Biomedical subjects

K Kagawa

Publications and source records attributed to K Kagawa.

At least 19 recordsLinked to original sources

PubMed1996

Cytogenetic analyses of hepatocellular carcinoma by in situ hybridization with a chromosome-specific DNA probe.

BACKGROUND: Numerical chromosome analysis has been established in solid tumors by using in situ hybridization (ISH) with a chromosome-specific probe. We analyzed human hepatocellular carcinoma (HCC) by ISH for chromosome 17 and investigated the correlation of its copy number with histologic malignancy, proliferative activity, p53 mutation, and DNA ploidy. METHODS: Chromosome 17 was hybridized with a pericentromere-specific DNA probe directly on the tumor cells isolated from paraffin blocks of 25 surgically resected HCCs. Proliferative activity was measured by Ki-67 immunohistochemistry, p53 mutation was analyzed by p53 immunohistochemistry, and DNA ploidy was estimated by cytofluorometry. RESULTS: Forty-four percent of the 25 HCCs showed numerical abnormality of chromosome 17. Many disomic cases had a less malignant histology, whereas many polysomic cases had a more malignant histology. The Ki-67 positive index of polysomic cases was higher than that of disomic cases. In 22 cases (88.0%), the copy number of chromosome 17 was well matched with DNA ploidy. However, the numerical abnormality of chromosome 17 did not show a significant correlation with p53 mutation. Two of four HCCs that showed histologic heterogeneity were also heterogenous on ploidy pattern and the copy number of chromosome 17. Conversely, there was one case in which only ISH could demonstrate heterogeneity, although the other features exhibited homogeneity. CONCLUSIONS: Numerical chromosome abnormalities correlated with the increase of histologic malignancy proliferative activity, and DNA ploidy. Moreover, ISH analysis was useful in assessing the intratumoral heterogeneity in HCC, especially when current methods failed to detect it. Thus, ISH provides information on important biologic features, such as malignant potential and intratumoral heterogeneity, in HCC.

Adult↗

PubMed1996

Globin digest, acidic protease hydrolysate, inhibits dietary hypertriglyceridemia and Val-Val-Tyr-Pro, one of its constituents, possesses most superior effect.

Globin digest (GD), prepared from globin by acidic protease treatment, suppressed the elevation of serum triglyceride level in not only total but also chylomicron fraction after oral administration of olive oil. By screening with this lowering activity, we concluded that Val-Val-Tyr-Pro (VVYP) would be most effective constituent having hypotriglyceridemic action in GD. The mode of their action was dose dependent and did not show species specificity. Neither the repression of peristaltic movement of intestine nor the delaying of gastric emptying was caused by intake of GD or VVYP, however, the excretion of administered lipid was much more than that of control. Furthermore, administration of GD caused more prominent activation of hepatic triglyceride lipase (HTGL) and the increase of hepatic free fatty acid (FFA) concentration in early phase after administration of fat. From these results, it could be elucidated that GD, and also VVYP, inhibited fat absorption from digestive tract and enhanced activity of HTGL, so that more rapid clearance of dietary hypertriglyceridemia was caused.

Amino Acid Sequence↗

PubMed1995

The role of extrinsic nervous system in jejunal absorption during elevation of intraluminal pressure in anesthetized dogs.

The aim of this study was to investigate the role of the extrinsic nervous system in jejunal absorption under elevated intraluminal pressure of the jejunum. Increase in intraluminal pressure from 0 to 70-100 mmHg decreased net absorption of fluid, Na+ and Cl-, from 7.6 +/- 0.5 to 5.6 +/- 0.3 ml/15 min, 1.1 +/- 0.1 to 0.7 +/- 0.1 mEq/15 min, and 1.2 +/- 0.1 to 0.8 +/- 0.1 mEq/15 min, respectively. To examine the role of the extrinsic nervous system in the depressed net jejunal absorption induced by the increase in intraluminal pressure, jejunal afferent and efferent nerve activities were measured in response to the increase in intraluminal pressure. Both afferent and efferent nerve activities increased to 224 +/- 14 and 236 +/- 18% in response to the increase in intraluminal pressure. In the extrinsic denervated jejunal loop, the responses of net absorption to the elevation of intraluminal pressure were quite different from those in innervated jejunum. That is, in the denervated jejunal loop the elevation of intraluminal pressure converted jejunal absorption to jejunal secretion. These results indicate that elevation of intraluminal pressure elicits the jejuno-jejunal reflex, and this mechanism counteracts jejunal secretion.

