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Biomedical subjects

K Sawada

Publications and source records attributed to K Sawada.

At least 181 records · Page 10Linked to original sources
PubMed1997

Does the presence of serum autoantibodies influence the responsiveness to interferon-alpha 2a treatment in chronic hepatitis C?

The serum autoantibodies, antinuclear antibody, anti-DNA antibody, anti-smooth muscle antibody, antithyroglobulin antibody, antimicrosomal antibody, antimitochondrial antibody, rheumatoid factor and antibody to deoxyribonucleoprotein were measured at the baseline and on completion of interferon-alpha 2a (IFN-alpha 2a) treatment in chronic hepatitis C (CHC) patients who did not present with any autoimmune disease prior to treatment. Of the 57 patients examined, 27 spontaneously manifested at least one autoantibody. Only the prevalence of rheumatoid factor (26%) was significantly higher in the CHC patients than in the control subjects. There were no differences in the prevalence of the 8 autoantibodies examined between hepatitis C virus (HCV) genotypes 1b and 2a/2b. Twenty-six patients responded to IFN-alpha 2a. Subclinical hypothyroidism developed in two patients with elevated antithyroid antibody titres during treatment. No relationship was observed between changes in the status of autoantibodies and either response to IFN-alpha 2a or HCV genotype. Irrespective of the HCV genotype, autoantibodies might be present in CHC patients before and during the IFN-alpha 2a treatment. The presence of such antibodies does not represent a contraindication to the use of IFN-alpha 2a in CHC patients not complicated by autoimmune diseases. Careful observations are necessary for CHC patients positive for antithyroid antibodies during the IFN-alpha 2a treatment. Preexisting or newly developed autoantibodies do not necessarily predict a poor response to IFN-alpha 2a.

Adult↗
PubMed1997

[Remission by leukocytapheresis for a patient with ulcerative colitis found refractory by conventional drug therapies].

A 40-year-old male was admitted to our hospital on August 30, 1994 to receive a new ulcerative colitis (UC) therapy, leukocytapheresis (LCAP). On the admission day, he had bloody stool 5 to 6 times/day, abdominal pain, slight fever, and hypoproteinemia. His UC type was moderately severe left-sided colitis with pseudopolyposis. Prior to admission to our hospital, his condition had not improved for about 9 months, despite drug therapies such as salicylazosulphapyridine, intravenous high dose prednisolone, protease inhibitor, intraarterial hydrocortisone sodium succinate, 4 series of pulse therapies with metylpredonisolone, enema of corticosteroid, azathioprine (Imuran), and cyclosporine at another hospital. Thus he was introduced to our college hospital and treated by LCAP since September 1. After 10 LCAP sessions, remission was observed and the patient discharged on December 23. Until he was later operated on for heavy bleeding after he had discontinued treatment and had drunk heavily, he had maintained remission for 13 months with LCAP only once a month even after we gradually decreased the other medical supports and stopped all of them. After LCAP, the normalization of high percentage of leukocytes presented HLADR+ and lymphocytes presented CD 11 a+ CD 8+ was also observed. This suggests LCAP intercepts the excess immune reaction in UC by removing leukocytes.

Adult↗
PubMed1997

Structural comparisons of cell organelles and nuclei in rat hepatocytes with three different fixation techniques.

The morphological properties of cell organelles and nuclei in rat hepatocytes were compared, when the hepatocytes were either chemically fixed in glutaraldehyde and osmium (GA-Os), chemically fixed only in osmium (Os-2h) or physically fixed with a microwave-irradiated osmium (Mw-Os) fixative for a short duration. Judging from the fine structure, the mitochondria and rER were best preserved after physical fixation; because of the smooth surfaces and regular open contours, but both organelles shrank in the two chemical fixatives. The Golgi complexes and peroxisomes of the hepatocytes were not markedly changed by any of the fixative procedures. However the lysosomes and sER were changed to some extent after physical fixation. In the nucleus, the two kinds of chromatins and the nucleolus were best preserved with physical fixation. In conclusion, physical fixation is a very simple and fast procedure that is convenient for routine electron microscopy if some attention is paid to the morphological changes.

Animals↗
PubMed1997

Application of a colon delivery capsule to 5-aminosalicylic acid and evaluation of the pharmacokinetic profile after oral administration to beagle dogs.

