Biomedical subjects

K Kaji

Publications and source records attributed to K Kaji.

At least 37 records · Page 2Linked to original sources

PubMed2000

Ultra-small-angle neutron scattering studies on phase separation of poly(vinyl alcohol) gels

Time-resolved light scattering measurements during the gelation process of a poly(vinyl alcohol) (PVA) solution in a mixture of dimethyl sulfoxide and water (H2O) have shown that a spinodal decomposition (SD) type phase separation takes place in the early stage of gelation. In this case the kinetics of SD is valid only before macroscopic gelation occurs because the growth rate is slowed down by gelation. Such SD type phase separation makes the solution opaque as it proceeds, and hence the structural change can no longer be followed by light scattering. To investigate the structure of the opaque PVA gel as well, we have employed an ultra-small-angle neutron scattering technique using a Bonse-Hart camera. These observations reveal that even after the macroscopic gelation the structure due to the microphase separation on a spatial scale of several &mgr;m continues to grow against the elasticity. This may be because at first the gel structure is too soft to suppress the growth of the microphase separation, but within 24 h after the quenching the growth terminates. On the basis of the results, we will discuss a possible mechanism of the microphase separation after gelation.

Journal Article↗

PubMed2000

Further evidence of spinodal decomposition during the induction period of polymer crystallization: time-resolved small-angle x-ray scattering prior to crystallization of poly(ethylene naphthalate)

Aiming to clarify spinodal decomposition of polymers in the induction period of crystallization, time-resolved small-angle x-ray scattering measurements have been made in situ for poly(ethylene naphthalate) while it was crystallized from the glass, or in the case of the so-called glass crystallization. It is confirmed for this polymer that in the very beginning of the induction period a scattering peak appears at around 0.03 A (-1) in scattering vector q, which corresponds to a characteristic wavelength of 200 A in density fluctuations, and grows with time. Time evolution of this scattering peak is described by the kinetics of the spinodal decomposition as previously reported for the glass crystallization of poly(ethylene terephthalate).

Journal Article↗

PubMed2000

Identification and characterization of the new osteoclast progenitor with macrophage phenotypes being able to differentiate into mature osteoclasts.

Osteoclasts are thought to belong to a macrophage lineage. However, the nature of common precursors of osteoclasts and macrophages remains to be investigated. We have characterized the differentiation potential of mouse bone marrow macrophages into mature osteoclasts. Monocyte macrophage-colony-stimulating factor (M-CSF) stimulated the proliferation of bone marrow macrophages in a dose-dependent manner and these M-CSF-dependent bone marrow macrophage (MDBM) cells efficiently differentiated into the tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts in the presence of soluble RANKL (sRANKL) and M-CSF in the in vitro culture. The macrophage-like cell line TMC16 was established from tsA58 (temperature-sensitive SV40 large T-antigen) transgenic mice in the same manner to the preparation of MDBM cells and also differentiated into mature osteoclasts. During this differentiation in vitro, the morphology of the cells changed from spindle to round and smaller (termed pOC) on day 2 and to multinuclear (termed multinucleated cells [MNCs]) on day 4. The surface expression of macrophage marker CD14 was down-regulated and that of CD43 was up-regulated on pOC, analyzed by flow cytometry. RNA analysis revealed that osteoclast marker genes such as calcitonin receptor (CTR), carbonic anhydrase II (CAII), cathepsin K (cath K), MMP9, and TRAP were strongly expressed in MNCs and weakly in pOC whereas MDBM cells did not express these genes. However, the osteopontin (OPN) gene was strongly expressed in MDBM cells and this expression became weakened after differentiation into pOC. The TMC16 cell line weakly expressed cath K, TRAP, and OPN, suggesting that the TMC16 cell line is immortalized at a stage slightly differentiated from MDBM cells. Furthermore, cell sorting analysis revealed that osteoclast early progenitors in bone marrow cells are preferentially present in the Mac-1- F4/80dull population, which differentiated into MDBM cells (the osteoclast progenitor) expressing Mac-1+ F4/80int, suggesting that M-CSF plays roles of a differentiation factor as well as a growth factor for osteoclast early progenitors. These results showed the transition of morphology, surface markers, and gene expression from the early to mature stage in osteoclast differentiation. We propose three differentiation stages in the osteoclast lineage: the pro-osteoclast (spindle-shaped macrophage cells), the pre-osteoclast (small round mononucleated TRAP-positive cells), and the mature osteoclast (multinucleated TRAP-positive cells) stage.

