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Biomedical subjects

K Nishida

Publications and source records attributed to K Nishida.

At least 19 recordsLinked to original sources
PubMed1992

Insulin-dependent formation of a complex containing an 85-kDa subunit of phosphatidylinositol 3-kinase and tyrosine-phosphorylated insulin receptor substrate 1.

Monoclonal antibodies raised against the 85-kDa subunit (p85) of bovine phosphatidylinositol (PI) 3-kinase were found to recognize uncomplexed p85 or p85 in the active PI 3-kinase. Immunoprecipitation studies of Chinese hamster ovary cells, which overexpress the human insulin receptor when treated with insulin, showed increased amounts of p85 and PI 3-kinase activity immunoprecipitable with monoclonal anti-p85 antibody and no increase in the tyrosine phosphorylation of p85. Insulin also induced an association of p85 with the tyrosine-phosphorylated insulin receptor substrate 1 (IRS-1) and other phosphorylated proteins ranging in size from 100 to 170 kDa but not with the activated insulin receptor. In vitro reconstitution studies were used to show p85 in the active PI 3-kinase associated with the tyrosine-phosphorylated IRS-1 but not with the activated insulin receptor. Competition studies using synthetic phosphopeptides corresponding to potential tyrosine phosphorylation sites of IRS-1 revealed that phosphopeptides containing YMXM motifs inhibited this association with different potencies, whereas nonphosphorylated analogues and a phosphopeptide containing the EYYE motif had no effect. Src homology region 2 domains of p85 expressed as glutathione S-transferase fusion proteins also bound to tyrosine-phosphorylated IRS-1. These results suggest that insulin causes the association of PI 3-kinase with IRS-1 via phosphorylated YMXM motifs of IRS-1 and Src homology region 2 domains of p85.

Amino Acid Sequence↗
PubMed1992

Anaplastic ganglioglioma of the brain stem demonstrating active neurosecretory features of neoplastic neuronal cells.

An autopsy case of anaplastic ganglioglioma in the brain stem of a 12-year-old girl is reported. The ill-defined tumor involved the right cerebellar peduncle, medulla oblongata and upper cervical spinal cord, and showed mixed proliferation of many ganglioid cells and atypical pilocytic astrocytes with necrotic areas. Immunohistochemical studies revealed the presence of chromogranin A in most ganglioid cells and of metenkephalin in some large ganglioid cells. Glial cells were positive for glial fibrillary acidic protein and vimentin. Ultrastructurally, numerous dense-core granules of 90-220 nm in diameter were demonstrated in ganglioid cells and abundant glial filaments in glial cells. High neurosecretory activity in neuronal cells, suggested by chromogranin-immunoreactivity and dense-core granules, seems to be the most characteristic property of ganglion cell tumors.

Brain Neoplasms↗
PubMed1992

Na+/K(+)-ATPase activity and its alpha II subunit gene expression in rat skeletal muscle: influence of diabetes, fasting, and refeeding.

We have examined the effects of diabetes, fasting, and refeeding on Na+/K(+)-adenosine triphosphatase (ATPase) activity and its catalytic alpha II subunit gene expression in skeletal muscle. Two hypoinsulinemic states, streptozotocin-induced diabetes and 48-hour fasting caused a significant decrease (P less than .05) in skeletal muscle Na+/K(+)-ATPase activity and a marked increase (P less than .01) in the levels of alpha II subunit mRNA. A decrease in enzyme activity was observed on the 2nd and the 14th day of diabetes, whereas an increase in alpha II mRNA levels was found only on the 14th day. The levels of alpha I mRNA were not affected, while the levels of mRNA of the structural beta subunit were decreased on the 14th day of diabetes. Correction of hyperglycemia with insulin restored enzyme activity and alpha II isoform mRNA levels toward normal in diabetic animals. Refeeding for 48 or 72 hours restored these parameters to normal in skeletal muscle of previously fasting rats. These observations suggest that a decrease in muscle Na+/K(+)-ATPase activity may lead to a compensatory increase in its alpha II subunit gene expression. The levels of insulin and not of glycemia appear to be critical in modulating Na+/K(+)-ATPase activity and gene expression.