Pressure-controlled colon delivery capsule (PCC) containing 5-aminosalicylic acid (5-ASA) for the treatment of inflammatory bowel disease (IBD) was prepared and evaluated by an in vivo experiment using beagle dogs. As a reference drug, sulfasalazine (SASP), prodrug of 5-ASA, was used as a plain gelatin capsule preparation. After the oral administration of SASP at the does of 25.0 mg/kg, the mean time when the plasma 5-ASA concentration reaches to its maximum (Tmax) was 9.0 hr. In the case of 5-ASA administered in PCC, at the doses of 12.5 and 25.0 mg/kg, Tmaxs were 5.3 and 5.3 hr, respectively. Although the time for the first appearance of 5-ASA into the systemic circulation was almost the same value between SASP capsule and PCC containing 5-ASA, longer Tmax was observed from SASP capsule than from PCC. These results suggest that this 5-ASA preparation would be an useful dosage form for the therapy of IBD from the point of avoiding the side effect of sulfapyridine, one of the metabolites of SASP.

Administration, Oral↗
PubMed1997

The expression of murine cutaneous late phase reaction requires both IgE antibodies and CD4 T cells.

BACKGROUND: Exposure of atopic patients to a specific allergen evokes an immediate response which is followed, in many cases, by a late phase reaction (LPR) some hours later. Here we have examined the immunological mechanisms required for the expression of cutaneous LPR in mice. METHODS: BALB/c mice were immunized by i.p. injection of ovalbumin (OVA) and alum actively or by i.v. injection of anti-OVA IgE monoclonal antibody (mAb) passively. After challenge by intradermal injection of OVA into ears, the changes in ear thickness, the number of eosinophils, and the levels of IL-4 and IFN-gamma protein at the site of antigen challenge were examined. RESULTS: Actively immunized mice developed a biphasic response at the site of OVA injection, while mice passively immunized with IgE anti-OVA mAb displayed a strong early response but no LPR. Cell transfer experiments using BALB/c nu/nu mice revealed that both OVA-specific IgE mAb and OVA-primed CD4 T cells were required to evoke LPR. Moreover, LPR was associated with increased levels of IL-4 production concomitant with reduced IFN-gamma production and was abolished by pretreatment with anti-IL-4 neutralizing mAb. CONCLUSION: It is suggested that murine cutaneous LPR against OVA is a type 2 inflammatory response in which both IgE antibodies and CD4 T cells play an obligatory role.

Animals↗
PubMed1997

[Leukocytapheresis for ulcerative colitis].

Major inclusion criteria for leukocytapheresis (LCAP) therapy were mainly insufficient response to conventional drugs therapy. LCAP was administered once a week for 5 weeks of intensive therapy and once approximately a month for maintenance therapy, for 38 patients with UC. LCAP could remove approximately 1 x 10(10) white blood cells in each session. In the evaluation, we classified the response to the LCAP as: 1) excellent, 2) moderately improved, 3) no change, and 4) deterioration. Clinical improvement was recognized in 29 of 38 patients (76%) including 8 with dramatic response during the intensive therapy, and continued throughout the maintenance therapy in 26 patients (68.4%). Even though their symptoms were mild, the patients with more than 5 years UC history seemed to be not effective. The patients with moderately improvement and with excellent response have kept remission for about 20 months and about 2.5 years on an average, respectively. Clinical and blood examinations showed no side effects in any cases. It suggests that LCAP is able to be a UC treatment between drug therapies and an operation.

Adult↗
PubMed1997

Hepatitis B virus carriers in the treatment of malignant lymphoma: an epidemiological study in Japan.

BACKGROUND: Hepatitis B after the withdrawal of cytotoxic chemotherapy in hepatitis B virus (HBV) carriers is well known and may lead to fatal hepatic failure. We retrospectively analyzed the prevalence of HBV carriers, the incidence, and the risk factors of hepatitis B in the treatment of malignant lymphoma. PATIENTS AND METHODS: HBV carriers were defined as patients with positive HBs-antigen, either with normal or abnormal serum aminotransferase level at patient presentation. Questionnaires to the members of the Japan Lymphoma Treatment Study Group included general information, details about HBV carriers, and further information about hepatitis B. RESULTS: Among 1380 patients collected from eight institutions, 45 patients (3.26%) were determined to be HBV carriers, Hepatitis B developed in 17 of the HBV carrying patients (37.8%). Seven of those 17 (41.2%) died of hepatic failure. Hepatitis developed at a high rate in patients who were negative for HBe-antigen (50%), and who had received second- or third-generation chemotherapy (63.2%). CONCLUSION: We confirmed that hepatitis B developed with high frequency in HBV carriers with malignant lymphoma. Moreover, hepatitis often resulted in fatal hepatic failure. It is necessary to prevent the hepatitis B developing in HBV carriers when receiving intensive chemotherapy for malignant lymphoma.

