Biomedical subjects

H Saeki

Publications and source records attributed to H Saeki.

At least 109 records · Page 6Linked to original sources

PubMed1996

HLA-DM gene polymorphisms in atopic dermatitis.

HLA-DM molecules are involved in the antigen-processing pathway of HLA class II-restricted antigen presentation. We investigated polymorphisms of HLA-DM genes in atopic dermatitis by using the polymerase chain reaction-restriction-fragment length polymorphism method to examine a possible contribution of these genes to the pathogenesis of atopic dermatitis. Genomic DNA was extracted from 37 Japanese patients with atopic dermatitis and 52 control subjects. After polymerase chain reaction amplification of the polymorphic third exon of DMA and DMB genes, amplified products were digested with restriction endonucleases to determine HLA-DM alleles. FokI, HinfI, AciI and SfaNI were used for DMA; HhaI, BsrI, ApaLI, and Bsp1286I for the DMB gene. We identified three DMA alleles and also three DMB alleles. One of 37 patients possessed the DMA*0103 allele, which has been reported as a rare allele in Caucasian populations. Any DMA and DMB alleles were not increased in the patients. The DMA*0102 allele was estimated to constitute a haplotype with DRB1*1201/DQB1*0301 and DRB1*0901/DQB1*0301 in a Japanese population. HLA-DM genes are not considered to contribute primarily to the susceptibility of atopic dermatitis. Further investigation of the functional roles of HLA-DM gene polymorphisms will be useful for a better understanding of susceptibility loci in HLA class II-associated disease.

Adolescent↗

PubMed1996

A new in vitro model of specific targeting therapy of cancer: retargeting of PWM-LAK cells with bispecific antibodies greatly enhances cytotoxicity to hepatocellular carcinoma.

For the purpose of establishing a new in vitro model of adoptive immunotherapy, we synthesized two kinds of bispecific antibodies (BsAbs), i.e., (OK x L) BsAbs constructed with both OKT-3 (anti-CD3) and L-7-6 (anti-HCC), and (3G x L) BsAbs constructed with 3-G-8 (anti-CD16) and L-7-6 antibodies. These two BsAbs, having pairs of binding arms on their single molecule, showed similar binding to target cells as the parental monoclonal antibodies (OKT-3, 3-G-8 and L-7-6), when examined with FACS. Newly devised in vitro cytotoxicity tests revealed that LAK or PWM-stimulated LAK (PWM-LAK) cells did not show any significant cytotoxic activity to HCC cells, while both effector cells equally showed greatly enhanced cytotoxicity to HCC even at a low effector/target (0.3) in the presence of BsAbs (OK x L) for the efficient retargeting of the effector cells. Inasmuch as PWM-LAK cells proliferate in vitro 3-5 times faster than LAK cells, adoptive immunotherapy using PWM-LAK cells in combination with (OK x L) BsAbs should be very promising.

Antibodies, Bispecific↗

PubMed1996

A fibrous histiocytoma with a polypoid pattern of growth in a major bronchus.

A 47-year-old man was admitted to our hospital for abrupt onset of hemoptysis and dyspnea. Chest roentgenography revealed a left lower mass shadow with obstruction of the left main bronchus. However, on the third hospital day, he expectorated a coagulum-like substance which resembled bronchial tree, and his symptoms then dramatically subsided. Except for small amounts of bleeding from left B10a, the endobronchus was intact on bronchoscopic examination, and the pathologic diagnosis of the tumor using resected material was fibrous histiocytoma of low-grade malignancy. In addition, given the similarity in histologic findings between the expectorated substance and resected tumor, the expectorated substance was considered to be a part of the tumor which had grown along the endobronchial tree.

Bronchi↗

PubMed1996

[Changes in serum lipoprotein (a) levels related to hyperlipidemia during pregnancy--comparing normal pregnancy and toxemia of pregnancy].

