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Biomedical subjects

A Yoshioka

Publications and source records attributed to A Yoshioka.

At least 19 recordsLinked to original sources
PubMed1992

The interaction of botrocetin with normal or variant von Willebrand factor (types IIA and IIB) and its inhibition by monoclonal antibodies that block receptor binding.

We have recently shown the existence of two distinct forms of botrocetin (one-chain and two-chain), and demonstrated that the two-chain species is approximately 30 times more active than the one-chain in promoting von Willebrand factor (vWF) binding to platelet glycoprotein (GP) Ib. The N-terminal sequence of two-chain botrocetin is highly homologous to sea-urchin Echinoidin and other Ca(2+)-dependent lectins (Fujimura et al., Biochemistry 1991; 30: 1957-64). Present data indicate that purified two-chain botrocetin binds to vWF from plasmas of patients with type IIA or IIB von Willebrand disease and its interaction is indistinguishable from that with vWF from normal individuals. However, an "activated complex" formed between botrocetin and IIB vWF expresses an enhanced biological activity for binding to GP Ib whereas the complex with IIA vWF has a decreased binding activity. Among several anti-vWF monoclonal antibodies (MoAbs) which inhibit ristocetin-induced platelet aggregation and/or vWF binding to GP Ib, only two MoAbs (NMC-4 and RFF-VIII RAG:1) abolished direct binding between purified botrocetin and vWF. This suggests that they recognize an epitope(s) on the vWF molecule in close proximity to the botrocetin binding site.

Antibodies, Monoclonal↗
PubMed1992

Search for human T-cell leukemia virus type I (HTLV-I) proviral sequences by polymerase chain reaction in the central nervous system tissue of HTLV-I-associated myelopathy.

Using the polymerase chain reaction (PCR), proviral DNA sequences of the pol and env regions of human T-cell leukemia virus type I (HTLV-I) were directly amplified in paraffin-embedded and frozen tissue sections of active inflammatory central nervous system (CNS) lesions in three autopsy cases of HTLV-I-associated myelopathy (HAM) with serological confirmation. In parallel, the enumeration of UCHL-1 (monoclonal antibody reactive to T-cells) positive cells in the tissue sections subjected to PCR were carried out. Although the control DNA sequence of parathyroid hormone-like peptide gene was definitely amplified, no signals for HTLV-I proviral sequences were detected in these specimens. The number of UCHL-1 positive cell nuclei was almost on the border line of our PCR sensitivity in formalin-fixed tissue, which was estimated to be 20-200 copies. Therefore, it is unlikely that the central nervous system tissue damage in HAM/TSP is a consequence of productive infection of HTLV-I in the CNS tissue.

Aged↗
PubMed1992

Acute myelomonocytic leukemia with marrow eosinophilia showing 5q- and 16q22 mosaicism.

We report an 82-year-old Japanese female with acute myelomonocytic leukemia with dysplastic marrow eosinophilia (FAB M4Eo) exhibiting a partial deletion of the long arm of chromosome 5, del(5)(q13q31) and a derivative chromosome 16 with a breakpoint at band 16q22, in addition to 5q-. The patient had a history of a preleukemic phase for several months with marked dysplasia in trilineage marrow cells, in addition to leukemic features compatible with M4Eo. These findings strongly suggested that the leukemic cells in this case were derived from a preleukemic clone with a del(5q).

Aged↗
PubMed1992

Erythema multiforme: pathomechanism of papular erythema and target lesion.

Skin lesions of erythema multiforme show time-dependent changes from early papular erythema to the late target lesion which consists of a peripheral elevated erythematous area and a central depressed area. We investigated the pathomechanism of erythema multiforme, by examining the papular erythema and target lesion separately. In the early papular erythema, a small number of polymorphonuclear leukocytes and nuclear debris were seen intermingled with mononuclear cells around the slightly swollen blood vessels, on which immunoglobulin and complement components were deposited. Circulating immune complex levels were occasionally elevated. Sera from the patients generated high levels of reactive oxygen species and nitroblue tetrazolium test revealed positive reaction on the infiltrating cells around the blood vessels. These findings suggest that the papular erythema develops via incomplete type III allergic reaction, followed by damage through reactive oxygen species. In the target lesion, the activity of histamine-N-methyltransferase, which is the major histamine-degrading enzyme, was markedly decreased in the peripheral elevated erythematous area and it was recovering in the central clearing area. ICAM-1 and HLA-DR antigens were expressed on the surfaces of the keratinocytes. An increased number of epidermal Langerhans cells and CD4 cell infiltration were observed in the peripheral elevated erythematous area, while a decreased number of epidermal Langerhans cells and CD8 cell infiltration in the central depressed area were observed. These findings suggest that impaired histamine metabolism and cellular allergic reactions play important roles in the development of the target lesion.