Adolescent↗
PubMed1997

[A study on antiprothrombin antibodies in antiphospholipid syndrome].

In this study we investigated the frequency and the type of manifestations of antiprothrombin antibodies (aFII) in patients with antiphospholipid syndrome (APS). In 16 (84.2%) of 19 patients with lupus anticoagulant (LA) and either anticardiolipin antibodies or antiphosphatidylserine antibodies, two types of abnormal patterns were shown on a crossed immuno-electrophoresis technique using anti-human prothrombin murine IgG. The slow-moving peak of prothrombin was detected in 8 patients, while a peak in the other patients had the slow-moving shoulder. These slow-moving materials might represent prothrombin-aFII complexes. In 13 patients who were studied on Western blots, IgGs of 11 patients (84. 6%) bound to human purified prothrombin, and the IgGs of 7 (53.8%) of these patients also bound to human purified alpha-thrombin. Our results indicate that aFII detected in patients with APS may explain part of the mechanism of LA.

Adolescent↗
PubMed1997

[A case of IAHS (infection associated hemophagocytic syndrome) successfully treated with etoposide].

This report details a case of infection associated hemophagocytic syndrome (IAHS). A 20-year-old female was admitted to our hospital with persistent high fever in July, 1994. Physical examination revealed high body temperature (40 degrees C), marked hepatosplenomegaly and no superficial lymph node swelling. Laboratory examination revealed leukopenia and abnormal liver function on admission. Serum ferritin levels were surprisingly elevated. The coagulation tests showed high FDP and D-dimer. Specific viral antibody titers were not elevated such as Epstein-Barr virus or Cytomegalovirus. Bone marrow examination revealed histiocytic hyperplasia with hemophagocytosis, and the histiocytes were well matured. We diagnosed IAHS. Corticosteroids were administered on the 3rd hospital day (methylprednisolone 1 g/day, 3 days), but persistent high fever and laboratory findings did not improve. So we tried etoposide (etoposide 200 mg/day, 5 days) therapy on the 13th hospital day. After administration of etoposide, she failed to recover from severe leukopenia and suffered from meningitis. We administered G-CSF, gamma-globulin and antibiotics for intensive supportive therapy. As the leukocyte count increased, her symptoms and laboratory data improved. There was no hemophagocytosis in her bone marrow before discharge. Recently, etoposide is said to be effective for reactive monocytic proliferation. Administration of etoposide was very effective for IAHS, although corticosteroids, were ineffective.

Adult↗
PubMed1996

Role of cytokines in leukemic type growth of myelodysplastic CD34+ cells.

The clonal growth of progenitor cells from myelodysplastic syndromes (MDS) can be subdivided into four growth patterns: (1) normal, (2) no growth or low plating efficiency, (3) low colony and high cluster number, and (4) normal or high colony number with a large number of clusters. The former two (1 and 2) can be referred to as nonleukemic patterns and latter two (3 and 4) as leukemic. In a search for a role for cytokines in leukemic-type growth of MDS progenitor cells, marrow CD34+ cells were purified up to 94% for 8 normal individuals and 88% for 12 MDS patients, using monoclonal antibodies and immunomagnetic microspheres (MDS CD34+ cells). The purified CD34+ cells were cultured for 14 days with various combinations of cytokines, including recombinant human macrophage colony-stimulating factor (rM-CSF), granulocyte-CSF (rG-CSF), granulocyte-macrophage-CSF (rGM-CSF), interleukin-3 (rIL-3), and stem cell factor (SCF; a ligand for c-kit) in serum-free medium. The clonal growth of MDS CD34+ cells supported by a combination of all of the above cytokines was subdivided into the two patterns of leukemic or nonleukemic, and then the role of individual or combined cytokines in proliferation and differentiation of MDS CD34+ cells was analyzed in each group. Evidence we obtained showed that SCF plays a central role in the leukemic-type growth of MDS CD34+ cells and that G-CSF, GM-CSF; and/or IL-3 synergize with SCF to increase undifferentiated blast cell colonies and clusters over that seen in normal CD34+ cells. SCF is present in either normal or MDS plasma at a level of nanograms per milliliter, and this physiologic concentration of SCF can stimulate progenitor cells. This means that progenitor cells are continuously exposed to stimulation by SCF in vivo and that MDS leukemic cells have a growth advantage over normal blast cells. This depends, at least in part, on cytokines such as G-CSF, GM-CSF, IL-3, and SCF.

