Biomedical subjects

T Terada

Publications and source records attributed to T Terada.

At least 37 records · Page 2Linked to original sources

PubMed2001

Proteolytic activation of SREBPs during adipocyte differentiation.

A member of sterol regulatory element-binding protein (SREBP) family, SREBP-1, is a key regulator of adipocyte differentiation. Expression of the SREBP-1 gene is induced during adipocyte differentiation, but proteolytic activation of the synthesized precursor form of SREBP-1 has not been well analyzed. The proteolytic processing of SREBPs is severely suppressed in sterol loaded culture cells. Here we report that a splicing isoform, SREBP-1a, is predominantly expressed in 3T3-L1 preadipocytes and adipocytes, and that the nuclear active form of SREBP-1 protein increases in adipocyte differentiation. We further show that the amount of nuclear SREBP-2 protein also increases despite no increase in SREBP-2 mRNA, suggesting that proteolytic cleavage of SREBPs is induced in lipid loaded adipocytes. Northern blot analyses reveal that mRNA levels for SREBP cleavage-activating protein (SCAP), Site-1 protease (S1P), and Site-2 protease (S2P), which participate in the proteolytic processing of SREBPs, are relatively unaffected in adipogenesis. These results demonstrate that SREBP-2 appears to promote adipocyte differentiation as well as SREBP-1 and that the proteolytic activation of SREBPs may be induced by an as-yet unidentified mechanism in lipid loaded adipocytes.

3T3 Cells↗

PubMed2001

Mutational analyses of cysteine residues of bovine dihydrodiol dehydrogenase 3.

The cloning, bacterial expression and purification of bovine liver cytosolic dihydrodiol dehydrogenase 3 (DD3) cDNA (1330 bp in full length) using the pKK223-3 expression vector has been reported previously. Recombinant DD3 (rDD3) was characterized in terms of its substrate specificity and inhibitor sensitivity [Terada et al., Adv. Exp. Biol. Res. 414 (1997) 543-553]. The nucleotide sequence of DD3 cDNA completely matched with that of bovine liver-type prostaglandin F synthase [Suzuki et al., J. Biol. Chem. 274 (1999) 241-248]. In the present study, we succeeded in high level expression of rDD3 in Escherichia coli BL21 (DE3) using the pET28a expression vector. rDD3 was easily and quickly purified to apparent homogeneity by one-step column chromatography using Ni(2+)-affinity resin. Furthermore, rDD3 showed essentially the same substrate specificity and inhibitor sensitivity to that of purified liver DD3. To analyze the role of cysteines (145, 154, 188, 193 and 206) in the enzymatic activity of DD3, site-directed mutagenesis of DD3 using the polymerase chain reaction method was performed. Mutants (C145S, C154S, C188S, C193S and C206S) were analyzed for substrate specificity, cofactor binding and inactivation by disulfide (dithio-bis(2-nitrobenzoic acid), alkylating reagent (N-ethylmaleimide) and oxidants (naphthoquinone and H(2)O(2)) Results indicated that these five cysteines of rDD3 may not be directly involved in substrate or cofactor binding. Mutant C193S showed strong resistance to SH-reagents unlike wild-type DD3 (WT) or other mutants. Both the WT and the other mutants showed essentially the same sensitivity to SH-reagents. Cofactor (NADP(+)) protected mutants C145S, C188S and C206S from inactivation as well as WT, while NAD(+) was not protective. Our present results indicate that Cys193, which is located close to the NADP(+)-binding site, may be involved in the alteration of enzymatic activity.

Animals↗

PubMed2001

GATA DNA-binding protein expressed in mouse I-10 Leydig testicular tumor cells.

