Purple diaper syndrome in geriatrics.
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Aged, 80 and over↗
Biomedical subjects
Atsushi Komiyama
Publications and source records attributed to Atsushi Komiyama.
Vertical conjugate eye deviation in postresuscitation coma.
Vertical eye deviation in hypoxic coma is considered to be rare. In contrast, we found that in a consecutive series of 50 postresuscitation comatose patients, 28 (56.0%) developed tonic upward or downward eye deviation. We suggest that both the upward and the downward deviations resulted from diffuse cerebrocerebellar damage sparing the brainstem. Upward deviation is an early sign, whereas downward deviation appears later and generally implies a transition to the vegetative state.
Adult↗
Brain-specific potential guanine nucleotide exchange factor for Arf, synArfGEF (Po), is localized to postsynaptic density.
We cloned from a rat brain cDNA library a novel cDNA and named it a potential synaptic guanine nucleotide exchange factor (GEF) for Arf (synArfGEF (Po)) (GenBank Accession no. AB057643) based on its domain structure and localization. The cloned gene was 7410 bases long with a 3585-bp coding sequence encoding a protein of 1194 amino acids. The deduced protein contained a coiled-coil structure in the N-terminal portion followed by Sec7 and Plekstrin homology (PH) domains. Thus, the protein was a member of the Sec7 family of proteins, GEFs. Conservation of the ADP-ribosylation factor (Arf)-binding sequence suggested that the protein was a GEF for Arf. The gene was expressed specifically in the brain, where it exhibited region-specific expression. The protein was highly enriched in the postsynaptic density (PSD) fraction prepared from the rat forebrain. Uniquely, the protein interacted with PSD-95, SAP97 and Homer/Vesl 1/PSD-Zip45 via its C-terminal PDZ-binding motif and co-localized with these proteins in cultured cortical neurons. These results supported its localization in the PSD. The postsynaptic localization was also supported by immunohistochemical examination of the rat brain. The mRNA for the synArfGEF was also localized to dendrites, as well as somas, of neuronal cells. Thus, both the mRNA and the protein were localized in the postsynaptic compartments. These results suggest a postsynaptic role of synArfGEF in the brain.
ADP-Ribosylation Factors↗
Phenotypic and functional alterations of peripheral blood monocytes in neutrophil-specific granule deficiency.
Neutrophil-specific granule deficiency (SGD) is a rare, congenital disease characterized by atypical neutrophil structure and function, resulting in recurrent bacterial infections from early infancy. Homozygous recessive mutations in the CCAAT/enhancer-binding protein epsilon (C/EBPepsilon) gene were described in two of five SGD patients, indicating loss of C/EBPepsilon function as the primary genetic defect in this disease. C/EBPepsilon is expressed in murine and human macrophages. Macrophages from the C/EBPepsilon-deficient mice show impaired differentiation, phagocytic activity, and transcription of macrophage-specific genes. To determine if monocyte/macrophage cells are impacted in SGD, we analyzed phenotypic features of peripheral blood (PB) monocytes in a SGD individual lacking functional C/EBPepsilon. Flow cytometric analysis of PB leukocytes revealed aberrant expression of CD45, CD11b, CD14, CD15, and CD16 on cells from the SGD individual. Also, the PB CD14(+) cells from this individual, weakly stained for the monocyte-specific enzyme, nonspecific esterase, and electron microscopic examination, indicated morphologic differences between the SGD cells and those from normal controls. Serum interleukin (IL)-6 levels in the SGD individual during a severe bacterial infection were lower compared with levels in other non-SGD individuals with sepsis. In contrast, serum IL-8 levels were markedly elevated in the SGD individual compared with those of non-SGD individuals in sepsis. PB CD14(+) cells from the SGD individual expressed higher IL-8 mRNA levels compared with normal controls in response to lipopolysaccharide and interferon-gamma. These phenotypic and functional alterations of PB monocytes in the SGD individual suggest that C/EBPepsilon plays a critical role in monocyte/macrophage development of humans and is consistent with observations in the murine system. This study implicates abnormalities in monocytes/macrophages and neutrophils in the onset and development of SGD.
Animals↗
STI571 inhibits growth and adhesion of human mast cells in culture.