Acute Disease↗
PubMed1996

Interactions of the F1-ATPase subunits from Escherichia coli detected by the yeast two-hybrid system.

Subunit interactions among the F1-ATPase subunits were studied by the yeast two-hybrid system. Various pairwise combinations of genes encoding alpha, beta, gamma, delta and epsilon subunits of Escherichia coli H+-ATPase fused to the DNA-binding or activation domain of the yeast GAL4 gene were introduced into yeast and expression of a reporter gene encoding beta-galactosidase was detected. Combinations of the alpha and beta subunit genes, and of the epsilon and gamma subunit genes showed high levels of reporter gene expression, while those of alpha and delta, beta and delta, gamma and delta, and delta and epsilon demonstrated weak but significant reporter gene expression. However, combinations of alpha and gamma, beta and gamma, alpha and epsilon, and beta and epsilon did not induce reporter expression. None of the fused genes alone induced reporter gene expression. These results suggested that specific and strong interactions between the alpha and beta, gamma and epsilon, and weak interactions between the alpha and delta, beta and delta, and gamma and delta subunits occurred in yeast cells in the two-hybrid system. Effects of previously identified mutant beta subunits with Leu-40 to Pro. Glu-41 to Lys or Pro-332 to Gln substitutions which caused defects in molecular assembly of F1-ATPase were analyzed with regard to alpha-beta interactions. No interaction of the alpha and beta subunits was observed in this system using the beta subunit with mutation of Pro-332 to Gln. However, for the other two mutations, alpha-beta interactions were observed. This system may be useful for isolating mutants which have defects in interaction of F1-ATPase subunits.

Escherichia coli↗
PubMed1996

Reconstitution of the F1-ATPase activity from purified alpha, beta, gamma and delta or epsilon subunits with glutathione S-transferase fused at their amino termini.

Systems for overexpression and purification of active alpha, beta and gamma subunits of Escherichia coli H(+)-ATPase were established. The alpha and beta subunits recovered as soluble form were purified by hydroxyapatite column chromatography. Since the gamma subunit was overexpressed as the insoluble form, this subunit was purified by polyacrylamide gel-electrophoresis containing sodium dodecyl sulfate. By subsequent denaturation of this subunit with guanidine hydrochloride and renaturation, the active gamma subunit for reconstitution of the F1-ATPase activity with the purified alpha and beta subunit was obtained. The delta and epsilon subunits which were fused to the carboxy terminus of glutathione S-transferase (GST) were overproduced and purified by affinity chromatography. These fused proteins (delta-GST and epsilon-GST) were incubated with the purified alpha, beta and gamma subunits and applied to affinity chromatography. The alpha beta gamma delta-GST and alpha beta gamma epsilon-GST complex were eluted specifically by addition of glutathione and exhibited high and low ATPase activity, respectively, with a subunit stoichiometry similar to that in the native F1-ATPase, indicating that active complexes could be reconstituted with the fused proteins. These results suggested that the amino-terminal ends of the delta and epsilon subunits are not involved in formation of the active complex. The fused epsilon-GST bound the gamma subunit strongly, and the alpha subunit weakly. The delta-GST bound the gamma subunit significantly, and the alpha and beta subunits very weakly.

Base Sequence↗
PubMed1996

Preclinical Cushing's syndrome: report of four cases and analysis of steroid contents in adenomas.

We report 4 cases of preclinical Cushing's syndrome (PCS) that were discovered incidentally by computed tomography (CT) as adrenal incidentalomas. Routine endocrine examinations revealed a suppressed plasma ACTH level. A final diagnosis was made by means of precise endocrine assessments and adrenal scintigraphy with radiolabelled iodocholesterol. Although endocrine data varied, the positive accumulation of radioisotope in the adrenal tumor, with nonvisualization of the contralateral side, was observed in all cases. Endocrine studies and analyses of steroid contents in tumors by HPLC suggested that subtypes or heterogeneous forms of this disease entity may exist. One type shows small tumors with relatively elevated cortisol production, and a disturbed diurnal rhythm and suppression of plasma cortisol with dexamethasone (DXM). The other type showed large tumors with weak-to-average cortisol production, and the diurnal rhythm of cortisol was preserved.

17-alpha-Hydroxyprogesterone↗
PubMed1996

Generation of new intercellular junctions between cardiocytes. A possible mechanism compensating for mechanical overload in the hypertrophied human adult myocardium.

