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Biomedical subjects

K Takada

Publications and source records attributed to K Takada.

At least 37 records · Page 2Linked to original sources
PubMed2003

Magnetic resonance cholangiopancreatography on postoperative work-up in children with choledochal cysts.

This study aimed to assess the clinical usefulness of magnetic resonance cholangiopancreatography (MRCP) as a postoperative diagnostic tool in children with choledochal cysts. Magnetic resonance cholangiopancreatography was performed postoperatively in 19 patients and image quality was compared with that obtained by intravenous cholangiography spiral computed tomography (IVC-SCT). While the detectability by MRCP was inferior to that by IVC-SCT, MRCP highly (84.2%) depicted the anastomotic site together with the reconstructed bowel and intrahepatic bile ducts. Magnetic resonance cholangiopancreatography also clearly delineated the postoperative condition of pancreaticobiliary maljunction (PBM), residual distal common bile duct, common channel, and pancreatic duct. Since MRCP is noninvasive and requires neither radiation exposure nor a contrast agent, and is useful for detecting both anastomosis and pancreatico-biliary ducts around PBM, MRCP might be superior to IVC-SCT as an imaging technique for outpatient clinics performing long-term follow-up studies in children with choledochal cysts.

Anastomosis, Surgical↗
PubMed2003

Hepatoblastoma associated with Beckwith-Wiedemann syndrome and hemihypertrophy.

Both Beckwith-Wiedemann syndrome (BWS) and hemihypertrophy (HH) have been recognized to be overgrowth syndromes associated with an increased risk of cancer. We report an infant with hepatoblastoma associated with both BWS and HH in whom high serum alpha-fetoprotein (AFP) levels persisted even after complete tumor resection with no tumor recurrence. This phenomenon might be partly due to the nature of the proliferative disease. It is important to recognize that in some infants with BWS prolonged high serum AFP levels mimic the existence of a tumor, and that treatment should be based not only on AFP measurement, but also on repeated radiologic imaging.

Beckwith-Wiedemann Syndrome↗
PubMed2003

Lymphocyte depletion with fludarabine in patients with psoriatic arthritis: clinical and immunological effects.

OBJECTIVE: To obtain preliminary information on the safety and efficacy of fludarabine in PsA and analyse its immunomodulatory effects in peripheral blood and synovial tissue. METHODS: 15 patients with active PsA who did not respond to DMARDs were randomly allocated to receive fludarabine every four weeks or placebo. Primary outcomes were the proportion of patients who met the ACR20 and the psoriatic arthritis response criteria (PsARC) at 16 weeks. Secondary outcomes were changes in tender or swollen joint counts and scores of the psoriasis area and severity index (PASI). Phenotypic analysis of peripheral blood mononuclear cells (PBMC), synovial immunohistochemistry, and functional analysis of PBMC were used to determine the immunomodulatory effects of fludarabine. RESULTS: At 16 weeks the ACR20 criteria were met by 3/7 (43%) fludarabine treated v 0/8 placebo treated patients (p=0.08); the PsARC was achieved by 4/7 (57%) fludarabine treated v 2/8 (25%) placebo treated patients; and 3/7 (43%) fludarabine treated v 0/7 placebo treated patients had > or =20% improvement in the PASI. Marked peripheral lymphopenia involving naive (CD4(+) CD45RA(+)) and memory (CD4(+) CD45RO(+)) T cells, CD8(+) T cells, and B cells was seen in fludarabine treated patients. CONCLUSIONS: In PsA fludarabine induces significant peripheral, but modest, synovial lymphopenia, and a trend towards improved clinical response.

Adult↗
PubMed2003

Adjustment of the occlusal vertical dimension in the bite-raised guinea pig.

