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M Shima

Publications and source records attributed to M Shima.

At least 91 records · Page 5Linked to original sources
PubMed1997

Effects of medium-chain fatty acids and their acylglycerols on the transport of penicillin V across Caco-2 cell monolayers.

The transport-enhancing effects of medium-chain fatty acids (caproic, caprylic, and capric acids) and their acylglycerols (mono-, di-, and triacylglycerols) were investigated by using Caco-2 cell monolayers as a model of the human intestinal epithelium. Penicillin V was used as a model for a hydrophilic bioactive compound. Among the fatty acids and acylglycerols tested, 1,2-dicaproin, monocaprin, monocaprylin, and capric acid sodium salt effectively enhanced the transport rate, whereas other substances enhanced the rate only slightly or not at all. With each of these four substances, the rate of enhancement was proportional to the concentration at low concentrations, but leveled off at high concentrations. The transport-enhancing effects were well correlated with the reduction in surface tension and with a physico-chemical parameter, denoted by the surface energy-lowering coefficient, characterizing the surface activity of a substance.

Caco-2 Cells↗
PubMed1997

[Factors related to attitudes of outpatients toward "Iyaku-Bungyo" (the separation of dispensing from medical practice)].

In order to evaluate factors related to the attitudes of patients toward "IYAKU-BUNGYO" (the separation of dispensing from medical practice), a questionnaire survey was conducted among outpatients of three public hospitals in Chiba Prefecture. Of these patients, about 60% preferred that the present form of dispensing service would continue in the future. The results of multiple logistic regression analysis showed that shortening of time required for receiving medical care was the most important factor for the outpatients choosing pharmacies for receiving prescribed drugs. The patients who received drugs from pharmacies located near their homes and who waited for less than 10 minutes, tended to prefer being served in the same way at the pharmacies in the future. The patients who received drugs from hospital pharmacies preferred out-of-hospital pharmacies in the future if their waiting time was more than 30 minutes at present. The patients who had experience receiving drugs from pharmacies near their homes, also tended to prefer to have them dispensed at the pharmacies. These results were unchanged when the patients whose choice was the present dispensing form were excluded from the analysis. This study indicated that "IYAKU-BUNGYO" may be accepted by more patients, if medications can be dispensed at community pharmacies near their homes, and the waiting time for dispensing is shortened.

Attitude↗
PubMed1997

Factor VIII Ise (R2159C) in a patient with mild hemophilia A, an abnormal factor VIII with retention of function but modification of C2 epitopes.

We found a patient with mild hemophilia A who had no detectable factor VIII antigen (FVIII:Ag), as shown by two-site ELISA using inhibitor alloantibodies (TK). We then analyzed A2, A2/B, and C2 antigen of the patient's DDAVP-induced FVIII using several anti-FVIII monoclonal antibodies. Factor VIII activity (FVIII:C) was increased from 12 to 42 U/dl by the administration of DDAVP. The DDAVP-induced increases in the A2 and A2/B antigens were 40 and 36 U/dl, respectively. However, the increase in the C2 antigen was only 7.5 U/dl. SSCP analysis and subsequent sequencing demonstrated an Arg to Cys transition at codon 2159. The anti-FVIII:C titer of monoclonal antibody, NMC-VIII/5 which recognized the C2 domain, against normal plasma was 450 Bethesda U/mg of IgG. However, the titer against DDAVP-treated patient's plasma was only 15 Bethesda U/mg. We also tested DDAVP-induced increase in the FVIII:Ag in another mild hemophilia A patient with the same mutation at Arg2159. Increase in his C2 antigen levels was only 19% of those in the A2 and A2/B antigen. We designate this abnormal FVIII as FVIII Ise. Our results show that a missense mutation at Arg2159 to Cys modifies the antigenicity of the C2 domain.

Adolescent↗
PubMed1997

[Jeune syndrome].

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Asphyxia Neonatorum↗
PubMed1997

[A case of postencephalitic intractable partial epilepsy with multiple brain lesions demonstrated by MRI].