Intercellular dehiscence is a common cardiocytic response to pathological conditions. However, little consideration has been given to the possibility of new intercellular junctions developing between cardiocytes within developed myocardium. To examine this possibility as it may relate to useful compensation for hemodynamic overloads, changes in cardiocytic connection were evaluated by scanning electron microscopy in hypertrophied myocardium of adult human hearts. Transmural myocardium of left ventricle was obtained at autopsy from five hearts with concentric hypertrophy, five hearts with eccentric hypertrophy, and five control hearts (noncardiac death). After formalin fixation, the number of cardiocytes connected to an individual cardiocyte was counted in tissues from the middle portion of the transmural samples by scanning electron microscopy. Cardiocytic diameter and connective tissue volume fraction were measured on the transmural sections by light microscopy. In concentrically hypertrophied hearts present both increased cardiocytic diameter and connective tissue volume fraction, the number of other cardiocytes connected to an individual cardiocyte (4.60 +/- 0.10 [mean +/- SE] was significantly increased (P < .05) compared with control hearts (4.19 +/- 0.12) or eccentrically hypertrophied hearts (4.11 +/- 0.10). The increase in junctions per cardiocyte in concentrically hypertrophied hearts suggests that new connections had been generated. More junctions developing during hypertrophy could add another structural advantage to those of cardiocytic hypertrophy and connective tissue proliferation as compensatory adjustments to hemodynamic overload in concentrically hypertrophied hearts.

Adult↗
PubMed1996

Separation of functional domains for the alpha-1,4 and alpha-1,6 hydrolytic activities of a Bacillus amylopullulanase by limited proteolysis with papain.

An amylopullulanase (APase) from alkalophilic Bacillus sp. KSM-1378 hydrolyzes both alpha-1,6 linkages in pullulan and alpha-1,4 linkages in other polysaccharides, each maximally active at an alkaline pH, to generate oligosaccharides. We analyzed proteolytic fragments that were produced by exposing pure APase to various proteases, to identify its catalytic domain(s). The intact, pure 210-kDa APase was partially digested with papain for a short time, yielding simultaneously two smaller non-overlapping active fragments, designated amylose-hydrolyzing fragment (AHF114, 114 kDa) and pullulan-hydrolyzing fragment (PHF102, 102 kda). The two truncated protein fragments, each containing a single catalytic domain, were purified to homogeneity. The purified AHF114 and PHF102 had similar enzymatic properties to the amylase and pullulanase activities, respectively, of intact APase. The partial amino-terminal sequences of APase and AHF114 were both Glu-Thr-Gly-Asp-Lys-Arg-Ile-Glu-Phe-Ser-Tyr-Glu-Arg-Pro and that of PHF102 was Thr-Val-Pro-Leu-Ala-Leu-Val-Ser-Gly-Glu-Val-Leu-Ser-Asp-Lsy-Leu. These results were direct evidence that the alpha-1,6 and alpha-1,4 hydrolytic activities were associated with two different active sites in this novel enzyme. Our alkaline APase is obviously a "biheaded enzyme".

Amino Acid Sequence↗
PubMed1996

Immunological, genetic, and microbiological study of family members manifesting early-onset periodontitis.

From the standpoint of host-parasite interactions, family studies help us understand the host defensive factors and the molecular mechanisms involved in the periodontal immune response. In this study, we report the immunological profile of host-defensive functions, human leukocyte antigen (HLA) phenotypes, and the microflora of a mother (rapidly progressive periodontitis), an older son (periodontally healthy), a younger son (localized juvenile periodontitis), and a daughter (localized juvenile periodontitis). We examined the peripheral neutrophil functions, phenotypic and functional analysis of peripheral lymphocytes, serum immunoglobulin G (IgG) antibody titers against periodontopathic bacteria, serological type of HLA class II antigens, and bacterial flora in all periodontal pockets. The results showed that Actinobacillus actinomycetemcomitans was dominant in the pockets of all subjects. The mother and two sons showed a depressed neutrophil chemotaxis to N-formyl-methionyl-leucyl-phenylalanine. All subjects except the older son exhibited low T4/T8 ratios. The mother and daughter had raised levels of IgG titers to Porphyromonas gingivalis. All subjects had HLA phenotypes of DRw52 and DQ1 in common. We found that the family members had similar disorders in certain defensive functions. This family has been a model for our understanding of the host defensive factors in the development of early-onset periodontitis.

Adolescent↗