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T Toma

Publications and source records attributed to T Toma.

At least 19 recordsLinked to original sources

Selective expansion of CD16highCCR2- subpopulation of circulating monocytes with preferential production of haem oxygenase (HO)-1 in response to acute inflammation.

Monocytes are composed of two distinct subpopulations in the peripheral blood as determined by their surface antigen expressions, profiles of cytokine production and functional roles played in vivo. We attempted to delineate the unique functional roles played by a minor CD16(high)CCR2(-) subpopulation of circulating monocytes. They produced significant levels of interleukin (IL)-6 and tumour necrosis factor (TNF)-alpha, but very low levels of IL-10 upon in vitro stimulation. Characteristic profiles of cytokine production were confirmed by stimulating purified subpopulations of monocytes after cell sorting. It was noteworthy that freshly isolated CD16(high)CCR2(-) monocyte subpopulations produced significant levels of haem oxygenase (HO)-1, whereas the major CD16(low)CCR2(+) subpopulation produced little. These results were contrary to the generally accepted notion that the CD16(high)CCR2(-) monocyte subpopulation plays a predominantly proinflammatory role in vivo. The CD16(high)CCR2(-) subpopulation increased in Kawasaki disease and influenza virus infection. In accord with this, HO-1 mRNA expression by mononuclear cells was significantly increased in these illnesses. These results indicate that CD16(high)CCR2(-) subpopulations are of a distinct lineage from CD16(low)CCR2(+) monocytes. More importantly, they may represent a monocyte subpopulation with a unique functional role to regulate inflammation by producing HO-1 in steady state in vivo.

Acute Disease↗

Oligoclonal expansion of circulating and tissue-infiltrating CD8+ T cells with killer/effector phenotypes in juvenile dermatomyositis syndrome.

Although triggering by infectious agents and abnormal immune responses may play some role in the pathogenesis of juvenile dermatomyositis syndrome (JDMS), the precise mechanism of muscle destruction and vascular damage is largely unknown. In this study, we tried to elucidate the role of cytotoxic T cells in two patients with JDMS, who were diagnosed based on the characteristic symptoms, laboratory data, MRI findings and electromyographic patterns. Peripheral blood T cell phenotypes were determined by flow cytometry, using mAbs against specific T cell receptor (TCR) Vbetas. Complementarity-determining region3 (CDR3) size analysis was performed by gene scanning of CDR3 polymerase chain reaction (PCR) amplification products specific for each Vbeta. Subsequently, CDR3 nucleotide sequences were obtained after cloning of the predominant products. The distribution of lymphocytes infiltrating the muscle tissue was analysed by immunohistochemistry. In both patients examined, a unique combination of TCR Vbeta repertoires was increased within the CD8+ T cells. These subpopulations expressed a characteristic phenotype, indicating that they are memory/effector T cells with killer functions. At the same time, immunohistological and molecular biological examinations of the biopsied muscle samples revealed that identical CD8+ T cell clones with identical phenotypes/TCR Vbeta infiltrated within the inflammatory tissue, in particular around vessels. These findings indicate that oligoclonal expansion of CD8+ T cells plays a central role in the pathogenesis of muscle injury in the juvenile form of dermatomyositis syndrome and may provide a useful clinical parameter of disease activity and responsiveness to anti-inflammatory therapy.

Antigens, CD↗

Clearance of antiphospholipid antibodies in pregnancies treated with heparin.

OBJECTIVE: To describe the natural history of serum antiphospholipid antibodies (lupus anticoagulant and anticardiolipin antibodies) in pregnant women treated with heparin, and to identify a possible association between changes in antibody status and outcomes of subsequent pregnancies. METHODS: Thirty-six women with antiphospholipid antibodies who had three or more repeated miscarriages were enrolled. Intravenous heparin was used for each of the first pregnancies after referral. Changes in antibody status were investigated with relation to outcomes of the index and subsequent pregnancies. RESULTS: Eighteen of 23 pregnancies in 36 antibody-positive women treated with heparin resulted in term or preterm deliveries with live-born infants, and five ended in abortions. Antibodies cleared in ten of 12 term pregnancies, in five of six preterm pregnancies, and in one of five abortions. There was a statistically significant difference between the term pregnancy and abortion groups (P <.05). Eleven second and third pregnancies in nine women in whom antibodies cleared resulted in term or preterm deliveries of live-born infants, without heparin therapy. The second and third pregnancies in one woman whose antibodies persisted ended in miscarriages despite repeated heparin administration. CONCLUSION: Antiphospholipid antibodies cleared spontaneously in some pregnant women treated with heparin. Subsequent pregnancies among women in whom antibodies cleared were managed successfully without medication, whereas pregnancies in women with persistent antibodies required treatment.

