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Biomedical subjects

K Amano

Publications and source records attributed to K Amano.

At least 145 records · Page 8Linked to original sources
PubMed1996

Induction of tolerance in murine autoimmune diabetes by transient blockade of leukocyte function-associated antigen-1/intercellular adhesion molecule-1 pathway.

The present study demonstrated that a short-term administration of mAbs against leukocyte function-associated antigen-1 (LFA-1) and intercellular adhesion molecule-1 (ICAM-1) at critical periods resulted in complete protection of autoimmune diabetes in non-obese diabetic (NOD) mice. When these mAbs were administered for only 6 days at 2 wk of age, neither diabetes nor insulitis was observed at 30 wk of age. It appears that the tolerance against beta cell Ag(s) was induced by this transient blockade of the LFA-1/ICAM-1 pathway. Protective suppressor activity was not enough to prevent diabetes because co-transfer of splenocytes from female NOD mice, which had received these mAbs at 2 wk of age, resulted in only a short delay of the diabetic onset caused by adoptive transfer of splenocytes from acutely diabetic NOD mice. Transfer of these splenocytes to young NOD mice could not also abrogate the spontaneous diabetes and insulitis. Furthermore, cyclophosphamide treatment could not abrogate the protection. When splenocytes from the treated NOD mice were transferred to NOD-SCID mice, none of the recipient mice developed significant insulitis and subsequent overt diabetes, suggesting the absence or the inactivation of diabetogenic effector T cells. However, splenic T cells from the insulitis-free NOD mice that had received the mAb treatment preserved proliferative responses to both islet cells and 65-kDa glutamic acid decarboxylase (GAD65) in vitro. These results suggest that a unique peripheral tolerance was induced by the transient blockade of the LFA-1/ICAM-1 pathway in an early age of NOD mice.

Adoptive Transfer↗
PubMed1996

Moderation of hemophilia A phenotype by the factor V R506Q mutation.

Although many examples of unrelated hemophilia A patients carrying identical point mutations in the factor VIII (FVIII) gene have been reported, the clinical phenotype is not always the same among patients sharing the same molecular defect. Possible explanations for this discrepancy include undetected additional mutations in the FVIII gene or coinheritance of mutations at other genetic loci that modulate FVIII function. We report molecular genetic analysis of potential modifying genes in two sets of unrelated patients carrying common FVIII missense mutations but exhibiting different levels of clinical severity. Both mutations (FVIII R1689C and R2209Q) are associated with severe hemophilia A in some patients and mild/moderate disease in others. The common von Willebrand disease type 2N mutation (R91Q) was excluded as a modifying factor in these groups of patients. However, analysis of the recently described factor V (FV) R506Q mutation (leading to activated protein C resistance) identified a correlation of inheritance of this defect with reduced hemophilia A severity. Two moderately affected hemophilia A patients, each with either of two FVIII gene mutations, were heterozygous for FV R506Q, whereas two severely affected patients and two moderately affected patients were homozygous normal at the FV locus. Our results suggest that coinheritance of the FV R506Q mutation may be an important determinant of clinical phenotype in hemophilia A and that modification of the protein C pathway may offer a new strategy for the treatment of FVIII deficiency.

Alleles↗
PubMed1996

Q fever pneumonia in children in Japan.

The prevalence of Q fever pneumonia among children with atypical pneumonia from whom only an acute-phase serum sample was available was traced by using an indirect immunofluorescence (IF) test, nested PCR, and isolation. Twenty (34.5%) of 58 sera were found to have both polyvalent and immunoglobulin M antibodies to the phase II antigen of Coxiella burnetii by the IF test. Q fever pneumonia was present in 23 (39.7%) of 58 patients as determined by both the nested PCR and isolation and in 20 patients as determined by the IF test. The sensitivities for nested PCR and isolation were 100%, and that for the IF test was 87%. Our results indicate that nested PCR was faster and more sensitive than isolation and the IF test in the diagnosis of acute Q fever when a single acute-phase serum was available. These findings suggest that C. burnetii is an important cause of atypical pneumonia in children in Japan.

Antibodies, Bacterial↗
PubMed1996

Effect of erythropoietin treatment on blood pressure and intracellular cation concentrations in maintenance hemodialysis patients.

