[HIV vif, vpr, vpu genes: structure and function].
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Animals↗
Biomedical subjects
M Sumiya
Publications and source records attributed to M Sumiya.
Identical point mutation leading to low levels of mannose binding protein and poor C3b mediated opsonisation in Chinese and Caucasian populations.
A common opsonic defect occurring in 7% of the Caucasian population is associated with low serum levels of the lectin mannose binding protein (MBP). This study sought to determine whether the deficiency was also present in a Chinese population using sera obtained from 100 healthy Chinese children (age range 6 weeks-16 years). The distribution profiles of MBP levels and C3b/C3bi fragments binding to mannan coated plates were both bimodal and similar to the corresponding Caucasian profiles. Serum MBP levels were low in 9% of the Chinese children and all of these sera generated low levels of C3b/C3bi fragments. Overall there was a high significant correlation between MBP levels and C3b opsonin generation (r = 0.77; P less than 0.001). By analogy with similar findings in a Caucasian population we believe this correlation to be a reflection of antibody independent complement activation by MBP. In a pilot study of DNA obtained from three adult Chinese with low MBP levels the point mutation causing MBP deficiency in Caucasians was identified in all three cases.
Adolescent↗
High frequencies in African and non-African populations of independent mutations in the mannose binding protein gene.
We have previously identified, in three British families having an index child with frequent infections, a point mutation (GGC-->GAC) in codon 54 of exon 1 of the gene for the human lectin mannose binding protein (MBP). This was associated with low serum levels of this complement activating protein and would be anticipated to impair opsonization of mannose rich microorganisms. We now report a second point mutation (GGA-->GAA) in Gambians from West Africa, involving codon 57 of exon 1. By substituting carboxylic acids for axial glycines in the translated proteins both mutations would be expected to disrupt the secondary structure of the collagenous triple helix of the 96 kDa MBP subunits. In the Gambians the codon 57 mutation was studied by PCR, sequence analysis and restriction analysis and found to be remarkably common (frequency of the mutant gene 0.29 in adults and 0.23 in newborns) whereas the codon 54 mutation was very rare (frequency 0.003). However, the codon 54 mutation was frequent in both a British Caucasian and a Hong Kong Chinese population (frequency of the mutant gene 0.17 and 0.11 respectively). It was predicted that both homozygous and heterozygous individuals would have profoundly reduced serum levels of the protein and this was confirmed by immunoassay as was the reduced capacity of such sera to activate complement through the MBP initiated classical pathway. Our data indicate that the two mutations have arisen independently since the divergence of African and non African populations and both have attained high frequencies.
Adult↗
Cells surviving infection by human immunodeficiency virus type 1: vif or vpu mutants produce non-infectious or markedly less cytopathic viruses.
Under conditions in which a clonal cell line (M10) isolated from a human T cell lymphotrophic virus type I-transformed MT-4 cell line was completely killed by infection with wild-type human immunodeficiency virus type 1 (HIV-1), equivalent M10 cells survived infection with HIV-1 vif, vpr or vpu mutant virus after transient cytopathic effects. Several cell clones, which were isolated from the proliferating M10 cells after infection with vif and vpu mutant viruses (M10/vif- and M10/vpu-), had heterogeneous HIV-1 phenotypes in terms of HIV-1 antigen expression, their syncytium forming capacity, reverse transcriptase activity and the infectivity of HIV-1 particles produced. When the replication kinetics of the HIV-1 particles produced were assayed in M10 cells, the clones could be classified into three types, i.e. type I producing non-infectious HIV-1, type II producing infectious HIV-1 with low replicative ability and type III producing infectious HIV-1 with a replicative ability similar to that of wild-type HIV-1. HIV-1 major viral cell proteins and virus particle fractions were almost typical in types II and III but not in type I. Electron microscopic examination of particles released by I, II and III clones revealed rare defective, predominantly defective and essentially normal virions, respectively. Northern and Southern blot analyses revealed no apparent deletion in the proviral DNA and mRNA prepared from these clones, except in the case of type I and II clones isolated from M10/vpu- which contained large deletions in the mRNAs for gag and gag-pol proteins. Thus, M10 cells surviving infection with HIV-1 vif or vpu mutants are heterogeneous, persistently expressing HIV-1 antigens and producing non-infectious or less cytopathic virus.
Blotting, Northern↗
The B cell repertoire in patients with systemic autoimmune diseases: analysis of Epstein-Barr virus (EBV)-inducible circulating precursors that produce autoantibodies against nuclear ribonucleoprotein (nRNP).
