Search PubMed⌕ Search

Biomedical subjects

Junji Kato

Publications and source records attributed to Junji Kato.

At least 73 records · Page 4Linked to original sources
PubMed2003

[Successful induction and long-term molecular remission with imatinib mesylate and chemotherapy in a case of Ph-positive acute lymphoblastic leukemia].

The patient was a 68-year-old woman who was diagnosed as having Ph-positive acute lymphoblastic leukemia (ALL). Complete remission (CR) was not obtained with the induction therapy of the Japan Adult Leukemia Study Group Protocol. We then considered administration of imatinib (ST1571). The institutional review board of our hospital approved this therapy, and we initiated the administration of imatinib 400 mg/day after obtaining written informed consent from the patient. At day 10 of the regimen, CR was achieved, treatment had to be discontinued RT-PCR showed no induction of detectable minor bcr-abl mRNA after three courses of consolidation chemotherapy combined with imatinib. We changed the administration protocol of Imatinib to two weeks out of every in four, weeks, and conducted 9 courses of consolidation chemotherapy. The negative result of RT-PCR has been maintained 10 months after diagnosis. The adverse effects were body weight gain and retaining pleural effusion, and these were controlled by the diuretics. The negative result of RT-PCR in Ph positive ALL after chemotherapy has rarely been reported, so the combination of imatinib and chemotherapy may be considered to be effective for Ph positive ALL.

Aged↗
PubMed2003

[IgM type multiple myeloma expressing various surface adhesion molecules and demonstrating an aggressive clinical course].

A 70-year-old woman was admitted for anemia, elevated serum total protein and a right axillary mass. Laboratory data showed monoclonal x IgM with a decrease in serum IgG and IgA levels. An occipital punched-out lesion was detected on a cranial X-ray. A tumor lesion was detected on chest X-ray and computed tomography. Biopsy specimen revealed plasmacytoma with cytoplasmic IgM. Bone marrow aspiration revealed an elevated plasma cell count. An immunophenotype analysis of the plasma cells showed positivity of cytoplasmic IgM, x, CD5, CD38, CD11a (LFA-1), CD44 (HCAM), CD49d (VLA-4) and CD54 (ICAM-1). From the above results, we diagnosed the patient as having IgM myeloma associated with plasmacytoma. Melphalan and prednisolone therapy were prescribed, their effect on the myeloma was short term, so we changed the chemotherapy to VAD (vincristine, adriamycin and dexamethasone), but this treatment had little effect. The patient developed bacterial pneumonia and died. IgM myeloma is a rare disease and reports of immunophenotype analysis are also rare. There is no case report of plasmacytoma associated with IgM myeloma.

Aged↗
PubMed2003

[Effective use of combination chemotherapy with paclitaxel and 5-fluorouracil in a case of non-resectable advanced gastric cancer].

The patient was a 67-year-old man who had gastric cancer located in the posterior wall of the stomach and who underwent surgery on June 27, 2001. The operative finding was carcinomatous peritonitis in which the primary lesion was considered to be surgically unresectable. Therefore, only a probe laparotomy was performed. Under full informed consent, we performed combination chemotherapy with paclitaxel and 5-fluorouracil, 5-fluorouracil (600 mg/m2/day) was infused continuously for 120-hours (day 1-5) on administration and paclitaxel (60 mg/m2) was infused for 1.5 hours after premedication at day 8, 15 and 22 on an outpatient basis. After 2 courses of the chemotherapy, the tumor markers were reduced remarkably, ascites had completely disappeared, and abdominal lymph nodes had decreased. No serious adverse event was observed and the patient maintained good QOL throughout the treatment.

Aged↗
PubMed2002

Ex vivo expansion of human umbilical cord hematopoietic progenitor cells using a coculture system with human telomerase catalytic subunit (hTERT)-transfected human stromal cells.