Anesthetics↗

PubMed1995

Autoantibody to factor VIII that has less reactivity to factor VIII/von Willebrand factor complex.

To determine the difference in reactivity of factor VIII (FVIII) inhibitor to FVIII/von Willebrand Factor (vWF) complex and FVIII free of vWF, an autoantibody to FVIII light chain was tested. A patient (1-3) suffered from autoimmune hemolytic anemia with autoantibody to FVIII. Epitope specificity of the patient's IgG (I-3 IgG) was shown to be the C2 domain of FVIII light chain (2170-2332) by Western blotting using recombinant FVIII deletions expressed in Escherichia coli. The inhibitory effect on FVIII procoagulant activity (VIII:C) of I-3 IgG was tested against a conventional FVIII concentrate; Haemate P, a monoclonal antibody-purified FVIII concentrate; Hemofil M, and a recombinant FVIII (rFVIII); Kogenate. I-3 IgG showed only 1.3 BU/mgIgG for Haemate P, in contrast to 20 BU/mgIgG for both Hemofil M and Kogenate. The ratio of VIII:C/vWF:Ag in Haemate P and Hemofil M was 1/3.43 and 1/0.01, respectively, while Kogenate did not contain vWF. The inhibitory effect of the I-3 IgG was then compared with Kogenate and its complex with vWF. The inhibitory effect was decreased against the rFVIII by forming a complex with vWF from 22 BU/mgIgG to 0.5 BU/mgIgG. Fab from the I-3 IgG had the same effect. In addition, vWF showed a protective effect on FVIII inactivation by the I-3 IgG in a dose dependent manner. Fifty-nine percent of residual VIII:C was retained in the presence of 8 U/ml of vWF after 1 hr incubation with I-3 IgG. These results suggested that vWF could compete with the I-3 IgG for binding to FVIII.

Adult↗

PubMed1995

Factor VIII inhibitor developed in a 60-year-old patient with mild hemophilia A after surgery for colon cancer.

Most factor VIII inhibitors are developed at an early age and in patients with severe type of hemophilia A. We report a case of newly developed factor VIII inhibitor in a 60-year-old patient with mild hemophilia A who had been treated with several kinds of factor VIII concentrates. The patient was treated with a total of 103,580 units of recombinant factor VIII concentrate by continuous and bolus infusions for the open surgery of sigmoid colon cancer. On the 95th postoperative day, the patient had right low limb muscle bleeding and was infused with 1,000 units of recombinant factor VIII concentrate for three days. Subsequently, the level of factor VIII inhibitor in the patient's plasma was 2 Bethesda units (BU)/ml. Since then numerous subcutaneous hemorrhages developed, but an adequate hemostatic effect was not obtained even with the administration of a high dose of recombinant factor VIII concentrate. The patient was switched to bypass therapy using human plasma-derived factor VIIa concentrate, which showed a favorable hemostatic effect.

Adenocarcinoma↗

PubMed1995

BDM compared with P(i) and low Ca2+ in the cross-bridge reaction initiated by flash photolysis of caged ATP.

Using flash photolysis of caged ATP in skinned muscle fibers from rat psoas, we examined the inhibitory effects of 2,3-butanedione monoxime (BDM) on the contraction kinetics and the rate of ATP hydrolysis of the cross-bridges at approximately 10 degrees C. The hydrolysis rate was estimated from the stiffness records. The effects of BDM were compared with those of orthophosphate (P(i)) and of reduction in [Ca2+] (low Ca2+), and it was found that i) BDM and low Ca2+ inhibited ATPase activity to the same extent as they inhibited the steady tension, whereas P(i) inhibited ATPase activity much less than tension; ii) BDM and P(i) decreased tension per stiffness during the steady contraction more than did low Ca2+; iii) neither BDM nor low Ca2+ affected the initial relaxation of the fiber on release of ATP, but P(i) slightly slowed it; and iv) BDM hardly influenced the rate of contraction development after relaxation, although P(i) and low Ca2+ accelerated it. We concluded that BDM inhibits the Ca(2+)-regulated attachment of the cross-bridges and force-generation of the attached cross-bridges.

Adenosine Triphosphate↗

PubMed1995

Alternations in atrial natriuretic peptide release after DC cardioversion of non-valvular chronic atrial fibrillation.