Stem cell factor (SCF)/c-kit system is critical for human mast cell development. We thus examined the effects of STI571, an inhibitor of the c-kit tyrosine kinase receptor, on the proliferation and function of human mast cells. STI571 at concentrations of 10(-6) M or higher almost completely abolished the SCF-dependent progeny generation from cord blood-derived cultured mast cells through an inhibition of the tyrosine phosphorylation of c-kit. The compound also suppressed the early phase of mast cell development. The extinction of mast cell growth induced by STI571 may be due largely to apoptosis according to the flow cytometric analysis and gel electrophoresis. Two-hour exposure to STI571 that failed to influence the total viable cell number suppressed adhesion of the cells to fibronectin in the presence of SCF without altering the expressions of integrin molecules. Our results may provide a fundamental insight for the clinical application of STI571 in allergic disorders.
Antigens, CD↗
Novel Artemis gene mutations of radiosensitive severe combined immunodeficiency in Japanese families.
A subgroup of patients with severe combined immunodeficiency (SCID) and increased cellular radiation sensitivity (RS-SCID) have mutations of Artemis, a gene that encodes a protein essential for V(D)J recombination and DNA double-strand break repair. RS-SCID described to date are either of European origin or are Athabascan-speaking native Americans belonging to the Navajo and Apache tribes. We have identified three Japanese boys and one girl from four unrelated families with RS-SCID caused by a genomic exon 3 deletion of the Artemis gene, resulting in loss of exon 3 and skipping of exon 4. Two patients were homozygous and two patients were heterozygous for this novel mutation. Those parents studied were heterozygous for this mutation. These findings suggest the genomic exon 3 deletion is unique to Japan and may be considered as a founder haplotype. Although two infants underwent successful bone marrow transplantation and immune reconstitution, the long-term outcome of this procedure is uncertain, because Artemis is expressed in most tissues and lack of its function in cells other than those derived from hematopoietic stem cells may increase the risk of malignancies.
Antigens, CD↗
Specific autoantibodies to platelet glycoproteins in Epstein-Barr virus-associated immune thrombocytopenia.
In this study, we detected autoantibodies to platelet glycoproteins GPIIb/IIIa and GPIb/IX on platelets and in plasma in a patient with immune thrombocytopenia associated with Epstein-Barr virus-related infectious mononucleosis. In addition, we present our findings on the effectiveness of intravenous immunoglobulin therapy for immune thrombocytopenia associated with Epstein-Barr virus.
Autoantibodies↗
Expansion of clonotype-restricted HLA-identical maternal CD4+ T cells in a patient with severe combined immunodeficiency and a homozygous mutation in the Artemis gene.
We have observed a male infant with severe combined immunodeficiency (SCID) responsible for Artemis gene mutation, in whom marked expansion of the transplacentally grafted maternal CD4(+) T cells was observed in various tissues. His class I and II major histocompatibility antigens (MHC) were identical to his mother's. We analyzed the T-cell populations within target tissues at a molecular level in order to determine whether different T-cell clonotypes are expanded in different types of tissue. Prior to T-cell expansion, the T-cell receptor variable beta (TCRBV) 5.1 subfamily predominated in peripheral blood (PB) lymphocytes. Third complementarity determining region (CDR3) size spectratyping and amino acid sequencing showed that the range of T-cell clonotypes was very restricted. After T-cell expansion, different TCRBV subfamilies were found to predominate in different target tissues; these included TCRBV 5.1 and 17 in the PB, TCRBV 13 and 21.3 in the bone marrow, and TCRBV 17 in lymph nodes. CDR3 size analysis showed that the expression of different proliferating T-cell clonotypes remained restricted after T-cell expansion. These results indicate that highly restricted maternal T-cell clonotypes can markedly expand, possibly in response to tissue-specific antigens, in a MHC-identical recipient.
Amino Acid Sequence↗
Prevention of antibiotic-associated diarrhea in children by Clostridium butyricum MIYAIRI.
BACKGROUND: Clostridium butyricum MIYAIRI (CBM) is a probiotic bacteria used for anti-diarrheal medicine in Japan. The preventive effect of CBM was investigated for antibiotic-associated diarrhea (AAD) in children. METHODS: One hundred and ten children who suffered from upper respiratory tract infection or gastroenteritis were divided into three groups. Twenty-seven of the patients received only antibiotics, 38 received CBM from the mid point of the antibiotic treatment and 45 concomitantly received CBM from the beginning of the antibiotic treatment. To examine the effects of CBM on AAD, the changes in intestinal flora were investigated. RESULTS: Diarrhea was observed in 59% of the subjects who received only antibiotics, and total fecal anaerobes, especially Bifidobacterium, were remarkably decreased. In contrast, diarrhea in the subjects who received CBM from either the middle or the beginning of the antibiotic therapy was decreased to 5% and 9%, respectively. Concomitant administration of CBM increased anaerobes and prevented the decrease of Bifidobacterium in the subjects who received antibiotics. CONCLUSIONS: Clostridium butyricum MIYAIRI is effective for both the treatment and the prophylaxis of AAD in children, as it normalizes the intestinal flora disturbed by antibiotics.