A nuclear extract of the mouse I-10 Leydig tumor cell line was analyzed by gel mobility shift assay with a combination of antibodies for various mammalian GATA proteins. Antibodies for GATA-4 caused a super-shift of the DNA-protein complex, which is formed through GATA-4 binding to an oligonucleotide with a typical GATA motif, while ones for GATA-1, GATA-2, GATA-3, and GATA-6 did not. These results indicated that I-10 cells express GATA-4 protein. Western blotting analysis of cellular proteins also demonstrated the presence of GATA-4 protein, the size of which corresponds to that of the rat orthologous protein transiently expressed in Cos-1 cells. A significant level of GATA-4 expression in I-10 cells would be advantageous for studying the roles of this protein, especially in view of gonadal function. We further examined the binding site preference of GATA-4 expressed in I-10 cells. GATA-4 showed broad sequence specificity similar to GATA-6, the order of binding core site preference being GATA > GATT > GATC, and adenine was favored on both sides of the core for strong binding. Thus the conserved zinc finger domain of GATA proteins is suggested to contribute to the binding sequence preference. GATA-4 expressed in I-10 cells was not susceptible to proteolysis coupled with cAMP signaling.

Animals↗

PubMed2001

Site-directed mutagenesis studies of bovine liver cytosolic dihydrodiol dehydrogenase: the role of Asp-50, Tyr-55, Lys-84, His-117, Cys-145 and Cys-193 in enzymatic activity.

A previous report on the cloning, bacterial expression and purification of bovine liver cytosolic dihydrodiol dehydrogenase (DD3) cDNA (1,330 bp in full length) using pKK223-3 expression vector characterize the properties of the recombinant DD3 in the aspects of substrate specificity and inhibitor sensitivity (Terada et al., Adv. Exp. Biol. Res. 414 (1997) 543-53). The nucleotide sequence of this DD3 cDNA completely matches that of bovine liver-type prostaglandin F synthase (PGFS) (Suzuki et al., J. Biol. Chem. 274 (1999) 241-8). In the present study, a large amount of recombinant DD3 (rDD3) was expressed in Escherichia coli BL21 (DE3) with a pET28a expression vector. The recombinant DD3 (rDD3) was easily and quickly purified to an apparent homogeneity with one step column chromatography of Ni(2+)-affinity resin. The rDD3 showed essentially the same substrate specificity and inhibitor sensitivity as purified liver DD3 (DD3). To analyze the role of amino acid residues of DD3 in its enzymatic activity, site-directed mutagenesis of DD3 with PCR method was performed. The results of the analyses of these mutants in the aspects of substrate specificity and cofactor-binding suggested a variety of functions in the enzymatic activity: as an active site Tyr-55 may act as a general acid and Asp-50, Lys-84 and His-117 may play an important role in the control of protonation of Tyr-55 as a general acid in the dehydrogenase activity under higher pH conditions, though these residues may not be involved in reductase activity under lower pH conditions. Though the mutated DD3s (Cys to Ser) did not show significant differences in their substrate specificities, these mutants showed different sensitivities to SH-reagents. Present results indicate that Cys-193 may play an important role in the modulation of enzymatic activity under redox conditions generated with GSH+GSSG among five cysteines in DD3.

Alcohol Oxidoreductases↗

PubMed2001

Characterization of multiple Chinese hamster carbonyl reductases.

