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Biomedical subjects

T Kashiwagi

Publications and source records attributed to T Kashiwagi.

At least 19 recordsLinked to original sources

Increased plasma adrenomedullin in acute myocardial infarction.

Adrenomedullin has a potent vasodilating effect comparable to that of calcitonin gene-related peptide. To investigate the pathophysiologic role of endogenous adrenomedullin, we determined sequentially the plasma adrenomedullin level in 15 consecutive patients with acute myocardial infarction (AMI). Plasma adrenomedullin was higher immediately after the onset of AMI and decreased gradually; plasma levels during the 3-week period after the AMI were higher than plasma levels in 15 healthy control subjects (p < 0.001), with higher levels in patients with congestive heart failure than in patients without congestive heart failure throughout the period of the study (p < 0.05). Plasma adrenomedullin was positively correlated with pulmonary capillary wedge pressure, pulmonary arterial pressure, right atrial pressure, and heart rate in the early stage of AMI. These findings suggest that the elevation of plasma adrenomedullin is related to the retention of body fluid volume, the enhancement of sympathetic activity, and/or the elevation of pressure in pulmonary vascular beds. Adrenomedullin may act against excessive vasoconstrictors increased in AMI.

Adrenomedullin

Changes in serum fibrogenesis markers during interferon therapy for chronic hepatitis type C.

We serially measured the levels of serum N-terminal peptide of type III procollagen (PIIINP), the 7S domain of type IV collagen (IV-7S), and hyaluronate (HA) before (0 month), at the end (6 months), and 24 weeks after the end of interferon therapy (12 months) in patients with chronic hepatitis type C to estimate the effects of interferon alfa (IFN-alpha) on serum levels of hepatic fibrogenesis markers. One hundred twenty-one patients with chronic hepatitis type C received intramuscular injection of 6 million U of natural IFN-alpha for 24 weeks. Patients were divided into three groups: sustained complete response (CR-S), complete response with rebound (CR-R), and nonresponse (NR). Serum PIIINP, IV-7S, and HA levels were significantly decreased and reached normal levels at 12 months in CR-S; only IV-7S levels were significantly decreased at 12 months in CR-R, whereas these levels remained abnormally high in the NR. These results suggest that IFN-alpha therapy could lower the levels of serum hepatic fibrogenesis markers along with improvements in hepatic inflammation.

Adult

Proposal for new catalytic roles for two invariant residues in Escherichia coli ribonuclease HI.

Three mutants of Escherichia coli ribonuclease HI, in which an invariant acidic residue Asp134 was replaced, were crystallized, and their three-dimensional structures were determined by X-ray crystallography. The D134A mutant is completely inactive, whereas the other two mutants, D134H and D134N, retain 59 and 90% activities relative to the wild-type, respectively. The overall structures of these three mutant proteins are identical with that of the wild-type enzyme, except for local conformational changes of the flexible loops. The ribonuclease H family has a common active site, which is composed of four invariant acidic residues (Asp10, Glu48, Asp70 and Asp134 in E.coli ribonuclease HI), and their relative positions in the mutants, even including the side-chain atoms, are almost the same as those in the wild-type. The positions of the delta-polar atoms at residue 134 in the wild-type, as well as D134H and D134N, coincide well with each other. They are located near the imidazole side chain of His124, which is assumed to participate in the catalytic reaction, in addition to the four invariant acidic residues. Combined with the pH profiles of the enzymatic activities of the two other mutants, H124A and H124A/D134N, the crystallographic results allow us to propose a new catalytic mechanism of ribonuclease H, which includes the roles for Asp134 and His124.

Aspartic Acid

Gastric mucosal energy metabolism and intracellular mucin content changes in patients with liver cirrhosis.