Animals↗
PubMed1992

A case of ectopic opening of vasa deferentia into müllerian duct cyst.

We report very rare case in which the vasa deferentia entered a large Müllerian duct cyst in a 4-month-old infant. The presenting findings were lower abdominal mass and the complaint of urinary retention. A computed tomography scan of the pelvis showed a monolocular cystic mass between the bladder and the rectum. Surgical removal of the cyst was done because the mass increased in size and both hydronephroses and hydroureters were getting worse despite the use of antibiotics. The patient has no urological difficulty after the operation. This case was characterized as follows: the cyst was located on the midline, the vasa entered the cyst directly, the size of the cyst was large, and it was not associated with other malformations of the genitourinary system.

Choristoma↗
PubMed1992

Development of a prodrug of salicylic acid, salicylic acid-L-alanine conjugate, utilizing hydrolysis by rabbit intestinal microorganisms.

The hydrolysis of salicylic acid-L-alanine conjugate (salicyl-L-alanine) following oral, intravenous, intracaecal and rectal administration (60, 10, 5 and 5 mg kg-1, respectively: salicylic acid equivalent) was examined in rabbits. Salicylic acid was detected in the blood 2 h after oral administration of salicyl-L-alanine and reached a maximum concentration at 10 h, whereas salicyl-L-alanine was rapidly eliminated. In contrast, unchanged salicyl-L-alanine only was found following intravenous administration of salicyl-L-alanine, suggesting that presystemic de-conjugation of salicyl-L-alanine was involved. The intestinal mucosal de-conjugation of salicyl-L-alanine was not recognized in the in-situ intestinal sac preparation with complete mesenteric venous blood collection. Immediate and very extensive salicylic acid formation in the caecum was found following intracaecal administration of salicyl-L-alanine. After oral pretreatment of rabbits with kanamycin sulphate, a significant inhibition of salicylic acid formation following intracaecal administration of salicyl-L-alanine was observed, indicating that the intestinal microorganisms were responsible for the biotransformation of salicyl-L-alanine. In-vitro incubation of salicyl-L-alanine with gut contents showed that the major source of its hydrolysis was the hind gut. Consequently, the blood concentration of salicylic acid was prolonged extensively following rectal administration of salicyl-L-alanine, suggesting the usefulness of salicyl-L-alanine as a prodrug of salicylic acid.

Administration, Oral↗
PubMed1992

A novel prodrug of salicylic acid, salicylic acid-glycylglycine conjugate, utilizing the hydrolysis in rabbit intestinal microorganisms.

The hydrolysis of salicylic acid-glycylglycine conjugate (salicyl-glycylglycine) following oral, intravenous, intracaecal and rectal administration (434, 72, 36 and 36 mumol kg-1, respectively: equivalent to salicylic acid) was examined in rabbits to develop a novel prodrug of salicylic acid. Salicylic acid was detected in the blood 2 h after oral administration of salicyl-glycylglycine and it reached a maximum level (55.6 micrograms mL-1) at 15 h, whereas a small amount of salicyl-glycylglycine was found in the blood. In contrast, unchanged salicyl-glycylglycine was found mainly in the blood following its intravenous administration, suggesting the involvement of presystemic deconjugation in the hydrolysis of salicyl-glycylglycine. Immediate and very extensive salicyclic acid formation in the caecum was observed following intracaecal administration of salicyl-glycylglycine, suggesting that the intestinal microorganisms were responsible for the biotransformation of this compound. In-vitro incubation of salicyl-glycylglycine with caecal content showed that salicyl-glycylglycine was hydrolysed efficiently in the caecum. Consequently, the blood concentration of salicylic acid was prolonged extensively following rectal administration of salicyl-glycylglycine, indicating the usefulness of salicyl-glycylglycine as a prodrug of salicylic acid.

Administration, Oral↗
PubMed1992

Molecular cloning and characterization of the constitutive bovine aortic endothelial cell nitric oxide synthase.

