Biomedical subjects

A Ida

Publications and source records attributed to A Ida.

17 recordsLinked to original sources

PubMed2001

Autoantigen glycoprotein 70 expression is regulated by a single locus, which acts as a checkpoint for pathogenic anti-glycoprotein 70 autoantibody production and hence for the corresponding development of severe nephritis, in lupus-prone PXSB mice.

Retroviral envelope glycoprotein gp70 is present in the sera of immunologically normal and autoimmune-prone strains of mice. However, only lupus-prone mice spontaneously develop gp70-anti-gp70 immune complexes (gp70IC), and these have been implicated in the development of nephritis. We investigated the genetic factors that affect the production of both free serum gp70 and gp70IC in the lupus-prone BXSB mouse strain by analyzing (BXSB x (C57BL/10 x BXSB)F(1))- and (C57BL/10 x (C57BL/10 x BXSB)F(1))-backcrossed male mice. Production of gp70 mapped to a single major locus located on chromosome 13 (Bxs6) with a maximum log likelihood of the odds of 36.7 (p = 1.6 x 10(-38)). The level of gp70IC was highly dependent on Bxs6-related gp70 production, and high titer autoantibody production only occurred when serum gp70 levels were greater than a threshold value of approximately 4.0 microg/ml. The subdivision of the (BXSB x (C57BL/10 x BXSB)F(1))-backcrossed mice into those homozygous or heterozygous for Bxs6 enabled a remarkable association to be observed between high levels of gp70IC and severe nephritis in the Bxs6 homozygote population. A further mapping study in these two subgroups identified a previously unrecognized interval associated with the production of autoantibodies.

Animals↗

PubMed2001

Segmental intestinal preservation and enteral nutrition help to maintain the intestinal function after a massive intestinal resection: report of a case.

We report a case in which both segmental intestinal preservation and enteral nutrition helped to maintain the intestinal function after a massive bowel resection for superior mesenteric artery (SMA) thrombosis. A 53-year-old Japanese man was admitted to our hospital with acute abdomen. Extensive necrosis of the small intestine was found during the operation; however, a loop of the ileum appeared to be viable. A massive resection of the small intestine which preserved a 50-cm length of the viable ileum loop was thus performed. However, diffuse stenosis of the remaining ileum was found after surgery. An end-to-end anastomosis of the distal end of the preserved ileum loop and the terminal ileum was made in the second operation, and enteral nutrition was infused to improve the remnant intestinal function. A jejunoileostomy was performed in the final operation. An X-ray study after the final operation showed the stenosis of the remaining ileum to have improved. The patient therefore did not need any nutritional support after being discharged.

Constriction, Pathologic↗

PubMed2000

Detection of tumor cells in blood using CD45 magnetic cell separation followed by nested mutant allele-specific amplification of p53 and K-ras genes in patients with colorectal cancer.

A new method for detecting circulating tumor cells that is based on magnetic-activated cell separation (MACS) and nested mutant allele-specific amplification (nested MASA) was evaluated in patients with colorectal cancer using the p53 and K-ras genes as genetic markers. By negative selection with anti-CD45 monoclonal antibody-conjugated supermagnetic microbeads, the proportion of tumor cells was enriched 9-fold. By the combination of MACS and nested MASA, 10 tumor cells in 10(7) normal peripheral blood mononuclear cells could be detected without false-positives. Using this method, we examined blood taken from the tumor drainage veins of 23 patients with colorectal cancer. Eighty-seven percent (20/23) of primary tumor tissues showed p53 and/or K-ras gene mutations. Forty-five percent (9/20) of patients with p53 and/or K-ras mutations in the primary tumor showed the same mutated genes in the blood samples. There was a significant association between the presence of p53 and K-ras gene mutation in the blood and tumor size, depth of invasion, and venous invasion. Blood gene mutation was detected in 80% (4/5) of samples from patients with synchronous liver metastases. Sixty percent (3/5) of patients with mutant genes in the blood developed asynchronous liver metastases after surgery. The overall survival of patients with p53 and/or K-ras gene mutation-positive findings in blood was significantly shorter than that of patients testing negative on Kaplan-Meier analysis. Our results suggest that the method may be useful for reliable detection of tumor cells circulating in the blood and may help to identify patients at high risk for relapse.