We encountered a case of focal encephalitis. A 5-year-old boy developed high fever and he was admitted to our hospital on the third day with generalized tonic-clonic convulsions. Cerebrospinal fluid showed slight pleocytosis. CT showed diffuse low-density area in the left temporal, parietal and occipital regions. T2 weighed MRI showed swelling and hyperintense regions in the left temporal, parietal and occipital cortex. With the disappearance of generalized convulsion, the cortical swelling improved. But aphasia and intractable complex partial seizures appeared. On MRI, the atrophic findings of the left hippocampus and temporal lesion became developed. We considered this case corresponds to focal encephalitis related to "a peculiar type of post-encephalitic/encephalopathic epilepsy" reported by Awaya et al.

Child↗
PubMed1997

[Transient inhibitors developed in two cases of hemophilia A].

This report describes the transient development of inhibitors in two cases of hemophilia A. Case 1 was an 8-month-old boy who suffered from subcutaneous hematoma with extremely low level (1.5%) of plasma factor VIII activity (F VIII:C). He showed an inhibitor titer of 2.5 Bethesda units (BU)/ml when he suffered from measles at age 24 months with poor clinical response to factor VIII. This inhibitor elevated to 11.6 BU/ml at 29 months, but completely disappeared at 32 months. Case 2 was a 5-month-old boy who suffered from subcutaneous hematoma with extremely low level (< 1%) of plasma F VIII:C. At 8 months his inhibitor titer peaked at 19 BU/ml but subsequently declined to 11.5 BU/ml at 12 months and completely disappeared at 14 months. A review of the literature revealed that the median (range) titer of transient inhibitor initially developed at 2 (0.5-19) BU/ml on 225 (79-448) days, immediately peaked at 3.6 (0.5-60) BU/ml and disappeared by 665 (282-1140) days, suggesting that careful monitoring of F VIII inhibitors is required in the treatment of hemophilia A.

Autoantibodies↗
PubMed1996

Slowed release of thrombin-cleaved factor VIII from von Willebrand factor by a monoclonal and a human antibody is a novel mechanism for factor VIII inhibition.

The anti-factor VIII (fVIII) C2 domain monoclonal antibody ESH8 inhibits fVIII activity only when fVIII is bound to von Willebrand factor (vWf). However, ESH8 binds with similar affinity to fVIII and fVIII.vWf complex, and it does not affect the kinetics of thrombin cleavage at positions 372 and 740 within the fVIII heavy chain and at 1689 within the light chain. The latter is required for fVIII release from vWf. We showed that ESH8 reduced the initial rate of thrombin-activated fVIII (fVIIIa) release from vWf by 4.3-fold compared to that in the absence of antibody. The complex of vWf. fVIII.ESH8 was activated, and the rate constant determined for fVIIIa dissociation from vWf was 4 x 10(-3) s-1. We constructed a mathematical model incorporating the measured rates for fVIIIa release from vWf and for inactivation of heterotrimeric fVIIIa due to the spontaneous loss of the A2 subunit and found that the decreased release rate is sufficient to explain our experimentally observed inhibition of fVIII activity by ESH8. We hypothesize that the slowed rate of fVIIIa release from vWf in the presence of ESH8 allows time for inactivation of unstable fVIIIa prior its participation in the formation of the factor Xase complex. The relevance of these findings is illustrated by our observation that reduction of fVIIIa release from vWf represents an additional mechanism of fVIII inhibition by an anti-C2 domain antibody (epitope 2218-2307) from a hemophilia A patient. This rare antibody binds to a more amino-terminal epitope than other human anti-C2 inhibitors, resulting in its lack of inhibition of fVIII binding to vWf but not to phospholipid. These two fVIII ligands therefore bind to C2 sites which do not overlap completely.

Antibodies, Monoclonal↗
PubMed1996

Measurement of anti-factor IX IgG subclasses in haemophilia B patients who developed inhibitors with episodes of allergic reactions to factor IX concentrates.