Animals↗

PubMed2000

Indices for nutritional condition and thresholds for winter survival in sika deer in Hokkaido, Japan.

We derived fat indices for sika deer (Cervus nippon yesoensis) in eastern Hokkaido, Japan, and estimated the probability of over-winter survival with a logistic regression model using fat indices. Kidney fat mass (KFM) appears to be an adequate index of wide range of physical conditions before the onset of severe nutritional stress. When KFM values fell below 20 g, femur (FMF) and mandible cavity fat (MCF) indices declined sharply. FMF and MCF were useful indices for detecting malnourished deer. A logistic regression model describes survival thresholds in two bone fat indices for calves (45%) and three fat indices for adult females (FMF = 25%, MCF = 30%, KFM = 20 g). These models are useful for estimating the probability of winter survival in Hokkaido sika deer.

Adipose Tissue↗

PubMed1999

Serum levels of soluble interferon Alfa/Beta receptor as an inhibitory factor of interferon in the patients with chronic hepatitis C.

Human serum contains a soluble form of interferon alfa/beta (sIFN alpha/beta) receptors, the functional and clinical significance of which has not been investigated in patients with chronic hepatitis C. In the present study, serum levels of sIFN alpha/beta receptor were assessed in 81 patients with chronic hepatitis C and correlated with the effectiveness of IFN therapy in these patients. Serum levels of sIFN alpha/beta receptor were significantly higher in patients with chronic hepatitis C than in healthy control patients (P <.0001). In these patients, serum levels of sIFN alpha/beta receptor were correlated with those of alanine transaminase (ALT) (P <.05), (2'-5')serum oligo(A) synthetase (2-5AS) (P <.0001), and pathological stages of liver fibrosis (P <.01). In 55 patients with chronic hepatitis C who underwent IFN therapy, there was an inverse correlation between the pretherapeutic serum levels of sIFN alpha/beta receptor and the rate of increase in serum levels of 2-5AS after the start of IFN (P <.01). Pretherapeutic serum levels of sIFN alpha/beta receptor were significantly lower in patients who showed sustained response to IFN therapy compared with those who did not respond to the therapy (P <.05). Multivariate analysis showed that low levels of serum sIFN alpha/beta receptor (</=4.0 ng/mL) (P <.05) and serological hepatitis C virus genotype II (P <.05) were independent variables contributing to sustained response to IFN therapy. Thus, pretherapeutic serum levels of sIFN alpha/beta receptor were correlated with the effectiveness of IFN therapy, suggesting that sIFN alpha/beta receptor suppresses the effectiveness of IFN therapy in patients with chronic hepatitis C.

2',5'-Oligoadenylate Synthetase↗

PubMed1999

Sarcomatoid hepatocellular-carcinoma showing rhabdomyoblastic differentiation in the adult cirrhotic liver.

An unusual case of a massive liver tumour composed of rhabdomyosarcoma with a small focus of hepatocellular carcinoma in a 52-year-old man is presented. He had hepatitis B virus (HBV) surface antigen in his serum. Macroscopically, a large tumour with satellite nodules occupied the right lobe of the cirrhotic liver. Microscopically, the tumours were composed of small and short spindle-shaped undifferentiated cells, mixed with desmin-positive round rhabdomyoblasts and elongated striated muscle cells, strongly suggestive of rhabdomyosarcoma of the liver. Elevated levels of alpha-fetoprotein in the serum led us to examine the liver tumour closely in multiple sections, which disclosed a hepatocellular carcinoma component measuring 2 cm in diameter within the massive tumour. Immunohistochemically, the hepatocellular carcinoma cells were alpha-fetoprotein positive. There was neither a tumour capsule, nor distinct demarcation, and cytokeratin-positive clusters of undifferentiated cells were intermingled with the hepatocellular carcinoma and rhabdomyosarcoma at the border. The invading tumour outside the liver and metastatic tumours were pure rhabdomyosarcomas. It is suggested that the present case should be diagnosed as rhabdomyosarcoma transformed from hepatocellular carcinoma.

Carcinoma, Hepatocellular↗

PubMed1999

Investigation of albumin-synthesizing ability in rat cirrhotic liver-derived hepatocytes using primary hepatocyte culture.

