity-onset diabetes of the young (MODY) is a form of non-insulin-dependent (type 2) diabetes mellitus (NIDDM) which is characterized by an early age at onset and an autosomal dominant mode of inheritance. Except for these features, the clinical characteristics of patients with MODY are similar to those with the more common late-onset form(s) of NIDDM. Previously we observed tight linkage between DNA polymorphisms in the glucokinase gene on the short arm of chromosome 7 and NIDDM in a cohort of sixteen French families having MODY. Glucokinase is an enzyme that catalyses the formation of glucose-6-phosphate from glucose and may be involved in the regulation of insulin secretion and integration of hepatic intermediary metabolism. Because the glucokinase gene was a candidate for the site of the genetic lesion in these families, we scanned this gene for mutations. Here we report the identification of a nonsense mutation in the gene encoding glucokinase and its linkage with early-onset diabetes in one family. To our knowledge, this result is the first evidence implicating a mutation in a gene involved in glucose metabolism in the pathogenesis of NIDDM.

Base Sequence↗
PubMed1992

Identification of the contact sites of a factor that interacts with motif I (alpha CE1) of the chicken alpha A-crystallin lens-specific enhancer.

A lens-specific enhancer, an 84bp element between base pairs -162 and -79, of the chicken alpha A-crystallin gene is composed of two motifs, alpha CE1 (-162 and -134) and alpha CE2 (-119 and -99). Previous studies showed that a nuclear factor which binds to alpha CE1, termed alpha CEF1, is present at high levels in lens cells. Methylation interference analysis identified an inverted repeat of 5bp separated by 4bp, 5'-CTGGTTCCCACCAG-3', between positions -153 and -140 as an alpha CEF1-binding site. Gel mobility shift assays using synthetic oligonucleotides with site-directed mutations revealed that the alpha CEF1-binding consensus sequence is 5'-C(T/A)GGN6CC(A/T)G-3'. Comparison of this binding motif with regulatory sequences of diverse crystallin genes from diverse species suggests that alpha CE1 may be a ubiquitous crystallin gene enhancer.

Animals↗
PubMed1992

Insulin stimulates novel protein kinase C in rat adipocytes.

Insulin is known to rapidly stimulate and/or translocate Ca2+/phospholipid-dependent protein kinase (conventional PKC; cPKC) in rat adipocytes. Presently we examined whether insulin also stimulates/translocates Ca(2+)-independent, phospholipid-dependent protein kinase (novel PKC; nPKC). Total Mono Q column-elutable nPKC (like cPKC) activities were decreased in cytosolic and increased in membrane fractions with insulin treatment. Immunoblot study of novel PKC epsilon also showed insulin-induced translocation of immunoreactive PKC from cytosol to membrane, similar to the translocation of cPKC, PKC beta. These results suggest that nPKC has an important role in insulin-induced signal transduction.

Adipose Tissue↗
PubMed1992

Congenitally defective aldosterone biosynthesis in humans: the involvement of point mutations of the P-450C18 gene (CYP11B2) in CMO II deficient patients.

The gene for steroid 18-hydroxylase (P-450C18) has been recently assigned to encode corticosterone methyl oxidases Type I and Type II which were previously postulated to catalyze the final two steps in the biosynthesis of aldosterone in humans. Molecular genetic analysis of the P-450C18 gene is three patients from three different families affected with CMO II deficiency has indicated that a point mutation of CGG----TGG (181Arg----Trp) in exon 3 and one of GTG----GCG (386Val----Ala) in exon 7 occur exclusively in the gene of the patients. Analysis of PCR products by restriction enzymes (HapII and HphI) has indicated that the patients are homozygous and the unaffected parent is heterozygous for both mutations, in accordance with the established concept that CMO II deficiency is inherited in an autosomal recessive manner. These data clearly provide the molecular genetic basis for the characteristic biochemical phenotype of CMO II clinical variants.