In humans, the inappropriate occlusal vertical dimension (OVD) causes several orofacial disorders, such as bruxism and pain in the masticatory muscles and temporomandibular joint. However, it is still unclear how strictly the OVD is adjusted. To answer this question, we studied the temporal change of the OVD in bite-raised young guinea pigs. The OVD was raised by fixation of a bite-raising appliance to the lower incisors, and increased by either 3 or 1.5 mm at the first molars. After the space produced between the upper and lower molars was filled within 10 days due to eruption of the molars, the appliance was removed. In the bite-raised animals, the raised OVD was reduced until it attained that observed in the control animals, after which the OVD increased according to cranial growth. These results show that the OVD is developmentally changed and strictly controlled.

Adaptation, Physiological↗
PubMed2002

Successful treatment of advanced peripheral T-cell lymphoma with an angiocentric growth pattern complicated with hemophagocytic syndrome by high-dose chemotherapy and autologous peripheral blood stem cell transplantation.

Peripheral T-cell lymphomas (PTCL) account for about 10% of all lymphomas in Western countries, respond poorly to therapy, and have short survival with no sustained remission. Furthermore, the complication of hemophagocytic syndrome (HPS) sometimes makes the prognosis of this disease extremely worse. We report here a case of PTCL with an angiocentric growth pattern complicated with HPS successfully treated by high-dose chemotherapy and autologous peripheral blood stem cell transplantation. Our case suggests this approach is an excellent candidate for the treatment of this disease.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2002

Protection against dextran sulfate sodium-induced colitis by microspheres of ellagic acid in rats.

Ellagic acid (EA), a naturally occurring plant phenol, has the antioxidant and anti-inflammatory activities. In the present study, we examined the effect of EA contained in microspheres on the ulcerative colitis induced experimentally in rats by dextran sulfate sodium (DSS). Experimental colitis was induced in male Fisher 344 rats by daily treatment with 3% DSS solution in drinking water for 7 days. EA of microspheres (mcEA: 1 approximately 10 mg/kg as EA contents) was administered p.o. twice daily for 6 days. In a preliminary study, we found that these microsphere capsules, when administered p.o., are effectively dissolved in the proximal to the ileo-cecal junction and distributed to the terminal ileum and the colon. The ulceration area, colon length, and mucosal myeloperoxidase (MPO) activity as well as thiobarbituric acid-reactive substances (TBARS) were measured on 7th day after the onset of DSS treatment. The DSS treatment for 7 days caused severe mucosal lesions in the colon, accompanied with the increases of MPO activity and TBARS as well as the decreases of body weight gain and colon length. Administration of mcEA reduced the severity of DSS-induced colitis in a dose-dependent manner, and a significant effect was observed at 10 mg/kg, the ED50 being 2.3 mg/kg. This mcEA treatment also significantly mitigated changes in various biochemical parameters in the colonic mucosa induced by DSS. Although plain EA (without using microspheres) was also effective in reducing the severity of DSS-induced colitis, this effect was much less potent as compared with that of mcEA; the ED50 was about 15 times higher than that of mcEA. In addition, a significant effect on DSS-induced colitis was also obtained by intra-rectal administration of superoxide dismutase, an anti-oxidative agent. These results suggest that EA prevents the ulcerative colitis induced by DSS, probably by radical scavenging and/or anti-oxidative actions. The microspheres used in this study may be useful for delivering an orally administered drug specifically to the colon.

Animals↗
PubMed2002

A case of true malignant histiocytosis: identification of histiocytic origin with use of immunohistochemical and immunocytogenetic methods.

We report here an autopsy case of true malignant histiocytosis. The patient was a 67-year-old woman who exhibited fever, wasting, hepatosplenomegaly, and progressive pancytopenia. The bone marrow aspiration disclosed hemophagocytosing cells, which resembled histiocytes. The molecular analysis did not show the clonal gene rearrangement of T-cell receptor or immunoglobulin heavy chain. Although the patient had been started on methylprednisolone pulse therapy and chemotherapy with etoposide, she died from cerebral hemorrhage. The autopsy specimens of spleen and liver showed extensive infiltration of atypical cells, for which histiocytic origin was identified with an immunohistochemical method using monoclonal antibodies against CD11c, CD68, macrophage colony-stimulating factor (M-CSF), M-CSF receptor, lysozyme, antitrypsin and alpha1-antichymotrypsin. Recent investigations have disclosed that in most cases diagnosed as malignant histiocytosis, hemophagocytosis was reactive and not evoked by histiocytic malignancy. True malignant histiocytosis, for which histiocytic origin is confirmed, is extremely rare.