BACKGROUND/AIMS: In cirrhosis, despite a decrease in the total number of hepatocytes, a normal serum albumin level is maintained during the compensatory stage of the disease in many cases. Therefore, to elucidate the mechanism in hepatocytes related to the regulation of the serum albumin level, the albumin-synthesizing ability of individual hepatocytes was investigated in cirrhotic rats. METHODS: Cirrhotic rats were prepared by oral administration of furfural to male Wistar rats for 20 weeks. Albumin-synthesizing abilities of liver and of isolated hepatocyte culture were evaluated by measuring the albumin concentration in blood and culture supernatant. Expressions of albumin mRNA were compared using Northern blotting. Furthermore, transcriptional activity of the albumin gene was measured using the promoter domain of the gene. RESULTS: The total number of hepatocytes in rat cirrhotic liver was significantly decreased compared to that in normal rat liver. However, there were no significant differences in levels of serum albumin or albumin mRNA expression between cirrhotic and normal liver. In primary hepatocyte culture, albumin mRNA expression, the amount of albumin secretion and the albumin promoter activity were clearly enhanced in cirrhotic hepatocytes compared to normal hepatocytes. CONCLUSION: Although the total number of hepatocytes was decreased in the rat cirrhosis models used in this study, the serum albumin level was maintained and albumin-synthesizing ability was enhanced at the transcriptional level in the individual hepatocytes. These results suggest that the maintenance of serum albumin levels in compensated cirrhosis may be due to enhanced albumin synthesis by the hepatocytes.

Animals↗

PubMed1999

Microscopic basis of free-volume concept as studied by quasielastic neutron scattering and positron annihilation lifetime spectroscopy.

We have reexamined the free-volume concept presented by Cohen and Turnbull on the basis of two microscopic quantities: the excess mean-square displacement (f) and the total free volume V(PA,t), of poly- butadiene evaluated from the quasielastic neutron scattering and the positron annihilation lifetime spectroscopy (PALS) data, respectively. Comparing with the viscosity eta we found two relations, eta=eta(0) exp u( 2)(0)/ (f) and eta=eta(0) exp V(*)(PA,0)/V(PA,t)=eta(0) exp V(*)(PA,0)/v(PA,f), where u(2)(0), V(*)(PA,0) and v(*)(PA,0) are the critical values for the mean-square displacement, the total PALS free volume, and the PALS free volume per molecule, respectively, and further v(*)(PA,0)=V(*)(PA,0)/N, N being the total number of molecules or segments. On the basis of these relations, we discuss the microscopic basis of the free-volume theory. The experimentally evaluated critical values u(2)(0) and v(*)(PA,0) are much larger than the average values of (f) and v(PA,f) calculated from the distributions. This has been explained from the low probability of escaping motions from a molecular cage. The free volume per monomer and the free-volume fraction were calculated from the excess mean-square displacement (f). The former was compared with the free-volume hole obtained by PALS, suggesting that 22 monomers are required for one PALS free-volume hole. The free-volume fraction obtained from the excess mean-square displacement was found to be 6.4% at 250 K, which is in reasonable agreement with that evaluated from the rheological data (9.0%).

Journal Article↗

PubMed1999

Immobilization of sika deer with medetomidine and ketamine, and antagonism by atipamezole.

Forty wild sika deer (Cervus nippon) were immobilized with medetomidine and ketamine and reversed by atipamezole in summer and fall captures from September 1994 to October 1995. For large yearling and older deer, mean +/- SD doses of 57.0+/-15.6 microg/kg medetomidine and 1.64+/-0.49 mg/kg (male) or 4.02+/-1.16 mg/kg (female) of ketamine were administered by intramuscular injection. For calves and small yearlings, 69.3+/-7.0 microg/kg medetomidine and 2.69+/-0.44 mg/kg ketamine were administered. While immobilized, deer were easy to handle, and muscles were well relaxed. After intramuscular administration of atipamezole (about 5 times the dose of medetomidine), deer recovered rapidly and smoothly.

Adrenergic alpha-Agonists↗

PubMed1998

Increased hepatocyte growth factor production by aging human fibroblasts mainly due to autocrine stimulation by interleukin-1.

Hepatocyte growth factor (HGF), also known as scatter factor is a pleiotropic factor that is mainly produced by mesenchymal cells and acts on cells of epithelial origin which express the HGF receptor c-Met. Here we demonstrate that production of HGF by human embryonic lung fibroblasts increased sharply after about 70% completion of their lifespan in culture, which is regulated at the transcriptional level. In addition, human skin fibroblasts from old donors, over 80 years, also produced more HGF than cells from young and middle-aged donors. The increased production of HGF by aging fibroblasts from human embryonic lung tissue is mainly due to autocrine stimulation by interleukin-1.