Aldosterone↗
PubMed1992

Effect of one-legged exercise on the strength, power and endurance of the contralateral leg. A randomized, controlled study using isometric and concentric isokinetic training.

The purpose of this investigation was to study the effect of one-legged exercise on the strength, power and endurance of the contralateral leg. The performance of the knee extensor and flexor muscle of 20 healthy young adults (10 men and 10 women) was first tested by Cybex II+ and 340 dynamometers. Then 10 subjects were chosen at random to train using one leg three times a week for 7 weeks whilst the other 10 served as controls. During the 8th week, the tests were repeated. Both quadriceps and hamstring muscles of the trained subjects showed a cross-transfer effect from the trained limb to the untrained side. This concerned the strength and power, as well as endurance characteristics of these muscles. The average change in peak torque of the quadriceps muscle was +19% (P less than 0.001) in the trained limb, +11% (P less than 0.01) in the untrained limb and 0% in the control limbs. In hamstring muscles the changes were +14% (P less than 0.01), +5% and -1%, respectively. Concerning muscle endurance (work performed during the last 5 contractions in the 25-repetition test) the corresponding changes were +15% (P less than 0.01), +7% (P less than 0.01), and -1% in quadriceps muscle, and +17% (P less than 0.05), +7%, and -3% in hamstring muscles. The average strength benefit in the untrained limb was +36% (hamstring muscles) and +58% (quadriceps muscle) of that achieved in the trained limb. Untrained hamstring muscle showed better benefits in the endurance parameters than in strength or power parameters, while in the quadriceps muscle this effect was reversed. A positive relationship was observed between the changes (greater improvement in the trained limb resulted in greater improvement in the untrained limb) (hamstring muscles: r = 0.83, P less than 0.001, quadriceps muscle: r = 0.53, P less than 0.001). In endurance parameters, this relationship was almost linear while in the strength and power parameters the results were more in favour of a curvilinear relationship with limited benefit.

Adult↗
PubMed1992

Using microparticle labeling and counting for attomole-level detection in heterogeneous immunoassay.

A new heterogeneous "sandwich" immunoassay utilizing microparticles as labels to realize high sensitivity is described. In this method, antibody fixed on the microparticles reacts with antigen previously trapped on a microplate surface, which makes the antigen molecules visible and countable with an inverted optical microscope. The method is highly sensitive because the reacted single microparticle, therefore single antigen molecule, can be detected. The sensitivity depends both on the reaction efficiency of the immunoreaction and on nonspecific adsorption of the microparticles on the microplate surface. Therefore, the protocol for preparing microparticle having antibody on the surface and a microplate having capture antibody was investigated to realize high sensitivity. Carboxylated microparticles of 0.76 microns in diameter were conjugated with affinity-purified antibody using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide. It was determined that 1 g microparticles had 880 micrograms antibody (approximately 1100 antibody molecules per 1 microparticle). The immunoreaction efficiency reached 18% at 1 x 10(-13) mol/liter antigen concentration. The lower detection limit was 3.1 x 10(-14) mol/liter (1.6 amol) using human alpha-fetoprotein as a model antigen.

Adsorption↗
PubMed1992

Increased oxidized form of human serum albumin in patients with diabetes mellitus.