Peripheral blood B cells from patients with systemic autoimmune disease and healthy volunteers were immortalized using EBV and the frequencies of B cell precursors that produced immunoglobulin class-specific antibodies against anti-nRNP, a specific marker for mixed connective tissue disease, were assessed using limiting dilution analysis. The frequencies of EBV-induced B cell precursors that produced IgG anti-nRNP were correlated closely with the serum titres of the corresponding autoantibodies, which indicates that B cell precursors that produced potentially pathogenic autoantibodies could be immortalized from the peripheral blood of the patients by EBV. In contrast, the frequency of EBV-induced B cell precursors that produced IgM anti-nRNP in patients with systemic autoimmune disease was comparable to that in healthy volunteers and greater than those that produced IgG and IgA anti-nRNP. Moreover, many of the clones that produced IgM antibodies against nRNP reacted with other autoantigens, such as double-stranded DNA, single-stranded DNA and rabbit IgG. These polyreactive IgM antibodies are believed to belong to the 'natural antibodies', to be coded by the germline immunoglobulin V genes, and to react with evolutionarily conserved structural cellular components, including nRNP. Our finding that nRNP is one of the target antigens for this polyreactive autoantibody may lead to the elucidation of the origin of the pathogenic IgG and IgA anti-nRNP antibodies found in sera from patients with systemic autoimmune diseases.
Adult↗
[A systemic lupus erythematosus patient with multiple aseptic bone necroses, thrombosis of superior mesenteric artery and anti-phospholipid antibody].
A 38 year old woman with systemic lupus erythematosus (SLE) was admitted because of epigastralgia and fever. The diagnosis of SLE was made 22 years ago based on Raynaud's phenomenon, butterfly rash, hair loss, photosensitivity and positive antinuclear antibody. She had episodes of consciousness disturbance, transient visual disturbance of the left eye, and a necrosis of the left big toe. She underwent artificial arthroplasty of bilateral femoral heads 11 years ago, when multiple aseptic necroses of thirteen bones were found, and when anti-cardiolipin (CL) antibody was found to be positive. An echogram of abdomen suggested an obstruction of superior mesenteric artery (SMA) when she was admitted. Selective angiography revealed a complete obstruction of SMA and splenic artery, and incomplete obstruction of celiac artery. Conservative treatment with urokinase infusion and prednisolone 50 mg/day was not effective, and small intestine and right colon were resected on the 23rd hospital day. The pathological examination showed thrombosis of SMA. There was no evidence of arteritis or atherosclerosis. Anti-CL antibody and lupus anticoagulant were positive on admission, but the level of both anti-DNA antibody and complement was normal. Therefore, it was suggested that the thrombosis was related with anti-phospholipid antibody. The characteristic clinical feature were multiple aseptic bone necroses and thromboses of several arteries. We discussed the relationship of thrombosis and the etiology of multiple bone necrosis in this case with anti-phospholipid antibody.
Adult↗
Molecular basis of opsonic defect in immunodeficient children.
Low serum mannose-binding protein (MBP) concentrations are associated with a common opsonic defect. Sequence analysis of the MBP gene in three children with recurrent infections, the opsonic defect, and low serum MBP concentrations showed a point mutation at base 230 of exon 1 causing a change of codon 54 from GGC to GAC. The replacement of glycine with an aspartic acid residue disrupts the fifth Gly-Xaa-Yaa repeat in the collagen-like domain of each 32 kD MBP peptide chain and probably prevents the formation of the normal triple helix. Study of sixteen members of the three families showed autosomal dominant co-inheritance of the mutation and low serum MBP concentrations.
Alleles↗
Human immunodeficiency virus type 1 vif, vpr, and vpu mutants can produce persistently infected cells.
A series of human immunodeficiency virus type 1 (HIV-1) mutants in vif, vpr, vpu, and nef were constructed from an infectious plasmid (pNL 432) containing the full-length HIV-1 DNA by frameshift mutations. The capacities for replication and cell killing of these mutant viruses were examined in a clonal cell line (M 10) isolated from HTLV-I-transformed MT-4 cells. In all cases, the mutant viruses replicated, expressed HIV-1 antigens, and induced drastic cytopathic effects. However, some M 10 cells survived infection with vif, vpr, and vpu mutant viruses and became persistently HIV-1-infected, whereas no cells survived infection with the nef mutant as well as the wild-type virus. The HIV-1 particles produced from the surviving cells after infection with the vif, vpr, or vpu mutant viruses were fully replicative in M 10 cells without apparent cytopathic effects.