We developed a new human stromal cell line that could expand human hematopoietic progenitor/stem cells. Primary human bone marrow stromal cells were infected with retrovirus containing the human telomerase catalytic subunit (hTERT) gene, resulting in increased population doubling and the acquisition of cell immortalization. Characteristics of the hTERT-transduced stromal (hTERT-stromal) cells were identical with those of the primary stromal cells in terms of morphologic appearance and expression of surface antigens. Human cord blood (CB) CD34(+) cells were expanded by coculture with primary stromal or hTERT-stromal cells in the presence of stem cell factor, thrombopoietin, and Flk-2/Flt-3 ligand under serum-free condition. The degree of expansion of CD34(+) cells and total number of colony-forming units in culture (CFU-Cs) after 2 weeks' coculture with the hTERT-stromal cells were nearly the same as those after 2 weeks' coculture with primary stromal cells (CD34(+) cells, 118-fold +/- 8-fold versus 117-fold +/- 13-fold; CFU-Cs, 71-fold +/- 5-fold versus 67-fold +/- 5-fold of initial cell number). CB expansion on hTERT-stromal cells occurred at a similar rate through 7 weeks. In contrast, the rate of CB expansion on primary stromal cells had drastically declined at 7 weeks. In nonobese diabetic/severe combined immunodeficiency (SCID) mice, the degree of engraftment of SCID-repopulating cells that had been cocultured with hTERT-stromal cells for 4 weeks was significantly higher than that of precocultured CB cells. These results indicate that this hTERT-stromal cell line could be useful for ex vivo expansion of hematopoietic progenitor/stem cells and for analyzing the microenvironment of human bone marrow.

Animals↗
PubMed2002

Induction of heat shock protein 47 synthesis by TGF-beta and IL-1 beta via enhancement of the heat shock element binding activity of heat shock transcription factor 1.

With most immunological reactions, tissue fibrosis, collagen overproduction caused by immune cytokines, is inevitably associated. Among the various immune cytokines, heat shock protein 47 (HSP47) is a procollagen-specific molecular chaperon and is essential for secretion of procollagen from cells. Induction of HSP47 by TGF-beta has been previously reported in rat skeletal myoblasts and mouse osteoblasts, but not in human diploid fibroblasts. As for IL-1beta, its effect on HSP47 has not been elucidated. In the present study, using human embryonic lung fibroblast cells, we first disclosed that both TGF-beta and IL-1beta induced HSP47 synthesis. We then revealed that the binding of the heat shock element (HSE) by heat shock transcription factor 1 (HSF1) was enhanced by both cytokines. We further demonstrated that trimer formation of HSF1, which is essential for its binding to HSE, was induced by these cytokines. The enhancement of HSP47 synthesis and their trimer formation of HSF1 were augmented by using a combination of both cytokines. Collectively, TGF- beta and IL-1beta were found to induce trimer formation of HSF1 which in turn bound to HSE of HSP47, resulting in the enhancement of HSP47 expression. Thus, HSP47 could well be a good candidate for molecular targeting in controlling tissue fibrosis, given that both principal fibrinogenetic cytokines (TGF-beta, IL-1beta) are commonly involved in its induction through HSF1 trimerization.

Cell Line↗
PubMed2002

Granulocyte-colony stimulating factor enhances the expression of transforming growth factor-beta mRNA in CD4-positive peripheral blood lymphocytes in the donors for allogeneic peripheral blood stem cell transplantation.

The degree of acute graft-versus-host disease (GVHD) after allogeneic peripheral blood stem cell transplantation (allo-PBSCT) has been observed to be, unexpectedly, of an equal level to that after bone marrow transplantation. To explain this phenomenon, we hypothesized that granulocyte-colony stimulating factor (G-CSF) administration may induce transforming growth factor (TGF)-beta producing T cells in the donors. Five donors received 10 microg/kg G-CSF subcutaneously for 4 days. The TGFbeta mRNA expression in CD4(+) cells as measured by real time reverse transcription-polymerase chain reaction increased after G-CSF administration. This elevation is considered to be one additive mechanism of repression of acute GVHD after allo-PBSCT.