Biopsy samples from patients with liver cirrhosis were investigated for changes in gastric mucosal energy metabolism and intracellular mucin content using high performance liquid chromatography and an image analysing system. The test group consisted of eight non-cirrhotic patients with endoscopically normal mucosa (controls) and eight cirrhotic patients with oesophageal varices. The amount of ATP, energy charge level and intracellular mucin content were all significantly decreased in cirrhotic patients when compared with those of the controls. The decrease in energy charge also correlated well with the decrease in intracellular mucin content in the gastric mucosa. The results indicate that gastric mucosal energy metabolism is impaired in cirrhotic patients concomitantly with a decrease in the intracellular mucin content in the gastric mucosa. These changes may weaken defensive mechanisms against acid and NSAID, resulting in gastric mucosal injury in cirrhotic patients.

Adenosine Diphosphate

Atomic model of a pyrimidine dimer excision repair enzyme complexed with a DNA substrate: structural basis for damaged DNA recognition.

T4 endonuclease V is a DNA repair enzyme from bacteriophage T4 that catalyzes the first reaction step of the pyrimidine dimer-specific base excision repair pathway. The crystal structure of this enzyme complexed with a duplex DNA substrate, containing a thymine dimer, has been determined at 2.75 A resolution. The atomic structure of the complex reveals the unique conformation of the DNA duplex, which exhibits a sharp kink with a 60 degree inclination at the central thymine dimer. The adenine base complementary to the 5' side of the thymine dimer is completely flipped out of the DNA duplex and trapped in a cavity on the protein surface. These structural features allow an understanding of the catalytic mechanism and implicate a general mechanism of how other repair enzymes recognize damaged DNA duplexes.

Adenine

Management of intraaortic balloon entrapment.

Two cases of intraaortic balloon entrapment were presented. In patient 1, urokinase was injected into the gas driver lumen of the intraaortic balloon catheter, then it could be removed. In patient 2, the intraaortic balloon was removed retrogradely through the left axillary artery. If the entrapped intraaortic balloon is encountered, it is effective to try a clot-lysis method initially, followed by a surgical approach through a left axillary artery.

Aged

Senile dementia-Alzheimer's type and estrogen.

Some reports have suggested the ameliorative effects of estrogens on clinical symptoms, such as short memory, in women suffering from senile dementia-Alzheimer's type, in vivo. The action mechanism of estrogen remains to be clarified, but 1) an anti-depressive effect, 2) improvement of cerebral blood flow, 3) direct stimulation of neuron, 4) development of gliacyte and 5) suppression of apolipoprotein E have been suggested. Some mechanisms may be combined, contributing to the beneficial effects on clinical symptoms.

Alzheimer Disease

Angiomyxoid tumour in the renal peripelvic tissues with features of aggressive angiomyxoma.

A case of angiomyxoid tumour in the renal peripelvic soft tissue of a 45 year old woman is reported. The encapsulated tumour, measuring 12 x 9 x 6 cm, was solid and firm. The cut surface revealed a yellowish-white, gelatinous, and glistening tumour. Histologically, the tumour was composed of loosely textured spindle and stellate cells with prominent blood vessels of variable calibre. The tumour cells stained strongly for vimentin. These findings strongly resemble those associated with aggressive angiomyxoma in the vulva and perineum.

Female

[A technique for removal of entrapped intra-aortic balloon catheter through the left axillary artery].

A case of intra-aortic balloon pumping (IABP) entrapment in which the ruptured catheter could be removed through the left axillary artery was reported. A 68-year-old man was admitted with persistent chest pain, and because of his poor cardiac condition, an IAB catheter was inserted by the Seldinger technique. During attempted extraction of the IAB catheter resistance was encountered and it turned out to be entrapped. Then a guide-wire was passed through the IAB lumen to the left axillary artery, the artery was exposed, and the tip of the guide-wire and IAB catheter were led to the arteriotomy site. After the balloon was dissected, the IAB catheter could be removed through the axillary artery. Finally, left femoro-left branchial artery bypass was performed with e-PTFE graft because of the arterial injury and ischemia of the involved arm. The patient recovered from this episode.