To assess the effect of recombinant human erythropoietin (EPO) on the factors regulating blood pressure (BP), we determined the hemoglobin level (Hgb), blood viscosity (BV), plasma renin activity (PRA), plasma concentrations of aldosterone (PAC), adrenaline (Ad), noradrenaline (NAd), and atrial natriuretic peptide (ANP), and serum and intracellular concentrations of cations before and after 3 months of EPO treatment (40 units/kg/week of EPO intravenously after each hemodialysis session) in 11 patients undergoing maintenance hemodialysis. Intracellular sodium concentration ([Na+]i) was measured using erythrocytes with flame photometry. EPO treatment was associated with significant increases in Hgb (7.1 +/- 1.4 to 8.4 +/- 1.8 g/dl, p<0.01), mean BP (103 +/- 11.4 to 116 +/- 19.9 mmHg, p<0.01), [Na+]i (4.99 +/- 0.78 to 6.22 +/- 0.96 mmol/l, p<0.01) and BV (1.39 +/- 0.14 to 1.53 +/- 0.18 c.p., p<0.05), but no significant alteration in PRA, PAC, Ad, NAd, ANP, or in the serum concentration of Na+, K+, and Ca2+. The changes in mean BP (deltaMBP) were significantly correlated with delta[Na+]i (R=0.676, p=0.022) and deltaBV (R=0.668, p=0.034), but not with deltaHgb. By multiple regression analysis, delta[Na+]q and deltaBV independently contributed to deltaMBP; deltaMBP=2.27 X delta[Na+]i+32.2 X deltaBV +3.37 (R=0.695). These data suggest that intracellular sodium accumulation as well as increased blood viscosity may be independently involved in the blood pressure elevation after EPO treatment in patients under maintenance hemodialysis. We found no evidence supporting a role of circulating hormonal factors, such as the renin-angiotensin system, adrenaline, or ANP, in the change in blood pressure.

Aged↗
PubMed1996

McArdle's disease with non-insulin-dependent diabetes mellitus: the beneficial effects of hyperglycemia and hyperinsulinemia for exercise intolerance.

A 64-year-old female with McArdle's disease and non-insulin-dependent diabetes mellitus (NIDDM) is reported. She had none of the characteristic symptoms of McArdle's disease such as muscle cramps but her serum creatine kinase level was elevated. Muscle biopsy with negative muscle phosphorylase staining showed McArdle's disease. Modified forearm ischemic exercise test was done at two conditions; fasting and two hours after a meal. When fasting, the level of lactic acid did not elevate after exercise. After a meal, however, the serum lactic acid level rose with the elevation of plasma glucose and IRI. Thus, we suggested that high plasma glucose and insulin due to NIDDM may induce blood-borne glucose uptake with exercise.

Biopsy↗
PubMed1996

[Significance of fetal arterial oxygen saturation (SpO2) monitoring].

The significance of fetal arterial oxygen saturation (SpO2) monitoring and its relationship with FHR patterns were studied. Continuous fetal SpO2 was obtained by infrared pulse oximetry (Nellcor N-400) in 76 cases. After amniotomy, a reflectance fetal oximetry sensor (Nellcor FS-10) was placed onto the fetal cheek. The relationship between SpO2 and FHR pattern was then studied and the following results were obtained. 1. Mean recording time was 218 min. and satisfactory records were obtained during 75% of that time. 2. Whenever the FHR was reassuring, the range of SpO2 was stable within 40-80%. 3. Variations in SpO2 values were noted during decelerative patterns. When the FHR was not reassuring, the SpO2 value tended to be lower than 40%. A more acidotic tendency was found in cases where SpO2 was below 40% prior to delivery (umbilical arterial pH 7.135 +/- 0.100 vs 7.282 +/- 0.047, p < 0.005). 4. In cases of fetal arrhythmia (congenital complete heart block 3, supra ventricular tachycardia 1), SpO2 monitoring seemed to be an effective tool for fetal surveillance during labor. Fetal SpO2 measurement seemed to be an alternative to scalp blood sampling and is especially effective in cases with a nonreassuring or uninterpretable FHR pattern such as fetal arrhythmia.

Arrhythmias, Cardiac↗
PubMed1996

Factor VIII inhibitor antibodies with C2 domain specificity are less inhibitory to factor VIII complexed with von Willebrand factor.