Adenocarcinoma↗

PubMed2000

IL-18 in pregnancy; the elevation of IL-18 in maternal peripheral blood during labour and complicated pregnancies.

Serum interleukin-18 (IL-18) levels were measured in women in different trimesters of pregnancy, in labour, puerperium and in various complicated pregnancies. There was a significant elevation of IL-18 levels in pregnant sera from the first trimester until the onset of labour. Once labour began, IL-18 levels increased further and remained until at least the third day of puerperium. The high levels of IL-18 in sera were also observed in various complicated pregnancies, such as premature rupture of membranes (PROM), acute fatty liver of pregnancy and fetal growth restriction. IL-18 is likely to play a role in pregnancy.

Female↗

PubMed1999

Prenatal diagnosis of thanatophoric dysplasia by mutational analysis of the fibroblast growth factor receptor 3 gene and a proposed correction of previously published PCR results.

Thanatophoric dysplasia (TD) is the most frequent form of neonatal lethal skeletal dysplasia. Recently. mutations in the fibroblast growth factor receptor 3 (FGFR3) gene that cause two subtypes of this disorder, type I (TDI) and type II (TDII), have been identified. This discovery has now made it possible to make a definite diagnosis of TD by molecular methods. To date, prenatal diagnosis of TD has been accomplished by ultrasonography in the second trimester. However, it is not always possible to distinguish TD fetuses it utero from the other osteochondrodysplasias by ultrasonography or radiography. We report on the prenatal diagnosis of a TD fetus, showing severe shortness of limbs and polyhydramnios, by identification of a mutation in the FGFR3 gene. Genomic DNA was isolated from the amniotic fluid and then subjected to PCR amplification. The common TDI mutation, C-->T transition at nucleotide 742 in the FGFR3 gene, was identified using restriction enzyme analysis. This information was critical in obstetric management decisions later in pregnancy. However, although the mutation responsible for TDI was detected previously, we noticed some inconsistencies in the published PCR results and have proposed a correction.

Adult↗

PubMed1999

Genetic polymorphism of murine tissue plasminogen activator associated with antiphospholipid syndrome.

In a subset of patients with systemic lupus erythematosus (SLE), antiphospholipid syndrome characterized by thrombocytopenia, thrombosis, recurrent abortion and antiphospholipid antibodies develops. Male (NZW x BXSB) F1 mice are widely used as a model for SLE-associated antiphospholipid syndrome. Our earlier genetic studies showed that one susceptibility allele for thrombocytopenia and associated IgG platelet-binding autoantibodies in male (NZW x BXSB) F1 mice was linked to the BXSB-type polymorphic microsatellite D8Mit96, located in proximity to the gene Plat for tissue-type plasminogen activator (t-PA). In the present studies, sequence analyses for structural and promoter regions of Plat revealed a single nucleotide polymorphism encoding a catalytic domain of t-PA, with an amino acid substitution of anionic Glu366 in NZW for a cationic Lys in BXSB. Progeny studies using NZW x (NZW x BXSB) F1 male backcross mice showed that the BXSB Plat allele was significantly associated with high levels of both platelet-binding antibodies and thrombocytopenia. Furthermore, these two traits appeared to be regulated by a complementary effect of two BXSB alleles; one is linked to Plat and the other to the H-2 complex and the gene for plasminogen. Thus, the BXSB-type Plat may be one susceptibility allele for the multigenic antiphospholipid syndrome seen in (NZW x BXSB) F1 mice. Potential mechanisms are discussed.

Amino Acid Sequence↗

PubMed1999

[Ulcerative colitis and pregnancy].

