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Biomedical subjects

M Sumiya

Publications and source records attributed to M Sumiya.

At least 37 records · Page 2Linked to original sources
PubMed1997

Association of mutations in mannose binding protein gene with childhood infection in consecutive hospital series.

OBJECTIVE: To determine the extent to which mutations in the mannose binding protein gene predispose to childhood infection. DESIGN: Clinical details and genotype of mannose binding protein determined in consecutive children attending a paediatric department. SETTING: Inner city hospital paediatric service in London. SUBJECTS: 617 children attending hospital between October 1993 and August 1995. MAIN OUTCOME MEASURE: Infection as the cause for attendance or admission in relation to mutations in the mannose binding protein gene. RESULTS: The prevalence of mutations in the mannose binding protein gene in children with infection (146/345) was about twice that in children without infection (64/272) (P < 0.0001). Increased susceptibility to infection was found in both heterozygotic and homozygotic children. 13 out of 17 children homozygotic for variant alleles presented with strikingly severe infections, including 6 with septicaemia. CONCLUSIONS: The findings suggest that mutations in the mannose binding protein gene are an important risk factor for infections in children. Screening for such mutations should be included in the investigation of severe or frequent infections.

Adolescent↗
PubMed1997

The role of collectins in host defense.

Mannose-binding protein (MBP) belongs to a group of Ca(2+)-dependent lectins called collectins that play a role in first-line host defense. It recognizes specific carbohydrate residues (mannose and N-acetylglucosamine) on the surface of microorganisms and promotes the killing of microbes either by acting directly as an opsonin or by activating the lectin complement pathway. The collagenlike domain of MBP is important for the binding of MBP to the collectin receptors expressed on different phagocytes, and for activation of complement. The binding of MBP to bacteria, viruses, and parasites has been demonstrated in vitro. Three major mutations have been found in exon 1 of the MBP gene, which encodes the collagenous domain of the protein. These mutations cause low levels of serum MBP and have been linked with lifelong risk of infection. The homozygotes for these mutations are especially susceptible to severe infections.

Animals↗
PubMed1997

Histological evaluation of destructive monoarthropathy in mixed connective tissue disease.

The synovium from a patient with mixed connective tissue disease and destructive ankle monoarthritis was studied in detail to determine its immunohistological characteristics. Fibrinoid necrotic tissue on the surface of the synovium, multi-layered lining cells, increased numbers of capillaries, interstitial edema, infiltration of macrophages, relatively small numbers of lympho-plasma cells and polymorphonuclear leukocytes, scattered bone fragments, and multinucleated giant cells were observed. Many cells in the lining and sublining area were positive for CD68 and MAC387. Lower layers of increased lining cells which had a spindle shape were positively stained with anti-HLA-DR antibody. The small arteries in the deeper part of the synovium revealed obstruction or highly stenotic change. These findings suggest that obstructive circulatory disturbance due to endothelial injury might influence the progression of arthritis.

Adult↗
PubMed1997

[Antinuclear antibody screening by an enzyme-linked immunosorbent assay using multiple nuclear antigens].

We assessed the clinical value of an enzyme-linked immunosorbent assay (ELISA) kit (MESACUP ANA, MANA) which uses multiple nuclear antigens for screening antinuclear antibody (ANA). Since the screening procedure for ANA by the indirect fluorescence method (FANA) requires trained personnel and gives rather subjective results, development of a suitable screening test for ANA by ELISA which uses specific nuclear antigens has been long awaited. Serum samples from 350 patients with connective tissue diseases (CTD), and from 300 normal subjects were assayed for ANA by ELISA and the results were compared with those of FANA and of single-antigen ELISAs for RNP, Sm, SS-A, SS-B, Scl-70, Jo-1, dsDNA, and ssDNA. For discrimination between patients with systemic lupus erythematosus and normal subjects, the sensitivity, specificity and accuracy for MANA were 85.7%, 97.5%, and 91.6%, and those for FANA were 95.8%, 77.0%, and 86.4%, respectively. Analysis of CTD sera showing discordant results between FANA and MANA using single-antigen ELISAs revealed that FANA - MANA + sera (n = 8) contained antibodies against SS-A (n = 1) or dsDNA (n = 3) or ssDNA (n = 3), and that some FANA + MANA - sera (n = 82), which were frequently found in RA patients (43/98, 43.9%), also contained antibodies against RNP (n = 3) or ssDNA (n = 13). MANA + normal sera (n = 9) were found to contain antibodies against SS-A (n = 1) or dsDNA (n = 1) or ssDNA (n = 2). In conclusion, MANA was found to be objective, much less labor intensive and suitable for screening large numbers of CTD sera for disease-specific ANAs.