Blood Donors↗
PubMed2002

E1B-55K-deleted adenovirus expressing E1A-13S by AFP-enhancer/promoter is capable of highly specific replication in AFP-producing hepatocellular carcinoma and eradication of established tumor.

Here, we constructed a recombinant replication-competent adenovirus (rRCAd; AdAFPep/Rep) that expresses both E1A-13S driven by the alpha-fetoprotein (AFP) enhancer/promoter (AFPep) lacking any silencers in the 5'-flanking region of the AFP gene, and 55K-deleted E1B driven by the cytomegalovirus (CMV) promoter. We then examined the feasibility of gene therapy utilizing this virus for AFP-producing hepatocellular carcinoma (HCC). AdAFPep/Rep lysed all the AFP-producing HCC cell lines (HuH7, HepG2, PLC/PRF/5 (P5)) examined at a multiplicity of infection (MOI) as low as 0.1 and did not lyse primary human hepatocytes (Hc) at a MOI as high as 100, indicating that the rRCAd virus can lyse AFP-producing HCC cells with a higher specificity and potency than previously reported. Furthermore, this virus was capable of complete eradication of a preestablished HuH7-cell tumor by a single intratumoral injection of 10(8) plaque-forming units (pfu) of AdAFPep/Rep. Thus, AdAFPep/Rep may be applicable for clinical use.

Adenovirus E1A Proteins↗
PubMed2002

Recent advance in molecular iron metabolism: translational disorders of ferritin.

Ferritin, composed of H-subunits and L-subunits, plays important roles in iron storage and in the control of intracellular iron distribution. Synthesis of both subunits is controlled by common cytoplasmic proteins, iron regulatory proteins (IRP-1 and IRP-2) that bind to the iron-responsive element (IRE) in the 5'-untranslated region of ferritin messenger RNA (mRNA). When intracellular iron is scarce, IRPs display IRE binding to suppress translation of mRNA. When cellular iron is abundant, IRPs become inactivated (IRP-1) or degraded (IRP-2). In the last few years, IRE mutations that cause disorders due to dysregulation of ferritin subunit synthesis have been identified. Hereditary hyperferritinemia-cataract syndrome is associated with point mutations or deletions in the IRE of L-subunit mRNA and is characterized by constitutively increased synthesis of L-subunits but is unrelated to iron overload. A single-point mutation in the IRE of H-subunit mRNA in members of a family affected with dominantly inherited iron overload has been reported. This review summarizes the current understanding of the translational disorders caused by IRE mutations in ferritin mRNA.

Cataract↗
PubMed2002

Transferrin receptor in tissue and serum: updated clinical significance of soluble receptor.

The transferrin receptor is an essential component of cellular uptake of iron, and it binds to serum transferrin. Recently, 2 different types of transferrin receptors have been recognized: transferrin receptor (TfR or transferrin receptor 1) and transferrin receptor 2. Most cells possess a ubiquitous system controlling the biosynthesis of TfR at the posttranscriptional level to avoid excess iron influx into the cells through TfR. During the process of recycling of transferrin receptors, some are shed and appear as soluble or serum transferrin receptors. Measurement of serum transferrin receptor is a new marker of iron metabolism that reflects body iron stores and total erythropoiesis. It has been shown that serum transferrin receptor to ferritin ratios have significant predictive value for differentiating iron deficiency anemia from non-iron deficiency anemia, such as anemia of chronic disorders, whereas serum ferritin is the only significant independent predictor of iron deficiency anemia.

Anemia, Iron-Deficiency↗
PubMed2002

Mechanisms for increment of platelet associated IgG and platelet surface IgG and their implications in immune thrombocytopenia associated with chronic viral liver disease.