Aged↗
PubMed2002

Renal flares are common in patients with severe proliferative lupus nephritis treated with pulse immunosuppressive therapy: long-term followup of a cohort of 145 patients participating in randomized controlled studies.

OBJECTIVE: Immunosuppressive agents have become the standard of therapy for proliferative lupus nephritis, but some patients may relapse after discontinuing treatment. We reviewed the cases of renal flares in a cohort of patients who participated in 2 randomized controlled clinical trials at the National Institutes of Health and explored the prevalence, outcome, and predictive factors of renal flares. METHODS: Data were obtained on 145 patients treated with pulse cyclophosphamide, pulse methylprednisolone, or the combination of both. Patients had not received immunosuppressive therapy for at least 6 months and had experienced complete or partial response according to defined criteria. Renal flares were classified as either proteinuric or nephritic based on changes in urinary protein and sediment. Most patients who experienced a flare received additional immunosuppressive therapy. RESULTS: Seventy-three patients had a complete response, and 19 had partial response/stabilization. Forty-one of these patients (45%) experienced renal flares (nephritic in 33, proteinuric in 8) after a mean followup of 117 months; 31 of them received additional immunosuppressive therapy. The median time to renal flare was 36 months in the complete responders and 18 months in the partial responders. Eleven of the 41 patients (27%) progressed to end-stage renal disease (ESRD); 9 had nephritic flares (all severe except for 1) and 2 had proteinuric flares (1 in each responder group). Compared with patients who had a complete response, those with a partial response were more likely to experience a flare, to have a severe nephritic flare, or to progress to ESRD. Low C4 at the time of response and African American ethnicity were significant independent risk factors for renal flare, by multivariate Cox proportional hazards analysis. CONCLUSION: Nephritic flares are common in patients with proliferative lupus nephritis, even in those with a complete response to therapy, but they do not necessarily result in loss of renal function if treated with additional immunosuppressive agents. Renal flares are an important feature of the natural history of lupus nephritis and provide an opportunity for additional preventive strategies, as well as measures of efficacy in future therapeutic trials.

Adult↗
PubMed2002

Postoperative intussusception after incidental appendicectomy.

Postoperative intussusception of the appendiceal stump is a rare complication of appendicectomy. We report an infant who developed an intussusception of the appendiceal stump 2 days following an appendicectomy performed during a right inguinal herniotomy as a day case. The intussusception was diagnosed on ultrasonography and was to be treated laparoscopically, but spontaneous reduction occurred during induction of general anesthesia.

Abdomen↗
PubMed2002

Cloning of canine 21-hydroxylase gene and its polymorphic analysis as a candidate gene for congenital adrenal hyperplasia-like syndrome in Pomeranians.

A Strong breed predisposition to canine congenital adrenal hyperplasia-like syndrome (CAH-LS) exists and implies there is an hereditary cause. Pomeranians, one of the most predisposed breeds, have been reported to have partial adrenal dysfunction that could be associated with the pathogenesis of CAH-LS. In this study, the full-length complementary DNA (cDNA) of canine 21-OH, whose mutations are most likely responsible for the adrenal dysfunction in Pomeranians, was initially obtained from adrenal gland RNA by reverse transcription-polymerase chain reaction (RT-PCR), and its nucleotide sequence was determined. Genomic DNA samples from 16 Pomeranians and 30 control dogs, of seven different breeds, were tested for 21-OH gene polymorphisms by direct sequencing. No mutations affecting the primary structure and the transcriptional level of the 21-OH enzyme were found in Pomeranians. Our results indicate that the adrenal dysfunction in Pomeranians is not due to mutations of the 21-OH gene. This contrasts with the human form of CAH where 21-OH gene mutations are the major cause of the disease.