Antibodies, Antinuclear↗
PubMed1996

Mutation of gene of mannose-binding protein associated with chronic hepatitis B viral infection.

BACKGROUND: Persistent with hepatitis B virus (HBV) affects 350 million people worldwide, and 20-40% of infected patients die of cirrhosis and liver cancer. Little is known about the host factors that determine the variable natural history. Studies have focused on the role of acquired rather than innate immunity. We have investigated the prevalence of mutations in the gene for mannose-binding protein (MBP), which have been associated with susceptibility to bacterial and fungal infections. METHODS: Mutations in the MBP gene were sought by sequence-specific oligonucleotide hybridisation, site-directed sequencing in Caucasian and Asian patients with HBV infection, and in HBsAg-negative controls. FINDINGS: A mutation in codon 52 of the MBP gene was present in two (11%) of 19 Caucasian patients with acute hepatitis B and nine (27%) of 33 Caucasian patients with chronic hepatitis B, compared with four (4%) of 98 Caucasian controls (p = 0.0004). By contrast the prevalence of the mutation was similar in Asian patients with chronic hepatitis B and in Asian controls (one [5%] of 20 vs two [2%] of 117). Mutations in codon 54 and codon 57 were found in similar proportions of patients and controls. INTERPRETATION: These findings show in Caucasian, but not Asian, patients an association of the codon 52 mutation of the MBP gene with persistent HBV infection. They suggest an important role for this gene, or a gene in linkage disequilibrium with MBP, in determining outcome after HBV infection in adult but not neonatal life.

Acute Disease↗
PubMed1996

Deposition velocity of gaseous organic iodine from the atmosphere to rice plants.

To obtain parameter values for the assessment of 129I transfer from the atmosphere to rice, deposition of CH3I to rice plants has been studied. The mass normalized deposition velocity (VD) of CH3I for rough (unhulled) rice was 0.00048 cm3 g-1 s-1, which is about 1/300 of that of I2. Translocation of iodine, deposited as CH3I on leaves and stems, to rice grain was negligibly small. Distribution of iodine between hull and inner part of the grain was found to depend also on the chemical forms of atmospheric iodine to be deposited. The ratio of the iodine distribution in a grain exposed to CH3I was as follows: rough rice:brown rice (hulled rice):polished rice = 1.0:0.49:0.38. The distribution ratio in polished grains for CH3I exposed rice was about 20 times higher than that for I2.

Food Contamination, Radioactive↗
PubMed1996

Mutations in the human mannose-binding protein gene: frequencies in several population groups.

Mannose-binding protein (MBP; mannan-binding protein, mannan-binding lectin) is a member of the collectin family of proteins and is thought to be important in innate immunity. We have previously shown high frequencies of two distinct mutations in codon 54 and codon 57 of exon 1 of the MBP gene in non-African and African populations, respectively. These result in low levels of the protein and an opsonic deficiency but the frequencies also suggest some selective advantage for low MBP levels. A third mutation in codon 52 occurs at a much lower frequency. We have now extended our earlier studies to other populations. In the south-west Pacific (Papua New Guinea and Vanuatu) neither the codon 52 nor the codon 57 mutation was detected and the codon 54 mutation was significantly less common (gene frequencies of 0.07 and 0.01, respectively) than in other non-African populations (gene frequencies 0.11-0.16). This could be explained by relatively recent admixture. The ancestral Melanesian population probably diverged some 50,000-60,000 years ago and our data suggest that the codon 54 mutation may have occurred after that even but before the divergence of European-Asian groups (40,000 years ago). Two further sub-Saharan populations were also studied: a group of Xhosa from South Africa were similar to Gambians, with a high gene frequency for the codon 57 mutation (0.27) and no evidence of the codon 52 or 54 mutations. In contrast, San Bushmen from Namibia had low frequencies of both the codon 57 mutation (0.07) and the codon 54 mutation (0.03). Again the codon 52 mutation was not found. This pattern is unique amongst sub-Saharan populations studied to date and suggests that this population may have been subjected to different selective pressures.