Anti-Bacterial Agents↗
Thalidomide therapy for juvenile-onset entero-Behçet disease.
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Adolescent↗
[Medical support for Belarus after Chernobyl accident using a telemedicine system].
To achieve a close relationship among Gomel Regional Hospital (Gomel, Belarus), Belarusian Children Center of Hematology/Oncology (Minsk, Belarus) and Shinshu University Hospital, we established a telemedicine system using the Inmarsat satellite. The system consists of a TV conference system, a digital microscopic imaging system and a high-definition image server/viewer network system (DICOM). The detailed case conference is possible among three areas of physicians.
Child↗
Synergism between stem cell factor and granulocyte-macrophage colony-stimulating factor on cell proliferation by induction of cyclins.
Synergism between stem cell factor (SCF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) has been shown to be essential for hematopoietic cell proliferation. Since HML-2 cells proliferate exponentially in the presence of SCF and GM-CSF together, we analyzed the molecular mechanism of the interaction between these two factors in the cells. An immediate-early gene product, c-myc, was additively upregulated in HML-2 cells by addition of a combination of SCF and GM-CSF. c-myc antisense oligonucleotides effectively suppressed cell proliferation and downregulated the induction of D3, E, A, and B cyclins in HML-2 cells stimulated with the two-factor combination. HML-2 cells arrested at the G0/G1 phase with SCF alone and expressed modest amounts of c-myc and cyclin D3, but not cyclin E. With GM-CSF treatment alone, the cells could not progress to the G2/M phase and expressed c-myc, cyclin D3 and cyclin E but not cyclins A or B. The addition of the counterpart cytokine resulted in cell cycle completion by induction of the deficient cyclins. Taken together, it appears that the induction of c-myc is an indispensable event in the proliferation of HML-2 cells and that the cytokines SCF and GM-CSF interact reciprocally for expression of all cyclins required for cell cycle progression.
Cell Cycle↗
ASC, which is composed of a PYD and a CARD, is up-regulated by inflammation and apoptosis in human neutrophils.
ASC is an adaptor protein that is composed of two protein-protein interaction domains, a PYRIN domain (PYD), and a caspase-recruitment domain (CARD). Recently, ASC was identified as a binding partner of pyrin, which is the product of MEFV, a gene causing familial Mediterranean fever (FMF). Mutations in MEFV result in defects in control of neutrophil-mediated inflammation. Thus we focused on the expression of ASC in neutrophils. Immunohistochemical study showed that ASC is increased in neutrophils in severe inflammatory sites of gangrenous appendicitis. We, then, tested whether proinflammatory mediators induce ASC using peripheral blood neutrophils in vitro. ASC expression was transiently up-regulated by IL-1alpha, IL-1beta, IFN-alpha, IFN-gamma, TNFalpha, and LPS. ASC was also increased by incubation with either anti-Fas antibody or recombinant soluble Fas ligand. The Fas-mediated induction of ASC was inhibited by a general caspase inhibitor, z-VAD-fmk, and an immunocytochemical study showed that ASC was increased in neutrophils exhibiting characteristic phenotypes for apoptosis. These findings suggest that up-regulation of ASC is closely associated with inflammation and apoptosis in neutrophils.
Apoptosis↗
The different process of class switching and somatic hypermutation; a novel analysis by CD27(-) naive B cells.