Carbonyl reductase (CR) is an enzyme which can catalyze the oxidoreduction of various carbonyl compounds in the presence of NAD(P)H. With the PCR method, using primers carrying the conserved nucleotide sequence among mammalian CRs, we isolated three different cDNAs (CHCR1, CHCR2 and CHCR3) which encode a unique carbonyl reductase from the Chinese hamster. The PCR products of CHCR1 and CHCR2 were clearly isolated with Bpu1102I, BspEI and XmaI restriction enzymes. The nucleotide-sequence of CHCR3 was completely different from those of CHCR1 and CHCR2. The predicted double-wound betaalphabetaalpha-structures of the CHCRs suggests the presence of a typical NADP(+)-binding motif and is similar to the corresponding region of 3alpha,20beta-hydroxysteroid dehydrogenase and mouse lung tetrameric carbonyl reductase. The deduced amino acid sequence of CHCR1 showed a high homology to CHCR2 (>96%) and the other mammalian CRs (>81%). However, CHCR3 showed a high homology to human CBR3 (>86%) and a relatively lower homology to the other CHCRs (<76%). Bacterial recombinant CHCRs showed typical carbonyl reductase activities towards 4-benzoylpyridine, 4-nitrobenzaldehyde and pyridine 4-carboxyaldehyde. These three CRs showed not only 3-keto reductase of steroids, but also 20-keto reductase. However, these CRs did not show any activity of 17-keto reductase activity. Both CHCR1 and CHCR2 have prostaglandin 9-keto reductase and 15-hydroxyprostaglandin dehydrogenase activities towards PGE(2) and PGF(2alpha) from the analyses of enzymatic reaction products. The results of Western blotting and RT-PCR suggest these CHCRs have a tissue-dependent-distribution in the Chinese hamster.

Alcohol Oxidoreductases↗

PubMed2001

Solution structure of the human parvulin-like peptidyl prolyl cis/trans isomerase, hPar14.

The hPar14 protein is a peptidyl prolyl cis/trans isomerase and is a human parvulin homologue. The hPar14 protein shows about 30 % sequence identity with the other human parvulin homologue, hPin1. Here, the solution structure of hPar14 was determined by nuclear magnetic resonance spectroscopy. The N-terminal 35 residues preceding the peptidyl prolyl isomerase domain of hPar14 are unstructured, whereas hPin1 possesses the WW domain at its N terminus. The fold of residues 36-131 of hPar14, which comprises a four-stranded beta-sheet and three alpha-helices, is superimposable onto that of the peptidyl prolyl isomerase domain of hPin1. To investigate the interaction of hPar14 with a substrate, the backbone chemical-shift changes of hPar14 were monitored during titration with a tetra peptide. Met90, Val91, and Phe94 around the N terminus of alpha3 showed large chemical-shift changes. These residues form a hydrophobic patch on the molecular surface of hPar14. Two of these residues are conserved and have been shown to interact with the proline residue of the substrate in hPin1. On the other hand, hPar14 lacks the hPin1 positively charged residues (Lys63, Arg68, and Arg69), which determine the substrate specificity of hPin1 by interacting with phosphorylated Ser or Thr preceding the substrate Pro, and exhibits a different structure in the corresponding region. Therefore, the mechanism determining the substrate specificity seems to be different between hPar14 and hPin1.

Amino Acid Sequence↗

PubMed2001

Protection of boar spermatozoa from cold shock damage by 2-hydroxypropyl-beta-cyclodextrin.

This study examined whether 2-hydroxypropyl-beta-cyclodextrin (HBCD) could play a role in protecting spermatozoa from cold shock, as judged by motility parameters, intact acrosomes, and membrane integrity. Motility parameters were assessed by a computer-assisted sperm motility analysis (CASA) system, and the acrosome and membrane integrity were evaluated by fluorescent staining with FlTC-labeled peanut agglutinin and SYBR-14 plus Propidium Iodide, respectively. The addition of HBCD to the BF5 extender significantly increased the percentages of spermatozoa with intact acrosomes and increased membrane integrity after cold shock. The motility, progressive motility, and progressive velocity of the cold-shocked spermatozoa in the presence of HBCD were significantly higher than in the absence of HBCD. In contrast, further supplement of HBCD with cholesterol-3-sulfate (a cholesterol analogue) resulted in a decrease in all the aforementioned criteria, suggesting that the ability of HBCD to protect spermatozoa from cold shock injury is blocked by saturating the cholesterol binding sites of HBCD. It is therefore concluded that HBCD protects spermatozoa against cold shock injury, possibly due to its ability to remove membrane cholesterol.