Abortion, Spontaneous↗

Cytoprotective role of heme oxygenase (HO)-1 in human kidney with various renal diseases.

BACKGROUND: We previously reported that glomerular changes in the renal specimen of a human case with heme oxygenase-1 (HO-1) deficiency were mild, but tubulointerstitial injury advanced progressively. This study examined the patterns of HO-1 production in the kidney in various renal diseases. Furthermore, the critical cytoprotective roles of HO-1 were evaluated in the kidney by comparing HO-1 production and expressions of carboxymethyllysine (CML) and pentosidine, both of which are markers of oxidative stress. METHODS: Renal biopsy or autopsy materials were obtained from a total of 74 patients. Degrees of hematuria and proteinuria and the levels of urinary N-acetyl-beta-D-glucosaminidase (NAG), beta2-microglobulin (beta2m), and creatinine were evaluated. Immunohistochemical studies for HO-1, CML, and pentosidine expressions were performed with their specific antiserum. RESULTS: HO-1 staining was observed within tubular epithelial cells in all of the renal diseases, but was not detected within intrinsic glomerular cells. HO-1 staining tended to be more intense within distal tubuli than in proximal tubuli. Within distal tubuli, there was no significant correlation between intensity of HO-1 staining and degree of hematuria or presence of proteinuria. Within proximal tubuli, HO-1 staining tended to be more intense with greater degrees of hematuria, presence of proteinuria, and moderate tubulointerstitial damage. Intense staining of CML and pentosidine was observed within renal tubular epithelial cells only in HO-1-deficient patients. CONCLUSIONS: HO-1 plays important roles in protecting renal tubuli from oxidative injuries, as these cells are constantly exposed to various oxidative stresses. It is suggested that renal tubular epithelia are more susceptible to oxidative stress due to the lack of this critical enzyme in HO-1 deficiency.

Adolescent↗

Two cases of supernumerary ovary: one with large fibroma with Meig's syndrome and the other with endometriosis and cystic change.

Reports of supernumerary ovaries are rare. We describe two such cases, one with fibroma and the other with endometriosis and cystic change. A large fibroma measuring 17.4 x 12.0 x 7.5 cm in size was found in the supernumerary ovary of the omentum in the first case of a 47-year-old married woman with Meig's syndrome. The second case was associated with endometriosis and cystic change, measuring 11 x 5 x 3 cm in size and located in the upper abdominal cavity. It was attached to the uterus of a 28-year-old pregnant woman who had neither fibroma nor Meig's syndrome. Histologically, corpus albicans and a few primordial germ cells were demonstrated, respectively. A fibroma showing a storiform pattern was found in the first case. The second case had endometriosis and a thin-walled cyst with bleeding and necrosis caused by torsion. Immunohistochemically, desmin, alpha-smooth muscle actin, c-kit, CA125, Na+/K+ATPase, overexpression of p53, myc and ras were all negative in the fibroma cells of the first case, and in the endometriosis and cyst wall of the second case. The fibroma cells were positive for vimentin and estrogen receptor, and the proliferating cell nuclear antigen was sporadically demonstrated in their nuclei. The mutation of the p53 gene at exons 5-8 was not detected by sequence analysis. Using RT-PCR, bax, bcl-2 and p16 were not detected either. Clinically, the two cases presented here did not show abnormal hormonal symptoms. They were diagnosed as abdominal tumors or masses. Based on these considerations, one might assume that supernumerary ovaries are probably more frequent than reported at present.

Adult↗

Aedes (Finlaya) japonicus (Diptera: Culicidae), a newly recognized mosquito in the United States: analyses of genetic variation in the United States and putative source populations.