Antigen-Antibody Complex↗
PubMed1992

A monoclonal antibody (NMC-VIII/10) to factor VIII light chain recognizing Glu1675-Glu1684 inhibits factor VIII binding to endogenous von Willebrand factor in human umbilical vein endothelial cells.

The monoclonal antibody NMC-VIII/10 is a neutralizing antibody which recognizes the Glu1675-Glu1684 sequence of the factor VIII light chain and inhibits factor VIII (FVIII) binding to immobilized von Willebrand factor (vWf). In this study we immunohistochemically determined, using human umbilical cord tissue, whether or not NMC-VIII/10 has an inhibitory effect on FVIII binding to endogenous vWF in endothelial cells. Tissue sections were reacted with purified FVIII followed by peroxidase-conjugated monoclonal antibody (C5) recognizing the 54 kD fragment of the FVIII heavy chain. The labelling pattern of bound FVIII was similar to that of endogenous vWF and appeared as a fine granular deposit in the endothelial cells. Addition of purified vWF completely inhibited the binding of FVIII to endothelial cells. Furthermore, FVIII did not bind to endothelium in the presence of 0.25 M CaCl2, and similarly, thrombin-treated FVIII did not bind to the vascular site. These findings suggested that FVIII was bound to endogenous vWF in the endothelial cells. The binding reaction was completely inhibited by NMC-VIII/10, confirming that the monoclonal antibody recognizes the specific epitope responsible for FVIII binding to endogenous vWF.

Antibodies, Monoclonal↗
PubMed1992

Effect of aminophylline on brain tissue oxygenation in patients with chronic obstructive lung disease.

BACKGROUND: It is known that theophylline reduces cerebral blood flow in humans. To quantitatively assess the possible adverse effect of theophylline on brain tissue oxygen tension (PO2) due to decreased cerebral blood flow, two sets of experiments were conducted in mildly hypoxaemic patients with chronic obstructive lung disease. METHODS: Firstly, internal jugular venous PO2 (PjO2) was measured simultaneously with arterial and mixed venous blood PO2 (PaO2 and PvO2) during right heart catheterisation in 10 subjects (mean PaO2 73 mm Hg; conversion factor: 10 mm Hg = 1.33 kPa)) before and after intravenous infusion of aminophylline (6 mg/kg). The PjO2 and PvO2 were considered to reflect the average tissue PO2 for the brain and for the whole body respectively. Secondly, the relation between PaO2 and PjO2 over a wide range, with the PaCO2 similar to that in the first study, was investigated in a different group of 12 subjects by stepwise changes in inspiratory gas composition. RESULTS: The mean PjO2 decreased by as much as 6 mm Hg 15 minutes after an infusion of aminophylline, whereas PaO2 stayed at the same level and PvO2 showed only a small decrease. The low PjO2 value of 29 (SD 6) mm Hg with aminophylline in the first study was similar to the PjO2 value of 30 (2) mm Hg obtained during severe hypoxia (PaO2 45 mm Hg) in the second study. The coefficient of oxygen delivery for the brain decreased by 29% with aminophylline treatment, but did not change significantly during severe hypoxic challenge. CONCLUSIONS: These data suggest that an infusion of aminophylline lowers brain tissue PO2 appreciably when given to mildly hypoxaemic patients with chronic obstructive lung disease.

Aminophylline↗
PubMed1992

Epinephrine augments von Willebrand factor-dependent shear-induced platelet aggregation.

