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Biomedical subjects

S Kawano

Publications and source records attributed to S Kawano.

At least 163 records · Page 9Linked to original sources
PubMed1996

The F(ab')2 fragment of an anti-ICAM-1 monoclonal antibody attenuates liver injury after orthotopic liver transplantation.

Long-term storage of liver grafts results in increased adhesion of leukocytes onto the sinusoidal walls. This eventually leads to posttransplant graft damage through disturbances of hepatic microcirculation. Intracellular adhesion molecule-1 (ICAM-1) is known to be involved in attachment of leukocytes. This study was designed to examine whether ICAM-1 participated in the pathogenesis of posttransplant liver injury. Inbred Lewis rats were used as both donors and recipients to avoid immunoreactivity. Donor livers were stored for either 1 or 6 hr in ice-cold Euro-Collins solution and subsequently implanted. Expression of ICAM-1 was examined immunohistochemically. In some rats that received livers stored for 6 hr, the intact IgG (1.0 mg/kg) or the F(ab')2 fragment (0.5 mg/kg) of an anti-ICAM-1 mAb (1A29) was administered via the tail vein immediately after reperfusion of portal blood. In the group receiving livers stored for 6 hr, ICAM-1 began to be expressed on the sinusoidal endothelial cells as early as 15 min after reperfusion of the portal blood. Strong ICAM-1 expression was observed from 2 hr up to 24 hr after reperfusion. In contrast, expression of ICAM-1 was not evident at any time point after surgery in the 1-hr storage group as well as in untransplanted, normal livers. Serum alanine aminotransferase (ALT) levels were significantly higher in the 6-hr storage group compared with those of the 1-hr storage group (1-hr: 171 +/- 9 IU/L; 6-hr: 825 +/- 109 IU/L, P < 0.05; mean +/- SEM) 24 hr after transplantation. Serum ALT levels were markedly reduced by treatment with the F(ab')2 fragment of 1A29 (247 +/- 34 IU/L, P < 0.05 vs. 6-hr storage group). This was associated with reduced accumulation of leukocytes in the liver. In marked contrast, treatment with the intact IgG of 1A29 increased serum ALT levels dramatically (5297 +/- 634 IU/L, P < 0.05 vs. 6-hr storage group) and reduced serum complement. Histological examination revealed focal hepatocellular necrosis 24 hr after surgery in the 6-hr storage group. Treatment with the F(ab')2 fragment decreased the liver damage; in marked contrast, treatment with the intact IgG strikingly aggravated the injury, as characterized by massive necrosis throughout the liver. Liver damage caused by the intact IgG might be related to activation of the complement system by the Fc portion of the antibody. Taken together, these results indicate that ICAM-1 is involved in the mechanism of postoperative liver injury following liver transplantation.

Animals↗
PubMed1996

Pathophysiologic significance of left ventricular hypertrophy in dilated cardiomyopathy.

BACKGROUND AND HYPOTHESIS: Patients with dilated cardiomyopathy (DCM) with left ventricular hypertrophy (LVH) have been found to have a better prognosis than patients without LVH. However, the pathophysiologic mechanism for that has not been investigated. We sought to clarify the pathophysiologic significance of LVH in DCM. METHODS: We performed isoproterenol infusion echocardiography (0.02 micrograms/kg/min) in 17 patients with DCM, and measured plasma epinephrine and norepinephrine levels at rest and at the end of ergometer exercise in 14 of the 17 patients. Patients were classified into groups according to the presence (9 patients) (LVH+) or absence (8 patients) (LVH-) of LVH. Left ventricular hypertrophy was defined as an inter-ventricular thickness or posterior wall thickness > or = 13 mm. RESULTS: Although there was no significant difference between groups in fractional shortening at rest during isoproterenol infusion, fractional shortening was significantly higher in the LVH(+) group than in the LVH(-) group (29 +/- 9 vs. 17 +/- 8%; p < 0.025). Although there was no significant difference in plasma norepinephrine level, it was significantly lower in the LVH(+) group than in the LVH(-) group (233 +/- 169 vs. 519 +/- 258 pg/ml; p < 0.05) at the end point of the exercise. CONCLUSION: Systolic reserve, represented by the response to isoproterenol, is greater in patients with DCM with LVH than in those without LVH, and a lower plasma level of norepinephrine is needed to activate the myocardium during exercise in patients with DCM with LVH. This pathophysiologic characteristic could be one of the mechanisms which explain a better prognosis in patients with DCM with LVH.