We have established a simple enzyme-linked immunosorbent assay (ELISA) for the detection of anti-factor IX IgG subclasses in haemophilia B patients with inhibitors. The assay was performed using immobilized purified factor IX. Specific IgG subclasses were detected by peroxidase-conjugated anti-human IgG1,2,3 and 4. Ten plasma samples from 6 haemophilia B patients with inhibitors ranging from 1.0 to 253 Bethesda Units/ml were analyzed. All samples were positive for IgG4. Six out of 10 samples were positive only for IgG4. Three samples were positive for IgG2. Five of the 6 patients had previously had allergic reactions to factor IX concentrates. Three patients had allergic episodes within the past month. Three samples from these latter patients taken on the day when the allergy had occurred showed positive also for IgG1. In later samples, however, taken at 4 days and 4 weeks respectively from two of these same patients. IgG1 was not detected. In two of the five patients in whom allergic reactions had occurred more than one month previously IgG1 was not detected. The results suggested that allergic reactions in patients with haemophilia B treated with factor IX concentrates were associated with the development of the specific IgG1 subclass of antibody to factor IX.

Adolescent↗
PubMed1996

Association of respiratory symptoms with serum protease inhibitors and albumin levels in Japanese children.

BACKGROUND: Some individuals are more susceptible than others to the effects of environmental factors, although the physiological reasons for this are unknown. This study investigates the fundamental association between some serum proteins and respiratory symptoms in Japanese children. METHODS: The serum alpha 1-antitrypsin (alpha 1AT), alpha 2-macroglobulin (alpha 2MG), and albumin concentrations were determined in 480 schoolchildren living in an area with low air pollution levels. Their respiratory symptoms were assessed from responses to questionnaires. RESULTS: Serum alpha 1AT levels were significantly lower in children with histories of allergic diseases, while their alpha 2MG levels were increased. Serum albumin levels were significantly decreased in children with asthma compared with those without, and the levels did not differ significantly for those children with wheezing symptoms or histories of allergic diseases. Serum alpha 1AT levels were only significantly lower in girls with asthma. Fourteen children (2.9%) were found to have decreased alpha 1AT levels of < 160 mg/dl. All of these children had histories of allergic diseases, and the prevalence of asthma was remarkably higher in these children. Children with only wheezing symptoms showed no significant changes in serum alpha 1AT, alpha 2MG, or albumin levels. CONCLUSIONS: These findings suggest that serum alpha 1AT, alpha 2MG, and albumin levels are associated with respiratory and allergic diseases in children. A decreased alpha 1AT level should be considered as a biological risk marker for these diseases.

Child↗
PubMed1996

Effect of depolymerized holothurian glycosaminoglycan (DHG) on the activation of factor VIII and factor V by thrombin.

Our previous study has shown that depolymerized holothurian glycosaminoglycan (DHG) has two different inhibitory activities in the blood coagulation cascade: heparin cofactor II-dependent thrombin inhibition; and antithrombin III- and heparin cofactor II-independent inhibition of the intrinsic factor Xase complex [Nagase et al. (1995) Blood 85, 1527-1534]. In the present study, the effect of DHG on the activation of factor VIII and factor V by thrombin was examined with purified human components. DHG inhibited the activation of factor VIII by thrombin at concentrations exceeding 80 nM, but not the activation of factor V by thrombin at concentrations of up to 8 mu M. On Western blot analysis, DHG inhibited the cleavage of factor VIII light chain at concentrations exceeding 0.8 mu M. The interaction between DHG and factors VIII and V and thrombin was examined with a DHG-cellulofine column. DHG had strong affinity for factor V and thrombin, but slight affinity for factor VIII. The interaction of DHG with thrombin was analyzed, using fluorescein isothiocyanate-labeled DHG. One mole of DHG bound 2 mol of thrombin, with a dissociation constant (Kd) of 3.04 x 10(-6) M. These results suggest that DHG interferes with the interaction between thrombin and factor VIII, probably by making a binary complex through the anionic binding exosite II of thrombin.

Animals↗
PubMed1996

A case of West syndrome with atypical massive gray matter heterotopia that is well controlled by ACTH therapy.

A 4 month old female infant with atypical asymmetrical massive gray matter heterotopia diagnosed as West syndrome is described. Her seizure initially appeared as afebrile general tonic and clonic convulsion and progressed to typical West syndrome consisting of clusters of myoclonic spasms of the extremities, mainly on the left side, accompanied by head and eye deviation to the right side. Electroencephalogram (EEG) presented typical hypsarrhythmia and cranial computerized tomography (CT) and magnetic resonance imaging (MRI) showed massive heterotopic gray matter in the right hemisphere with the same density or intensity as cortical gray matter. Single photon emission computed tomography (SPECT), using N-isopropyl-p-123I-iodoamphetamine (123 I-IMP), demonstrated decreased blood flow in the ectopic lesion. Although clinical response to several anti-epileptic drugs was poor, her seizures were well controlled by relatively low dose adrenocorticotropic hormone (ACTH) therapy of 0.015 mg/kg per day followed by a combination of valproic acid and clonazepam.