5' Flanking Region↗
PubMed2002

Gastrointestinal mucoadhesive patch system (GI-MAPS) for oral administration of G-CSF, a model protein.

A new gastrointestinal mucoadhesive patch system (GI-MAPS) has been designed for the oral delivery of protein drugs. The system consists of four layered films, 3.0 x 3.0 mm2, contained in an enteric capsule. The 40 microm backing layer is made of a water-insoluble polymer, ethyl cellulose (EC). The surface layer is made of an enteric pH-sensitive polymer such as hydroxypropylmethylcellulose phthalate (HP-55), Eudragit L100 or S100 and was coated with an adhesive layer. The middle layer, drug-containing layer. made of cellulose membrane is attached to the EC backing layer by a heating press method. Both drug and pharmaceutical additives including an organic acid, citric acid, and a non-ionic surfactant, polyoxyethylated castor oil derivative (HCO-60), were formulated in the middle layer. The surface layer was attached to the middle layer by an adhesive layer made of carboxyvinyl polymer (Hiviswako 103). Fluorescein (FL), 30mg, was first used as a model drug for oral administration of GI-MAPS having different surface layers in beagle dogs. The plasma FL concentration vs. time profiles demonstrated that the targeting of the systems was obtained, because the Tmax, the time when plasma FL concentrations reaches to its maximum lelev, was 2.33+/-0.82 h for HP-55 system, 3.33+/-0.41 h for Eudragit L100 system and 5.00+/-0.00 h for Eudragit S100 system. The same three kinds of GI-MAPSs containing 125 microg of recombinant human granulocyte colony-stimulating factor (G-CSF) were prepared and orally administered to dogs and the increase in total white blood cell (WBC) counts were measured as the pharmacological index for G-CSF. Comparison with the total increase of WBCs after iv injection of the same amount of G-CSF (125 microg) indicated the pharmacological availabilities (PA) of G-CSF were 23%, 5.5% and 6.0% for Eudragit L100, HP-55 and Eudragit S100 systems. By decreasing the amount of HCO-60 and citric acid, the PA of G-CSF decreased. These results suggest the usefulness of GI-MAPS for the oral administration of proteins.

Administration, Oral↗
PubMed2002

Hypogalactosylation of serum IgG in patients with ANCA-associated systemic vasculitis.

The triad of small vessel vasculitides (SVV) comprise Wegener's granulomatosis (WG), microscopic polyangiitis (MPA) and Churg-Strauss syndrome (CS). All three are associated with presence of circulating IgG antineutrophil cytoplasm antibodies (ANCA) which target autoantigens contained, primarily, within neutrophil azurophilic granules. The widely accepted model of pathogenesis suggests that ANCA activate cytokine-primed neutrophils within the microvasculature, leading to by-stander damage to endothelial cells, and rapid escalation of inflammation with recruitment of mononuclear cells. Activation may be initiated, in vitro, by the coligation of the PR3 or MPO antigen, translocated to the cell surface, and FcgammaRIIa/FcgammaRIIIb receptors. This suggests that the IgG subclass profile of ANCA and, possibly, its glycosylation status could influence the inflammatory mechanisms activated. The glycosylation status of total IgG isolated from the sera of patients with WG (13), MPA (6) and CSS (1) was determined by analysis of the released oligosaccharides. A deficit in IgG galactosylation is demonstrated for all patient samples, compared to controls. The mean percentage values for the agalactosylated (G0) oligosaccharides were 57% (SD +/- 9.71), 47% (SD +/- 4.25) and 28% (SD +/- 4.09) for WG, MPO and control samples, respectively. The G0 levels for polyclonal IgG isolated from the sera of both WG and MPA patients were significantly increased compared to controls (P < 0.0001). The major glycoform present therefore is agalactosylated (G0) IgG. In previous studies the G0 glycoform of IgG has been shown to bind and activate mannan binding lectin, and hence to activate the complement cascade, and to facilitate mannose receptor binding and the uptake of IgG complexes by macrophages and dendritic cells. Both of these activities could impact on the processing and presentation of self-antigens in autoimmune disease.