Introduction of potential disease vectors into a new geographic area poses health risks to local human, livestock, and wildlife populations. It is therefore important to gain understanding of the dynamics of these invasions, in particular its sources, modes of spread after the introduction, and vectorial potential. We studied the population genetics of Aedes (Finlaya) japonicus japonicus (Theobald), an Asian mosquito that was recognized for the first time in the United States in 1998. We examined patterns of genetic diversity using random amplified polymorphic DNA and sequences of ND4 of mtDNA by comparing samples from populations spanning the range of this mosquito in Japan (six samples) and the United States (nine samples) as well as specimens intercepted in New Zealand in 1999. We found geographically differentiated populations in Japan, indicating limited gene flow even on small spatial scales. In the United States, we found evidence of significant genetic differentiation between samples from New York, Connecticut, and New Jersey and those from mid-Pennsylvania and Maryland. We were unable to pinpoint the source location(s) in Japan, although some of the U.S. samples are genetically close to samples from south Honshu and western Kyushu. Further studies should include samples from Korean populations. Distinct genetic signatures in U.S. populations undergoing expansion suggest the possibility of local increases in genetic diversity if and where they meet.

Aedes↗

The relationship between anthropometric indicators of nutritional status and malaria infection among youths in Khammouane Province, Lao PDR.

We assessed anthropometric indicators of the nutritional status among children and adolescents in Khammouane Province in the Lao PDR and examined the relation between malnutrition and malaria infection. The survey was conducted from July to August 1999 using a sample of 309 youths aged 2 to 18 years. Malnutrition was categorized as stunting (below -2 Z scores height-for-age) and wasting (below -2 Z scores weight-for-height). The prevalence of stunting and wasting were 45.1% and 9.2%, respectively, which were classified by WHO as "very high" prevalence. Compared with the results of previous national surveys in Lao PDR, similar prevalence was shown. The prevalence of wasting in youths with P. falciparum infection was 17%, significantly higher than those of not infected (4%). On the other hand, P. vivax infection was not associated with any indicators of malnutrition. In conclusion, this study showed that the nutritional status in youths was poor and P. falciparum infection was associated with acute malnutrition.

Adolescent↗

Possibility of false-positive detection for sporozoites in mosquitos (Diptera: Culicidae) by nested polymerase chain reaction using Plasmodium yoelii genomic DNA.

Anopheles stephensi Liston and An. saperoi Bohart and Ingram infected with the rodent malaria parasite Plasmodium yoelii nigeriense. They were examined 12 and 19 days after blood feeding for sporozoites in head with anterior thorax (HT) and oocysts in abdomen with posterior thorax (AB) by light microscopy and by the nested polymerase chain reaction (nested PCR-based on the amplification of the sequences of the small subunit ribosomal RNA gene). The detection rate of parasite DNA by nested PCR in HT samples 12 days after blood feeding was similar to that by microscopic method. However, in HT samples 19 days after blood feeding, the rate by the PCR method was higher than that by the microscopic method. The incidence of sporozoites in salivary glands of infected mosquitos for 12 days after blood sucking was examined by the PCR method. Parasite DNA in HT of Aedes albopictus Skuse (a non vector for the rodent malaria) as well as An. stephensi and An. saperoi was detected for up to 4 days after feeding on mouse with the rodent malaria parasites. The results indicate that when the PCR method is used for detection of sporozoites of human malaria in mosquitos collected in the field, there are possibilities of including false-positive data for mosquitos that have just or recently fed on human blood infected with malaria (erythrocytic form).

Aedes↗

Structural evidence of genomic exon-deletion mediated by Alu-Alu recombination in a human case with heme oxygenase-1 deficiency.