2-Hydroxypropyl-beta-cyclodextrin↗

PubMed2001

E-cadherin gene mutations in human intrahepatic cholangiocarcinoma.

Deletions or mutations of the E-cadherin gene may result in reduced cell adhesiveness. In particular, conservative point mutations within the N-terminal calcium-binding pocket (including exons 7, 8, and 9) are frequently detected in several cancers and are enough to abolish cell-cell adhesion. There have been no studies on E-cadherin gene mutations in human intrahepatic cholangiocarcinoma (ICC). Human ICCs were therefore investigated for E-cadherin gene mutations within exons 7, 8, and 9. In addition, the relationships were analysed between their mutations and the immunohistochemical expression of E-cadherin, histological grade, and clinicopathological parameters. The E-cadherin gene was analysed in 34 tumours by nested polymerase chain reaction/single-strand conformation polymorphism (PCR/SSCP) followed by DNA sequencing. In four of the 34 cases (11.8%), tumour-restricted mobility shifts were observed; two cases harboured a single shift, one case presented two different mobility shifts, and one case presented three different mobility shifts within exons 7 and 8, encoding extracellular domains of E-cadherin. Polymorphism as previously reported was not identified and all seven new DNA alterations were not present in genomic DNA of non-tumour origin. The E-cadherin gene mutations correlated significantly with down-regulated E-cadherin protein expression and high ICC histological grade. These data suggest that E-cadherin gene mutations in ICC are associated with reduced cell adhesiveness and high histological grade.

Adult↗

PubMed2001

Distinct transport characteristics of basolateral peptide transporters between MDCK and Caco-2 cells.

The cellular polarity of [14C]glycylsarcosine (Gly-Sar) transport in Madin-Darby canine kidney (MDCK) cells was compared with that in the human intestinal cell line Caco-2. In MDCK cells, [14C]Gly-Sar accumulation was greater at the basolateral side than at the apical side, and there was little net transcellular transport. In Caco-2 cells, [14C]Gly-Sar accumulation was greater at the apical side and unidirectional transcellular transport occurred from the apical to basolateral side. Efflux of [14C]Gly-Sar from MDCK cells to either side was negligible, whereas that from Caco-2 cells was significantly faster to the basolateral side. The basolateral peptide transporter in MDCK cells possessed a similar substrate specificity, but a much higher substrate affinity, than that in Caco-2 cells. The basolateral peptide transporter in MDCK cells did not accumulate Gly-Sar during hypertonic stress. These findings indicate that the basolateral peptide transporter in MDCK cells is involved in the cellular uptake of small peptides, but not in the extrusion of small peptides to the extracellular space.

Animals↗

PubMed2001

Protein expression of matrix metalloproteinases 2 and 9 and tissue inhibitors of metalloproteinase 1 and 2 in papillary thyroid carcinomas.

Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) play an important role in tumor invasion and metastasis. There have been only a few studies on the protein expression of MMPs and TIMPs in thyroid carcinomas. Therefore, we investigated the protein expression of MMP-2, MMP-9, TIMP-1 and TIMP-2 in 86 papillary thyroid carcinomas using immunohistochemistry, semiquantitative scoring morphometry of immunohistochemistry, gelatin zymography, and western blotting. We also examined the correlations between the immunohistochemical scores and several clinicopathological parameters. The immunoreactivities of MMP-2, MMP-9, TIMP-1, and TIMP-2 were largely located in the tumor cells or non-tumor follicular cells and to a much lesser extent in the fibroblasts and endothelial cells in the tumor and non-tumor regions. Compared with non-tumor regions, these four proteins tended to be overexpressed in the tumor cells; the overexpression was found in 64 of 86 (74%), 80 of 86 (93%), 79 of 86 (92%), and 64 of 86 (74%) cases for MMP-2, MMP-9, TIMP-1, and TIMP-2, respectively. Gelatin zymography showed distinct bands of MMP-2 and MMP-9 in tumor extracts but vague bands in non-tumor extracts. Western blotting revealed the specific bands of MMP-2 and MMP-9 in both tumor and non-tumor extracts. Morphometric scoring revealed that high expression of these proteins significantly correlated with large tumor size, presence of lymph node metastasis, high clinical stage, high intrathyroidal invasion, and high vascular invasion. These data suggest that MMP-2, MMP-9, TIMP-1, and TIMP-2 proteins and activities are increased in tumors cells of papillary thyroid carcinomas and that they play an important role in the invasion and metastasis of papillary thyroid carcinomas.