Adolescent↗
PubMed2002

A three-dimensional method of visualizing the temporomandibular joint based on magnetic resonance imaging in a case of juvenile chronic arthritis.

AIM: The purpose of this study was to present a new visualizing method for temporomandibular joint (TMJ) pathology in 3D at several condylar positions and to apply the method to a case of juvenile chronic arthritis (JCA) with previously diagnosed bilateral TMJ disorder and to a subject without signs and symptoms from the TMJ. SUBJECT: The 20-year-old female patient had suffered from polyarticular JCA from the age of 6 years 8 months. The present study is based on a follow-up examination after the completion of orthodontic treatment with the Herbst appliance. Both TMJs were examined using magnetic resonance imaging (MRI) at closed and open mouth positions. The mandibular condyle, the glenoid fossa and the articular disc were segmented and 3D reconstruction of these structures was carried out. RESULTS: The condyle was characterized by an increased sagittal diameter with osteophyte-like formation at the anterior aspect of the condylar head and flattening of the superior surface. The depth of the glenoid fossa was reduced and the articular eminence was remarkably flat. The articular disc was markedly diminished and posteriorly placed on the condylar head. The distance of the condylar path during mouth opening was reduced and the curvature of the condylar path was quite flat. The disc moved slightly posteriorly on the condylar head and remained in the glenoid fossa during mouth opening. CONCLUSION: The imaging modality described improves visualization of TMJ morphology and gains insight into the TMJ pathology of the JCA patient, adding to understanding of the clinical problems.

Adult↗
PubMed2002

Human masticatory muscle volume and zygomatico-mandibular form in adults with mandibular prognathism.

Although several investigators have reported associations between masticatory muscles and skeletal craniofacial form, there is no agreement on the association. We tested the hypothesis that masticatory muscle volume correlates with the size and form of the adjacent local skeletal sites. For this purpose, we investigated the morphological association of the cross-sectional area and volume of temporal and masseter muscles with zygomatico-mandibular skeletal structures using computerized tomography (CT) in 25 male adults with mandibular prognathism. Muscle variables significantly correlated with widths of the bizygomatic arch and temporal fossa but not with the cranium width. Masseter volume significantly correlated with cross-sectional areas of the zygomatic arch and mandibular ramus. Masseter orientation was almost perpendicular to the zygomatic arch and mandibular antegonial region. The zygomatic arch angle significantly correlated with the antegonial angle. The results of the study suggest that the masticatory muscles exert influence on the adjacent local skeletal sites.

Adolescent↗
PubMed2001

Normalization of elevated hepatic 8-hydroxy-2'-deoxyguanosine levels in chronic hepatitis C patients by phlebotomy and low iron diet.

Accumulation of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in DNA, which may result from the continuous reactive oxygen species (ROS) generation associated with chronic inflammation, has been reported in various human preneoplastic lesions and in cancerous tissues. However, no direct causative relationship between the 8-OHdG formation and carcinogenesis has been thus far demonstrated in humans. Directly proving the causality requires showing that depletion of 8-OHdG levels in tissue by interfering with ROS generation results in a reduction in cancer. Chronic hepatitis C virus (HCV) infection is associated with a high risk of hepatocellular carcinoma (HCC). Several studies on patients with chronic HCV have shown that hepatic iron overload is attributable to liver injury and that iron depletion improved serum aminotransferase levels. Excess iron is known to generate ROS within cells, which causes mutagenic lesions, such as 8-OHdG. In this study, therefore, we have evaluated whether therapeutic iron reduction (phlebotomy and low iron diet) with a long-term follow-up (6 years) would decrease the hepatic 8-OHdG levels and the risk of HCC development in patients with chronic HCV. Patients (34) enrolled were those who had undergone standard IFN therapy but had no sustained response. Quantitative immunohistochemistry using the KS-400 image analyzing system and electrochemical detection was used for 8-OHdG detection. With this treatment, elevated hepatic 8-OHdG levels in patients with chronic hepatitis C (8.3 +/- 4.6/10(5) dG) significantly decreased to almost normal levels (2.2 +/- 0.9/10(5) dG; P < 0.001) with concomitant improvement of hepatitis severity, including fibrosis, whereas HCV titers were unaffected. None of these patients developed HCC. Thus, long-term iron reduction therapy in patients with chronic hepatitis C may potentially lower the risk of progression to HCC.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2001