In this study, we investigated fluctuations in serum lipoprotein (a) (Lp(a)) levels in normal and toxemic pregnancy. We measured serum total cholesterol (TC), triglyceride (TG), phospholipid (PL), high-density lipoprotein (HDL), apolipoprotein and Lp(a) levels in 33 normal pregnant and 11 toxemic pregnant women at delivery and in 47 normal pregnant women throughout gestation. Lp(a) and apolipoproteins were detected by turbidimetric immunoassay. The levels of serum lipids, HDL and apolipoproteins were all increased in pregnancy. In toxemia of pregnancy, serum TC and PL levels were lower (p < 0.05) and the apolipoprotein C-III level was higher (p < 0.005) than in normal pregnancy. Serum Lp(a) levels increased until the 20th week and reached a value which was 1.5 times higher than at the 10th week. Thereafter Lp(a) levels were constant until the late stage of pregnancy. In contrast, serum TC and TG levels increased steadily throughout gestation. The serum Lp(a) level was 18.1 +/- 27.5mg/dl in normal pregnancy and 17.8 +/- 17.9mg/dl in toxemia of pregnancy. These results revealed changes in serum Lp(a) levels during pregnancy. Further studies will be required to clarify the metabolic control of Lp(a) in pregnancy and the matabolic disorders of lipids and lipoproteins in toxemia of pregnancy.

Adult↗

PubMed1996

A case of generalized pustular psoriasis followed by bullous disease: an atypical case of bullous pemphigoid or a novel bullous disease?

We describe a 31-year-old Japanese woman with generalized pustular psoriasis treated with PUVA who subsequently developed a bullous disease. Throughout the disease course, there was no phase of psoriasis vulgaris. Although several reports describe coexistence of psoriasis vulgaris and bullous disease such as bullous periphigoid, coexistence of generalized pustular psoriasis without any phase of psoriasis vulgaris and bullous disease is rare. As for the bullous disease, direct immunofluorescence study showed IgG and C3 deposition along the basement membrane zone. Indirect immunofluorescence disclosed IgG antibasement membrane zone antibodies. Indirect immunofluorescence on 1 mol/l sodium chloride-split skin demonstrated linear IgG staining almost exclusively on the dermal side of the split. Western immunoblot analysis revealed that the antibody was directed to neither epidermolysis bullosa acquisita antigen nor bullous pemphigoid antigens. Considering the unusual clinical course, we suspect the possibility of a novel autoimmune blistering disease.

Adult↗

PubMed1996

[Chemotherapy for peritoneal dissemination in gastric cancer under ureteral catheterization].

The treatment of peritoneal dissemination of gastric cancer is mainly chemotherapy, but it use is often limited by ileus, hydronephrosis and jaundice. We employed a ureteral catheter for 6 patients with hydronephrosis due to peritoneal dissemination. Chemotherapy (CDDP + ADM + 5-FU or MTX + 5-FU) was administered in 5 patients. After ureteral catheterization, renal function was kept within normal ranges, so chemotherapy was performed safely. One of five patients became CR and the effect of the treatment was satisfactory (PR: 1, NC: 2). Thus, chemotherapy after ureteral catheterization may be effective for patients with peritoneal dissemination and hydronephrosis.

Adenocarcinoma↗

PubMed1995

A novel human monoclonal antibody, TONO-1, reactive with T-lymphocytic leukemia cells.

Mononuclear cells from the peripheral blood of patients with systemic lupus erythematosus (SLE) were transformed with the Epstein-Barr virus (EBV) and the resultant polyclonal B-lymphoblastoid cell lines were tested for antibody activity to membrane antigens of certain T-cell lines. B lymphoblastoid cell lines secreting specific antibodies were fused with (mouse x human) heteromyeloma SHM-D33 cells. Among the large number of hybridomas generated, one which produced a human monoclonal antibody (MAb) TONO-1 (IgM, lambda) was selected. MAb TONO-1 proved to be reactive with 4 human T-cell lines, HPB-MLT, L-MAT, MOLT-3 and MOLT-4F, but not with B-leukemia, Burkitt's lymphoma, myelomonocytic leukemia, erythroleukemia or non-hematopoietic malignant cell lines. MAb TONO-1 reacted positively with fresh leukemia cells from 2 of 7 patients with acute T-lymphocytic leukemia, but no reaction was observed in non-T-cell leukemia cases. Normal lymphocytes, monocytes, granulocytes, red blood cells and platelets in the peripheral blood did not demonstrate remarkable binding. Neither thymocytes nor bone-marrow cells from healthy volunteers were reactive. The antigens defined by MAb TONO-1 were polypeptides of 57 kDa and 68 kDa. Immunohistological studies revealed no staining of thymocytes in the thymus of a 6-month-old child, but showed epithelial reticular cells and Hassall's corpuscles to stain positively. These results suggest that MAb TONO-1 is directed to T-leukemic cells and some components of thymus tissue.