Cell Death↗
Concentrations of radiocesium and potassium in basidiomycetes collected in Japan.
Concentrations of 137Cs, 134Cs and 40K in about 60 mushroom samples (fruit bodies of basidiomycetes) belonging to 25 species collected in Japan have been studied. The levels of 137Cs varied very widely, ranging from less than 3 to 1520 Bq kg-1 (dry wt), while those of 40K were relatively constant. Concentrations of 137Cs in common edible mushrooms of Japan such as Lentinus edodes, Flammulina velutipes, Pleurotus ostreatus and Pholiota nameko were low (normally less than 50 Bq kg-1, dry wt). Concentrations of 134Cs in many samples were below the limit of detection (usually less than 5 Bq kg-1, dry wt). The median concentrations of 137Cs and 40K were 41 (dry wt) and 1150 Bq kg-1 (dry wt), respectively. From the 137Cs/40K ratios it was found that cesium rather than potassium was selectively taken up from the soils by fungi such as Suillus granulatus and Lactarius hatsudake. The 134Cs/137Cs ratios in mushrooms are related to the depth of the mycelium in the soil. The effective dose equivalent due to the dietary intake of radiocesium through mushrooms was estimated to be only 1.6 x 10(-7) Sv.
Basidiomycota↗
Biological half-life of gaseous elemental iodine deposited onto rice grains.
In order to obtain the biological half-life (Tb) of iodine deposited on rough rice grains, rice plants of four different growing stages--heading, milky, dough, and yellow ripe--were exposed to elemental gaseous iodine. After the exposure, the rough rice samples were collected at different intervals and analyzed for iodine to estimate the value of Tb. The average value of Tb obtained by the experiments at the dough and yellow ripe stages was about 200 d. This value is considerably larger than those for pasture grass and leafy vegetables.
Food Contamination, Radioactive↗
Noninfectious doughnut-shaped human immunodeficiency virus type 1 can induce syncytia mediated by fusion of the particles with CD4-positive cells.
A defective doughnut-shaped human immunodeficiency virus type 1 (HIV-1)-producing cell clone (designated as L-2) was isolated from persistently HIV-1-infected MT-4 cells. The syncytium-forming capacity of the cell and virus particle fractions was examined in human CD4-positive T cells. Several cell lines producing infectious HIV-1 particles, such as persistently HIV-1-infected MOLT-4 (MOLT-4/HIV-1) cells, were used as controls. Syncytia were formed within 20 h by the cell fraction of both L-2 and MOLT-4/HIV-1 and the virus particle fraction of L-2, but not MOLT-4/HIV-1. These formations were not affected by 3'-azido-3'-deoxythymidine (ZDV). In contrast, similar syncytium formation was first observed 2 days after the incubation of the virus particle fraction of MOLT-4/LAV-1 and this syncytium formation mediated by the cell fractions of MOLT-4/HIV-1 and L-2 or the virus particle fraction of L-2 differently.
Antibodies, Monoclonal↗
[A case of primary Sjögren's syndrome presenting as osteomalacia secondary to renal tubular acidosis].
We report a 43-year-old female with primary Sjögren's syndrome (SjS) who presented as osteomalacia due to distal renal tubular acidosis (RTA). Osteomalacia was thought to be a rare complication of RTA in SjS, although it had been often described in association with RTA in general. In 1979, she presented with dry mouth, parotid gland swelling and leg purpura. A diagnosis of primary SjS and hyperglobulinemic purpura was made on the basis of positive staining with Rose Bengal stain, sialography of the parotid gland and histological examination of the salivary gland of the lip. She was admitted to Jichi Medical School Hospital in March 1988 with chest pain. X-ray films revealed pseudofractures of bilateral ribs. Bone scanning showed abnormal multiple accumulation of RI on the same parts. Laboratory studies on admission revealed: GOT 50 IU/ml, GPT 9 IU/ml, ALP 190 IU/ml, LDH 301 IU/ml, BUN 11.0 mg/dl, creatinine 1.0 mg/dl, uric acid 2.7 mg/dl, total protein 7.4 g/dl (gamma globulin 22.3%), sodium 141 mEq/l, potassium 3.7 mEq/l, chloride 106 mEq/l, calcium 8.9 mg/dl, and phosphorus 2.4 mg/dl. Arterial blood gas studies on room air showed: PO2 96.7mmHg, PCO2 35.5mmHg, HCO3-19.1 mEq/l, PH 7.347 and base excess -5.4 mEq/l. The urinalysis showed: specific gravity 1.008, PH 7.0, and no protein and glucose. Immunologically, antinuclear antibody was positive at 1:640 with a speckled pattern. Anti-DNA antibody was negative. Antibodies to SS.A and SS.B were 1:64 and 1:32 respectively. Distal RTA was confirmed by the sodium bicarbonate and NH4Cl loading test.(ABSTRACT TRUNCATED AT 250 WORDS)
Acidosis, Renal Tubular↗
[Clinical study and therapy of systemic lupus erythematosus and pregnancy].
