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Biomedical subjects

K Fujiwara

Publications and source records attributed to K Fujiwara.

At least 505 records · Page 28Linked to original sources

[The pharmacokinetics of intraperitoneal (IP) carboplatin (CBDCA) and dose-up study of intravenous (IV) cyclophosphamide (CPM) in combination with IP CBCDA for advanced ovarian cancer patients].

The pharmacokinetics of IP CBDCA was compared with IV CBDCA and a dose-up study of IV CPM was performed in combination with 400 mg/m2 IP CBDCA for advanced ovarian cancer patients. The maximum concentration of free platinum (F-Pt) in serum following IP CBDCA administration was approximately 1/3 that of F-Pt following IV CBDCA. F-Pt in serum remained more than 90% of total platinum following IP CBDCA until 12 hours after administration. The t1/2 of F-Pt in serum after IP CBDCA administration was two times longer when compared with t1/2 following IV CBDCA, showing the slow peritoneal clearance of CBDCA. The area under curve (AUC) following IP CBDCA was approximately 67% of AUC following IV CBDCA. Cumulative urinary secretion (CUS) of platinum following IP CBDCA was 37% of CUS after IV CBDCA. The maximum tolerable dose of IV CPM in combination with 400 mg/m2 IP CBDCA was 550-600 mg/m2. The dose limiting factor of this combination therapy was leukocytopenia. Thrombocytopenia was mild in this study. Combination of 400 mg/m2 IP CBDCA and 550-600 mg/m2 seemed to be a tolerable and repeatable therapy for most patients with advanced ovarian carcinoma. Since thrombocytopenia was mild and the pharmacokinetics showed the smaller AUC of free platinum in serum following IP CBDCA, a dose-up study for IP CBDCA should be considered.

Adenocarcinoma↗

Left main coronary trunk compression by dilated main pulmonary artery in atrial septal defect. Report of three cases.

Narrowing of the left main coronary trunk, which was compressed by the dilated pulmonary artery, was associated with atrial septal defect in three adults. One of them had severe pulmonary hypertension. Coronary angiograms revealed localized narrowing of the left main coronary trunk, and the left main coronary trunk had a concave shape. No stenosis of other coronary arteries was observed. In all patients the atrial septal defect was closed with a polytetrafluoroethylene patch. In the patient with 75% narrowing of the left main coronary trunk, aorta-coronary bypass was performed; it was not performed in the two with 50% narrowing. In two survivors postoperative coronary angiograms showed that the narrowing of the left main coronary trunk improved or disappeared. These results suggest that markedly dilated pulmonary arteries easily compress the left main coronary trunk and cause narrowing, which improves after atrial septal defect closure.

Constriction, Pathologic↗

[The superior approach technique for total anomalous pulmonary venous return (type I b)].

Two infants with total anomalous pulmonary venous return (type I b) were operated on successfully through the superior approach. The technique of anastomosis was designed for making large anastomosis between the common pulmonary vein and left atrium according to each pattern of pulmonary venous drainage. In these patients, the angiocardiogram at one year after the operation showed no stenosis between pulmonary vein and left atrium and electrocardiogram revealed no arrhythmias, postoperatively. The operative procedures which used in these patients are described.

Anastomosis, Surgical↗

[Total correction of truncus arteriosus with severe truncal valve insufficiency in neonate].

The prognosis of infants with truncus arteriosus associated with severe truncal valve insufficiency is quite poor. Total correction was successfully performed in a neonate with such a complicated anomaly. The patient was 21 days old female with anuria due to severe congestive heart failure preoperatively in spite of medical treatment. She underwent Rastelli operation and pulmonary artery was reconstructed using autologous pericardial 3 valved conduit. Truncal valve was 4 cusps with the malformed nodular margins and one cusp had cleft. This cleft was closed suturing the cleft cusp and adjacent cusp each other and annuloplasty was added in 4 commissures. She survived and her truncal valve insufficiency was still mild at 2 years post-operative period. Although total correction with truncal valve repair for such a severely ill neonate and young infant with truncus arteriosus as this patient has not been reported, our experience suggests that severe truncal valve insufficiency could be fairly well repaired by valvulo-annuloplasty.