The constitutive endothelial cell nitric oxide synthase (NOS) importantly regulates vascular homeostasis. To gain understanding of this enzyme, a pEF BOS cDNA library of 5 x 10(5) clones was prepared from bovine aortic endothelial cells (BAEC) and screened with a 2.8-kb cDNA BamHI fragment of rat brain NOS. Clone pBOS13 was found to express NO synthase activity when transfected into COS-7 cells. Sequence analysis revealed sequences compatible with binding domains for calcium/calmodulin, flavin mononucleotide, flavin adenine nucleotide and NADPH. The deduced amino acid sequence revealed a protein with a relative mol mass of 133,286, which is 58% homologous to the rat cerebellar NOS and 51% homologous to the mouse macrophage NOS. The amino-terminal portion of the protein exhibits several characteristics peculiar to the endothelial cell NOS. These include a proline-rich region and several potential sites for proline-directed phosphorylation as well as a potential substrate site for acyl transferase. Northern hybridization to mRNA from cultured BAEC revealed an abundant 4.8-kb message, which was not increased by coincubation with tumor necrosis factor alpha, but was markedly increased by exposure to shear stress for 24 h. The unique features of the endothelial cell NO synthase, particularly in the amino terminal portion of the molecule, may provide for novel regulatory influences of enzyme activity and localization.

Amino Acid Oxidoreductases↗
PubMed1992

An assessment of mucosal damage in vivo: effect of oral pretreatment with 5-fluorouracil on the intestinal first-pass metabolism of salicylamide in rabbits.

An assessment of 5-fluorouracil (5-FU)-induced mucosal damage in vivo by measuring the metabolism of salicylamide (SAM) was investigated in rabbit intestine. The mucosal damage in the intestine 48 h after oral administration of 5-FU (30 mg/kg) was examined using a scanning electron microscope. By the oral pretreatment with 5-FU, the morphological changes of jejunal and ileal mucosa were recognized compared with the control. The intestinal first-pass metabolism of SAM was studied using in situ intestinal sacs with complete mesenteric venous blood collection. The appearance of both SAM and its metabolites into the mesenteric venous blood was measured directly by cannulating the mesenteric vein of exposed intestine and collecting all venous blood draining from the absorbing region. Following oral pretreatment with 5-FU, the appearance of SAM glucuronide (SAMG) in the mesenteric venous blood was significantly increased. The increased blood concentration of SAMG following intraduodenal administration of SAM in vivo was observed in rabbits pretreated with 5-FU orally. However, the blood concentration of SAMG after intravenous administration of SAM was not increased compared with the control. These findings suggest that the change in intestinal first-pass metabolism of SAM may be due to the intestinal mucosal damage by oral pretreatment with 5-FU. The alteration of intestinal first-pass metabolism of a marker compound may be utilized for the assessment of intestinal mucosal damage in vivo.

Administration, Oral↗
PubMed1992

An assessment of indomethacin-induced mucosal damage in vivo by measuring the metabolism of salicylamide in rabbit intestine.

Indomethacin-induced mucosal damage was assessed in vivo by measuring salicylamide (SAM) metabolism in rabbit intestine. Intestinal mucosal damage 48 h after oral indomethacin (500 mg/kg) administration was examined using a scanning electron microscope. Duodenal, jejunal and ileal mucosal toxicity was compared with that in controls. Intestinal first-pass metabolism of SAM was studied using in situ intestinal sacs with intact mesenteric venous blood collection. The appearance of both SAM and its metabolites in the mesenteric venous blood was measured following cannulation of the mesenteric vein of the exposed intestine and collecting all venous blood draining from the absorbing region. Following oral pretreatment with indomethacin, the appearance of SAM and SAM glucuronide (SAMG) in the mesenteric venous blood was significantly increased. The concentrations of SAM and SAMG in the blood increased following intraduodenal administration of SAM in vivo in rabbits orally pretreated with indomethacin compared with controls. However, after intravenous administration of SAM, the blood concentration of SAM and SAMG was not increased compared with controls. These findings suggest that the differences in intestinal first-pass metabolism of SAM may be due to the intestinal mucosal damage induced by oral indomethacin pretreatment. The results indicate that the alteration of intestinal first-pass metabolism of a marker compound may be utilized to assess intestinal mucosal damage in vivo.