In order to clarify the potential role of von Willebrand factor (vWf) in attenuating the inactivation of factor VIII (fVIII) by those antibodies with C2 domain specificity, we investigated a panel of 14 human antibodies to fVIII. Immunoblotting analysis localized light chain (C2 domain) epitopes for four cases, heavy chain (A2 domain) epitopes in five cases, while the remaining five cases were both light and heavy chains. The inhibitor titer was considerably higher for Kogenate, a recombinant fVIII concentrate, than for Haemate P, a fVIII/vWf complex concentrate, in all inhibitor plasmas that had C2 domain specificity. In five inhibitor plasmas with A2 domain specificity and in five with both A2 and C2 domain specificities, Kogenate gave titers similar to or lower than those with Haemate P. The inhibitory effect of IgG of each inhibitor plasma was then compared with recombinant fVIII and its complex with vWf. When compared to the other 10 inhibitor IgGs, IgG concentration, which inhibited 50% of fVIII activity (IC50), was remarkably higher for the fVIII/vWf complex than for fVIII in all the inhibitor IgGs that had C2 domain reactivity. Competition of inhibitor IgG and vWf for fVIII binding was observed in an ELISA system. In 10 inhibitors that had C2 domain reactivity, the dose dependent inhibition of fVIII-vWf complex formation was observed, while, in the group of inhibitors with A2 domain specificity, there was no inhibition of the complex formation except one case. We conclude that a subset of fVIII inhibitors, those that bind to C2 domain determinants, are less inhibitory to fVIII when it is complexed with vWf that binds to overlapping region in the C2 domain.

Antibody Specificity↗
PubMed1996

Comparison of serological reactions of Rickettsiae-infected patients and rabbit anti-Proteus OX antibodies with Proteus OX2, OX19 and OXK lipopolysaccharides.

The reactivity of anti-Rickettsiae human antibodies with Proteus OX cells is used as a presumptive rickettsial diseases diagnostic test Weil-Felix reaction. In presented studies we compare the reactivity of human anti-Rickettsiae and rabbit anti-Proteus antibodies with series of Proteus OX2, OX19 and OXK lipopolysaccharides (LPS). Polyclonal rabbit anti-OX2, anti-OX19 and anti-OXK sera reacted only with the homologous LPS--OX2, OX19 and OXK, respectively. The antibodies of Japanese spotted fever patients were less specific and reacted with OX2 as well as OX19 LPS. The antibodies of scrub typhus patients recognized Proteus OXK LPS, only. The serological reactions of O-antigen of P. mirabilis S1959 indicated that this, previously serologically not classified, strain may belong to the OXK group. Bacteria, used in the studies, came from the American, Japanese and European strain collections. The series of OX2, OX19 and OXK LPS, isolated from these Proteus strains, presented pattern of electrophoretic mobility and serological reactivities specific for each of OX-group types.

Animals↗
PubMed1995

Effects of T-helper 2-type cytokines, interleukin-3 (IL-3), IL-4, IL-5, and IL-6 on the survival of cultured human mast cells.

Although stem cell factor (SCF) has been identified as a critical cytokine for the development of human mast cells from their progenitors, the effects of other cytokines on human mast cells are less well understood. We examined the effects of several cytokines on the survival of human mast cells of 100% purity generated in suspension cultures of umbilical cord blood mononuclear cells in the presence of 100 ng/mL recombinant human (rh) SCF and interleukin-6 (IL-6). Mast cells suspended in conventional serum-containing medium died over a period of 2 to 6 days after the withdrawal of SCF and IL-6. The cells became pyknotic and underwent DNA fragmentation characteristic of apoptosis. The addition of SCF, IL-3, IL-4, IL-5, or IL-6 to the cultures in both serum-containing and serum-free medium prolonged their survival in a dose-dependent manner. Some other cytokines, such as IL-2, IL-9, IL-10, IL-11, tumor necrosis factor-alpha, transforming growth factor-beta 1, and nerve growth factor, had no survival-promoting effect at 100 ng/mL. Preincubation of mast cells with SCF, IL-4, IL-5, or IL-6 for 24 hours during sensitization with IgE enhanced IgE/anti-IgE antibody-induced histamine release from mast cells, whereas IL-3 showed a negligible effect. Polymerase chain reaction amplification of alpha-chains of IL-3 receptor (R), IL-4 R, IL-5 R, and IL-6 R yielded products of the correct size predicted from the sequence of each receptor. The binding assay using 125I-labeled IL-3 indicated that these mast cells bear receptors for IL-3. These findings suggest that IL-3, Il-4, IL-5, and IL-6, which are mainly produced by T-helper 2 lymphocytes, might regulate the functions of human mast cells in vivo via specific receptors in allergic reactions.