Adult↗
PubMed1996

Liposome-encapsulated dichloromethylene diphosphonate induces macrophage apoptosis in vivo and in vitro.

Dichloromethylene diphosphonate (MDPCl2) encapsulated in multilamellar liposomes was selectively incorporated by macrophages, immediately transferred to lysosomes, then released from liposomes into lysosomes by enzymatic digestion of the liposomal lipid layers. From 4 h after ingesting liposome-encapsulated MDPCL2 murine macrophages in vivo and in vitro acquired the ultrastructural features of apoptosis, such as condensed nuclear chromatic, nuclear fragmentation, cell shrinkage, and blebbing of the plasma membrane. Murine peritoneal macrophages and isolated rat Kupffer cells incubated in the medium containing liposome-encapsulated MDPCl2 increased DNA fragmentation in a dose-dependent manner. Electrophoretic analysis of extracted DNA from the isolated Kupffer cells showed DNA fragmentation. Another diphosphonate, Alendronate (4-amino-1-hydroxy-butylidene-1,1-diphosphonate) had less potent macrophage cytotoxicity. However, MDPCl2, Alendronate, and gadolinium chloride in solution were not cytotoxic to macrophages. These results implied that the intralysosomal accumulation of MDPCl2 generates signals to induce macrophage apoptosis.

Alendronate↗
PubMed1996

Alteration of T cells and natural killer cells during chickenpox in infancy.

To determine the reasons for the low immune response and the mild morbidity of chickenpox in infancy, we investigated alteration of T cells and natural killer (NK) cells during chickenpox in children < 1 year and > or = 2 years old using flow cytometry. The CD4/CD8 ratio decreased only in the < 1-year-old group from the acute to the convalescent phase (P < 0.05). The CD3-CD16+CD56+ and CD57-CD16+ counts increased in the < 1-year-old group, but those in the > or = 2-year-old group did not increase from the acute to the convalescent phase. The CD3-CD16+CD56+ counts and the CD57-CD16+ counts and percentage were larger in the < 1-year-old group than those in the > or = 2-year-old group (P = 0.001, P = 0.002, and P < 0.05) in the convalescent phase. These results seem to indicate that the low immune response in infancy after chickenpox are related to the small number of CD8 in contrast with CD4 and that increased subsets of NK cells during chickenpox may correlate to the mild morbidity of chickenpox in infancy.

Acute Disease↗
PubMed1996

Wall composition in intravascular ultrasound layered appearance of human coronary artery.

To evaluate the impact of histological factors on the appearance of the wall of the coronary artery by intravascular ultrasound (IVUS), we performed an in vitro study of 34 coronary artery segments from eight autopsied patients. We assumed the coronary cross section to be divided into four equal parts, and assessed the quadrants with maximal and minimal wall thickness by IVUS (30 MHz; 4.3 Fr; 1800 rpm) and by a histological study. The histological layer thickness and composition were also evaluated in terms of their contribution to the appearance of the ultrasound layer. Fifty-eight quadrants were clearly visible on ultrasound. A three-layered appearance, with inner echogenic, subjacent sonolucent, and outer echogenic layers, was observed in 32 quadrants, while 26 quadrants showed a two-layered appearance with inner and outer echogenic layers. The thickness of the inner echogenic layer (0.77 +/- 0.38 mm) was moderately correlated with the intimal thickness (0.51 +/- 0.45 mm; r = 0.85, standard error of estimate [SEE] = 0.24 mm); however, the correlation was significantly improved when the thickness of the inner echogenic plus sonolucent layers (0.89 +/- 0.47 mm) was compared with that of the intima plus media (0.69 +/- 0.47 mm; r = 0.94, SEE = 0.15 mm; P = 0.012 between the coefficients). Discriminant analysis showed that intimal hyalinization, associated with intimal thickening, was strongly related to the presence of the three-layered appearance on IVUS (F to enter 40.0, P < 0.0001). These results indicate that the ultrasound layered appearance of human coronary arteries varies with histological alterations. We suggest that the thickness of the inner echogenic plus sonolucent layers on IVUS represents the intimal plus medial thickness observed by histology, and that the use of this value may be appropriate in the assessment of coronary wall thickening associated with atherosclerosis.