Animals↗

PubMed1995

Reactivity of anti-erythrocyte antibody induced by Babesia gibsoni infection against aged erythrocytes.

Effects of ageing treatment of erythrocytes to binding activity of the anti-erythrocyte antibody(s) in the serum of dogs infected artificially with Babesia gibsoni were examined by enzyme-linked immunosorbent assay (ELISA) using fixed cell antigen. When erythrocytes made senescent by two artificial ageing treatments, one of which was storing erythrocytes at 37 degrees C in medium for some days and the other was oxidation of erythrocytes with phenylhydrazine, reactivity of anti-erythrocyte antibody(s) in the infected serum to both types of treated erythrocytes was increased. These results suggest that such antibody(s) could play a role as one of the causes of anemia in canine babesiosis.

Anemia↗

PubMed1995

Lack of primary association between transporter associated with antigen processing genes and atopic dermatitis.

We examined polymorphisms of transporter associated with antigen processing (TAP) genes in 37 Japanese patients with atopic dermatitis and 52 control subjects. We have evaluated, again, the specificity polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method since our previous report and have also developed a mismatch PCR-RFLP method for discriminating two dimorphic sites of TAP1 gene and four dimorphic sites of TAP2 gene. Amplified products from genomic DNA were digested with restriction endonucleases: Sau3A1 for TAP1 codon 333 (Ile-Val), AccI for TAP1 codon 637 (Asp-Gly), and BfaI for TAP2 codon 687 (Stop-Gln). The other sites of TAP2 gene were analyzed by mismatch PCR-RFLP: AccII for TAP2 codon 379 (Val-Ile), RsaI for codon 565 (Ala-Thr), and MspI for codon 665 (Thr-Ala). We observed three TAP1 alleles and six TAP2 alleles. Infrequent allele TAP1 C was observed in one patient and one control subject. We did not identify any differences in TAP allele frequencies between those patients with atopic dermatitis and Japanese control subjects. Analysis of TAP gene polymorphisms will provide better understanding of susceptibility loci in HLA class II-associated disease because TAP genes are located between HLA-DQB1 and HLA-DPB1 loci.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1995

Analysis of disease-associated amino acid epitopes on HLA class II molecules in atopic dermatitis.

We investigated the association between HLA class II alleles and severe atopic dermatitis with high serum IgE levels (greater than 8000 U/ml). The frequencies of HLA-DRB1*1302 and DQB1*0604 were increased, whereas the frequency of HLA-DQB1*0302 was decreased. A strong haplotype, HLA-DRB1*1302-DQB1*0604, has been reported in the Japanese population, and this haplotype is conserved in patients with AD. Further analysis of the amino acid epitopes on the HLA-DR beta 1 and DQ beta 1 domains revealed that DR beta 1 71Glu (RR = 5.71, p < 0.05) and DQ beta 1 30His (RR = 3.25 p < 0.01), and 57Val (RR = 3.13, p < 0.05) were increased in frequency. DR beta 1 71Glu was exclusively unique to DRB1*1302. DQ beta 1 30His was shared by the following alleles: DQ beta 1*0501, *0502, *0503, and *0604, which were all increased in patients with AD. DQ beta 1 57Val was shared by DQB1*0501 and *0604. A well-known haplotype, HLA-DRB1*1302-DQB1*0604, contains DR beta 1 71Glu and DQ beta 1 30His and 57Val. Therefore HLA-DR beta 1 71Glu and/or DQ beta 1 30His/57Val are considered to play the most important role in the development of atopic dermatitis.

Adolescent↗

PubMed1995

Evaluation of anthelmintic efficacy of doramectin against gastrointestinal nematodes by fecal examination in cattle in Japan.