Ulcerative colitis(UC) commonly affects young adults, many of whom wish to have children themselves. Women with ulcerative colitis who are pregnant have many concerns, such as the effect of the gestational period on UC, the effect of UC on the pregnancy, and the safety of drugs used to control the disease. We suggested that there was no significant difference in fertility between the patient with UC and the general population. The pregnancy rates in the UC patients were similar to those in the general population. As compared with the patients with an inactive bowel disease, those with an active disease at the beginning of pregnancy had a little higher risk of spontaneous abortion and premature delivery. The clinical course of UC during pregnancy was correlated with the disease activity at the time of conception. Women with UC should be advised preferably to conceive at the time when their bowel disease is in an inactive stage. Medical treatment with sulphasalazine, 5-Aminosalicylic Acid and corticosteroids appeared to have no obvious deleterious effects on the fetus and new-born child.

Adult↗

PubMed1998

Susceptibility alleles for aberrant B-1 cell proliferation involved in spontaneously occurring B-cell chronic lymphocytic leukemia in a model of New Zealand white mice.

B-cell chronic lymphocytic leukemia (B-CLL) and autoimmune disease are a related event, and genetic factors are linked to both diseases. As B-CLL is mainly of B-1 cell type that participates in autoantibody production, genetically-determined regulatory abnormalities in proliferation and/or differentiation of B-1 cells may determine their fate. We earlier found that, in H-2-congenic (NZB x NZW) F1 mice, while H-2(d/z) heterozygosity predisposes to autoimmune disease, H-2(z/z) homozygosity predisposes to B-CLL. Studies also suggested the involvement of non-H-2-linked NZW allele(s) in leukemogenesis. Using H-2-congenic NZW and B10 mouse strains, their F1 and backcross progeny, we have now identified three major NZW susceptibility loci for abnormal proliferation of B-1 cells, which form the basis of leukemogenesis; one H-2-linked locus on chromosome 17 and the other two non-H-2-linked loci, each on chromosome 13 and chromosome 17. Each susceptibility allele functioned independently, in an incomplete dominant fashion, the sum of effects determining the extent of aberrant B-1 cell frequencies. The development of leukemia was associated with age-related increase in B-1 cell frequencies in the blood. Thus, these alleles probably predispose B-1 cells to accumulate genetic alterations, giving rise to B-CLL. Potentially important candidate genes and correlation of the findings with autoimmune disease are discussed.

Animals↗

PubMed1998

Multigenic control of lupus-associated antiphospholipid syndrome in a model of (NZW x BXSB) F1 mice.

In a subset of systemic lupus erythematosus (SLE) patients, antiphospholipid syndrome, characterized by occurrence of anti-cardiolipin (CL) antibodies, thrombocytopenia, thrombosis and recurrent intrauterine fetal death occurs. Male (NZW x BXSB)F1 mice, carrying the BXSB Yaa gene, serve as a model for SLE-associated antiphospholipid syndrome. Using microsatellite markers in the NZW x (NZW x BXSB)F1 backcross male progeny, we mapped BXSB alleles contributing to the generation of anti-CL antibodies, platelet-binding antibodies, thrombocytopenia and myocardial infarction. Generation of each disease character was controlled by two major independently segregating dominant alleles, i.e. those on chromosomes (Chr.) 4 and 17 for anti-CL antibodies, Chr. 8 and 17 for both anti-platelet antibodies and thrombocytopenia and, to our surprise, Chr. 7 and 14 for myocardial infarction, and that a combination of the two alleles appeared to produce full expression of each character, as a complementary gene action. The alleles on Chr. 17 linked to the above three characters were all mapped in close proximity to the H-2 complex. Therefore, no single factor such as anti-CL antibodies can explain the pathogenesis of SLE-associated antiphospholipid syndrome. Rather, a combination of susceptibility alleles such as described here, along with additional modifying loci, i.e. BXSB Yaa and some from NZW, characterizes unique SLE features in male (NZW x BXSB) F1 mice. There are potentially important candidate genes which may be linked to the syndrome.

Animals↗

PubMed1998

Novel missense mutation resulting in the substitution of tyrosine by cysteine at codon 597 of the type X collagen gene associated with Schmid metaphyseal chondrodysplasia.