Aged↗
PubMed1996

Rearrangements of mitochondrial DNA and the mitochondrial fusion-promoting plasmid (mF) are associated with defective mitochondrial fusion in Physarum polycephalum.

A specific linear mitochondrial plasmid (mF) is genetically associated with the fusion of mitochondria in the true slime mould, Physarum polycephalum. In matings between mF+ and mF- strains, which respectively carry and do not carry the mF plasmid, mitochondrial fusion occurs in the zygote. Mitochondrial fusion induces recombination between specific sites in the mitochondrial DNA (mtDNA) and in the mF plasmid. To detect a region which is associated with the mitochondrial fusion in the mF plasmid, we isolated, by fluorescence microscopy, strains which showed defective mitochondrial fusion (delta mif-) from those which showed normal mitochondrial fusion (mif+). Analysis of the mitochondrial genomes of delta mif- strains showed only mtDNA which recombined with the mF plasmid in mitochondria. Comparison of this recombinant mtDNA in one delta mif- strain (NG 15) with that of a mif+ strain showed that a 2.2-kbp region, which included the integration site of the mF plasmid, was deleted in the delta mif- strain by recombination between the main mtDNA and the mF plasmid. In other strains, in addition to this deletion, a 6-kbp region which included both termini was deleted by recombination at six repeats of AAT sequences in the mF plasmid. Moreover, transcripts of the mF plasmid were not detected in NG15 by slot hybridization.

Animals↗
PubMed1996

NSAIDS and the microcirculation of the stomach.

In this article, the effect of NSAIDs on the gastric mucosal microcirculation was reported. Although the precise mechanism of NSAID-induced ulcerogenesis is still unknown, most NSAIDs have been shown to impair gastric mucosal microcirculation and cause gastric mucosal damage.

Animals↗
PubMed1996

Evidences for involvement of cyclooxygenase-2 in proliferation of two gastrointestinal cancer cell lines.

Cyclooxygenase (COX) consists of two isozymes, COX-1 and COX-2. The roles of these isozymes in the gastrointestinal tract are unknown. We investigated messenger RNA expression of the COX-1 and COX-2 genes in the gastrointestinal cancer cell lines MKN28, MKN45, KATO III CACO-2, DLD-1 and LoVo. These cell lines expressed comparable levels of COX-1 mRNA, although their expression of COX-2 varied. Therefore, we studied the effects of NS-398 and indomethacin, specific and non-specific inhibitors for COX-2, on proliferation of the cell lines. Both of the inhibitors suppressed proliferation of the two cell lines that highly expressed COX-2 (MKN45 and CACO-2). However, these inhibitors exerted minimal effects on proliferation of the other cell lines, which expressed significantly lower levels of COX-2. Therefore, it was proposed that COX-2 participates in proliferation of cancer cells because of over expression of the COX-2 gene.

Cell Division↗
PubMed1996

Isolation and developmental expression of male reproductive organ-specific genes in a dioecious campion, Melandrium album (Silene latifolia).

