Biomedical subjects

K Kagawa

Publications and source records attributed to K Kagawa.

At least 91 records · Page 5Linked to original sources

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↗

PubMed1994

Relationship between the suppressive actions on intestinal absorption and on cGMP production for the natriuretic peptide family in dogs.

1. The aim of this study was to investigate whether the suppressive effects of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP) on net intestinal absorption were related to guanosine 3',5'-cyclic monophosphate (cGMP) production in the intestine. 2. We measured the plasma cGMP concentration of the arterial, jejunal and ileal venous blood after intravenous infusions of natriuretic peptides (97 pmol/kg per min for 30 min) in anaesthetized dogs. 3. The infusion of ANP increased cGMP concentration of the aortic blood by 49.9 +/- 9.0 (pmol/mL), BNP by 71.8 +/- 12.3 and CNP by 5.5 +/- 1.3. The increases in cGMP after ANP and BNP were larger than after CNP. The infusion of ANP increased jejunal arteriovenous differences in cGMP concentration by 69.9 +/- 3.5 (pmol/mL) and ileal arteriovenous differences by 8.7 +/- 3.2. In BNP infusion, the jejunal and ileal arteriovenous differences in cGMP concentration tended to increase by 15.6 +/- 5.8 (pmol/mL) and by 14.8 +/- 6.6 but neither were significant. CNP infusion did not change the jejunal and ileal arteriovenous differences in cGMP concentration. 4. These results suggest that, while the actions of ANP on intestinal absorption may be mediated by cGMP, those of BNP and CNP are not.

Animals↗

PubMed1994

Usefulness of the pulmonary vein flow velocity-time profile as an estimate of left atrial storage fraction.

During ventricular systole, the left atrium (LA) stores a certain amount of ventricular stroke volume; this is defined as an LA storage volume. From cineangiocardiograms, an LA storage fraction is obtained as the ratio of the LA storage volume to left ventricular stroke volume. From the pulmonary vein (PV) flow velocity-time profile, the LA storage fraction may be estimated as a ratio of the PV flow velocity-time integral during systole (Sa) to a sum of that during systole and diastole (Sa+Da), namely, Sa/(Sa+Da), provided that the PV cross-sectional area remains relatively unchanged during one cardiac cycle and that the PV flow velocity-time profile is similar in any of the PVs draining to the LA. To evaluate usefulness of Doppler echocardiographic method of estimating the LA storage fraction, the authors measured the LA storage fraction from the left upper PV flow velocity-time profile by transesophageal Doppler echocardiography and compared it with the LA storage fraction from conventional cineangiocardiographic volumes. Subjects were 23 patients with a variety of cardiac diseases in normal sinus rhythm, ranging from eighteen to seventy-four years of age. The LA storage fraction was 0.58 +/- 0.12 (mean +/- SD) from cineangiocardiography and 0.64 +/- 0.08 from Doppler echocardiography larger than that from cineangiocardiography (P < 0.01), the correlation was good (r = 0.643). The authors conclude that the left upper PV flow velocity-time profile appears to provide a better correlation with that by cineangiography and may be used as a reliable quantitative estimate of the LA storage fraction.

Adult↗

PubMed1994

A study on left atrial transport function. Effect of age or left ventricular ejection fraction on left atrial storage fraction.

Left atrial (LA) storage fraction is defined as the ratio of storage volume of the left atrium (LA) during ventricular systole to left ventricular (LV) stroke volume. To test their hypothesis that left atrial (LA) storage fraction is increased to compensate for impaired LV filling in the heart of aged subjects or with impaired LV ejection fraction, the authors studied 33 "normal" subjects and 25 patients with coronary artery disease. LA volume was measured by LA cineangiocardiography, and LV stroke volume and LV ejection fraction were measured by LV cineangiocardiography. To further evaluate the determinants of changes in LA storage fraction, they measured the ratio of LA active release volume to LV stroke volume, and the ratio of LA passive release volume to LV stroke volume. In "normal" subjects, LA storage fraction was increased with age (r = 0.584, P < 0.01). In patients with coronary artery disease, LA storage fraction was increased as LV ejection fraction was decreased (r = -0.525, P < 0.01). In both cases, LA active release fraction was significantly associated with changes in LA storage fraction rather than in LA passive release fraction. They conclude that LA storage fraction may be an important determinant of LV filling mainly through the LA active release fraction.