The nematocidal effect of doramectin was assessed by subcutaneous injection of 200 micrograms/kg (single dosage) in cattle with naturally acquired gastrointestinal nematode infection in Japan. This study consisted of two experiments. In experiment 1, animals were randomly divided into a doramectin group (n = 21) and a non-treated control group (n = 21) by fecal egg count. In experiment 2, another group of ivermectin treatment (n = 12) was prepared in addition to doramectin (n = 23) and control (n = 10) groups, by random assignment as in study 1. After doramectin or ivermectin treatment, the egg count/5 g of feces was measured by the sucrose centrifugal flotation method at intervals of 7 days until Day 21 in experiment 1 and at Days 7, 14, 21, 35, 42, 49 and 63 in experiment 2. Coproculture was also carried out using some of the fecal samples. In the 2 doramectin-treated groups, 96.1%-100% egg reduction rates were obtained for Haemonchus, Cooperia, Mecistocirrus, Trichostrongylus, Ostertagia, Bunostomum, Strongyloides and Trichuris from the 7th day until the 49th day after treatment. Thus doramectin was confirmed to be highly effective against those species of adult nematoda. The effect against Mecistocirrus has not been previously determined. The nematocidal effect against Nematodirus was lower (egg reduction rate approximately 50%) than other species. No adverse reactions to treatment were seen in any animal during either study.

Animals↗

PubMed1995

Massive experimental infection with Strongyloides venezuelensis in rats and absence of sudden death.

Ten rats were divided into five groups, A - E, to determine the larval dose-effect of infection with Strongyloides venezuelensis (SVZ). The rat groups were exposed to SVZ infective larvae as follow: (A) 100, (B) 1,000, (C) 10,000, (D) 100,000 and (E) 1,000,000. The eight rats in Groups A - D survived the infection. Rats exposed to the higher doses of larvae had the higher egg per gram counts (EPG), but more rapid reduction in EPG counts. The four rats in Groups C and D had EPG counts greater than 10,000 EPG during days 7 - 21 after infection. Maximum EPG values in Group C were 85,400 and 106,600; those in Group D were 134,000 and 346,000. The two rats in Group E showed severe itching and bleeding on their digital pads at the time of infection. They became listless thereafter and died with hemorrhagic pneumonia at 4 days after infection. The sudden death that has been demonstrated in calves infected with massive doses of S. papillosus was not observed in SVZ-infected rats.

Animals↗

PubMed1995

mRNA levels and enzyme activities of protein phosphatases in drug-resistant rat ascites hepatomas.

mRNA levels and enzyme activities of the serine/threonine protein phosphatases (EC 3.1.3.16) type 1 (PP1) and 2A (PP2A) in drug-resistant rat ascites hepatoma cells were examined and compared with those in the parental drug-sensitive cell lines, under drug-free conditions. The mRNA levels of PP1 alpha were much higher in all the hepatomas, either sensitive or resistant, compared with normal liver. The mRNA level of PP2C alpha was decreased in the drug-resistant hepatomas compared with the parental drug-sensitive hepatomas, whereas mRNA levels of PP1 alpha, PP1 gamma 1 and PP2A alpha in resistant hepatomas showed diverse deviations, which are not drug-resistance-specific. However, both spontaneous and potential PP1 activities in particulate fractions of the resistant hepatomas were markedly increased compared with those of the sensitive hepatomas and normal rat liver. Western blot analysis showed that the resistant hepatomas contained larger amounts of PP1 alpha in both cytosolic and particulate fractions than the sensitive hepatomas and rat liver. In both groups of hepatomas, spontaneous and potential activities of PP2A were kept lower than those in normal rat liver, but there was no difference between drug-sensitive and -resistant hepatomas. These results suggest an involvement of PP1 in development of drug-resistant phenotype.

Animals↗

PubMed1994

Construction of a human B cell line, TKHMY, suitable for production of stable human hybridomas.

In order to produce stable hybridomas for generation of human monoclonal antibodies (HMAbs), an attempt was made to construct a suitable human parental B cell line with double selection markers, the strategy being to produce HMAbs by fusing a parental B cell line with EBV-transformed B cells producing specific antibodies. The resultant TKHMY cell line, constructed by transfecting the Blasticidin S resistant (bsr) gene into the HAT sensitive human B cell line LTR 228 could be used as a fusion partner for very efficient production of human hybridomas. Secretion of IgG monoclonal antibodies to antigens on lung cancer cells by one such hybridoma was very stable, indicating that this TKHMY cell line has practical advantage in the area of antibody production.