Africa↗
PubMed1996

Diffuse interstitial pulmonary amyloidosis in rheumatoid arthritis.

We describe a woman with seronegative rheumatoid arthritis (RA) who presented with diffuse septal pulmonary amyloidosis mimicking interstitial rheumatoid lung disease. Her systemic amyloidosis was diagnosed by biopsy of the kidney, stomach mucosa, and salivary glands 28 years after the onset of RA. Diffuse interstitial pulmonary infiltrates had been noted since that diagnosis, but infiltrates had been considered due to rheumatoid lung. Results of pulmonary function tests, which revealed restrictive changes and decreased diffusion capacity, were also compatible with rheumatoid lung disease. Pulmonary amyloidosis was diagnosed at autopsy. Pulmonary amyloidosis should be considered a cause of pulmonary infiltrates in patients with longstanding RA.

Amyloid↗
PubMed1996

Clinical features of patients with juvenile onset mixed connective tissue disease: analysis of data collected in a nationwide collaborative study in Japan.

OBJECTIVE: To analyze the clinical features and outcome of juvenile-onset mixed connective tissue disease (MCTD). METHODS: Clinical and laboratory findings were compared in 2 groups of MCTD patients divided according to age at onset: juvenile onset: under 16 yrs: adult onset: 16 yrs or older). RESULTS: Systemic lupus erythematosus-like symptoms, such as facial erythema, photosensitivity. LE cells, lymphadenopathy, and cellular casts, were more frequent in juvenile onset MCTD than in the adult form of the disease. On the other hand, scleroderma-like symptoms, such as esophageal hypomotility, scleroderma-like lesions evident on skin biopsy, pulmonary involvement, proximal scleroderma, and pitting scars, were less frequent in juvenile onset MCTD than in the adult form. Patients with juvenile onset MCTD more frequently met the classification criteria for systemic lupus erythematosus (SLE) and less frequently met those for progressive systemic sclerosis (SSc), compared to patients with adult onset MCTD. At disease onset, hand edema and stiffness were observed less frequently in juvenile onset MCTD than in the adult form. Furthermore, the mortality rate was lower in the former than in the latter (2.8% vs 8.4%). CONCLUSION: Although previous studies have reported severe symptoms and adverse outcome for juvenile onset MCTD, we conclude from this nationwide study in Japan that patients with juvenile onset MCTD exhibit more SLE-like and fewer SSc-like features and have a relatively favorable outcome.

Adolescent↗
PubMed1995

Mannose binding protein gene mutations associated with unusual and severe infections in adults.

A defect in opsonisation can cause a common immunodeficiency. A mutation in mannose binding protein (MBP) caused by point mutations in the MBP gene will lead to such a defect. This type of syndrome can cause recurrent infections in infants between 6 and 18 months of age but is not generally believed to predispose to adult infections. We looked at 4 patients with severe and unusual infections in whom MBP gene mutations were the only identified cause of immunodeficiency and one patient with combined MBP and IgA deficiency. We analysed the MBP genotypes of all the patients in whom we suspected an immunodeficiency because of their clinical history. Infections seen were recurrent skin abscesses, chronic cryptosporidial diarrhoea, meningococcal meningitis with recurrent herpes simplex, and fatal klebsiella lobar pneumonia. Both sexes were affected and ages ranged from 15 to 56 years. Two patients were homozygous for codon 54 mutations, one patient had codon 52 and codon 54 mutations and was phenotypically homozygous, and two patients were heterozygous for codon 54 mutations. Individuals homozygous for MBP mutations are unusual in the general population (approximate frequency 0.3%). The occurrence of three homozygotes for MBP mutations among these five infected patients suggests that MBP deficiency may confer a life-long risk of infection.