In addition to hypersplenism, immunological destruction of platelets by elevated platelet associated IgG (PAIgG) and platelet surface IgG (PSIgG) has been proposed as a causative factor for thrombocytopenia in chronic liver disease (CLD), although the implication of PAIgG may be debatable since recent investigations on idiopathic thrombocytopenic purpura disclosed the fact that PAIgG largely relates to the intra-platelet IgG in alpha-granules and not to PSIgG. Further, with regard to the elevated PSIgG of CLD, characterization as to whether it mainly represents anti-platelet glycoprotein (GP) antibodies or IgG contained in the immune complex has not been elucidated. Thirty-seven patients with chronic viral liver disease (CVLD); 31 hepatitis C and 6 hepatitis B were included in this study. First we monitored the changes in levels of PAIgG, alpha-granule IgG, PSIgG and mean platelet volume (MPV) during the course of partial splenic arterial embolization (PSE). The elevated level of PAIgG decreased after PSE, paralleling that of alpha-granule IgG, while PSIgG showed no change; MPV decreased reciprocally with the increase of platelet count. These results indicate that the increment of PAIgG in CVLD may be caused by accelerated destruction of platelets; this generally evokes hyperproduction of large-sized thrombocytes, which have an increased capability to uptake circulating IgG. To characterize PSIgG, we then tested CVLD patients for antiplatelet GP antibodies and found only a 5.4% positivity. It was also found that circulating immune complex levels in CVLD patients were clearly elevated, correlating with the levels of PSIgG. Thus, it was surmised that immune complexes bound to the platelet surface, and not platelet specific GP antibodies, may be playing a crucial role in platelet destruction of CVLD, possibly through phagocytosis by macrophages.

Journal Article↗
PubMed2002

A patient with paroxysmal nocturnal haemoglobinuria in whom granulocyte colony-stimulating factor administration resulted in improvement of recurrent enterocolitis and its associated haemolytic attacks.

We report an elderly patient with paroxysmal nocturnal haemoglobinuria (PNH), having recurrent enterocolitis and haemolytic attacks associated with cellular immunodeficiency. On admission, the patient had normal neutrophil count and function but a decreased T-cell count, decreased mitogenic reactions, and a negative tuberculin test. Granulocyte colony-stimulating factor (G-CSF) was administered, resulting in an increased T-cell count, normalization of T-cell function, increased blood levels of helper T cell (Th)1 and Th2 cytokines and improvement in the enterocolitis and haemolytic attacks. This suggests that G-CSF may be useful in the treatment of elderly PNH patients with cellular immunodeficiency.

Aged↗
PubMed2002

Clinical features of a form of Hirschsprung's disease caused by a novel genetic abnormality.

BACKGROUND/PURPOSE: The aim of this report is to describe the pattern of similarities among the patients, exemplifying a newly recognized form of Hirschsprung's disease (HSCR) caused by mutations of ZFHX1B encoding Smad interacting protein-1. METHODS: Fluorescence in situ hybridization (FISH) using several cDNAs and RP11-BAC clones and mutation gene scanning using direct nucleotide sequencing analysis of polymerase chain reaction (PCR) were conducted. Personal records of the patients also were analyzed retrospectively to confirm the clinical features. RESULTS: All the patients represented isolated cases without any familial tendency. Aganglionic segments were limited to the recto-sigmoid colon in 3 cases and the rectum in one. Chromosomal screening found normal karyotypes in all cases except one, in whom a translocation between chromosomes 2 and 13 was detected. In addition to HSCR, characteristic facial appearance (hypertelorism with strabismus and wide nasal bridge), microcephaly with epilepsy, and severe physical and mental disabilities were found in all the patients. FISH for the patient having the chromosomal abnormality showed that about a 5-Mb cytogenetic deletion flanked at the 2q22 translocation breakpoint. Among 3 genes mapping to this deleted region, 2 nonsense mutations and a 4-base pair deletion were detected in ZFHX1B. CONCLUSIONS: The clinical features of the patients have surprising resemblance and constitute a wide spectrum of neurocristopathies. These findings suggest that the ZFHX1B may be a very important gene for normal embryonic neural crest development. These also indicate that the HSCR can be regarded as a congenital malformation with a background of a multigenetic neurocristopathy. It is of great interest that mutations were located at the same spot (exon 8) of ZFHX1B in 3 of 4 cases, probably accounting for the unique clinical features of this newly recognized form of HSCR.