The response of atrial natriuretic peptide (ANP) release to haemodynamic influences after cardioversion of atrial fibrillation has not been fully examined. We measured plasma concentrations of ANP and assessed haemodynamic changes 60-120 min after DC cardioversion in 22 patients with non-valvular chronic atrial fibrillation. Passive leg elevation to enhance volume expansion was performed 60 min after DC cardioversion. Sinus rhythm was restored in 18 of the 22 patients (successful DC cardioversion group). The control group consisted of seven patients with non-valvular chronic atrial fibrillation who did not undergo DC cardioversion (atrial fibrillation control group). In the successful DC cardioversion group, the mean pulmonary artery wedge pressure decreased significantly 15 min after cardioversion (P < 0.05) and then remained unchanged. Plasma concentrations of ANP also decreased significantly 15 min after cardioversion (P < 0.05). Furthermore, there was an additional significant decrease in ANP levels for up to 60 min after cardioversion (P < 0.05 from 15 min). Passive leg elevation for 15 min led to an increase in the mean pulmonary artery wedge pressure (P < 0.01) and right atrial pressure (P < 0.05), but did not result in increased plasma concentrations of ANP (47.1 +/- 27.6 vs 43.9 +/- 34.4 pg.ml-1, mean +/- SD, P = ns). In the atrial fibrillation control group, passive leg elevation increased the mean pulmonary artery wedge pressure (P < 0.01), the mean right atrial pressure (P < 0.05) and plasma concentrations of ANP (139.9 +/- 85.8 vs 168.1 +/- 108.2, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1995

Piroxicam induced Stevens-Johnson syndrome.

Stevens-Johnson syndrome in a 63-year-old Japanese woman is described. Oral provocation test revealed the causative agent to be piroxicam.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed1995

[Planning for brachytherapy using a 3D-simulation model].

A 3D-simulation model made with a milling system was applied to HDR-brachytherapy. The 3D-simulation model is used to simulate the 3D-structure of the lesion and the surrounding organs before the actual catheterization for brachytherapy. The first case was recurrent prostatic cancer in a 61-year-old man. The other case was lymph node recurrence of a 71-year-old woman's upper gum cancer. In both cases, the 3D-simulation model was very useful to simulate the 3D-conformation, to plan the treatment process and to avoid the risk accompanying treatment.

Aged↗

PubMed1995

[Pneumothorax with reduced pulmonary function complicated by MRSA pneumonia: a case report].

The occurrence of pneumothorax in patients with compromised lung function or severe pulmonary disease may be fatal. We describe a 77-year-old patient with MRSA pneumonia complicated by pneumothorax and reduced pulmonary function. Although the patient was treated with drainage of the pleural cavity and nonsurgical pleurodesis, the pneumothorax could not be managed successfully. The patient underwent successful surgical treatment of the pneumothorax on 105 days after onset. The following factors must be considered in the surgical treatment of pneumothrax with reduced pulmonary function in patients with MRSA pneumonia: 1) When there is massive air leakage, adequate doses of VCM should be administered to prevent pyothorax, 2) when conservative treatment fails and surgical treatment becomes necessary, the operation should be instituted only when MRSA has been completely or almost completely eradicated so as to prevent the occurrence of postsurgical pyothorax, and 3) surgical intervention should be limited to what is necessary to repair the site of ruptured bulla; care should be exercised to preserve as much lung parenchyma as possible and to shorten the operation time.

Aged↗

PubMed1994

Regulation of hepatocyte albumin and alpha 1-acid glycoprotein secretion by monokines, dexamethasone, and nitric oxide synthase pathway: significance of activated liver nonparenchymal cells.

To clarify the mechanism involved in regulating the secretion of albumin and alpha 1-acid glycoprotein by rat hepatocytes, we studied hepatocyte culture and cocultures of hepatocyte and liver nonparenchymal cells. The secretion of alpha 1-acid glycoprotein by hepatocytes was stimulated and that of albumin was inhibited by combinations of dexamethasone and monokines, especially by dexamethasone and interleukin-6. The secretion of these proteins was equally inhibited during stimulation by lipopolysaccharide in cocultures. The inhibitory effect of sinusoidal endothelial cells was smaller than that of Kupffer cells. This inhibition was partially abolished by blocking the nitric oxide synthase pathway in cocultured cells and was completely abolished by dexamethasone. In conclusion, the secretion of albumin and alpha 1-acid glycoprotein by hepatocytes was regulated by monokines, dexamethasone, and the inducible nitric oxide synthase pathway in hepatocytes and liver nonparenchymal cells in vitro.

Albumins↗

PubMed1994

Morphological alterations of gap junctions in phalloidin-treated rat livers.