Adrenocorticotropic Hormone↗
PubMed1996

Thrombelastgram as a hemostatic monitor during recombinant factor VIIa treatment in hemophilia A patients with inhibitor to factor VIII.

Thrombelastgram (TEG) is an old but automated instrument that demonstrates changes occurring during blood coagulation and fibrinolysis. TEG was evaluated to be better than activated partial thromboplastin time (APTT) as a monitor of hemostatic effects when using recombinant factor VIIa (65-80 mu g/kg) in 3 hemophilia A patients with a high titer of factor VIII inhibitors. TEG was more suitable than APTT, because r, r + k and ma values of TEG were normalized at least for 4 h after the infusion, whereas APTT was variably shortened and was not always maintained at a normal level for 4 h.

Adult↗
PubMed1996

Comparative study of C-reactive protein in chronic hepatitis B and chronic hepatitis C.

C-reactive protein (CRP) is a liver-specific acute-phase protein, and its expression in hepatocyte is regulated by cytokines such as interleukin-1, interleukin-6 and tumor necrosis factor-alpha. Although several alterations in cytokines have been found in patients with chronic viral hepatitis, it remains obscure how CRP expression is associated with progression of the disease in chronic viral infection. In the present study, CRP expression was evaluated in 45 patients with chronic hepatitis B and in 38 patients with chronic hepatitis C. By the immunohistochemical analysis, the intensity of CRP expression in hepatocyte was closely associated with the histology activity index (HAI) score in chronic hepatitis B. In contrast, the association was not found in chronic hepatitis C. When serial changes in serum levels of CRP were compared in long-term follow-up patients including 5 patients with chronic hepatitis B and 4 patients with chronic hepatitis C, serum levels of CRP fluctuated simultaneously with serum levels of alanine aminotransferase in chronic hepatitis B, whereas the correlation was not recognized in chronic hepatitis C. These results suggest that CRP expression correlates with progression of the disease in chronic hepatitis B, but not in chronic hepatitis C. It is also possible that cytokine-mediated response is more pronounced in chronic hepatitis B than in chronic hepatitis C.

Adult↗
PubMed1996

[Successful induction of immune tolerance and novel hemostatic effects in a hemophilia A with high-responder inhibitor by regular infusions of factor VIII].

A hemophilia A patient with high responder inhibitor had been treated by (activated) prothrombin complex concentrates (A) PCC and activated factor VII until the occurrence of intracranial bleeding at the age of 6 years. Since the inhibitor titer was decreased less than 1 Bethesda Units/ml, high dose of factor VIII was given followed by the infusions of factor VIII concentrates (100 units/kg) three times a week. In spite of previous episodes of anamnestic responses by factor VIII products before, the inhibitor titer did not increase and disappeared completely 6 months after the FVIII infusion therapy. The specific anti-factor VIII IgG subclasses of the inhibitor were IgG2 and IgG4. The inhibitor recognized both light and heavy chains. He have no bleeding episode for 6 months since the beginning of the prophylactic with factor VIII concentrates.

Blood Coagulation Factors↗
PubMed1995

Some factor VIII inhibitor antibodies recognize a common epitope corresponding to C2 domain amino acids 2248 through 2312, which overlap a phospholipid-binding site.