Schmid metaphyseal chondrodysplasia (SMCD) is one of the most common forms of the osteochondrodysplasias. Mutations or deletions in the COL10A1 gene that encodes type X collagen have been shown to cause this disorder. Most of the gene mutations and deletions are located in the non-collagenous carboxy (C)-terminal (NC1) domain. We describe a novel missense mutation in a patient with SMCD that leads to the substitution of Tyr at codon 597 by Cys in the NC1 domain. Sequence analysis indicated that the proband was heterozygous for the mutation. Her parents were homozygous for the normal sequence, indicating the de-novo occurrence of this mutation.

Adult↗

PubMed1997

Effects of maternally administered immunoglobulin on platelet counts of neonates born to mothers with autoimmune thrombocytopenia: re-evaluation.

OBJECTIVE: Since immunoglobulin is transported across the placenta, maternal administration of it theoretically seems attractive as an antenatal treatment for a fetus. However, the effects of antenatally administered intravenous immunoglobulin (IVIG) on fetal platelet counts have been controversial. Our series of 11 cases of idiopathic thrombocytopenic purpura (ITP) and a review of previous reports are presented. A combined retrospective analysis to know whether maternal response to IVIG is associated with improvement of fetal thrombocytopenia was conducted. METHODS: IVIG was given to 11 steroid refractory pregnancies with ITP. Good maternal response to the therapy was defined as an increase in the platelet count to greater than 50 x 10(9)/L after completion of the IVIG infusion. Neonatal platelet counts of the umbilical cord were performed just after birth and followed-up for at least the first week of life. RESULTS: Seven of the 11 neonates had thrombocytopenia of less than 100 x 10(9)/L, and two of them had severe thrombocytopenia of less than 50 x 10(9)/L. Two out of two neonates born to mothers with a good response to IVIG were thrombocytopenic; whereas five out of nine neonates born to mothers with a poor response were thrombocytopenic. The combined retrospective analysis of our results and published reports have shown that fetal thrombocytopenia was not associated with the maternal response to IVIG but with the level of immunoglobulin G of neonates at birth. Passive thrombocytopenia was more frequently observed in neonates with normal levels of immunoglobulin G than those with elevated levels. CONCLUSION: This combined analysis confirmed the proposed hypothesis that the lack of effect of maternally administered IVIG on fetal platelet counts may mainly be attributed to the insufficient therapeutic level of transferred immunoglobulin G in the cord blood.

Female↗

PubMed1996

[A 43-year-old woman with 18 years history of parkinsonism].

We report a 43-year-old woman who died after 18 years history of parkinsonism. She was well until 25 years of the age (1976) when she noted a difficulty in stepping her feet. In the next year, she started to drag her feet. She was treated with levodopa with good response, however, she developed dyskinesia when she was 33 years of the age. She was evaluated in another hospital in 1984. She showed normal intelligence, normal ocular movement, masked face, small voice, small step gait, stooped posture, freezing of the gait, retropulsion, and cogwheel rigidity in limbs. No tremor or ataxia was noted. She received left ventrolateral thalamotomy at that time. Rigidity on the right side markedly reduced, however, she continued to show bradykinesia and motor fluctuations. On August 1 of 1994, she developed fever of 40 degrees C and dyspnea. On the next day, she expired from acute respiratory distress. She was able to walk unsupported until just before her last admission. The patient was discussed in a neurological CPC. The chief discussant arrived at the conclusion that this patient had Lewy body-positive young onset Parkinson's disease. Opinions were divided into two groups, i.e., young onset Lewy-body positive Parkinson's disease and Lewy-body negative young onset parkinsonism. Post-mortem examination revealed moderate loss of pigmented neurons in the substantia nigra more in the ventro-lateral part. Lewy bodies were found in the remaining neurons. Lewy bodies were more frequently seen in the locus coeruleus, although neuronal loss was less prominent in the locus coeruleus. The dorsal vagal motor nucleus showed moderate loss of neurons. Otherwise, the central nervous system was unremarkable. To our knowledge, this patient had the second youngest age of the onset so far reported in the literature for Lewy-body positive typical Parkinson's disease.

Adult↗

PubMed1982