The dioecious campion Melandrium album (Silene latifolia) has sex chromosomes, and male and female plants form different unisexual flowers. The very youngest buds have both sex organs but the development of either a gynoecium in the male bud or stamens in the female bud is arrested as the bud matures. To examine the molecular mechanism of male-specific differentiation, a cDNA library from male buds was differentially screened with cDNA from male and female buds. Four male reproductive organspecific cDNAs (corresponding to genes designated MROS1, MROS2, MROS3 and MROS4, respectively) were isolated. Northern blot analysis showed that the transcripts of MROS genes were expressed only in male reproductive organs. The transcripts of MROS3 and MROS4 accumulated in the early buds, while transcripts of MROS1 and MROS2 accumulated in the late buds and in the anthers of open flowers. The putative MROS2 protein has glycine-rich regions, while the putative MROS3 protein exhibits no similarity to known proteins. Genomic Southern blot analysis showed that male and female genomes included MROS2 and MROS3 genes. Non-radioactive in situ hybridization revealed the localization of the transcripts of MROS2 and MROS3 in male buds. MROS3 mRNA was distributed throughout the tapetum. After MROS2 mRNA had accumulated in the epidermis and the endothecium near the stomium, the accumulation of the mRNA increased significantly in the mature pollen. MROS2 seems to be a novel anther-specific gene that functions in dehiscence of anthers and the maturation of pollen.

Amino Acid Sequence↗
PubMed1996

Growth cone collapse and inhibition of neurite growth by Botulinum neurotoxin C1: a t-SNARE is involved in axonal growth.

The growth cone is responsible for axonal growth, where membrane expansion is most likely to occur. Several recent reports have suggested that presynaptic proteins are involved in this process; however, the molecular mechanism details are unclear. We suggest that by cleaving a presynaptic protein syntaxin, which is essential in targeting synaptic vesicles as a target SNAP receptor (t-SNARE), neurotoxin C1 of Clostridium botulinum causes growth cone collapse and inhibits axonal growth. Video-enhanced microscopic studies showed (a) that neurotoxin C1 selectively blocked the activity of the central domain (the vesicle-rich region) at the initial stage, but not the lamellipodia in the growth cone; and (b) that large vacuole formation occurred probably through the fusion of smaller vesicles from the central domain to the most distal segments of the neurite. The total surface area of the accumulated vacuoles could explain the membrane expansion of normal neurite growth. The gradual disappearance of the surface labeling by FITC-WGA on the normal growth cone, suggesting membrane addition, was inhibited by neurotoxin C1. The experiments using the peptides derived from syntaxin, essential for interaction with VAMP or alpha-SNAP, supported the results using neurotoxin C1. Our results demonstrate that syntaxin is involved in axonal growth and indicate that syntaxin may participate directly in the membrane expansion that occurs in the central domain of the growth cone, probably through association with VAMP and SNAPs, in a SNARE-like way.

Animals↗
PubMed1996

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↗
PubMed1996

Immunogenicity of the whole antigen and glycoprotein I of varicella-zoster virus (VZV) and the VZV skin test antigen.

Specific cellular immunity against the whole antigen and glycoprotein I (gp I) of varicella-zoster virus (VZV) and the skin test antigen were determined for 13 healthy immune adults to compare the immunogenicity of these antigens using a lymphoproliferative assay. The stimulation index values (mean +/- s.d.) were 16.4 +/- 11.2 against the whole VZV antigen, 4.2 +/- 2.9 against the VZV skin test antigen and 1.1 +/- 0.5 against gp I. The immunogenicity of the skin test antigen, which mainly contains gp III and gp IV, appears to be more favorable than that of gp I alone, but to be weaker than that of the whole VZV antigen.

Adult↗
PubMed1996

[Double infection of Chlamydia pneumoniae and Mycoplasma pneumoniae in children].

There have been fewer reports on Chlamydia pneumoniae infection during childhood than those in adults, although many of the C. pneumoniae infections occurred during childhood based on prevalence of the antibody. And there have been no reports concerning the double infection of C. pneumoniae and M. pneumoniae. We reported three cases of children with the double infection. We diagnosed this from significant alteration of these antibodies from the acute to convalescent phases. We omitted the cases without significant alteration of the antibodies, even diagnosed from isolation or detection of the antigens in the samples by direct fluorescent antibody. Case 1 was an 8-year-old-boy who was admitted to our hospital because of fever, cough with vomiting and erythema multiforme. The symptoms did not subside after administration of clindamycin but subsided after minocycline. Case 2 was an 1-year-old-boy who was admitted because of fever, cough, rhinorrhea and vomiting. C. pneumoniae organisms were isolated from the pharyngeal swab specimen, the symptoms subsided after administration of clindamycin. Case 3 was a 9-year-old boy who was admitted because of fever and a cough followed by erythema multiforme. The symptoms did not decrease after administration of clindamycin but after minocycline. The characteristic of these cases are a strong cough with vomiting, weak response of acute reactants on the laboratory data, and skin eruption similar with that due to M. mycoplasmae in two of the three cases. We suspect that these double infections may induce the eruption, about which there have been no previous reports.