Adult↗

PubMed2001

Two novel Pao-like retrotransposons (Kamikaze and Yamato) from the silkworm species Bombyx mori and B. mandarina: common structural features of Pao-like elements.

To characterize the structural features common to Pao-like retrotransposons, we analyzed two lambda phage clones which contain the Pao-like elements from the silkworm species Bombyx mori and B. mandarinia, and copies of Pao itself and ninja of Drosophila simulans, amplified by PCR. We previously identified two randomly amplified polymorphic DNAs (RAPDs), W-Kamikaze and W-Yamato, from B. mori and B. mandarina, which are part of two novel Pao-like retrotransposons, Kamikaze and Yamato, respectively. Complete characterization of these and other elements of this group reported here shows that Pao-like elements have common features that distinguish them from the other groups of LTR-retrotransposons. While the elements of the Ty1-copia group encode only one cysteine and histidine (Cys) motif in their gag-like region, the Pao-like elements specify three Cys motifs. The highly conserved D(35)E motif in the integrase domain of the retrotransposon polyprotein seems to be conserved in Pao-like elements, but the number of amino acid residues between D and E varies and is greater than 35. A comparison of the deduced amino acid sequences of the reverse transcriptase domain revealed the Pao-like elements are members of neither the Ty1-copia nor the gypsy-Ty3 groups. Therefore, we confirmed that the long-terminal-repeat (LTR) retrotransposons should be divided into three major groups (or families), namely the Ty1-copia, gypsy-Ty3, and Pao-like groups.

Amino Acid Sequence↗

PubMed2001

Combined surgery and endovascular stenting for basilar artery stenosis refractory to balloon angioplasty: technical case report.

The authors report a case of symptomatic basilar artery stenosis treated by stenting via the surgically exposed C1 vertebral artery. This case was initially treated by percutaneous transluminal angioplasty via a transfemoral route but resulted in unsatisfactory dilatation. Stenting via a transfemoral route also resulted in failure because of the coiling of the proximal vertebral artery. Direct puncture of the vertebral artery beyond the coiling portion was tried but a stent could not be delivered beyond the C2 vertebrae. Finally, the vertebral artery was surgically exposed between C1 and the occipital bone and a stent was introduced into the lesion from this portion under fluoroscopic control. The basilar artery was fully opened by stenting without new neurological deficits. Stenting of the basilar artery via a transfemoral route is not always possible even with newer generation stents if the vertebral artery has elongated tortuous curves. Combined surgery and endovascular stenting is one of the alternatives in such cases including our case.

Aged↗

PubMed2001

Transarterial intravenous coil embolization of dural arteriovenous fistula involving the superior sagittal sinus.

BACKGROUND: We report a rare case of traumatic dural arteriovenous fistula involving the superior sagittal sinus successfully treated by transarterial intravenous coil embolization. CASE PRESENTATION: A 38-year-old woman presented with tension headache. She had a past history of severe head injury at the age of three. Computed tomography scanning showed a heterogenous low-density area in the right frontal lobe, and magnetic resonance imaging demonstrated abnormal vascular structures in the same area. Angiography revealed a dural arteriovenous fistula involving the lateral wall of the fully patent superior sagittal sinus. The fistula was fed by scalp, meningeal, and cortical arteries, and drained into a cortical vein leading to the superior sagittal sinus. Femoral transarterial intravenous embolization with microcoils completely occluded the dural arteriovenous fistula. CONCLUSION: Severe head injury may lead to asymptomatic dural arteriovenous fistulas after a long time. Transarterial intravenous coil embolization can be effective in the treatment of dural arteriovenous fistulas involving the superior sagittal sinus.