Aged

Endothelin-1 is involved in the pathogenesis of ischemia/reperfusion liver injury by hepatic microcirculatory disturbances.

Hepatic microcirculatory perturbation is observed after ischemia/reperfusion. Endothelin-1, a potent vasoconstrictive peptide, is known to modulate local circulation. This study was designed to examine whether endothelin-1 participates in the mechanism of microcirculatory disturbance and damage of the liver after ischemia/reperfusion. Ischemia in the median and left lateral lobes of the liver was induced for 60 min; it was followed by reperfusion for 24 hr. In some rats, endothelin-1 antiserum or control serum without endothelin-1-blocking activity was administered intravenously just before reperfusion. Rats were divided into three groups: an ischemia/reperfusion group that was injected with control serum, an endothelin-1 antiserum-treated group and a sham-operated group. Endothelin-1 concentrations in blood collected from the suprahepatic vena cava were measured before and after ischemia/reperfusion by use of a sandwich enzyme immunoassay. Index of blood volume in regional hepatic tissue and index of blood oxygenation in regional hepatic tissue were assessed with an organ reflectance spectrophotometry system before and at 5 min and 1, 2, and 24 hr after reperfusion. The endothelin-1 concentration in the ischemia/reperfusion group started to rise immediately at onset of reperfusion from basal values around 1 pg/ml and reached a value of 5 to 6 pg/ml 5 min after reperfusion; it was maintained at significantly high levels during the reperfusion period compared with the sham-operated group. Hepatic microcirculatory disturbance indicated by lowered index of blood volume in regional hepatic tissue and index of blood oxygenation in regional hepatic tissue levels was observed in the early phase of reperfusion in the ischemia/reperfusion group.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine Transaminase

Jargonagraphia in Kanji and Kana in a Japanese crossed Wernicke's aphasic.

A right-handed Japanese crossed Wernicke's aphasic showed complete neologistic jargonagraphia in kanji and kana with anosognosia of his writing deficits. Prominent jargonagraphia in kanji is quite rare and has not been previously described in the literature. Marked dissociation between speaking and writing during the course suggested that his jargonagraphia might be unique to crossed aphasia. His condition was interpreted for the main part by Yokoyama, Okubo, Doseki, and Yamadori's hypothesis (1981) that free-running on of motor engrams of characters stored in the left hemisphere caused jargonagraphia in crossed aphasia. This case of jargonagraphia in kanji suggests that this hypothesis should be supplemented by the following points: (1) in kanji, not necessarily a character as a whole, but radicals or parts of radicals, function as motor units, which may be released to produce jargonagraphia in kanji; (2) free-running on of visual images as well as of kinesthetic images should be considered especially in written jargon in kanji.

Activities of Daily Living

Impaired gastric mucosal energy metabolism in congestive gastropathy in cirrhotic patients.

To clarify the characteristics of congestive gastropathy, we investigated gastric mucosal hemodynamics and energy metabolism in cirrhotic patients, using a reflectance spectrophotometry system and high performance liquid chromatography. The index of the gastric mucosal blood volume of cirrhotic patients with esophageal varices was significantly higher, and the index of gastric mucosal blood oxygenation significantly lower, than those in controls, thus indicating congestion and hypoxia in the gastric mucosa. Energy charge levels in the gastric mucosa of cirrhotic patients with esophageal varices were also significantly decreased. The energy charge level showed a strong linear correlation with the index of mucosal blood oxygenation in the antral (r = 0.996, P < 0.01) and body (r = 0.994, P < 0.01) mucosa of the stomach. These findings suggest that congestive gastropathy in a portal hypertensive state causes hypoxia in the gastric mucosa, leading to a mucosal energy deficit that may increase mucosal susceptibility to aggressive factors.

Chromatography, High Pressure Liquid

Vasoactive effect of endothelin-1 on rat liver in vivo.