Morphological alterations in the pattern of liver cell gap junctions were examined in phalloidin-treated rats to assess the role of gap junctions in experimental intrahepatic cholestasis. Double-labelled fluorescent staining of gap junctions and F-actin were performed using a monoclonal antibody against rat hepatocyte connexin 32 and rhodamine-phalloidin. Immunoelectron microscopy, using the anti-connexin 32 antibody, freeze-fracture replica electron microscopy, and conventional electron microscopy were also performed. In phalloidin-treated rat livers, the specific immunofluorescent staining of connexin 32 was markedly decreased in the pericentral area after 1 day of phalloidin treatment and, after 5 days of phalloidin treatment, there was a decrease in connexin 32 staining in the entire hepatic lobule. On the other hand, F-actin staining at the cell periphery and at the bile canaliculi was markedly increased in the pericentral area of the hepatic lobule after 1 day of phalloidin treatment and in the entire lobule after 5 days of treatment. Immunoelectron microscopy showed that both sides of the cytoplasmic domains of gap junctions were stained with anti-connexin 32 antibody in controls, whereas, in cholestatic rats, only one side of the cytoplasmic domain of some gap junctions was stained with anti-connexin 32 antibody after 1 or 3 days of phalloidin treatment. No gap junctions were observed after 5 days of phalloidin treatment either by freeze-fracture replica electron microscopy or by conventional electron microscopy. These results indicate that with phalloidin treatment, hepatocyte gap junctions decrease, first in the pericentral area, and finally throughout the entire lobule.

Actins↗

PubMed1994

Evaluation of hepatic proliferative activity in chronic liver diseases and hepatocellular carcinomas by proliferating cell nuclear antigen (PCNA) immunohistochemical staining of methanol-fixed tissues.

The proliferative activity of chronic liver diseases and hepatocellular carcinomas (HCCs) was studied by PCNA immunohistochemistry. Human liver tissues were obtained by surgical operation or needle biopsy, and PCNA was detected by immunohistochemistry. PCNA-labelling indices (PCNA-LIs) of methanol-fixed tissues corresponded with the incidence of S-phase cells previously reported, whereas paraformaldehyde-fixed tissues showed extremely high PCNA-LIs in all specimens. Therefore, methanol-fixed tissues were used for evaluation. The PCNA-LIs of the methanol-fixed tissues were: normal liver 0.78 +/- 0.38%, chronic persistent hepatitis 1.06 +/- 0.86%, chronic aggressive hepatitis 2A 1.01 +/- 0.50%, chronic aggressive hepatitis 2B 4.20 +/- 1.79%, inactive cirrhosis 0.81 +/- 0.49%, active cirrhosis 1.96 +/- 0.93%, HCC of Edmondson's type I 4.83 +/- 1.98%, type II 6.65 +/- 1.69%, and type III 38.7 +/- 30.6%. PCNA-positive cells showed little specific distribution; in periportal areas in chronic hepatitis, at the margins of pseudolobules in cirrhosis, and throughout the tumor in HCC. These findings indicated that proliferative activity increased during the progression of chronic hepatitis, but that it decreased at the stage of cirrhosis. In chronic liver diseases, the PCNA-LIs reflected hepatitis activity. HCC showed higher proliferative activity than liver cirrhosis, and the histological grade was correlated with the PCNA-LI.

Analysis of Variance↗

PubMed1994

Subcortical impairment in subclinical hepatic encephalopathy.

We have used short latency somatosensory evoked potential (SEP) in 108 patients with liver cirrhosis by viral hepatitis to evaluate hepatic encephalopathy. Short-latency SEPs were recorded by the MEM-4104 apparatus (Nihon Kohden Inc., Tokyo) in response to median nerve stimulation. For a precise analysis of the early components, we averaged 1000 responses during a 30-msec period. Early SEP components were prolonged in patients with decompensated, but not in those with compensated, cirrhosis. We also examined the relationship between consciousness level and interpeak latency (IPL) N13-N20 of SEP and between consciousness level and electroencephalograph in 51 patients among 108 patients with liver cirrhosis. The IPL N13-N20 was prolonged in the decompensated stage with normal consciousness, but EEG findings had not deteriorated in this stage. EEG grade became worse in the stage of abnormal consciousness. The prolongation of the IPL N13-N20 was attributed to the central conduction impairment. We postulate that subcortical impairment may occur in patients with subclinical hepatic encephalopathy. when the cortex is little affected.

Aged↗

PubMed1994

Transient contraction of muscle fibers on photorelease of ATP at intermediate concentrations of Ca2+.