Antibodies, Anti-Idiotypic↗
PubMed1995

Administration of monoclonal antibodies against vascular cell adhesion molecule-1/very late antigen-4 abrogates predisposing autoimmune diabetes in NOD mice.

The interaction of vascular cell adhesion molecule-1 and very late antigen-4 (alpha 4 beta 1-integrin) has been recently known to be profoundly involved in the trafficking of lymphocytes from the circulation into the inflammatory tissues. To elucidate the role of these molecules in the development of autoimmune diabetes, the expression of these adhesion molecules on inflamed islets and the effects of administration of monoclonal antibodies to these molecules on insulitis and overt diabetes were evaluated in nonobese diabetic (NOD) mice. Immunohistochemical study revealed the overexpression of vascular cell adhesion molecule-1 on vascular endothelium near or within inflamed islets and alpha 4-integrin on islet-infiltrating mononuclear cells. Either anti-vascular cell adhesion molecule-1 or anti-alpha 4-integrin monoclonal antibody prevented the transfer of diabetes in irradiated NOD mice which received spleen cells from acutely diabetic NOD mice. When both monoclonal antibodies were administrated to NOD mice during 2-30 weeks of age, neither lymphocytic infiltration to islets nor overt diabetes was observed. Furthermore, administration of these antibodies even from 10 weeks of age could inhibit the development of insulitis and diabetes, whereas administration during 2-5 weeks of age could not. Splenocytes obtained from these treated mice showed no significant change of cytokine production and preserved the ability to transfer diabetes into NOD scid/scid mice. This suggests that treatment with antibodies against these adhesion molecules can inhibit insulitis and diabetes without affecting the Th1/Th2 balance or effector T cells. The blockade of vascular cell adhesion molecule-1/very late antigen-4 interaction would be suitable for therapeutical treatment of the predisposing and latent type I (insulin-dependent) diabetic subjects.

Animals↗
PubMed1995

Autoantibody to factor VIII that has less reactivity to factor VIII/von Willebrand factor complex.

To determine the difference in reactivity of factor VIII (FVIII) inhibitor to FVIII/von Willebrand Factor (vWF) complex and FVIII free of vWF, an autoantibody to FVIII light chain was tested. A patient (1-3) suffered from autoimmune hemolytic anemia with autoantibody to FVIII. Epitope specificity of the patient's IgG (I-3 IgG) was shown to be the C2 domain of FVIII light chain (2170-2332) by Western blotting using recombinant FVIII deletions expressed in Escherichia coli. The inhibitory effect on FVIII procoagulant activity (VIII:C) of I-3 IgG was tested against a conventional FVIII concentrate; Haemate P, a monoclonal antibody-purified FVIII concentrate; Hemofil M, and a recombinant FVIII (rFVIII); Kogenate. I-3 IgG showed only 1.3 BU/mgIgG for Haemate P, in contrast to 20 BU/mgIgG for both Hemofil M and Kogenate. The ratio of VIII:C/vWF:Ag in Haemate P and Hemofil M was 1/3.43 and 1/0.01, respectively, while Kogenate did not contain vWF. The inhibitory effect of the I-3 IgG was then compared with Kogenate and its complex with vWF. The inhibitory effect was decreased against the rFVIII by forming a complex with vWF from 22 BU/mgIgG to 0.5 BU/mgIgG. Fab from the I-3 IgG had the same effect. In addition, vWF showed a protective effect on FVIII inactivation by the I-3 IgG in a dose dependent manner. Fifty-nine percent of residual VIII:C was retained in the presence of 8 U/ml of vWF after 1 hr incubation with I-3 IgG. These results suggested that vWF could compete with the I-3 IgG for binding to FVIII.

Adult↗
PubMed1995

Leukocytapheresis therapy, performed with leukocyte removal filter, for inflammatory bowel disease.