Adolescent↗
PubMed1995

Distinct physicochemical characteristics of human mannose binding protein expressed by individuals of differing genotype.

Mannose binding protein (MBP) is a serum collectin (collagenous lectin) believed to be of importance in innate immunity. Three point mutations, in codons 52, 54 and 57 of exon 1 of the human MBP gene, have been predicted to affect the tertiary structure of the collagenous region of the protein, and are known to be associated with low serum concentrations of MBP. However, other groups working with recombinant mutant proteins have claimed that the proteins are expressed and assembled normally. The aim of the present investigation was to characterize the effects of these mutations on the physicochemical nature of MBP that is present in the circulation in vivo, and for this we used polyacrylamide gel electrophoresis, gel filtration and sucrose density gradient centrifugation, followed by immunoblotting and enhanced chemiluminescence. The circulating wild-type MBP appeared to comprise a mixture of polymers formed from two to eight subunits (each based on three identical 32,000 MW polypeptide chains) of apparent molecular weights 200,000-700,000, with dimers and trimers constituting the predominant forms. Individuals homozygous for the codon 54 or 57 mutation had dramatically reduced concentrations of serum MBP, mainly comprising material of an apparent molecular weight of 120,000-130,000. Heterozygous individuals showed characteristics of both phenotypes. In contrast to the results obtained with artificial expression systems, our data suggest that individuals homozygous for the MBP mutations have very little circulating protein and that this comprises mainly low molecular weight material.

Carrier Proteins↗
PubMed1995

Molecular genetics of a receptor protein for D-xylose, encoded by the gene xylF, in Escherichia coli.

Mutants of Escherichia coli K12 have been isolated containing either the 'XylF' or the 'XylE' transport systems for D-xylose. This enabled the XylF system containing a D-xylose receptor-binding protein to be associated with high-affinity transport, apparent Km 0.2-4 microM, while the XylE sugar-H+ symporter system exhibited relatively low affinity, apparent Km 63-169 microM. Their apparent Vmax values were similar. Isolation of a xylose transport-negative mutation in a downstream gene, xylG, and a series of transduction experiments enabled the gene order xylB xylA p/o xyl(FG) mtlA to be proposed near 80 min on the E. coli chromosome. The xylose receptor protein (XylF) was highly purified from the periplasm and the sequence of its N-terminal 44 amino acids determined. From this a mixed oligonucleotide (14 mer) was synthesised of corresponding DNA sequence, hybridisation of which to restriction fragments from the ColE I hybrid plasmid, pLC32-9, which conferred xylose transport activity on a xylE- xylF- double mutant, enabled precise location of the xylF gene next to the xylose isomerase gene, xylA (3984 kbp on the Kohara physical map). The DNA sequence of the 2.5 kb Bgl II fragment containing the xylF gene was then determined, which confirmed the above gene order and revealed two divergent operons, probably regulated in a co-ordinate manner, one containing enzymes for catabolism of D-xylose, and the other proteins comprising the XylFG receptor-transport system. Analysis of the 330 amino acid sequence of the XylF receptor protein located the scission point of its leader peptide between Ala23 and Lys24, and revealed significant homologies with the other sugar receptor proteins for ribose (RbsB), galactose (MglB) and arabinose (AraF).

Amino Acid Sequence↗
PubMed1994

Enhanced synthesis of cytokines by peripheral blood monocytes cultured in the presence of autoantibodies against U1-ribonucleoprotein and/or negatively charged molecules: implication in the pathogenesis of pulmonary hypertension in mixed connective tissue disease (MCTD).