We isometrically activated skinned fibers in rigor by flash photolysis of caged ATP at various [Ca2+] at 8 degrees C. On release of ATP, tension initially decreased with the same time course at all [Ca2+]. At high [Ca2+] (pCa < or = 5.8), tension rose to the steady-state plateau after the brief relaxation. When the [Ca2+] was intermediate (7.0 < or = pCa < or = 6.0), tension temporarily overshot the final steady-state level. The half-time during this tension transient was longer at higher [Ca2+]. The transient contractions could be simulated by a simple kinetic model: R + ATP-->Q, and X<-->Q<-->A, where R, X, and A are the rigor, relaxed, and active-tension states, respectively; Q is a "pre-active" state where tension is very low; and Ca2+ affects only the X-Q transition. This scheme was also useful for predicting the tension transients in Ca(2+)- and P(i)-jump experiments at various [Ca2+]. ADP enhanced the Ca2+ sensitivity of the ATP-induced transient contraction, which was not in the scope of the model.

Adenosine Diphosphate↗

PubMed1994

PreS1 deleted variants of hepatitis B virus in patients with chronic hepatitis.

Defective hepatitis B virus lacking 183 bases of the 3'-terminus part of the preS1 region was found in the sera of two patients with chronic hepatitis B virus infection. Results of sequencing analysis of samples with or without polymerase chain reaction yielded the same result, proving that this deletion was not due to an artifact obtained during polymerase chain reaction. One of the deletion ends lay in TCAGG that appeared five times in the genome of subtype adr and the other end was identified as TCAGG in direct repeats of the genome. The mutated hepatitis B virus became predominant in one patient's serum only after consecutive interferon therapy, suggesting that the deleted part might play a role in viral elimination from the circulation.

Base Sequence↗

PubMed1994

Serum levels of macrophage colony stimulating factor (M-CSF) in liver disease.

We investigated the serum level of macrophage colony stimulating factor in acute and chronic liver disease. Levels of macrophage colony stimulating factor (mean +/- SD, ng/ml) were significantly higher in acute hepatitis (5.67 +/- 1.01, p < 0.01) and chronic active hepatitis (3.34 +/- 1.19, p < 0.01) than in healthy volunteers (1.90 +/- 0.25), asymptomatic hepatitis B virus carriers (1.98 +/- 0.40), and chronic persistent hepatitis (2.34 +/- 0.43). Levels of macrophage colony stimulating factor showed a highly significant correlation with the serum alanine aminotransferase levels in acute hepatitis (p < 0.01, rs = 0.903) and in chronic active hepatis (p < 0.01, rs = 0.672). Levels of macrophage colony stimulating factor in patients with cirrhosis (cirrhosis; 3.11 +/- 0.93 and hepatocellular carcinoma; 3.30 +/- 0.74) were significantly higher than in patients with chronic persistent hepatitis although the alanine aminotransferase levels were not significantly different. In cirrhosis, levels of macrophage colony stimulating factor correlated positively with the serum alanine aminotransferase levels (p < 0.05), total bilirubin levels (p < 0.05), and indocyanine green clearance (p < 0.05). An immunohistochemical study showed an increased number of macrophage colony stimulating factor positive mononuclear cells in portal areas in acute hepatitis. Our findings suggest that; (a) the serum levels of macrophage colony stimulating factor represent ongoing hepatocellular necrosis in acute and chronic liver disease, (b) the source of the increase in the serum macrophage colony stimulating factor levels in hepatic inflammation may be, in part, its production by infiltrating mononuclear cells in the liver, and (c) cirrhosis also causes elevated serum levels of macrophage colony stimulating factor.

Acute Disease↗

PubMed1994

X-ray equatorial diffraction during ATP-induced Ca(2+)-free muscle contraction and the effect of ADP.

We examined the equatorial X-ray diffraction of skinned fibers from rat psoas muscle in isometric contraction induced by photorelease of 1.1 mM ATP at 24 degrees C in the absence of Ca2+. At 15-20 ms after release of ATP, tension peaked at 21% of the maximum active tension. From the equatorial intensity ratio (I1,0/I1,1), we estimated the amount of myosin heads associated with actin filaments (A.M) at the tension peak. It was 32% of that in rigor and about half of that in the maximum contraction. ADP (0.7 mM) enhanced the contraction: tension peaked at 47% of the maximum at 25-30 ms. The estimated A.M at this peak was 50% of that in rigor, which was close to that in the maximum contraction. These results indicate that the association of myosin heads with the actin filaments in the Ca(2+)-free contraction is more than expected from the tension size, both in the absence and presence of ADP.

Actins↗