Adult↗
PubMed2002

Role of endotoxin in NF-kappaB activation by ethanol in rat hepatocytes.

BACKGROUND: Endotoxin plays an important role in the progression of alcoholic liver injury. However, the role of endotoxin in acute activation of NF-kappaB by ethanol remains unclear. METHODS: In primary rat hepatocyte cultures treated with ethanol and/or endotoxin, the DNA-binding activity of NF-kappaB in the nuclear extract was estimated by electrophoretic mobility shift assay. After pretreatment of a CYP2E1 inhibitor, 4-methyl pyrazole or diallyl sulfide, NF-kappaB activity was also measured in the same manner. RESULTS: Ethanol or endotoxin caused activation of NF-kappaB in primary rat hepatocytes. Taking 50 mM of ethanol and endotoxin together raised the rapid increase in NF-kappaB activation, but both 100 mM of ethanol and endotoxin treatment reduced the increase. Addition of diallyl sulfide decreased the activity at rapid phase but increased it after 60 min, whereas addition of 4-methyl pyrazole caused no change of the activity at rapid phase but raised it after 60 min. Pretreatment with both endotoxin and a CYP2E1 inhibitor raised the activation of NF-kappaB constantly after ethanol addition. These findings suggest that endotoxin plays a critical role in the metabolism-independent activation of NF-kappaB by ethanol. CONCLUSIONS: Endotoxin raised metabolism-independent activation of NF-kappaB by high ethanol in rat hepatocytes.

Animals↗
PubMed2002

[Application of a CO₂ laser for oral soft tissue surgery in children in Sri Lanka--introduction of a laser through activities of aid to a developing country].

The objective of this study was to clarify the effect of CO2 laser irradiation on oral tissue problems in children in Sri Lanka, through the activities of aid to a developing country by the Japan International Cooperation Agency. This study took about six months, during two times periods: from November 2000 to February 2001, and from July 2001 to October 2001, in the paedodontic clinic of the Faculty of Dental Science, University of Peradeniya, in Sri Lanka. A CO2 laser was used on 48 subjects (51 cases), aged between 1 and 15 years, having main indications for labial frenectomy, frenectomy in ankyloglossia, and excision of mucocele. The results indicated that the CO2 laser had the following advantages. 1. Soft tissue cutting was efficient, with no bleeding, giving a clear operative field during operation. 2. There was no need to use sutures. 3. The surgery itself was simple and less time-consuming. Hence, there was no need for general anesthesia for such cases as tongue tie operation in small children. 4. There was no postsurgical infection. As a result, there was no need for analgesics or antibiotics, as post-surgical pain and infection were prevented. 5. Wound contraction and scarring were decreased or eliminated. Considering the above advantages, the use of a CO2 laser proved to be very safe and effective for soft tissue surgery, especially for children in developing countries such as Sri Lanka.

Adolescent↗
PubMed2002

[Adult-onset Still's disease accompanied by hemophagocytic syndrome at onset].

A 43-year-old woman was admitted for examination of fever, an elevated transaminase level, LDH, skin eruption, sore throat and bicytopenia. As bone marrow examination revealed an increased proportion of histiocytes and active phagocytosis, hemophagocytic syndrome (HPS) was diagnosed. After admission, the peripheral blood counts recovered spontaneously and the HPS subsided, but other symptoms persisted and the neutrophil count increased. At this time, we diagnosed the patient as having adult Still's disease. All the symptoms disappeared after administration of prednisolone. The markedly increased concentrations of TNF-alpha and IFN-gamma in the peripheral blood at the time of HPS declined gradually, and the IL-6 concentration increased at the time of diagnosis of Still's disease. However, all of these concentrations normalized after administration of prednisolone. As HPS and Still's disease have a common etiology, and each shows high concentrations of IFN-gamma, IL 6 and TNF-alpha, the symptoms are similar in both diseases. In particular, a relationship between HPS and high concentrations of TNF-alpha and IFN-gamma is suspected.

Adult↗