Aminohydrolases↗

PubMed1994

Polymorphisms of transporter associated with antigen processing genes in atopic dermatitis.

We investigated polymorphisms of transporter associated with antigen process (TAP) genes in atopic dermatitis. We developed a polymerase chain reaction-restriction fragment length polymorphism method for discriminating TAP alleles. Genomic DNA was obtained from 29 Japanese patients with atopic dermatitis and 35 control subjects. Dimorphic regions of TAP1 and TAP2 genes were amplified by polymerase chain reaction. Amplified products were digested with restriction endonucleases to determine TAP alleles: Sau3A1 for TAP1 codon 333 (Ile-Val), AccI for TAP1 codon 637 (Asp-Gly), and EcoRII for TAP2 codon 687 (Gln-Stop). We observed four alleles for TAP1 and dimorphism for TAP2 codon 687. Six of 35 controls had the TAP1 D allele, which has been reported to be a rare allele in Caucasian populations. Gene frequency of TAP1 637Asp exhibited a tendency to increase in the patients with atopic dermatitis. TAP1 637Asp and TAP1 A alleles were estimated to constitute a haplotype with DRB1* 1302-DQB1*0604 and DRB1*0803-DQB1*0601 in the Japanese population. Because TAP1 and TAP2 genes are located between HLA-DQB1 and -DPB1 loci, analysis of TAP gene polymorphisms will be useful for a better understanding of susceptibility loci in HLA class II-associated disease.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1994

HLA and atopic dermatitis with high serum IgE levels.

Patients with atopic dermatitis usually exhibit allergen-specific IgE antibodies against several environmental antigens. HLA restriction is presumed to be involved in the recognition of such antigens, but several previous reports have so far failed to find a significant association between atopic dermatitis and HLA antigens. In this study we examined 38 unrelated Japanese patients with severe atopic dermatitis and high serum IgE levels (greater than 800 U/ml). We investigated the serological HLA types and HLA class II alleles in this group of patients with atopic dermatitis. Frequencies of HLA-A24, A33, Cwblank, B44, DR13 and HLA-DRB1*1302, DQB1*0604, DPB1*0301 alleles were increased in the patients. In contrast, frequencies of HLA-Cw1, Bw6, DR4, DR53, and HLA-DQB1*0302 allele were decreased. However, none of these remained significant after p values were corrected. Further study on HLA association with atopic dermatitis through characterization of specific antigens or antigen epitopes is needed.

Adolescent↗

PubMed1994

Mutations in the rod domain of keratin 2e in patients with ichthyosis bullosa of Siemens.

Ichthyosis bullosa of Siemens (IBS) is an autosomal dominant skin disorder that resembles epidermolytic hyperkeratosis (EHK). We have identified mutations in two families originally diagnosed with EHK and in four families diagnosed with IBS at the same codon in the highly conserved carboxy terminal of the rod domain of keratin 2e, thus revealing a mutational hot spot. Our results allow a differential diagnosis to be made between IBS and EHK at the genetic level and we suggest that patients diagnosed with EHK, but lacking keratin K1 or K10 mutations, should be re-examined for mutations in their K2e genes.

Adult↗

PubMed1994

Isolation of Strongyloides venezuelensis from Rattus norvegicus in Kagoshima Prefecture.

On 30 August 1984, Strongyloides sp. specimens were isolated from a rat (Rattus norvegicus) trapped at a pig farm in Kiire-cho, Ibusuki-gun, Kagoshima Prefecture. Both anterior and posterior ovaries of parasitic female were spirally coiled. The means of body length and width, esophagus length, and the distances from mouth to vulva and from anus to tail end were 2,493, 34.5, 719.8, 1,682.8 and 54.4 microns respectively. Filariform larvae measured 544.2, 15.6 and 238.5 microns in the means of body length and width, and esophagus length respectively. These measurements of the present Strongyloides species agreed with those described for S. venezuelensis. Infection rate by oral administration of larvae was low, while subcutaneous inoculation and percutaneous exposure to larvae produced high infection rate to rats which discharged many egg in the feces. The present parasite has been passaged through rats (SD strain) in these 8 years. This isolate is designated as the Kagoshima strain of S. venezuelensis.

Animals↗