The finding that human factor VIII (fVIII) inhibitor antibodies with C2 domain epitopes interfere with the binding of fVIII to phosphatidylserine (PS) suggested that this is the mechanism by which they inactivate fVIII. We constructed a recombinant C2 domain polypeptide and demonstrated that it bound to all six human inhibitors with fVIII light chain specificity. Thus, some antibodies within the polyclonal anti-light chain population require only amino acids within C2 for binding. Recombinant C2 also partially or completely neutralized the inhibitor titer of these plasmas, demonstrating that anti-C2 antibodies inhibit fVIII activity. Immunoblotting of a series of C2 deletion polypeptides, expressed in Escherichia coli, with inhibitor plasmas showed that the epitopes for human inhibitors consist of a common core of amino acid residues 2248 through 2312 with differing extensions for individual inhibitors. The epitope of inhibitory monoclonal antibody (MoAb) ESH8 was localized to residues 2248 through 2285. Three human antibodies and anti-C2 MoAb NMC-VIII/5 bound to a synthetic peptide consisting of amino acids 2303 through 2332, a PS-binding site, but MoAb ESH8 did not. These antibodies also inhibited the binding of fVIII to synthetic phospholipid membranes of PS and phosphatidylcholine, confirming that the blocked epitopes contribute to membrane binding as well as binding to PS. In contrast, MoAb ESH8 did not inhibit binding. As the maximal function of activated fVIII in the intrinsic factor Xase complex requires its binding to a phospholipid membrane, we propose that fVIII inhibition by anti-C2 antibodies is related to the overlap of their epitopes with the PS-binding site. MoAb ESH8 did not inhibit fVIII binding to PS-containing membranes, suggesting the existence of a second mechanism of fVIII inhibition by anti-C2 antibodies.

Amino Acid Sequence↗
PubMed1995

Macrophage-colony-stimulating factor regulates expression of the integrins alpha 4 beta 1 and alpha 5 beta 1 by murine bone marrow macrophages.

We observed that when monocyte/macrophage precursors derived from murine bone marrow were treated with macrophage-colony-stimulating factor (M-CSF), there was a dose-dependent increase in both the number of adherent cells and the degree to which the cells were highly spread. Attachment was supported by fibronectin, but not by vitronectin or laminin, suggesting that the integrins alpha 4 beta 1 and/or alpha 5 beta 1 might mediate this event. Binding to fibronectin was blocked partially by antibodies to either integrin, and inhibition was almost complete when the antibodies were used in combination. By a combination of surface labeling with 125I and metabolic labeling with [35S]methionine and [35S]cysteine, we demonstrated that M-CSF treatment led to increased synthesis and surface expression of the two beta 1 integrins. Since attachment to fibronectin and/or stromal cells plays an important role in the maturation of other hematopoietic lineages, we propose that the action of M-CSF in the differentiation of immature monocytes/macrophages includes stimulated expression of the integrins alpha 4 beta 1 and alpha 5 beta 1, leading to interactions with components of the marrow microenvironment necessary for cell maturation.

Animals↗
PubMed1995

Measurement of anti-factor VIII IgG, IgG4 and IgM alloantibodies in previously untreated hemophilia A patients treated with recombinant factor VIII. Kogenate Japanese Clinical Study Group.

Using enzyme-linked immunosorbent assay (ELISA), we measured anti-factor VIII immunoglobulin G (IgG), IgG4 and IgM in serum samples obtained from hemophilia A patients treated with a recombinant factor VIII (rFVIII) preparation (Kogenate). Twelve pre- and post-treatment serum samples from 3 previously untreated patients who developed an inhibitor (alloantibody) were evaluated. Both rFVIII and plasma-derived factor VIII (pdFVIII) were used as antigen. Serum samples were diluted 37.5-fold. For the measurement of IgM antibody, protein A Sephadex suspension was added to the patients' serum samples and the supernatant was assayed. Anti-human IgG, IgG4, and IgM monoclonal antibodies labelled with peroxidase were added and absorbance at 450nm was determined. The reactivity of the IgG antibody with rFVIII and pdFVIII was extremely low. Samples containing the IgG4 inhibitor with a neutralizing activity of approximately 7.5 Bethesda units (BU)/ml resulted in absorbance values of 0.451-0.551, thus demonstrating a considerably high degree of sensitivity. The correlation between the neutralizing activity and reactions of the IgG4 antibody with rFVIII and pdFVIII antigens was high, with correlation coefficients of 0.912 and 0.966, respectively. Furthermore, the correlation coefficient between the measured absorbance values for the antibody reacted with pdFVIII and rFVIII was 0.961. No correlation was found between the reactivity of IgM to rFVIII and pdFVIII.

Adult↗