Cardiac Surgical Procedures↗

Glycine cleavage system in astrocytes.

The localization of the glycine cleavage system was examined in the rat brain by immunohistochemistry using an antibody to P-protein (a constituent of the system). In all sites studied, the enzyme was confined to the astrocytes. The intensity of astrocyte staining varied in different brain regions, with the strongest staining being noted in the hippocampus, the cerebellar cortex, the Bergmann glia in the cerebellum and the Muller cells in the retina. The weakest staining was seen in the brainstem and spinal cord. P-protein was found to be located in the mitochondria by an ultrastructual study.

Aminomethyltransferase↗

Lipoylation of H-protein of the glycine cleavage system. The effect of site-directed mutagenesis of amino acid residues around the lipoyllysine residue on the lipoate attachment.

H-protein of the glycine cleavage system has lipoic acid on the Lys59 residue. Comparison of amino acid sequences around the lipoate attachment site of H-proteins from various sources and acyltransferases of alpha-keto acid dehydrogenase complexes indicated that Gly43, Glu56, Glu63 and Gly70 of bovine H-protein are highly conserved among these proteins. Modification of these conserved residues by site-directed mutagenesis indicated that Glu56 and Gly70 are important for the lipoylation of H-protein and suggested that the proper conformation around the lipoic acid attachment site is required for the association of H-protein to the enzyme responsible for the lipoylation.

Amino Acid Oxidoreductases↗

The primary structure of human H-protein of the glycine cleavage system deduced by cDNA cloning.

A full-length cDNA encoding the human H-protein of the glycine cleavage system has been isolated from a lambda gt11 human fetal liver cDNA library. The cDNA insert was 1091 base pairs with an open reading frame of 519 base pairs which encoded a 125-amino acid mature human H-protein with a 48-amino acid presequence. Human H-protein is 97%, 86%, and 46% identical to the bovine, chicken, and pea H-protein, respectively.

Amino Acid Oxidoreductases↗

Isolation and sequence determination of cDNA encoding T-protein of the glycine cleavage system.

T-protein is a component of the glycine cleavage system and catalyzes the tetrahydrofolate-dependent reaction. A partial cDNA for chicken T-protein was isolated by screening a chicken liver cDNA library with oligonucleotide probes based on amino acid sequences. The clone (CT5C) contains a 675-base pair insert encoding the C-terminal half of the T-protein. Screening of a bovine liver lambda gt10 cDNA library with the insert of CT5C as a probe detected a clone, BT5A, with an insert of about 2 kilobase pairs. The 1191-base pair coding region encodes a precursor protein of 397 amino acids (Mr 42,852) comprised of a 22-residue mitochondrial targeting sequence and a 375-residue mature protein (Mr 40,534). The 33 amino acids immediately following the targeting sequence correspond exactly to those determined by sequence analysis of the amino terminus of the purified bovine T-protein. The mature protein contains several hydrophilic segments with a cluster of arginine and lysine. The T-protein cDNA probe hybridized to an mRNA species of about 2 kilobases in bovine brain, lung, heart, and liver. A probe for H-protein hybridized with two species of mRNA in these tissues and weak signals were also found in spleen. Although the enzymatic activities of T-protein and H-protein were found in these tissues where transcripts were found, activity of P-protein was detected only in liver and brain. Southern blot analysis of genomic DNA suggested that T-protein is a single copy gene.

Amino Acid Sequence↗

Plasma thrombin-antithrombin III complexes in the diagnosis of primary hepatocellular carcinoma complicating liver cirrhosis.

Detection of hypercoagulable state might be helpful in the diagnosis of primary hepatocellular carcinoma (HCC) complicating liver cirrhosis (LC). Plasma levels of thrombin-antithrombin III complex (TAT) were determined in 50 patients of LC with or without HCC. The levels were above 2 ng/ml in 80% of 25 HCC patients, but only in 12% of 25 non-HCC patients (P less than 0.01). The levels over 2 ng/ml occurred even in five of six HCC patients whose serum alpha-fetoprotein levels were below 20 ng/ml as well as in two of three patients with HCC less than 2 cm in diameter. Those levels in HCC patients were significantly decreased within 8 days after treatment with transcatheter arterial embolization or infusion of antitumor agents, without affecting plasma antithrombin III levels. These results suggest that plasma TAT levels may be useful in the diagnosis of HCC complicating LC.