Adolescent↗

PubMed1994

The initial contraction of skinned muscle fibers on photorelease of ATP in the presence of ADP.

1) We photoreleased ATP in skinned muscle fibers from rat psoas, and examined the effects of ADP on the ATP-induced isometric transient. 2) On release of ATP, the muscle stiffness initially falls at any [Ca2+]. ADP slowed this stiffness decrease, suggesting competition between ADP and ATP. Even in the presence of ADP, the rate of stiffness decrease was proportional to the amount of released ATP, but was not affected by Ca2+, P(i), or the fiber tension. 3) In the absence of ADP, the Ca2+ sensitive contraction occurs only after the initial phase. However, in the presence of ADP, the fiber developed tension during the initial phase before the late contraction. The initial contraction was insensitive to Ca2+, resistant to P(i) and BDM, larger on releasing more ATP, but not markedly influenced by the fiber tension. 4) Our results seem to suggest that, in the physiological reaction cycle, the cross-bridges develop significant force immediately after the binding of ATP, before releasing P(i).

Adenosine Diphosphate↗

PubMed1993

Significance of pre-S region-defective hepatitis B virus that emerged during exacerbation of chronic type B hepatitis.

A defective form of the hepatitis B virus has been found in a patient with chronic type B hepatitis. Sequence analysis of the viral DNA after polymerase chain reaction amplification revealed a 117-base pair deletion (nucleotides 3129-53, subtype adr). This deletion includes the initiation codon of the pre-S2 region and a newly created in-frame stop codon in the pre-S1 region (nucleotide 3055) located 230 base pairs downstream from the pre-S1 initiation codon. This virus coexisted with the wild-type virus during the exacerbation period, as evidenced by an elevation of serum transaminase levels. It was not detected in the stable period, and the blood chemistry results were normal. We assayed antibodies against the mutation-related region by enzyme immunoassay in serial serum samples to clarify the mechanism of the emergence of this variant virus. Antibodies against the pre-S2 region were negative; however, the antibody response against the pre-S1 epitopes coincided with the appearance of the variant virus. These findings suggest that an activated T-cell and B-cell response had developed against the pre-S1 region during hepatic inflammation in this patient and that, consequently, selection occurred for a pre-S antigen-defective mutant strain of the virus that might be resistant to such an immune response.

Adult↗

PubMed1993

Transesophageal Doppler echocardiographic assessment of pulmonary venous flow pattern in subjects without cardiovascular disease.

This study was designed to assess pulmonary venous flow dynamics using transesophageal Doppler echocardiography. Under general anesthesia, we studied 54 surgical patients with no history or physical evidence of cardiac disorders. In all patients pulmonary venous flow was easily identified by transesophageal color flow mapping. Pulmonary venous flow pattern, which was obtained clearly in 85% (4654) of patients by transesophageal pulsed Doppler echocardiography, was tri- or quadriphasic. The first wave, which was often biphasic in elderly patients, occurred during ventricular systole (S wave). The second wave occurred in diastole during the early ventricular filling phase of mitral flow (D wave). The third wave was reverse flow toward the pulmonary vein during atrial contraction (A wave). The following variables were measured: the peak flow velocities of each wave (PFVs, PFVd, PFVa), and the ratio of PFVs to PFVd (PFV(S/D)). The PFVd correlated with age (r = -0.56, P < 0.001), indicating age-related decrease. The PFV(S/D) correlated with age (r = 0.61, p < 0.001), indicating age-related increase. These results would indicate that the contribution of pulmonary venous flow during diastole to total pulmonary venous flow decreases with age. Our data suggest that age-related diastolic dysfunction of the left ventricle would affect pulmonary venous flow dynamics and that left atrial storage volume during ventricular systole would increase with age.

Adolescent↗

PubMed1993

Time-course of recovery of atrial contraction after cardioversion of chronic atrial fibrillation.