Animals↗
PubMed1992

A novel prodrug of salicylic acid, salicylic acid-glutamic acid conjugate utilizing hydrolysis in rabbit intestinal microorganisms.

The fate of salicylic acid-glutamic acid conjugate (salicyl-glutamic acid) following oral, intravenous, intracecal and rectal administration (60, 10, 5 and 5 mg/kg, respectively: salicylic acid equivalent) was examined in rabbits. Salicylic acid was detected in the blood 2 h after oral administration of salicyl-glutamic acid and it reached the maximum level (69.4 micrograms/ml) at 18 h after the dose. A high blood concentration of salicylic acid (24.8 micrograms/ml) was observed up to 36 h. But only a small amount of salicyl-glutamic acid was detected in the blood (less than 2.5 micrograms/ml, as salicylic acid). In contrast, unchanged salicyl-glutamic acid was found mainly in the blood following intravenous administration of salicyl-glutamic acid, suggesting that presystemic de-conjugation of salicyl-glutamic acid predominantly occurred. The intestinal mucosal de-conjugation of salicyl-glutamic acid was negligible in the in situ intestinal sac preparation with complete mesenteric venous blood collection. Immediate and very extensive salicylic acid formation in the cecum was found following intracecal administration of salicyl-glutamic acid. After oral pretreatment of rabbits with kanamycin sulfate (6 x 400 mg), a significant inhibition of salicylic acid formation following intracecal administration of salicyl-glutamic acid was observed, indicating that the intestinal microorganisms were responsible for the biotransformation of salicyl-glutamic acid. Also, in vitro incubation of salicyl-glutamic acid with gut contents showed that the primary location of hydrolysis was the hind gut.

Animals↗
PubMed1992

Effect of oral pretreatment with antibiotics on the hydrolysis of salicylic acid-tyrosine and salicylic acid-methionine prodrugs in rabbit intestinal microorganisms.

We examined the hydrolysis mechanism of salicylic acid-tyrosine (salicyl-tyrosine) and salicylic acid-methionine conjugate (salicyl-methionine) in rabbits by exploring their behavior following intraduodenal and intracecal administration (72 and 36 mumol/kg, respectively: salicylic acid equivalent). A large amount of salicyl-methionine was absorbed following intraduodenal administration of salicyl-methionine, without being metabolized to salicylic acid in the small intestinal mucosa. On the contrary, salicylic acid was detected in the blood following intraduodenal administration of salicyl-tyrosine, suggesting that salicyl-tyrosine was metabolized in the small intestinal mucosa. After oral pretreatment of rabbits with kanamycin sulfate (6 x 400 mg) or tinidazole (6 x 160 mg), the hydrolysis of salicyl-tyrosine and salicyl-methionine following intracecal administration was inhibited significantly, indicating that the intestinal microorganisms were responsible for the biotransformation of these prodrugs. Furthermore, in rabbits orally pretreated with both kanamycin sulfate and tinidazole, a significant inhibition of salicylic acid formation from salicyl-tyrosine and salicyl-methionine following intracecal administration was observed.

Animals↗
PubMed1992

Unequal hydrolysis of salicylic acid-D-alanine and salicylic acid-L-alanine conjugate in rabbit intestinal microorganisms.

The behavior of salicylic acid-D-alanine conjugate (salicyl-D-alanine) following intravenous, oral and intracecal administration was examined in rabbits, then compared with that of salicylic acid-L-alanine conjugate (salicyl-L-alanine) as reported previously. Following intravenous administration, salicyl-D-alanine eliminated rapidly from the blood, and its blood concentration was almost identical with that of salicyl-L-alanine. In both cases, salicylic acid could not be detected in the blood, indicating that systemic de-conjugation of D-alanine might not occur. Unchanged salicyl-D-alanine was found in the blood mainly following oral and intracecal administration of salicyl-D-alanine. On the other hand, salicylic acid formed extensively following oral and intracecal administration of salicyl-L-alanine, suggesting that the presystemic de-conjugation of D-alanine and L-alanine was unequal. Furthermore, in vitro incubation of salicyl-D-alanine with cecal content, in which the major source of salicyl-L-alanine hydrolysis is found, showed that the hydrolysis of salicyl-D-alanine was negligible in rabbit intestinal microorganisms.