Adult↗

PubMed2001

Crk family adaptor proteins trans-activate c-Abl kinase.

BACKGROUND: c-Abl kinase is activated in response to a variety of biological stimuli. Crk family adaptor proteins can interact physically with c-Abl and be involved in the activation of c-Abl kinase. RESULTS: We report that the Crk family of adaptor proteins act as trans-acting activators of c-Abl kinase. The interaction of the amino-terminal Src-homology (SH) 3 domain of c-Crk and the proline-rich motifs of c-Abl is an essential step for the phosphorylation of c-Crk by c-Abl, as well as the activation of c-Abl by c-Crk. The activation of c-Abl by c-Crk is negatively regulated by phosphorylation of the tyrosine 221 of c-Crk. Our data suggest that, in the absence of phosphorylation of the tyrosine Y221, the SH2 domain of c-Crk becomes free to bind to target molecules while the carboxyl-terminal SH3 domain of c-Crk binds to the proline-rich region of c-Abl, inducing the activation of c-Abl by c-Crk. CONCLUSION: This study suggests that the Crk family functions as trans-acting activators of c-Abl kinase. The phosphorylation of c-Crk may regulate c-Abl kinase.

Animals↗

PubMed2001

Overexpression of p53 protein and MDM2 in papillary carcinomas of the thyroid: Correlations with clinicopathologic features.

Expression of p53 protein and MDM2 was evaluated in paraffin-embedded tissue from 78 patients with papillary carcinomas of the thyroid (PCT), in order to elucidate the relationship between them and their correlations with some clinicopathologic features implicated in tumor progression. These proteins were expressed in nuclei of tumor cells, but not in non-tumor cells. Staining was defined as positive when 10% or more of tumor cells expressed these proteins. The number of cases positive for p53 protein was 21/78 (27%), and that positive for MDM2 was 26/78 (33%). Co-overexpression of p53 protein and MDM2 was observed in 12/78 cases (15%). A significant positive relationship was found between them (P < 0.01); p53-positive cases tended to be also positive for MDM2 and vice versa. Statistical analysis revealed that overexpression of p53 protein significantly correlated with large tumor size (P = 0.0271) and the presence of capsular invasion (P = 0.04). There were significant positive correlations between tumor size and intrathyroidal invasion and between tumor size and capsular invasion in PCT, suggesting that p53 protein overexpression is associated only with tumor progression (tumor size). However, we could not find any significant correlations between MDM2 expression and clinicopathologic features. Our findings suggest that overexpression of p53 protein and MDM2 in papillary carcinoma of the thyroid is associated with the progression of the tumors, and that p53 may be a marker of the progression of PCT.

Adult↗

PubMed2001

S-100-positive nerve fibers in hepatocellular carcinoma and intrahepatic cholangiocarcinoma: an immunohistochemical study.

The aim of the present study was to determine whether or not liver carcinomas are innervated, since there have been no previous reports on the distribution of nerve fibers in human hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). We investigated nerve fibers by immunohistochemical and morphometric methods in 63 cases of HCC and 28 cases of ICC. An antibody to S-100 protein was used to visualize nerve fibers. In HCC, S-100-positive nerve fibers were absent in the tumoral region, including the sinusoids, and tumoral fibrous septa, while in the capsule of HCC some S100-positive nerve fibers (density: 0.08 +/- 0.03/mm2) were present in contact with vasculatures. In ICC, a few nerve fibers were noted in the tumoral stroma (density: 0.02 +/- 0.01/mm2). No nerve fibers were seen in the neovasculized vessels (tumor vessels) in both HCC and ICC. In invasive regions of HCC and ICC, there were S-100-positive nerve fibers in pre-existing residual portal tracts (density: HCC, 0.11 +/- 0.03/mm2; ICC, 0.13 +/- 0.04/mm2). In non-tumor regions of HCC and ICC, there were many S100-positive nerve fibers (density: 0.41 +/- 0.13/mm2) in portal tracts and, to a much lesser degree, in the sinusoids. These results suggest that tumor cells and vasculatures in HCC and ICC are rarely influenced by nerve fibers.