The purpose of this study was to evaluate the role of endothelin-1 in modulating hepatic microcirculation and liver damage. Rats were infused with endothelin-1 at doses ranging from 30 to 1,000 pmol/kg over 1 min through an indwelling cannula placed in the portal vein. In control rats, saline solution was infused at the same rate. Alterations in hepatic microcirculation were measured with an in vivo microscopy system. Serum lactate dehydrogenase activity, an indicator of hepatic damage, was measured 1 hr after endothelin-1 infusion. Immediately after infusion of endothelin-1, we noted a rapid increase in portal pressure, which remained increased for up to 30 min after endothelin-1 infusion. In contrast, systemic blood pressure remained unchanged, even at 1,000 pmol/kg of endothelin-1. Sinusoidal width was reduced and sinusoidal erythrocyte velocity was diminished in a dose-dependent manner. Oxygen saturation of blood in sinusoids was decreased in a dose-dependent manner, reaching values around 40% of control with 1,000 pmol/kg endothelin-1. The degree of decrease in oxygen saturation of blood in sinusoids had an excellent correlation with the calculated blood flow in the liver tissue. Serum lactate dehydrogenase levels were three to four times control values when endothelin-1 was administered at 1,000 pmol/kg. Thus endothelin-1 decreased hepatic tissue oxygenation associated with sinusoidal vasoconstriction. At high concentrations of endothelin-1, this decrease results in hepatocellular damage.

Animals

Interaction of heparin with amphiphile assemblies and biocompatibility of the heparin complexes.

Addition of heparin to preformed vesicles of a cationic surface-active compound, dioctadecyldimethylammonium bromide (DODAB), resulted in fast precipitation of the heparin/DODAB complex. On the other hand, heparin stabilized the vesicle composed of dipalmitoyl L-alpha-phosphatidylcholine (DPPC) which is a neutral lipid. However, DPPC precipitated with heparin by the addition of a small amount of stearylamine (SA), which is a cationic substance. Differential scanning calorimetry of the heparin/amphiphile mixtures showed that the heparin/DODAB complex possess a structure different from that of the original DODAB vesicle. The structure of the DPPC vesicle was unaffected by the addition of heparin, while the structure of the heparin/DPPC-SA complex was found to be different from that of the DPPC-SA vesicle. The interaction of heparin with vesicles depended on the nature of amphiphiles. Heparin was solubilized in organic solvent when complexed with DODAB or DPPC-SA vesicles. Polyurethaneurea membranes blended with heparin/DODAB or heparin/DPPC-SA complexes were highly nonthrombogenic, but somewhat cytotoxic.

1,2-Dipalmitoylphosphatidylcholine

Hepatitis B virus carrier with low titer of antibody to hepatitis B core antigen.

Of 798 hepatitis B virus (HBV) carriers, 22 had low titers (lower than 80% inhibition in 200- or 400-fold diluted serum) of antibody to hepatitis B core antigen (anti-HBc). Among these 22 patients, there were 12 (1.50%) with viremia who were positive for hepatitis B e antigen and had a high titer of HBV-associated DNA polymerase activity. Among these 12 patients, four showed no significant change in the anti-HBc titer, while four others showed significant increases in the anti-HBc titer during the follow-up periods. The former all remained asymptomatic carriers (ASCs), while the latter all developed chronic hepatitis (CH). The liver histology of four patients (ASC: 2, CH: 2) showed mild inflammation, and the localization of hepatitis B core antigen (HBcAg) in the liver specimens showed a nuclear pattern in the two ASCs, but a nuclear plus cytoplasmic pattern in the two CH cases. In HBV carriers, the increase in anti-HBc titer seems to be closely correlated to the change in HBcAg localization from the nucleus to the cytoplasm in the liver. Therefore, rising titers of anti-HBc were assumed to be associated with increased expression of HBcAg on the hepatocyte, and hence increased immune-mediated hepatic damage and the onset of hepatitis in ASC with low titer of anti-HBc.

Adolescent