An attempt was made to determine whether addition of purified autoantibodies against U1-ribonucleoprotein (RNP) and negatively charged molecules (cardiolipin and double-stranded (ds) DNA) to cultures of peripheral blood monocytes could enhance the synthesis of cytokines in patients with MCTD and normal healthy volunteers. It was found that: (i) at the baseline, levels of cytokines such as IL-1 alpha, IL-1 beta and IL-6 extracellularly released by or associated with monocytes were significantly higher in MCTD patients than in normal subjects; (ii) addition of antibodies against U1-RNP to cultures of MCTD monocytes resulted in a significant overall increase of the released and cell-associated IL-1 alpha, IL-1 beta and IL-6. On the other hand, addition of antibodies against cardiolipin or dsDNA to cultures of MCTD monocytes resulted in a significant increase of released and/or cell-associated IL-1 alpha and IL-1 beta; (iii) addition of these autoantibodies to cultures of normal monocytes resulted in a significant overall increase of released and cell-associated IL-1 alpha, IL-1 beta and IL-6. The extent of enhancement of cytokines released by or associated with monocytes was greater in normal subjects than in MCTD patients; (iv) a F(ab')2 preparation of autoantibodies against U1-RNP also enhanced the level of released and cell-associated IL-1 alpha. Our findings that both autoantibodies against U1-RNP and negatively charged molecules were able to enhance the synthesis of cytokines by monocytes suggest that these autoantibodies might cause derangement of endothelial cells and lead to proliferative vasculopathy, which is a characteristic of pulmonary hypertension in MCTD.

Autoantibodies↗
PubMed1994

Phylogenetic comparison between archetypal and disease-associated JC virus isolates in Japan.

We examined the phylogenetical correlation between two types of JC virus (JCV) isolates, archetypes derived from the urine of nonimmunocompromised individuals and PML-types derived from the brain of patients with progressive multifocal leukoencephalopathy (PML) in Japan. A phylogenetic tree was constructed for eight JCV isolates, five PML-types obtained in this and previous studies and three representative archetypes, from DNA sequence data on the VP1 (major capsid protein) gene. The eight isolates were divided into two major groups, named subtypes MY and CY after the representative archetypal isolates. Four of five PML-type isolates belonged to subtype MY, and the other one to subtype CY. Isolates belonging to subtype MY were further divided into two groups; one group containing archetype MY and three PML-types and the other one containing archetype YI and a PML-type. These findings, together with those in our previous study that correlated various JCV isolates in the world provide evidence for the hypothesis that JCVs associated with PML may have been generated from archetypal JCVs persisting in the patients.

Base Sequence↗
PubMed1994

Antiendothelial cell antibodies and their relation to pulmonary hypertension in systemic lupus erythematosus.

OBJECTIVE: Antiendothelial cell antibodies (aECA) have been demonstrated in patients with systemic lupus erythematosus (SLE), but their role in the pathogenesis of this disease remains unclear. We investigated the association of aECA and anticardiolipin antibodies (aCL) with clinical and laboratory findings in patients with active SLE. METHODS: Sera from 28 patients with active SLE and 22 healthy controls were assayed for IgG and IgM-aECA by cellular ELISA method using cultured human umbilical vein endothelial cells and IgG-aCL by ELISA method. RESULTS: Serum titers of both IgG and IgM-aECA were significantly higher in active SLE than in healthy controls. Titers of IgG-aECA were unrelated to titers of IgG-aCL. Patients with pulmonary hypertension demonstrated a marked elevation of serum titer of both IgG and IgM-aECA compared with patients without pulmonary hypertension. In addition, patients with digital vasculitis showed a significant elevation of serum titer of both IgG and IgM-aECA compared with patients without digital vasculitis. Serum titers of IgG-aECA in patients with Raynaud's phenomenon and of IgM-aECA in patients with serositis were each significantly increased compared with patients without such findings. CONCLUSION: aECA were unrelated to aCL. Serum titers of aECA are elevated in patients with active SLE, especially with pulmonary hypertension, digital vasculitis, Raynaud's phenomenon or serositis. Since pulmonary hypertension in SLE has been associated with digital vasculitis, Raynaud's phenomenon and serositis, aECA may be involved in the pathogenesis of vascular injury, leading to these manifestations.

Antibodies, Anticardiolipin↗