Bile Duct Neoplasms↗

PubMed2001

Absence of mutations in the beta-catenin and adenomatous polyposis coli genes in papillary and follicular thyroid carcinomas.

beta-Catenin has multiple functions both in intercellular adhesion and in signal transduction. As a signaling molecule, mutations in exon 3 of the beta-catenin gene stabilize this protein in the cytoplasm. Subsequently, accumulated beta-catenin protein translocates to nuclei with T-cell factor-4, and upregulates transcriptional activity of the target genes involved in carcinogenesis. Mutations in exon 3 of the beta-catenin gene have been detected in various carcinomas. We examined immunolocalization of beta-catenin protein and mutations in the beta-catenin and adenomatous polyposis coli (APC) genes in papillary carcinoma (25 cases), follicular carcinoma (two cases), and benign thyroid tumor (29 cases). We detected no mutation in exon 3 of the beta-catenin gene in both malignant and benign thyroid tumors by polymerase chain reaction (PCR) and direct sequencing. No mutations in the mutation cluster region of APC were found in any tumor samples analyzed. Immunohistochemically, beta-catenin showed membranous localization in most specimens. These results suggest that mutations of the beta-catenin and APC genes are rare and that activation of the Wnt signaling pathway may not contribute to pathogenesis in human papillary and follicular thyroid carcinomas.

Adenomatous Polyposis Coli Protein↗

PubMed2001

Analysis of Ig subclass deficiency: First reported case of IgG2, IgG4, and IgA deficiency caused by deletion of C alpha 1, psi C gamma, C gamma 2, C gamma 4, and C epsilon in a Mongoloid patient.

BACKGROUND: The cause of Ig class or subclass deficiencies has been unclear except for IgH gene deletions and a homozygous 1-base insertion (1793insG) in C gamma 2 exon 4 of IgG2 deficiency. In addition, there are no reports that IgH gene deletions are found in patients who are Mongoloid (a category that includes most of the people of Asia, such as the Japanese, Chinese, Indonesians and Malaysians). OBJECTIVE: To investigate the cause of Ig subclass deficiency, we extensively investigated 4 Japanese patients with low serum IgG2 levels. Patient 1 was a 23-month-old girl whose serum IgG2, IgG4, and IgA levels were under the detection limits; she also had idiopathic thrombocytopenic purpura. Patient 2 was a 5-year-old boy whose serum IgG2 level was under the detection limit. Patient 3 was a 14-month-old boy whose serum IgG2 and IgG4 levels were under the detection limits. Patient 4 was 3-year-old girl whose IgG2 level was low and whose IgA level was under the detection limit. METHODS: DNA was extracted from neutrophils, and Southern blot analysis was performed. RESULTS: Southern blot analysis revealed that patient 1 had lost the C alpha 1, psi C gamma, C gamma 2, C gamma 4, and C epsilon genes and was a homozygous carrier of the deletion described above. Her mother was of the heterozygous genotype. DNA from patients 2, 3, and 4 revealed no deletions in comparison with control DNA. CONCLUSION: This is a report of the first case of a Mongoloid in whom IgG2, IgG4, and IgA deficiency was caused by deletion of C alpha 1, psi C gamma, C gamma 2, C gamma 4, and C epsilon. Our finding contributes to investigations of Ig subclass deficiency.

Asian People↗