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Biomedical subjects

K Nishida

Publications and source records attributed to K Nishida.

At least 343 records · Page 19Linked to original sources

[Pulmonary venous obstruction after repair of total anomalous pulmonary venous drainage: report of a case with reoperation].

A 8-month-old infant with Darling' type Ib of total anomalous pulmonary venous drainage underwent surgical correction. Common pulmonary vein drained into superior vena cava. Pulmonary venous channel was constructed between orifice of common pulmonary vein and atrial septal defect (ASD) with pericardial baffle drainage. Pulmonary venous obstruction occurred at the site of ASD and pericardial baffle was atrophic. ASD was enlarged and new pulmonary venous channel was reconstructed with EPTFE graft. Post-reoperative clinical course was uneventful.

Female↗

Preventive effect of gamma-glutamylcysteinylethyl ester on immunological cell injury in isolated rat hepatocytes with anti-rat liver plasma membrane antiserum treatment.

We studied the mechanism by which gamma-glutamylcysteinylethyl ester (gamma-GCE), which is rapidly transported into hepatocytes and converted to reduced glutathione (GSH), prevents immunological hepatic injury. The effect of gamma-GCE on cell injury, as estimated by release of transaminases from cells, and changes in phospholipase A2 (PLA2) activity and of GSH, Ca2+, and lipid peroxide (LPO) contents were examined in isolated rat hepatocytes treated with anti-rat liver plasma membrane rabbit antiserum (ALPMA) and compared with that of GSH. gamma-GCE prevented not only the release of transaminases from hepatocytes treated with ALPMA but also a decrease in GSH content, activation of PLA2, and increases in Ca2+ and LPO contents in the damaged hepatocytes. However, the preventive effect of GSH on these changes was weaker than that of gamma-GCE. In addition, gamma-GCE prevented the development of cell injury in ALPMA-pretreated hepatocytes. These results suggest that gamma-GCE prevents immunological cell injury in ALPMA-treated rat hepatocytes mainly by maintaining the integrity of the plasma membrane through its conversion to GSH within the cells.

Alanine Transaminase↗

[Transforming growth factor-beta (TGF-beta) inhibits epithelial wound healing of organ-cultured rabbit cornea].

Transforming growth factor-beta (TGF-beta) is a unique polypeptide growth factor which has been found to stimulate mesenchymal cell proliferation and inhibit epithelial cell growth. Whether or not TGF-beta inhibits corneal epithelial wound closure remains controversial. This study evaluated the effects of TGF-beta on corneal epithelial wound healing in vitro. Rabbit corneas with an artificial 8 mm epithelial defect were organ-cultured for 48 hr in TC-199 supplemented with TGF-beta (100 pg/ml, 1 ng/ml, or 10 ng/ml). The contralateral eye served as control. TGF-beta at 1 ng/ml and 10 ng/ml concentrations showed significant decrease in wound-healing rate compared with the control. 5-bromo-2'-deoxyuridine-immunohistochemistry showed a significant decrease in S-phase cell count in the 1 ng/ml group compared with the control. These results strongly suggest that TGF-beta inhibits corneal epithelial wound healing.

Animals↗

[Change in levels of specific terminal sugar residues of glycoproteins in sera of patients with malignant tumor].

Serum sialic acid (N-acetylneuraminic acid, NANA) levels significantly increased in all of patients with stomach cancer, colo-rectal cancer, breast cancer and pancreas cancer. However, the positive rate for serum NANA levels was 35 approximately 60% in these diseases. In contrast, a significant increase in serum NANA-galactose (NANA-Gal) levels was found in only stomach cancer and colo-rectal cancer; especially, the positive rate for serum NANA-Gal levels was 77% in colo-rectal cancer. In colo-rectal cancer, increased serum NANA-Gal levels were decreased after operation. But, in patients with colo-rectal cancer, changes in serum NANA levels following operation were variable. These results indicate that the assay of serum NANA-Gal level provides more important clinical significances for the specificity of cancer and the change of its status than that of serum NANA level.

Biomarkers, Tumor↗

[Acute massive pulmonary embolism--report of a case].

A 72-year-old female, who had received medication for hypertension and angina pectoris was hospitalized with complaining of an abrupt dyspnea. Roentgenogram of the chest revealed no abnormal findings except cardiac enlargement. An electrocardiogram showed overloading of the right ventricle. Arterial blood gas analysis of room air showed 55.4 mmHg of PaO2, 25.5 mmHg of PaCO2 and 7.30 of PH, respectively. Acute and massive pulmonary embolism was diagnosed by an emergent pulmonary arteriography. Despite intensive treatment such as infusion of urokinase and heparin for four days, thrombus was still detected in the left main pulmonary artery by a transesophageal echocardiography. By the result of ineffective conservative therapy, embolectomy was performed under cardiopulmonary bypass. However mechanical respiratory support was required for a long time due to the right heart failure, she is doing well for a year after the operation.

Aged↗

[A combined sulbactam/cefoperazone and amikacin therapy for the treatment of infections complicated with hematological diseases].

Eighty-six patients with infections associated with hematological disorders were treated with sulbactam/cefoperazone (SBT/CPZ) and amikacin (AMK). Among 71 evaluable cases, 30 cases had acute non-lymphocytic leukemia, 3 acute lymphoblastic leukemia, 25 malignant lymphoma, and 7 myelodysplastic syndrome as underlying diseases. Excellent responses were obtained in 33 cases (46.5%) and good responses in 14 cases (19.7%), with an overall efficacy rate of 66.2%. The efficacy rate among cases with suspected sepsis was 72.5%. This treatment was also effective in 69.2% of cases in which neutrophil counts were less than 500/microliter through the course of administration. The eradication rate was 83.3% among 6 strains in which Gram-negative rods were detected. Side effects were minimum; skin rash in 1 case, slight elevation of APTT in 3 and slight elevation of total bilirubin in 1. Thus, this combination antibacterial chemotherapy is an effective and safe regimen for the treatment of severe infections in patients with hematological disorders.

Adult↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