Administration, Oral↗
PubMed1992

An assessment of salicylic acid-induced mucosal damage in vivo by measuring the metabolism of salicylamide in rabbit intestine.

An assessment of salicylic acid-induced mucosal damage in vivo by measuring the metabolism of salicylamide (SAM) was investigated in rabbit intestine. The intestinal first-pass metabolism of SAM was studied using in situ intestinal sacs with complete mesenteric venous blood collection. The appearance of both SAM and its metabolites into the mesenteric venous blood was measured directly by cannulating the mesenteric vein of exposed intestine and collecting all venous blood draining from the absorbing region. Following oral pretreatment with salicylic acid, the appearance of SAM glucuronide (SAMG) in the mesenteric venous blood was significantly increased compared with the control. The increased blood concentration of SAMG following intraduodenal administration of SAM in vivo was observed in rabbits pretreated with salicylic acid orally. The blood concentration of SAMG after the intravenous administration of SAM was not increased compared with the control. We suggest that the change in the intestinal first-pass metabolism of SAM may be due to the intestinal mucosal damage induced by oral pretreatment with salicylic acid. The measurement of SAM metabolites may be of value in the assessment of intestinal mucosal damage in vivo.

Animals↗
PubMed1992

Characteristics of physiological tremor in five fingers and evaluations of fatigue of fingers in typing.

Physiological tremor, which is the invisible mechanical vibration of body part, was measured for five fingers. It was obtained that the power spectrum always has two peaks at 10 and 25Hz for each of the five fingers. The peaks were considered to be generated in the following two loop systems: The component of the lower frequency originated from the central nervous system as a long loop, and that of the higher frequency originated from the muscle-spine loop system as a short loop. The total power, which was the sum of power spectra ranging from 1.5 to 50Hz, was defined as an evaluation index, and it showed characteristic results for the five fingers. The muscular load produced by two hours of typing work was responsible mainly for the increase of total power and for the change of peak frequencies. The mechanism for the change of the power spectrum due to muscular load was well explained by the two-loop theory. It was found that the fatigue of the fingers due to muscular load could be evaluated by the total power.

Adult↗
PubMed1992

Familial primary hyperparathyroidism: study of the pedigree in three generations.

The familial occurrence of primary hyperparathyroidism in which the proband is a 55-year-old man is reported. His 58-year-old sister and 40-year-old brother had undergone partial parathyroidectomy, and histological examination revealed hyperplasia in both cases. Their father and a daughter of the proband had a history of nephrolithiasis. The three siblings showed high levels of plasma parathyroid hormone (even the two postoperative cases). All of them had a history of nephrolithiasis and peptic ulcers. In the proband, image studies did not reveal any abnormality in the neck region. At present, the three cases do not exhibit any abnormalities in the pancreas or the pituitary by imaging studies and endocrine tests.

Adult↗
PubMed1992

[Upper gastrointestinal bleeding in the elderly].

Due to increasing number of the elderly, cases of hematemesis and melena in the aged have been increasing. The authors evaluated 69 such cases over 60 years old in whom emergency endoscopy of the upper digestive tract was carried out because of hematemesis and melena. Twenty cases are diagnosed as gastric ulcer (29%), 12 cases as esophageal ulcer and esophageal erosion (17.4%), 9 as duodenal ulcer (13.0%), 7 as gastric cancer (10.1%), 6 as Mallory-Weiss syndrome (8.7%), 6 as esophageal and gastric varices (8.7%), 4 as acute hemorrhagic gastritis (5.8%), 3 as Dieulafoy's ulcer (4.3%), and one case each of chronic pancreatitis (hemosuccus pancreaticus) and hemorrhage due to gastric angiodysplasia (1.4%). Of these cases, blood transfusion was performed in 46 cases (66.7%), and shock occurred in 27 cases (39.1%). The endoscopical hemostatic procedure was effective for detection of underlying diseases in the aged. Surgery was often impossible because of the rapid deterioration of the systemic condition due to the hemorrhage of the digestive tract.

Aged↗