Adult↗

PubMed1998

Expression of interferon alpha/beta receptor in the liver of chronic hepatitis C patients.

Interferon (IFN) demonstrates antiviral activity by binding to receptors on the cell surface. Expression of the IFN receptor in hepatocytes may be directly associated with a hepatitis C virus (HCV) infection and the response to IFN therapy. A competitive PCR method was developed to measure IFN alpha/beta (alphabeta) receptor mRNA in liver samples obtained by needle biopsy. Thirty-one patients with chronic hepatitis C (21 without cirrhosis, 10 with cirrhosis) and six normal subjects were used. Eighteen of the 21 patients without cirrhosis received the IFN therapy. Competitive PCR was carried out using IFN alphabeta receptor gene-specific primers and a specific competitor. Expression of the receptor was detected in all liver samples. There was no association between the expression level and serum alanine aminotransferase level, serum (2'-5') oligo (A) synthetase level, amount of serum HCV RNA, or HCV genotype. The expression level in patients with chronic hepatitis was significantly higher than that in normal livers (P < 0.05) and in cirrhotic livers (P< 0.01). Seven of the 18 patients treated with IFN demonstrated a sustained response to IFN (sustained responders), and the remaining 11 did not (nonsustained responders). The expression level of IFN alphabeta receptor mRNA in the sustained responders was significantly higher than that in the nonsustained responders (P< 0.01). Thus, the expression of IFN alphabeta receptor mRNA may be one of the host factors influencing the response to IFN therapy.

Adult↗

PubMed1998

Expression of co-stimulatory factor B7-2 on the intrahepatic bile ducts in primary biliary cirrhosis and primary sclerosing cholangitis: an immunohistochemical study.

Co-stimulatory factors B7-1 (CD80) and B7-2 (CD86) and their ligands, including CD28, are important for the efficient presentation and persistence of an antigen-specific immune reaction. Hitherto, there has been a paucity of data on the roles of such co-stimulatory factors in immune-mediated biliary diseases. In this investigation, the hepatic immunohistochemical expression of B7-1 and B7-2 has been studied, with emphasis on intrahepatic biliary epithelia, using wedge biopsies from 22 patients with primary biliary cirrhosis (PBC), seven with primary sclerosing cholagitis (PSC), and, as controls, eight cases of extrahepatic biliary obstruction, eight of chronic viral hepatitis C, and three histologically normal livers. In 10/22 (45 per cent) patients with PBC and 3/7 (43 per cent) patients with PSC, B7-2, but not B7-1, was expressed on the epithelial cells of small intrahepatic bile ducts and bile ductules. This expression was manifest as diffuse but variable cytoplasmic staining. Such B7-2-positive bile ducts were not seen in controls. Positive staining was found only in the early stage of PBC and PSC. In PBC and PSC, almost all lymphocytes in the portal tracts, including those around the damaged bile ducts, were positive for CD28, a ligand of B7-2. These results suggest that B7-2 expression on biliary epithelial cells is involved in antigen presentation and perhaps in bile duct destruction in PSC and PBC.

Antigens, CD↗

PubMed1998

Inhibition of bFGF activity by complement C1s: covalent binding of C1s with bFGF.

The first complement component C1s formed large aggregates with bFGF when bFGF and C1s were incubated at 37 degrees C overnight. Under non-reducing conditions, a part of the aggregates did not penetrate into 5% polyacrylamide gel in the presence of SDS, and the rest penetrated into 5% gel but not into 12% gel. The aggregates were dissociated into monomers by reducing with 2-mercaptoethanol. Both active and inactive C1s formed aggregates with bFGF. In addition, a portion of bFGF was degraded by active C1s but not by inactive C1s. Aggregates were not formed when 2-mercaptoethanol (2 mM) was added to the incubation mixture. After the incubation with C1s the growth-stimulating activity of bFGF was measured by using human umbilical vein endothelial cells (HUVEC) as indicator cells. The aggregate formation between C1s and bFGF significantly reduced the activity of bFGF.

Biological Assay↗

PubMed1998

TMIG-2DPAGE: a new concept of two-dimensional gel protein database for research on aging.