BACKGROUND: Shear-induced platelet aggregation (SIPA) is an important mechanism in thrombogenesis. von Willebrand factor (vWF) binding to platelet glycoprotein Ib (GP Ib) has been found to be crucial for platelet aggregation under the high shear force probably generated in stenosed coronary artery. The physiological significance of vWF-dependent SIPA has not been clarified. METHODS AND RESULTS: Blood samples were collected from 23 normal volunteers. SIPA was continuously monitored using a modified cone-plate viscometer adapted for measuring the transmitted light intensity of the material. The effects of low concentrations of epinephrine, ADP, and collagen on SIPA under both low shear (12 dyne/cm2) and high shear (108 dyne/cm2) force were investigated. All agonists tested enhanced SIPA under low shear force, whereas only epinephrine augmented SIPA under high shear force. The maximum extents of SIPA under high shear force in the absence and presence of epinephrine (10 ng/ml) were 37.9 +/- 11.5% and 59.7 +/- 13.9%, respectively. The antagonist of the alpha 2-adrenergic receptor yohimbine (1 microgram/ml) antagonized the effects of epinephrine. The monoclonal antibody NMC-4 against vWF, which was shown to inhibit its binding to GP Ib, completely abolished SIPA under high shear force, even in the presence of epinephrine. However, this antibody only partially inhibited SIPA under low shear force. CONCLUSIONS: Our findings suggest that epinephrine is the agonist that enhances SIPA mediated by vWF through its specific receptor. This may be clinically important because occlusion of the coronary artery often occurs in stenosed atherosclerotic vessels under sympathetic stimulation.

Adrenergic alpha-Antagonists↗
PubMed1992

The expression of a cerebellar degeneration-associated neural antigen in human tumor line cells.

We examined the expression of the paraneoplastic cerebellar degeneration-associated autoantigen (PCD-AA) protein in human tumor lines of different origins by using an immunoaffinity-purified antibody from a patient with paraneoplastic cerebellar degeneration (PCD) and uterine adenocarcinoma. Immunocytochemical studies revealed that this antigen is expressed in the cytoplasm of two different uterine carcinoma lines and the tumor lines of neural origin as well as in the cytoplasm of a normal skin fibroblast line. By immunoblot analysis, we detected a 52-kd antigen identical to the PCD-AA protein in all the cell lines studied, including a colon adenocarcinoma line, a small-cell lung carcinoma line, and a squamous cell lung carcinoma line. These results indicate that the PCD-AA protein is expressed in a wide range of tumor cells. In this respect, this antigen is distinguishable from the cerebellar degeneration-related--34 antigen, of which expression is confined to tumor lines of neuroectodermal origin and not detected in colon, breast, or ovarian carcinoma lines derived from patients without PCD. These findings suggest the variability of the immune response to antigens in PCD.

Antigens, Neoplasm↗
PubMed1992

[Immunohistochemical studies of paraneoplastic subacute sensory neuropathy--an analysis of antineuronal antibody and infiltrated lymphocytes].

In order to clarify the pathogenesis of paraneoplastic syndrome, immunohistochemical studies were performed in a patient with subacute sensory neuropathy secondary to a small cell lung cancer. The case was a 73-year-old ex-farmer, whose chief complaints were pins and needles sensation of distal limbs and gait difficulty. After 6 weeks prodromata of pain in the upper limbs and numbness in all the limbs, he became unable to stand up without assistance. Neurological examinations on admission revealed marked sensory disturbances with glove and stocking type hypalgesia to pin prick and the loss of position and vibration senses in the distal extremities. His deep tendon reflexes also decreased in all the limbs. A chest X-ray showed a mass in the left upper lung field. A transbronchial lung biopsy of the mass revealed a small cell carcinoma. He was treated with anti-cancer drugs and radiation but he died of pneumonia after 8 months illness. Autopsy revealed a marked demyelination of the entire posterior column of the spinal cord. Dorsal root ganglia were infiltrated by lymphocytes with significant neuronal loss. Immunohistochemically, most of the infiltrated cells around the neurons were classified as CD8+ with fewer CD4+ lymphocytes. No B-lymphocytes were detected in the ganglia. The HLA-ABC and HLA-DR positive cells were found only among the satellite cells, not in the neurons. The serum and CSF from the patient were immunohistologically reacted with the nuclei and cytoplasm of all neurons of human as well as of rats, indicating the presence of anti-Hu type antineuronal antibody in the patient's CSF as well as serum.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1991

Factor IX Amagasaki: a new mutation in the catalytic domain resulting in the loss of both coagulant and esterase activities.