Purification and identification of monoubiquitin-phosphoglycerate mutase B complex from human colorectal cancer tissues.

Ubiquitin-conjugated proteins in human colorectal cancer tissues were analyzed by the immunoprecipitation with the antibody FK2 against conjugated ubiquitin followed with SDS-PAGE. In these immunoprecipitable proteins, a 38-kDa protein was abundant in the tumor regions but almost absent in the adjacent normal regions in 17/26 patients, thus we attempted to purify it. Using immunoaffinity chromatography with the antibody FK2 followed by gel filtration and SDS-PAGE, approximately 10 pmol of this protein was separated from 34 g of the pooled cancerous tissue and transferred onto a PVDF membrane. The 38-kDa protein was further digested with Achromobacter protease I, resulting in several peptide fragments. Amino acid sequences of these peptides showed complete sequence identity to those derived from either ubiquitin or phosphoglycerate mutase-B, suggesting that the 38-kDa protein is monoubiquitinated phosphoglycerate mutase-B, whose calculated mass is 37,369 Da. Western blot using an antibody against phosphoglycerate mutase-B revealed the presence of the 38-kDa protein in the anti-ubiquitin immunoprecipitates derived from the tumor regions, but not from normal counterparts. In addition, part of non-ubiquitinated phosphoglycerate mutase-B (29 kDa) was also found in the anti-ubiquitin immunoprecipitates, whose levels were higher in the tumor regions than in the adjacent normal regions. These results suggest that monoubiquitination of phosphoglycerate mutase-B as well as formation of a noncovalent complex containing ubiquitin and phosphoglycerate mutase-B increases in colorectal cancer and novel modification of phosphoglycerate mutase-B might have a pathophysiological role.

Aged↗
PubMed2001

A novel emulsifier, labrasol, enhances gastrointestinal absorption of gentamicin.

Gentamicin (GM) is an important aminoglycoside antibiotic for the treatment of infections caused by a wide spectrum of aerobic gram-negative bacilli and gram-positive cocci. As a class, the aminoglycosides are poorly absorbed from the gastrointestinal (GI) tract and are commonly used as injectable and topical preparations. This study was aimed at finding the effect of a novel emulsifier, Labrasol, on the absorption of GM from the GI tract of rats. GM formulations were prepared, either as saline solution or as Labrasol microemulsions, and were administrated to rat small intestine and colon. Plasma GM levels following intestinal application were compared to those obtained with intravenous (i.v.) administration. A 5 mg/kg dose of GM preparation containing Labrasol, 1 ml/kg, administrated into colon resulted in the mean AUC of 21.179+/-1.374 microg x h/ml, compared to 7.813+/-0.105 microg x h /ml obtained with i.v. administration of GM, 1 mg/kg. The absolute bioavailability (BA) of the Labrasol preparation was 54.2%. Labrasol facilitates the transmucosal delivery of GM from rat colon by forming microemulsions, and the BA obtained with Labrasol microemulsion was higher than with other surfactants (8.4% for Tween 80 and 3.4% for Transcutol P). Additionally, in vitro permeation studies demonstrated that Labrasol also inhibited the intestinal secretory transport. The effect of Labrasol is ascribed to both (1) enhanced GM absorption from the GI lumen into the systemic circulation and (2) inhibition of efflux of GM from the enterocytes to the GI lumen.

Administration, Topical↗