High-performance liquid chromatographic (HPLC) analysis of human serum albumin (HSA) on Asahipak GS-520H columns at neutral pH (6.87) showed a clear resolution of human mercaptalbumin (HMA) and nonmercaptalbumin (HNA), which are reduced and oxidized form of HSA, respectively. We studied the conversion of HMA to HNA (mercapt-nonmercapt conversion) as an index of oxidative change of the tissues and organs in 28 normal subjects and in a total of 47 patients with non-insulin dependent diabetes mellitus (NIDDM). Mean (+/- SD) values of the HMA fraction of HSA, f(HMA), [HMA/(HMA + HNA)], was significantly lower in NIDDM patients than in normal subjects (0.63 +/- 0.067 vs 0.75 +/- 0.028, P < 0.001). It was lower in poorly controlled NIDDM patients (0.63 +/- 0.058, n = 20) than in well controlled NIDDM patients (0.67 +/- 0.032, n = 9) (P < 0.05). Plasma glucose values sampled on occasions including overnight fasting and postprandial ones (r = -0.441, n = 47, P < 0.01), but not plasma glucose values sampled on overnight fasting (r = -0.345, n = 29) or postprandial (r = -0.467, n = 18) conditions and HbA1c (r = -0.211, n = 34), negatively correlated with the f(HMA) values, indicating that mercapt-nonmercapt conversion may not be due to cumulative hyperglycemia over a month, but due to short-term alteration in blood glucose level. The presence or absence of diabetic complications including nephropathy, retinopathy and neuropathy did not affect the f(HMA) values. In conclusion, decreased f(HMA) values in the diabetic patients suggested the presence of a rapidly altered oxidative change of albumin due to hyperglycemia.

Adult↗
PubMed1992

Spontaneous oscillation of tension and sarcomere length in skeletal myofibrils. Microscopic measurement and analysis.

We have devised a simple method for measuring tension development of single myofibrils by micromanipulation with a pair of glass micro-needles. The tension was estimated from the deflection of a flexible needle under an inverted phase-contrast microscope equipped with an image processor, so that the tension development is always accompanied by the shortening of the myofibril (auxotonic condition) in the present setup. The advantage of this method is that the measurement of tension (1/30 s for time resolution and about 0.05 micrograms for accuracy of tension measurement; 0.05 microns as a spatial resolution for displacement of the micro-needle) and the observation of sarcomere structure are possible at the same time, and the technique to hold myofibrils, even single myofibrils, is very simple. This method has been applied to study the tension development of glycerinated skeletal myofibrils under the condition where spontaneous oscillation of sarcomeres is induced, i.e., the coexistence of MgATP, MgADP and inorganic phosphate without free Ca2+. Under this condition, we found that the tension of myofibrils spontaneously oscillates accompanied by the oscillation of sarcomere length with a main period of a few seconds; the period was lengthened and shortened with stretch and release of myofibrils. A possible mechanism of the oscillation is discussed.

Animals↗
PubMed1992

Effects of a sustained thromboxane synthase inhibition on exercise-induced changes in eicosanoid formation, catecholamine concentration, and platelet aggregation in humans.

In an effort to characterize an interaction between the eicosanoids and sympathoadrenal system on platelet aggregation, we tried to determine if a sustained thromboxane A2 (TXA2) synthase inhibition would modulate changes in eicosanoid formation, catecholamine concentration, and platelet aggregation induced by a physical stress. We measured thromboxane B2 (TXB2), 11-dehydro-TXB2, 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), norepinephrine, and epinephrine in vivo and platelet aggregation ex vivo before and after a treadmill exercise with and without the oral doses (400 mg twice daily for 7 days) of a new selective TXA2 synthase inhibitor (DP-1904) in nine healthy male subjects. The exercise tests performed on the pretreatment day (day 0) and posttreatment day (day 7) gave a similar result. DP-1904 caused a decrease in serum and urinary TXB2 and urinary 11-dehydro-TXB2 (p less than 0.001 to p less than 0.01) and an increase in serum 6-keto-PGF1 alpha (p less than 0.001 to p less than 0.05) throughout the dosing interval on days 4 and 7. Despite the drug effect on eicosanoid formation at rest and after exercise, the exercise-induced plasma norepinephrine and epinephrine concentrations did not differ between days 0 and 7. The 7-day treatment decreased (p less than 0.01) platelet aggregation induced both by adenosine diphosphate and by collagen at rest. However, the exercise increased (p less than 0.01) platelet aggregation by the two aggregators, resulting in the disappearance of the drug-induced antiaggregatory effects observed at rest. The treatment with a TXA2 synthase inhibitor does not appear to attain the antithrombotic action during an exercise despite the occurrence of a sustained endoperoxide shunting.