Factor IX Amagasaki (AMG) is a naturally occurring mutant of factor IX having essentially no coagulant activity, even though normal levels of antigen are detected in plasma. Factor IX AMG was purified from the patient's plasma by immunoaffinity chromatography with an anti-factor IX monoclonal antibody column. Factor IX AMG was cleaved normally by factor VIIa-tissue factor complex, yielding a two-chain factor IXa. Amino acid composition and sequence analysis of one of the tryptic peptides isolated from factor IX AMG revealed that Gly-311 had been replaced by Glu. We identified a one-base substitution of guanine to adenine in exon VIII by amplifying exon VIII using the polymerase chain reaction method and sequencing the product. This base mutation also supported the replacement of Gly-311 by Glu. In the purified system, factor IXa AMG did not activate factor X in the presence of factor VIII, phospholipids, and Ca2+, and no esterase activity toward Z-Arg-p-nitrobenzyl ester was observed. The model building of the serine protease domain of factor IXa suggests that the Gly-311----Glu exchange would disrupt the specific conformational state in the active site environment, resulting in the substrate binding site not forming properly. This is the first report to show the experimental evidence for importance of a highly conserved Gly-142 (chymotrypsinogen numbering) located in the catalytic site of mammalian serine proteases so far known.

Amino Acid Sequence↗
PubMed1991

Molecular study of the Prader-Willi syndrome: deletion, RFLP, and phenotype analyses of 50 patients.

Deletion and RFLP studies with 5 cloned DNA markers localized at 15q11.2 were performed in 50 patients with the Prader-Willi syndrome (PWS). A one-copy density (deletion) for at least one of 4 loci, D15S9, D15S11, D15S10, D15S12, was detected in 32 (64%) of the 50 patients; deletions of each of the 4 loci were found in 29, 30, 29, and 28 patients, respectively. Three patients showed 4 or more copy density for D15S12 locus, in addition to deletions. The remaining 18 patients showed two-copy densities for each of the 4 loci. A common site of rearrangements among our 32 patients as well as the reported patients seemed to be confined to a segment between D15S9 and D15S11, suggesting the putative PWS gene locus in this segment. Of 6 patients who have cytologic deletions but did not show any molecular deletions, 3 have normal size of hands and feet, and 4 have normally pigmented skin and hair. The normal pigmentation was also observed in 3 patients who had small molecular deletions in the examined 5-locus segment. These observations may support the conception of contiguous gene syndrome. RFLP analysis demonstrated maternal uniparental isodisomy of chromosomes 15 in both a patient with 45,t(15q;15q) and a karyotypically normal patient. Based on the results of the present study, a new model is proposed to explain the occurrence of PWS with a variety of chromosome abnormalities, including partial monosomy, disomy, trisomy, and/or tetrasomy for 15q11.2. The normal development may require an even or more "number ratio" of paternally derived allele(s) to maternally derived allele(s) of the gene(s) localized at 15q11.2, and a disturbance of the ratio would lead to the PWS phenotype.

Adolescent↗
PubMed1991

Haemophilia A: database of nucleotide substitutions, deletions, insertions and rearrangements of the factor VIII gene.

Mutations at the factor VIII gene locus causing Haemophilia A have now been identified in many patients from many ethnic groups. Earlier studies used biased methods which detected repetitive mutations at a few CG dinucleotides. More recently rapid gene scanning methods have uncovered an extreme diversity of mutations. Over 80 different point mutations, 6 insertions, 7 small deletions, and 60 large deletions have been characterised. Repetitive mutation has been proved for at least 16 CpG sites. All nonsense mutations cause severe disease. Most missense mutations appear to cause instability of the protein, but some are associated with production of dysfunctional factor VIII molecules, thereby localising functionally critical regions of the cofactor. Variable phenotype has been observed in association with three of the latter class of genotype. This catalogue of gene lesions in Haemophilia A will be updated annually.

Base Sequence↗
PubMed1991

Identification of a point mutation in type IIB von Willebrand disease illustrating the regulation of von Willebrand factor affinity for the platelet membrane glycoprotein Ib-IX receptor.