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Antibodies, Antinuclear↗
[A case of mixed connective tissue disease exacerbated by griseofulvin complicating aseptic meningo-encephalitis and disseminated intravascular coagulation].
A variety of drugs have been implicated in causing or exacerbating SLE (drug-related lupus). Griseofulvin, the most commonly used agent in the treatment of fungal infections in the skin, has been shown to be a possible SLE-activating drug in several case reports. In the literature, however, any similar drug reactions have not been reported in MCTD, despite sharing features of SLE. The first case of drug (griseofulvin)-exacerbated MCTD was described and discussed. The patient was a 36-year-old woman with a six-year history of MCTD and subclinical Sjögren's syndrome. She developed aseptic meningo-encephalitis and disseminated intravascular coagulation after two weeks of continuous oral administration of griseofulvin 375 mg per day for trichophytosis of the feet. Following cessation of griseofulvin with anticoagulants, antibiotics, and high dose steroids at the same time, she greatly improved within one week.
Adult↗
[A case of pulmonary thromboembolism due to circulating lupus anticoagulant].
A 22-year-old man was admitted because of hemosputum and progressive dyspnea with 3 attacks of chest pain and dyspnea over the previous 4 months. Chest roentgenography showed pulmonary infarction of the left lower lobe, and the diagnosis was confirmed by pulmonary perfusion and inhalation scintigraphy and pulmonary arteriography. Thrombolytic therapy was performed, but no significant effect could be obtained and anticoagulant therapy was performed continuously. No deep-vein thrombosis could be seen. He was considered to have autoimmune hemolytic anemia with lupus anticoagulant on the basis of auto-antibody data. Lupus anticoagulant is an antibody to phospholipid, and it is suggested that a decrease in the production of prostanoid in the endothelium causes thrombosis. In this case, as the patient showed a low level of 6-keto-PGF1 alpha in the blood, it is suggested that one of the etiological factors of pulmonary thromboembolism is a disorder of prostacyclin production in the endothelium, causing thrombosis by lupus anticoagulant.
Adult↗
Two types of antibodies inhibiting interleukin-2 production by normal lymphocytes in patients with systemic lupus erythematosus.
Decreased interleukin-2 (IL-2) production by lymphocytes in vitro has previously been demonstrated in patients with systemic lupus erythematosus (SLE). In the present study, we examined whether inhibitory factors in SLE patient sera are involved in defective IL-2 production. Our results indicate that purified IgG fractions of some SLE sera inhibit IL-2 production at 2 distinct phases of the IL-1-dependent IL-2 production system in vitro: first, by binding to adherent cells and probably inhibiting IL-1 production by macrophages, similar to the action of anti-HLA-DR antibodies, and second, by binding to T cells and blocking the interaction of IL-1 and T cells.
Autoantibodies↗
Deposition velocity of gaseous I to rice grains.
Among the routes of gaseous I transfer to rice grains, direct deposition to the hull of rice plants and the subsequent transfer to brown rice and polished rice should be more critical than leaf absorption-translocation. A grain number normalized deposition velocity (Vs) is recommended as a key parameter to assess the amount of gaseous I deposited on the rough rice. This parameter is given as "iodine content per unit number of grain per unit time" divided by "iodine concentration per unit volume of the air." After the heading period the surface area of rough rice is almost constant but weight increases with time. Therefore, mass normalized deposition velocity (VD) varies with time. By introducing Vs instead of VD, the variations could be converged into narrow ranges. The contribution of gaseous I from the atmosphere to rough rice, brown rice and polished rice were estimated using Vs values obtained experimentally and gaseous I concentration in the air.
Air Pollutants↗
[Pulmonary involvement in mixed connective tissue disease].
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Adult↗