6-Ketoprostaglandin F1 alpha↗
PubMed1992

Clinical application of ultrasonic probes in the biliary and pancreatic duct.

The clinical use of an ultrasonic probe with the radial scan transducer in the biliopancreatic ducts is reported in 35 patients with biliopancreatic lesions, including 11 cases of bile duct and 5 of pancreatic carcinoma. Two approaches are available for the intraductal scanning of bile and/or pancreatic ducts. One is the percutaneous insertion via a percutaneous transhepatic biliary fistula established for cholangioscopy. The other approach is the transpapillary insertion of the probe via the working channel of the duodenoscope. Using both approaches, ultrasonographic images of the bile duct wall, pancreas head and neighboring major blood vessels could be observed clearly. The extent of bile duct and pancreatic carcinoma could also be visualized. We believe that intraductal scanning using ultrasonic probes is a promising method in the staging of biliopancreatic malignancy.

Bile Duct Neoplasms↗
PubMed1992

Interactions between interferon gamma, tumour necrosis factor alpha, and interleukin-1 in modulating progesterone and oestradiol production by human luteinized granulosa cells in culture.

We have reported that the cytokines, interleukin-1 (IL-1), tumour necrosis factor alpha (TNF alpha), and interferon (IFN) alpha, beta, and gamma modulate the steroidogenic function of human luteinized granulosa cells in culture. In the present study we examined the interactions between these cytokines in modulating progesterone and oestradiol production by these cells. Neither IL-1 nor TNF alpha had significant effects on human chorionic gonadotrophin (HCG)-stimulated progesterone production, whereas IFN gamma (1-10 ng/ml) significantly reduced HCG-stimulated progesterone production by 26-37%. Concomitant treatment with IL-1 (1 ng/ml) did not further enhance the inhibitory effect of IFN gamma on HCG-stimulated progesterone production. In contrast, the combination of TNF alpha (1 ng/ml) and IFN gamma (10 ng/ml) acted synergistically to markedly inhibit HCG-stimulated progesterone production by 81%. In addition, IL-1 and TNF alpha, neither of which was effective alone, acted synergistically to reduce significantly HCG-stimulated progesterone production by 30%. The combination of TNF alpha and IFN gamma also markedly inhibited follicle stimulating hormone (FSH)-stimulated oestradiol production by 97%, a significantly greater inhibition than that obtained with either cytokine alone. These results suggest that the cytokines may interact to modulate the steroidogenic function of luteal cells in the developing corpus luteum.

Analysis of Variance↗
PubMed1992

Effects of interferon on the steroidogenic functions and proliferation of immature porcine granulosa cells in culture.

Recent studies suggest the relevance of several cytokines to the growth and differentiation of granulosa cells. In the present study, we investigated the effects of interferon (IFN) on the steroidogenic functions and proliferation of immature porcine granulosa cells. Human IFN-alpha inhibited FSH-induced progesterone secretion in a concentration-dependent manner. The effect of IFN-alpha was significant at a concentration as low as 10 pg/ml. Maximal inhibitory concentrations (10-50 ng/ml) of IFN-alpha reduced FSH-induced progesterone secretion by 70%. In contrast, estradiol secretion induced by FSH was significantly enhanced by relatively high concentrations (1-50 ng/ml) of IFN-alpha. IFN-alpha (0.1-10 ng/ml) reduced cAMP generation in response to FSH by as much as 80%, although its effect was not concentration-dependent. The proliferation of cultured granulosa cells was inhibited by IFN-alpha in a concentration-dependent manner. Human IFN-gamma did not affect granulosa cell functions. The stimulation of estradiol secretion and the inhibition of cell proliferation induced by IFN-alpha in cultured porcine granulosa cells in this study are in contrast with the effects of IL-1, which, as we reported previously, inhibited both progesterone and estradiol secretion and stimulated cell growth in these cell cultures. Such differences in the mode of action of cytokines may contribute to the regulation of granulosa cell functions under physiological or pathological conditions.

Analysis of Variance↗