We previously reported a family affected by heme oxygenase-1 (HO-1) deficiency [Yachie et al., 1999]. The proband was a compound heterozygote for a complete loss of exon 2 (the maternal allele) and a two-nucleotide deletion within exon 3 (the paternal allele). In this report, we describe a large genomic deletion (1730 bp) including entire exon 2 in this family as a specific mechanism generating exon-2 absence observed in the HO-1 mRNA. Analysis of the deletion junction demonstrated fusion of a 5' portion of Alu-Sx element with a 3' portion of Alu-Sq element. The junction contained sequences with high homology to the recombinogenic Alu "core" sequence. These structural features of the HO-1 gene suggest homologous recombination associated with Alu element. This study presents the initial characterization of the HO-1 gene defect causing a human case of HO-1 deficiency and provides the molecular basis for understanding this genetic disease.

Alleles↗

Tubular injury as a cardinal pathologic feature in human heme oxygenase-1 deficiency.

Heme oxygenase (HO) catalyzes degradation of heme to biliverdin, iron, and carbon monoxide. It consists of three isoforms: an inducible form (HO-1), a constitutive form (HO-2), and the third isoform (HO-3), with properties similar to HO-2. There is limited evidence to suggest that the induction of HO-1 may have anti-inflammatory effects in an in vivo model of oxidative stress-mediated renal injury. We experienced the first human case of HO-1 deficiency. The patient had persistent proteinuria and hematuria, with biochemical evidence of renal tubular injury. We obtained three consecutive renal specimens: two from renal biopsies at 2 and 5 years of age and the third from autopsy at 6 years of age. The patient had systemic vascular endothelial-cell injury with massive intravascular hemolysis. The serum was loaded with heme and a large amount of heme-conjugated haptoglobin. A high concentration of haptoglobin was also detectable in urine. Mesangial proliferation or change in glomerular capillary-wall thickness was relatively mild to moderate in all specimens. Electron microscopic examination showed widespread endothelial detachment and subendothelial deposits of an unidentifiable material. It was striking that tubulointerstitial injury, with tubular dilatation and/or atrophy, interstitial fibrosis, and inflammatory cell infiltration, advanced progressively. Tubular epithelial cells were injured, and massive deposition of iron and haptoglobin was detectable. Bowman's capsules were dilated significantly, probably secondary to the collapse of atrophic tubuli. This is the first report to show that HO-1 has critical roles in vivo in protecting renal tubuli, in addition to vascular endothelium, from oxidative injury.

Child, Preschool↗

Identification of Culex vishnui subgroup (Diptera: Culicidae) mosquitoes from the Ryukyu Archipelago, Japan: development of a species-diagnostic polymerase chain reaction assay based on sequence variation in ribosomal DNA spacers.

The Culex vishnui subgroup includes three important vectors of Japanese encephalitis virus, Culex tritaeniorhynchus Giles, Cx. pseudovishnui Colless, and Cx. vishnui Theobald, all of which occur in the Ryukyu Archipelago, Japan. Although these three species have been shown to be vectors of JE virus in many areas of Southeast Asia, it is not yet known what role each plays in the transmission of the virus in this region. Reliable identification of adult, field-collected specimens is a critical component in epidemiological studies of virus transmission. Mosquitoes in the Cx. vishnui subgroup can be reliably identified in the larval stage. However, because females of these species are very similar, it is difficult to distinguish among them using morphology. We developed a polymerase chain reaction (PCR) assay for the identification of these species. Three species-specific primers were developed for the PCR assay based on a comparative analysis of the nucleotide sequence of the first internal transcribed spacer (ITS1) in the ribosomal DNA gene array. The primers, CT2REV, CP1REV, and CV1REV were designed to amplify a single DNA fragment each from Cx. tritaeniorhynchus, Cx. pseudovishnui, and Cx. vishnui, respectively, when paired with a single forward primer that is complementary to the highly conserved 18S rDNA gene. The amplified fragments were separated easily and identified on an agarose gel to facilitate species identification.

Animals↗

Culex (Acallyntrum) miyagii (Diptera: Culicidae): new species from Seram Island, Indonesia, with keys to the species of the subgenus.

Culex (Acallyntrum) miyagii is described as a new species from Seram Island, Indonesia. The adult male, female, pupa, and larva are described in detail, and illustrations of the male genitalia, pupa, and larva are provided. Cx. miyagii is a forest species breeding in inflorescences of Costus sp. (Costaceae). Keys are provided for identifying the females and 4th-instar larvae of the species of Acallyntrum.

Animals↗