We aimed to study the time-course of recovery of atrial contraction after cardioversion of chronic atrial fibrillation (duration of more than 3 months) to sinus rhythm. Using M-mode, two-dimensional and pulsed Doppler echocardiography, we determined left atrial (LA) and ventricular (LV) dimensions, peak velocities, and velocity-time integrals of early and atrial filling velocity-time profiles in both LV and right ventricular (RV) inflows (peak E and peak A, Ea and Aa). Results of the LA and LV functions in seven elderly patients (an initial study group) were as follows. The extent of the LA dimensional reduction resulting from atrial contraction was significantly increased up to 5-8 weeks compared with values 0-1 day after cardioversion [from 1.3 +/- 0.8 (mean +/- SD) mm to 3.9 +/- 1.1, P < 0.01]. In conjunction with the progressive increase in peak A, the ratio of peak E to peak A (peak E/A) was significantly decreased and reached a plateau at 5-8 weeks (from 1.93 +/- 0.59 to 0.67 +/- 0.11, P < 0.01). LV fractional shortening was increased significantly 5-8 weeks after cardioversion (from 0.20 +/- 0.06 to 0.29 +/- 0.05, P < 0.01). Since a large part of the improvement in LA contraction was expected to occur in an early stage after cardioversion, we studied eight additional patients more frequently in the early stage (an additional study group). Furthermore, we studied the time course of LA and right atrial (RA) contractions.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1993

Right atrial contractile performance in patients with myocardial infarction.

To evaluate right atrial (RA) contractile performance in patients with myocardial infarction, we validated a cineangiographic method of RA volume measurement, and investigated RA volume change in 'normal' individuals and patients with a previous myocardial infarction. Sixteen silicone rubber RA casts made from human cadavers were filmed in the postero-anterior and left lateral projections. The cast volumes calculated following Simpson's rule were in good agreement with those measured by water replacement (r = 0.992, P < 0.01). At cardiac catheterization, biplane RA cineangiography was performed in 19 'normal' individuals (N group), in 14 patients with a previous antero-septal infarction (AMI group) and in seven patients with a previous inferior infarction (IMI group). The RA volume-time curve was constructed at 20-40 ms intervals for one cardiac cycle. RA volume at the beginning of the atrial contraction (RAVd), which was defined as the 'preload' of the RA, tended to be larger in both the AMI and IMI groups compared with 'normal' individuals. The RA ejection volume was significantly larger in both the AMI (18.4 +/- 2.1 ml.m-2, P < 0.01) and IMI groups (19.4 +/- 2.8, P < 0.01) than in the N group (14.5 +/- 1.9), even for a comparable level of RAVd (range from 26 to 36 ml.m-2) (18.6 +/- 2.1, P < 0.01, 18.2 +/- 2.0, P < 0.01, 14.7 +/- 1.9, respectively). These results suggest that RA contraction increases in patients with myocardial infarction by increasing both the 'preload' and 'contractility' of the RA.

Adult↗

PubMed1993

Platelet aggregation inhibitors in a Bhutanese medicinal plant, shug chher.

The 90% methanol-soluble fraction of a Bhutanese medicinal plant, Shug Chher, exhibited inhibition of platelet aggregation induced by platelet activating factor. Bioassay-directed fractionation led to the isolation of four new labdane diterpenoids, 3 alpha, 15-dihydroxy-labda-8(17), 13E-diene (5), 3 alpha-hydroxy-labda-8(17), 13E-dien-15-oic acid (6), 3 alpha-hydroxy-labda-8(17), 12E, 14-trien-19-oic acid (7), and 3 alpha-acetoxyisocupressic acid (8) and four known diterpenoids, manool (1), 3 alpha-hydroxymanool (2), 3 alpha-hydroxy-12, 13E-biformene (3), and isocupressic acid (4). The structures of the new compounds were determined spectroscopically. Compounds 2, 3, and 5 inhibited platelet aggregation.

Bhutan↗

PubMed1993

Synthesis of manool-related labdane diterpenes as platelet aggregation inhibitors.

Enantioselective total synthesis of the labdane diterpene (-)-1, was achieved starting from the R-(-)-enantiomer of the Wieland-Miescher ketone. The enantiomer (+)-1 was obtained by partial synthesis via microbial transformation of sclareol. These results established that the natural compound (+)-1, a platelet aggregation inhibitor, has a normal absolute stereochemistry like that of manool. The B-norlabdane-related compound 44 was also synthesized using a novel ring contraction reaction.

Crystallography, X-Ray↗