Child↗
PubMed1996

[A case with petechiae due to human parvovirus B19].

We reported a case of 10-year-old girl with petechiae mainly on the truncus, although who had more than 10 x 10(4)/microliter of platelets. Smears of her bone marrow demonstrated extreme reduction of erythroblasts with giant proerythroblast like cells, which does not consist with idiopathic thrombocytopenic purpura. Human parvovirus B19 (B19) DNA was detected in her serum and throat swab using PCR and significant alterations of B19 specific IgM and IgG antibody titers were demonstrated. The petechiae subsided on the 8th day after her admission. She had not shown anemia less than Hb 10 g/dl, but her reticulocytes counts had increased up to 3.5% on the 11th day after her admission. Smears of her bone marrow on the 17th day became normal with moderate erythroblasts. It is demonstrated that the cellular receptor of this virus is an antigen of the blood group P recently. P antigen is presented not only on erythrocytes and on erythroblasts but also on megakaryocytes and endotherial cells. Therefore, it is suggested that direct injury by B19 to endothelial cells could cause petechiae in this case.

Child↗
PubMed1996

Electrophysiologic Effects of Beta-blocking Agent, Tilisolol, on Isolated Guinea Pig Ventricular Myocytes.

BACKGROUND: Electrophysiologic effects of a beta-blocking agent, tilisolol, were studied with isolated guinea pig ventricular myocytes using the whole cell patch clamp technique. METHODS AND RESULTS: Tilisolol at 10 µM or higher concentrations prolonged action potential duration (APD) at 90% repolarization (APD(90)) and at 100 µM or higher concentrations shortened APD at 20% repolarization (APD(20)) without changes in resting membrane potential. At 10 µM concentration tilisolol prolonged APD(90) from 236.6 +/- 55.3 ms in the control to 253.4 +/- 52.4 ms (n = 16; P <.01), while APD(20) was unaffected. At 100 µM tilisolol, APD(20) was shortened from 143.6 +/- 15.7 ms in the control to 133.7 +/- 22.6 ms (n = 8; P <.05). Under voltage clamp, tilisolol decreased the delayed rectifier K(+) current (I(K1)). Applications of 10 µM and 100 µM tilisolol reduced the maximal conductance of I(K) by 35.7 +/- 3.5% and 47.4 +/- 3.5% of the control, respectively, without changes in voltage dependence (n = 10). Tilisolol at 100 µM decreased the L-type Ca(2+) current (I(Ca.L)) by 22.0 +/- 9.8% (n = 6) of the control, and the inactivation curve was shifted to a hyperpolarizing direction. CONCLUSIONS: Tilisolol has a direct membrane action to depress I(K) and I(Ca.L), in addition to its beta-receptor blocking action.

Journal Article↗
PubMed1996

Variability of mitochondrial subgenomic molecules in the meristematic cells of higher plants.

MtDNAs from BY-2 cells and rice root were analyzed by random amplified polymorphic DNA (RAPD) assay and Southern hybridization analysis. A number of differences were observed in the RAPD patterns amplified from mtDNAs sampled at different phases of the BY-2 cell culture. RAPD fragments also varied with the template DNAs derived from various areas of rice root tip. When a RAPD fragment was hybridized to restriction fragments of whole DNAs, isolated from the distal area of the apical meristem and differentiated elongation zone of a root, two distinct stoichiometric differences were observed in the hybridization signals. This suggests that the organization of mt-genome in prototypic cells in the root apical meristem differs from that found in the differentiated cells.

Blotting, Southern↗