Cellular proteins of a normal human diploid fibroblast line (TIG-3) at various stages of replicative aging were resolved by horizontal isoelectric focusing on an immobilized pH gradient, followed by vertical sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis (PAGE). Spot proteins were visualized by silver staining and quantitated by image processing. All corresponding spots were matched among two-dimensional gel images, and variation profiles in relative abundance of individual proteins during in vitro aging were classified into five categories, i.e., (i) increase, (ii) decrease, (iii) increase followed by decrease, (iv) decrease followed by increase, and (v) irregular or nonsignificant variation. The new concept of the Tokyo Metropolitan Institute of Gerontology two-dimensional gel protein database (TMIG-2DPAGE) was prepared from the above data to support research on cellular aging. The database was put on our World Wide Web home page at the URL of http://www.tmig.or.jp/2D/ to allow free access through the Internet. The individual protein data entries were linked to the standard spot protein map of the two-dimensional gel image in order to be accessible by clicking the mouse on it.

Aging↗

PubMed1998

Gastrointestinal amyloidosis secondary to hypersensitivity vasculitis presenting with intestinal pseudoobstruction.

A 22-year-old woman developed sudden hepatic encephalopathy and severe intestinal bleeding. She was diagnosed with acute fatty liver and hypersensitivity vasculitis and was successfully treated with whole plasma exchange, methylprednisolone pulse therapy, and transcatheter arterial embolization. Twenty-seven months later, she began complaining of lower abdominal fullness, tenderness, and nausea and vomiting. Histologic examination showed that she had developed gastrointestinal and renal amyloidosis with intestinal pseudoobstruction and proteinuria. The immunohistochemical study of the stomach, rectum, and kidney with anti-amyloid A fluorescent antibody showed that the systemic amyloid deposit was secondary to her underlying disease. This is the first report of amyloidosis occurring secondary to hypersensitivity vasculitis.

Adult↗

PubMed1998

Genetic variation and population structure of the Japanese sika deer (Cervus nippon) in Hokkaido Island, based on mitochondrial D-loop sequences.

Mitochondrial DNA (mtDNA) D-loop region sequences (602 bp) from 141 samples of the sika deer Cervus nippon collected from Hokkaido Island of Japan were investigated to elucidate population genetic structure. All animals possessed seven repeat units (38 or 39 bp each) in the sequences. Comparison of the 602-bp sequences showed four sites of transitional mutations (A<-->G or C<-->T). Based on combination of the substitutions, six D-loop haplotypes (a-f types) were identified in the Hokkaido population, suggesting the occurrence of at least six maternal lineages. Distribution maps of the haplotypes constructed using the Geographic Information System showed that the distribution of the major three types differed from haplotype to haplotype. In particular, distribution of the major three types (a-, b-, and c-types) almost overlapped with three main areas of coniferous forests in Hokkaido. These results suggest that expansion of the sika deer population could have occurred through the habitat of coniferous forests after the historical bottleneck in Hokkaido.

Animals↗

PubMed1998

A case of progressive multiple focal nodular hyperplasia with alteration of imaging studies.

Focal nodular hyperplasia (FNH) of the liver is a lesion characterized by a well circumscribed region of hyperplastic liver tissue with stellate fibrosis. The pathogenesis of the lesion is unknown but various authors consider that FNH may be a response to a preexisting vascular abnormality. We experienced a case of progressive multiple FNH, in which the hemodynamic change as shown by imaging modalities, may support this hypothesis. The patient, a 38-yr-old woman, was found by chance to have multiple portal venous shunts and multiple FNH in both lobes of her liver. Because of their benign characteristics, we followed the nodules periodically without any special treatment. After about 4 yr, the nodules increased both in size and number. In addition, digital subtraction angiography showed that the diameter of the artery had become larger. The hemodynamic change revealed by imaging studies in this case supports the hypothesis that one of the pathogens of FNH is a secondary hepatocellular response to arterial hyperperfusion caused by some vascular malformations.

Adult↗

PubMed1997

Purification of a vascular apoptosis-inducing factor from hemorrhagic snake venom.

Hemorrhagic snake venom induces apoptosis in vascular endothelial cells specifically. We report here the purification of an apoptosis-inducing factor from the venom of the rattlesnake Crotalus atrox. The purified factor was a homodimeric protein with a molecular mass of 110 kD and an isoelectric point of 8.5. When exposed to the factor, vascular endothelial cells in culture died, with the characteristic features of apoptosis, such as fragmentation of cells and cleavage of DNA into fragments that yielded a characteristic ladder pattern upon electrophoresis. The activity seemed to be specific to endothelial cells. This factor may prove to be a useful tool for studies of the molecular mechanisms of vascular apoptosis.

Animals↗