The relationship between class switch recombination (CSR) and somatic hypermutation has been unclear. By using human CD27(-) naive B cells, we investigated the somatic hypermutation and producibility of immunoglobulins (Igs) that occur after CSR. Although neither adult CD27(-) nor cord blood B cells, which showed the unmutated Ig V-region genes, produced IgG, IgM, or IgA in response to conventional stimuli, they produced IgG and IgM but not IgA in the presence of Staphylococcus aureus Cowan strain (SAC) + interleukin-2 (IL-2) + IL-10 + anti-CD40 mAb + CD32 transfectants (CD40/CD32T). The naive B cells also produced IgE when combined with IL-4 + CD40/CD32T. In parallel with IgG production, the expression of mature gamma1 and gamma 2 transcripts was induced from naive B cells by the stimuli. The CD27 expression on human naive B cells was induced remarkably by CD40 signaling or B-cell receptor engagement, but somatic hypermutation could not be induced. The proliferation and differentiation into plasma cells were induced from naive B cells, whereas most of the plasma cells displayed very low levels of mutations in Ig V-region genes. CD27(-) naive B cells expressed activation-induced cytidine deaminase messenger RNA by the stimuli later than CD27(+) memory B cells. Our results demonstrate that CSR, but not noticeable somatic hypermutation, can be induced from CD27(-) naive B cells upon B-cell receptor engagement and CD40 signaling in cooperation with cytokines, suggesting that CSR and somatic hypermutation processes can occur independently, and the antibodies produced in this in vitro system are low-affinity antibodies.
Adult↗
Absence of memory B cells in patients with common variable immunodeficiency.
The molecular basis of common variable immunodeficiency (CVID) is unknown. To assess humoral immunity in CVID, we selected 24 patients with early or late onset of disease. X-linked agammaglobulinemia (XLA), X-linked hyper-IgM syndrome (XHIM), and non-XHIM were excluded based on clinical phenotype, assessment of the immune response, presence of Bruton's tyrosine kinase (Btk) in monocytes or platelets, and normal expression of CD40 ligand by activated T cells. The number of circulating B cells was within the normal range or reduced. IgD(-) CD27(+) memory B cells were markedly reduced or absent in all 24 patients and IgD(+) CD27(+) B cells were diminished in 8 patients. Circulating B cells from all 6 patients examined, including CVID patients with IgD(+) CD27(+) cells, failed to undergo somatic hypermutation in immunoglobulin-variable (V)-region genes, similar to cord blood B cells. B cells from CVID patients produced IgM and IgG, but not IgA upon the engagement of Ig receptor and CD40 in the presence of IL-2 and IL-10. B cells from all but 5 patients secreted IgE when stimulated by CD40 crosslinking in the presence of IL-4. The observation of defective memory B cells with abnormal cell marker expression and function demonstrates that naive CVID B cells including those expressing IgD(+) CD27(+), in analogy to cord blood and hyper-IgM syndrome B cells, may be responsible for their failure to differentiate into plasma cells and to produce high-affinity antibodies of different isotypes.
Adult↗
Continuous venovenous hemodiafiltration in neonatal onset hyperammonemia.
We report on four cases of neonatal-onset hyperammonemia due to metabolic disorders treated with continuous hemodiafiltration (CHDF). CHDF accomplished prompt removal of serum ammonia under very stable circulation. To overcome the various difficulties of blood purification procedures to the neonate, we used: (1) a 7-Fr double lumen catheter from the internal jugular vein to the atrium to perform the procedure veno-venously, (2) a special circuit for neonates, (3) nafamostat mesilate as an anticoagulant, and (4) a circuit warmer. The serum ammonium level decreased under 200 microg/dL within 30 hours and lactic acidosis were corrected immediately. We conclude that CHDF is an extremely effective and safe treatment for fluminant neonatal-onset hyperammonemia due to metabolic disorders.
Adult↗
Pathophysiologic mechanism of convergence nystagmus.
The convergent eye movements in convergence nystagmus are reported to be opposed adducting saccades under excessive convergence drive. What occurs is a horizontal saccade of the adducting eye and a quick reversal of the abducting eye immediately after initiation of the original saccade. Accordingly, the opposed adducting saccades of the abducting eye have been explained by the dynamic overshoot mechanism. However, by electro-oculographic analysis of eye movements in a patient with convergence nystagmus, we found that the opposed adducting saccades of the abducting eye occurred not only after but also just before initiation of the original saccade. Our observation indicates that the opposed adducting saccades can occur without dynamic overshoot as the starter mechanism. Possibly, cessation of the discharge of omnipause neurons may lead to firing of the burst neurons for the medial rectus subnucleus via activation by the excessive convergence drive.
Aged↗
Familial Mediterranean fever in 2 Japanese families.
We describe 3 Japanese patients in 2 families with familial Mediterranean fever (FMF) as determined by gene analysis. FMF is an ethnically related, genetic disease, occurring commonly in some Mediterranean populations. The FMF gene (MEFV) mutation found in our patients is M694I. The patients may be remote from East Asian extraction.
Adolescent↗