Aged↗

Local structures in unfolded lysozyme and correlation with secondary structures in the native conformation: helix-forming or -breaking propensity of peptide segments.

CD spectra of reduced and S-3-(trimethylated amino) propylated lysozyme (TMAP lysozyme) have been measured in various solutions containing guanidine hydrochloride or trifluoroethanol (TFE). The CD spectra indicate that there remain residual secondary structures in protein in aqueous solution. The addition of TFE further promotes the formation of secondary structures. In order to examine whether secondary structures are evenly induced over all the polypeptide chain, or locally at particular segments, the limited proteolysis of TMAP lysozyme by trypsin has been performed, and the CD spectra of all the final and intermediate products have been observed in solutions containing TFE. As a result, the fragments vary in a helix-forming propensity. The CD spectra of peptide fragments T5, T7, T9T10, T12T13, T14T15T16, and T17T18 are not significantly affected by the addition of TFE, where T refers to the nomenclature of R.E. Canfield [(1963), Journal of Biological Chemistry, Vol. 238, pp. 2691-2697]. They are fragments of a helix-breaking propensity. On the other hand, fragment I2 composed of T1-T4, and fragments T6T7, T8, and T11, attain secondary structures with the addition of TFE. They are fragments of a helix-forming propensity. Further, it is found that the fragments of a helix-forming propensity just correspond to the helical segments in native lysozyme. We examine the interactions between neighboring fragments, which contribute to the stabilization of local structures along the polypeptide chain.

Amino Acids↗

Stimulation of putrescine production by epidermal growth factor in rat liver after partial hepatectomy.

When epidermal growth factor was given to rats after partial hepatectomy, hepatic putrescine content was significantly increased at 4, 6 and 10 hr compared with control rats. Ornithine decarboxylase activity was also increased. Hepatic ornithine decarboxylase messenger RNA content was significantly greater than control levels at 2 hr after epidermal growth factor treatment, but not at 10 hr, when the amount of ornithine decarboxylase messenger RNA in control animals was four times that at 2 hr. When actinomycin D was administered 6 hr after partial hepatectomy, hepatic ornithine decarboxylase activity at 10 hr was reduced to half the control levels. This reduction was attenuated by epidermal growth factor treatment at 6 and 8 hr. Hepatic immunoreactive ornithine decarboxylase protein content showed a highly positive correlation with hepatic ornithine decarboxylase activity at 4, 6 and 10 hr, irrespective of epidermal growth factor treatment. Hepatic spermidine N1-acetyltransferase activity was significantly increased at 6 hr compared with control rats. These results suggest that, after partial hepatectomy in rats, exogenous epidermal growth factor may stimulate hepatic putrescine production by increasing ornithine decarboxylase messenger RNA content and altering posttranscriptional ornithine decarboxylase regulation, as well as enhancing spermidine N1-acetyltransferase activity.

Acetyltransferases↗

Insulin and glucagon therapy of acute hepatic failure.

When insulin and glucagon are administered to rats with severe liver injury, survival is enhanced with an attenuation of the liver injury compared to that of untreated controls. In rats with acute liver injury both hormones produce a rapid normalization of hepatic protein content following initiation of DNA synthesis. When rats receive both hormones after partial hepatectomy, the first burst of DNA synthesis reaches a maximum earlier than that seen in controls. Both hormones enhance the increment of hepatic putrescine essential for DNA synthesis through activation of ornithine decaroxylase and/or spermidine-N1-acetyltransferase. The enhancement of putrescine content by each hormone is additive. Putrescine supplementation promotes hepatic DNA synthesis after hepatectomy. Based on these data, we conclude that a combination of insulin and glucagon is effective in the therapy of acute hepatic failure in rats. The restoration of liver function as well as the stimulation of liver cell proliferation via putrescine production may contribute to this effect.

Acetyltransferases↗