Leukocytapheresis (LCAP), performed with a leukocyte removal filter, was administered five times, at 1-week intervals, for 5 weeks of intensive therapy and five times, at approximately 1-month intervals, for approximately 5 months of maintenance therapy, to 13 patients with inflammatory bowel disease (IBD) diagnosed as ulcerative colitis (UC) in 8 and Crohn's disease (CD) in 5. Clinical and blood examinations showed no side effects in any of the patients. During the intensive therapy, excellent or moderate clinical response was recognized in 11 of the 13 patients (84.6%), of whom 6 had a dramatic response; the excellent or moderate clinical response continued throughout the maintenance therapy in 8 of the patients (61.5%). Flow cytometry showed that the patients who had improved generally had high values for percentages of HLADR+, HLADR+CD3+, and HLADR+CD8+ cells before the first LCAP, and that these values and the C-reactive protein levels and erythrocyte sedimentation rates had decreased to the normal range by the end of both intensive and maintenance therapy. In the patients who showed poor response, in contrast, all the above values had been at or near normal before the initial LCAP administration. The clinical improvement in the absence of any additional medical treatment suggests that LCAP has the capacity to influence the causal mechanism(s) of IBD and that IBD is strongly associated with the cell-mediated immune response.

Adolescent↗
PubMed1995

Improvement of anemia in W/WV mice by recombinant human erythropoietin (rHuEPO) mediated through EPO receptors with lowered affinity.

We studied the effects of recombinant human erythropoietin (rHuEPO) on anemic W/WV mice which manifested severe anemia accompanied by mutation of the W gene encoding tyrosine kinase type receptor (c-kit gene) of bone marrow hematopoietic cells. Nine-week-old male W/WV mice or normal littermates (+/+) were used. Since serum EPO concentration in W/WV mice increased in proportion to severity of anemia, EPO production in the kidneys of these animals was found to be regulated normally. Hematocrit in +/+ mice increased and a maximal response was also obtained with 2,000 IU/kg of rHuEPO. On the other hand, hematocrit in W/WV mice increased in a dose-responsive manner by administration with 2,000 and 10,000 IU/kg, showing different responses to rHuEPO in these two types of mice. The responsiveness of W/WV mice to rHuEPO was low in terms of increases in erythroblastic precursor cells (CFU-E), and immature cells in the bone marrow. Scatchard analysis of the specific binding of 125I-rHuEPO against bone marrow cells revealed that the different responsiveness to rHuEPO between W/WV and +/+ mice may be correlated with differences in affinity of EPO receptor of bone marrow cells in these mice. From these results, a high dose of rHuEPO is capable of improving the anemia in W/WV mice that had EPO receptors with lowered affinity, indicating the possible effectiveness of rHuEPO in anemic patients with EPO receptor abnormality.

Anemia↗
PubMed1995

A novel function of islet-derived CD8+T cells in initiating and developing autoimmune insulin-dependent diabetes mellitus in non-obese diabetic (NOD) mice.

Accumulated studies revealed that CD4+T cells were initially required for diabetes in NOD mice, whereas interaction of CD4+T/CD8+T cells is not fully understood. To address this question, we established islet-derived CD4+T cells and CD8+T cells from NOD mice. One NOD neonate that received CD4+T cells developed diabetes and insulitis with CD8+T cells. Administration of cyclophosphamide to non-diabetic recipients accelerated the development of diabetes, while none of the mice with anti-CD8 antibody did so. Similarly, it was observed that neonates that received islet-derived CD8+T cells developed diabetes and obvious insulitis mainly with CD4+T cells. Administration of anti-CD4 antibody with transfer of CD8+T cells inhibited insulitis. These results imply that CD8+T cells function as an initial element to recruit CD4+T cells to islets as well as a final effector.

Animals↗
PubMed1995

Factor VIII inhibitor developed in a 60-year-old patient with mild hemophilia A after surgery for colon cancer.

Most factor VIII inhibitors are developed at an early age and in patients with severe type of hemophilia A. We report a case of newly developed factor VIII inhibitor in a 60-year-old patient with mild hemophilia A who had been treated with several kinds of factor VIII concentrates. The patient was treated with a total of 103,580 units of recombinant factor VIII concentrate by continuous and bolus infusions for the open surgery of sigmoid colon cancer. On the 95th postoperative day, the patient had right low limb muscle bleeding and was infused with 1,000 units of recombinant factor VIII concentrate for three days. Subsequently, the level of factor VIII inhibitor in the patient's plasma was 2 Bethesda units (BU)/ml. Since then numerous subcutaneous hemorrhages developed, but an adequate hemostatic effect was not obtained even with the administration of a high dose of recombinant factor VIII concentrate. The patient was switched to bypass therapy using human plasma-derived factor VIIa concentrate, which showed a favorable hemostatic effect.

Adenocarcinoma↗