von Willebrand factor (vWF) supports platelet adhesion on thrombogenic surfaces by binding to platelet membrane glycoprotein (GP) Ib in the GP Ib-IX receptor complex. This interaction is physiologically regulated so that it does not occur between circulating vWF and platelets but, rather, only at a site of vascular injury. The abnormal vWF found in type IIB von Willebrand disease, however, has a characteristically increased affinity for GP Ib and binds to circulating platelets. We have analyzed the molecular basis of this abnormality by sequence analysis of a type IIB vWF cDNA and have identified a single amino acid change, Trp550 to Cys550, located in the GP Ib-binding domain of the molecule comprising residues 449-728. Bacterial expression of recombinant fragments corresponding to this vWF domain yielded molecules that, whether containing a normal Trp550 or a mutant Cys550 residue, bound directly to GP Ib in the absence of modulators and with similar affinity. In contrast, mammalian cell expression of the same segment of sequence yielded molecules that, when containing the normal Trp550, did not bind to GP Ib directly but, like native vWF, bound in the presence of ristocetin. However, molecules containing the point mutation (Cys550) behaved like type IIB vWF--namely, bound to GP Ib even without ristocetin modulation and, in the presence of ristocetin, had 10-fold higher affinity than molecules with normal sequence. These results identify a region of vWF that, although not thought to be directly involved in binding to GP Ib, may modulate the interaction through conformational changes.

Cloning, Molecular↗
PubMed1991

Studies on anti-von Willebrand factor (vWF) monoclonal antibody NMC-4, which inhibits both ristocetin- and botrocetin-induced vWF binding to platelet glycoprotein Ib.

Anti-von Willebrand factor (vWF) monoclonal antibody NMC-4 completely inhibited vWF binding to platelet glycoprotein (GP) lb induced by either ristocetin or botrocetin at an IgG concentration of approximately 10 micrograms/mL, and also blocked binding of asialo-vWF to GP lb. NMC-4 coupled beads isolated a 97-Kd fragment (Fr) from a whole tryptic digest of vWF. The N-terminal sequencing of the nonreduced 97-Kd Fr, in combination with amino acid analysis, showed it to be a homodimer of residues 449 through 728 of the constituent subunit. Present data, together with the results obtained from previous studies, confirm the existence of one or three possible inter-subunit disulfide bonds between cysteine residues 459, 462, and 464. NMC-4 bound to reduced vWF Fr(s) more weakly than to nonreduced Fr(s), but it did not react with Fr III-T2 of vWF, a disulfide-linked twin heterodimer of residues 273 through 511 and 674 through 728 (Marti et al, Biochemistry 26:8099, 1987). Fr III-T2 completely inhibited ristocetin-induced vWF binding at a concentration of 100 mumol/L but had no effect on botrocetin-induced binding. In addition, both the N- and C-terminal polypeptides, residues 449 through 549 and 674 through 728, generated by subdigestion of the 52/48-Kd Fr (Fujimura et al, J Biol Chem 261:381, 1986), inhibited preferentially ristocetin-induced vWF binding without affecting to botrocetin-induced vWF binding. These findings suggest that amino acid residues 512 through 673 of the vWF subunit are involved in botrocetin-induced vWF binding.

Antibodies, Monoclonal↗
PubMed1991

Upbeat nystagmus: clinicopathological and pathophysiological considerations.

We describe an electro-oculographic study of upbeat nystagmus in 4 patients, with neuropathological correlation in one. All patients had lesions in the pontine tegmentum. The electro-oculographic data may be explained by imbalanced vertical vestibular or smooth pursuit eye movement control. The nystagmus stopped or reversed direction during convergence or in supine head positions. We propose that changes in the intensity or direction of upbeat nystagmus that are induced by convergence or changes in head position, are caused by vertical imbalance in the otolithic-ocular reflex, when superimposed on an imbalanced vestibulo-ocular reflex (VOR). Imbalance of the otolithic-ocular reflex and the vertical VOR are caused by damage in the pontomedullary tegmentum.

Adult↗
PubMed1991

A novel anti-ENA antibody in sera of patients with childhood idiopathic thrombocytopenic purpura.

Circulating antibodies against certain extractable nuclear antigens (ENA) have been shown to have diagnostic and prognostic importance in connective tissue diseases. We described here an antibody against ENA found in the sera of patients with idiopathic thrombocytopenic purpura (ITP). The antigen, tentatively called WK according to the patients' initials, was distinct from U1 RNP/Sm, SSA/SSB, Scl-70, PCNA, PM-Scl, Jo-1, and Ku by immunodiffusion. On immunoblotting, the anti-WK serum recognized polypeptides of 99 kd, 98 kd, and 96 kd in rabbit thymus extracts and a 99 kd polypeptide in KB cell extracts. The anti-WK antibody was detected in the sera of 2 out of 360 ANA positive patients, both children with clinical features of ITP. One patient developed systemic lupus erythematosus eight years after the onset of ITP.

Antibodies, Antinuclear↗