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Biomedical subjects

S Ohtaki

Publications and source records attributed to S Ohtaki.

At least 37 records · Page 2Linked to original sources

Expression of CD26/dipeptidyl peptidase IV in adult T cell leukemia/lymphoma (ATLL).

The association of CD26/dipeptidyl peptidase IV (DPPIV) and human T lymphotropic virus type I (HTLV-I) was studied by two approaches. First, we examined the expression of CD26 in peripheral blood mononuclear cells (PBMC) from the patients with adult T cell leukemia/lymphoma (ATLL), an HTLV-I-related malignancy. The expression of CD26 on the surface of PBMC was decreased in all 20 patients with ATLL compared with those from normal individuals (P < 0.01) and the expression of the CD26 gene transcript was not detectable in seven out of eight patients with ATLL. Then we compared the quantity of viral DNA in CD26-negative (CD26-) and CD26-positive (CD26+) cells obtained from 17 HTLV-I healthy carries by using a polymerase chain reaction method. The CD26-cells had a higher copy number of viral DNA than CD26+ cells. These findings indicate that HTLV-I has in vivo tropism to CD26- cells, suggesting that some phenotypes of ATLL cells reflect the in vivo cellular tropism of HTLV-I.

Adult↗

Clinical significance of CD45RO expression on peripheral blood mononuclear cells in HTLV-I-infected individuals.

The phenotype of peripheral blood mononuclear cells (PBMC) was examined in 13 healthy volunteers, 26 HTLV-I carriers, and 58 ATL patients (22 smouldering, five chronic, 24 acute, and seven lymphoma type). The percentage of CD4+, CD25+, CD28+ and CD45RO+ cells in the PBMC of the chronic and acute type patients was significantly higher than that of the volunteers, whereas the percentage of CD8+ and CD45RA+ cells in these patients was significantly low. The histogram for CD45RO fluorescence intensity (FI) revealed two patterns: pattern A consisted of CD45RO+ cells with high FI (CD45ROhigh) and intermediate FI (CD45ROint). Pattern B consisted exclusively of CD45ROhigh. Pattern A was evident in all volunteers. The percentage of subjects showing pattern B was increased in an order that reflected disease progression. In the patients with pattern A, the CD45ROint cells were CD4+ and CD8-, and the FI of CD2, CD3, and Fas within the CD45ROint cells appeared to be lower than that within the CD45ROhigh cells. The acute type patients with pattern A had a significantly longer survival curve than that of these patients with pattern B. These results suggest that the presence of CD45ROint cells may be related to protection against disease progression in HTLV-I-infected individuals.

Acute Disease↗

Thyroid peroxidase: experimental and clinical integration.

Since TPO plays a cardinal role in regulating many cellular processes of thyroid hormone biosynthesis in thyrocytes, it is important to present a summary of the impact that TPO research on the basis of molecular structure has had on our understanding of thyroid diseases. This review has therefore been written to highlight the biochemical, molecular biological, immunological and clinical aspects of TPO in thyroid follicular cells. As for hormonogenesis, further details of the properties of the superoxide generating system remain unknown, but based on decisive evidence showing what active iodinating species are at initial and principal stages, a novel concept of the mechanism of two electron oxidation has been put forth. Recent progress in studies of analyses of TPO gene structure has also provided stimuli for renewed investigation into a much wider field of thyroidology, including thyroiditogenesis.

Autoantigens↗

Differential expression of dipeptidyl peptidase IV (CD26) and thyroid peroxidase in neoplastic thyroid tissues.

This paper reports the results of research to examine the possibility of using the differential expression of two enzymes, dipeptidyl peptidase IV (DPPIV/CD26, EC: 3.4.14.5) and thyroid peroxidase (TPO, EC: 1.11.1.7), as histochemical markers histopathologically to diagnose thyroid carcinomas. The research is based on previous reports that DPPIV/CD26 is overexpressed in differentiated thyroid carcinoma tissues, and that TPO activity is very low in thyroid carcinoma tissues. Differential expression of the two enzymes in 32 thyroid tissues of various thyroid diseases was studied by Northern blot analysis and histochemical analysis. On Northern blot analyses, all 14 differentiated thyroid carcinomas (11 papillary carcinomas and 3 follicular carcinomas) overexpressed DPPIV/CD26 mRNA, whereas all 17 benign thyroid tissues (4 normal thyroid tissues, 4 Graves' diseases, 2 adenomatous goiters and 7 follicular adenomas) showed faint mRNA expression of DPPIV/CD26. All 17 benign thyroid tissues expressed high levels of TPO mRNA, whereas all 11 papillary carcinomas strongly underexpressed TPO mRNA. Histochemically, all 17 benign tissues were DPPIV/CD26 negative and strongly TPO positive, while all 11 papillary carcinomas were strongly DPPIV/CD26 positive and TPO negative. Two of 3 follicular carcinomas were histochemically positive for the two enzymes. A medullary carcinoma did not show any mRNA expression of either enzyme. These results suggest that the differential expression of these two enzymes can be applied to study the thyroid tumorigenesis.

Adenocarcinoma, Follicular↗

High expression of heat shock protein 60 in follicular cells of Hashimoto's thyroiditis.

Heat shock protein 60 expression in the thyrocytes of Hashimoto's thyroiditis and Graves' disease was studied immunohistochemically. Thyrocytes of Hashimoto's thyroiditis showed high expression of heat shock protein 60 not only in tall eosinophilic-cells but also in low and flattened cells, although the former was stained with moderate to strong staining intensity and the latter weakly to moderately. Follicular cells around lymphoid cell follicles were stained more intensely, whereas cells apart from lymphoid cell follicles were stained weakly to moderately. In Graves' disease, only follicular cells around lymphoid cell follicles were stained with varying intensities. Since the pattern in all positive staining was granular, it was thought that heat shock protein 60 overexpressed in thyrocytes located on mitochondria. To investigate the immunological role of overexpression of self heat shock protein 60 in the thyrocytes of Hashimoto's thyroiditis, gamma delta TCR+ T-cells in the tissue and the IgG class of anti-self heat shock protein 60 antibodies were studied. gamma delta TCR+ T-cells were detected among lymphoid cells scattered in interfollicular connective tissue. No difference in antibody level was seen among subjects with Hashimoto's thyroiditis, Graves' disease and normal subjects. Self heat shock protein 60 overexpression in the thyrocytes of Hashimoto's thyroiditis may play a disease-modifying role, although it does not influence the anti-self heat shock protein 60 antibody level.

Animals↗

[CD26/dipeptidyl peptidase IV and thyroid peroxidase as molecular markers for differentiated thyroid carcinoma].

Differential expression of two enzymes, dipeptidyl peptidase IV (CD26/DPP IV) and thyroid peroxidase (TPO), in neoplastic thyroid tissues was studied by Northern blot analysis and histochemical analysis using 31 thyroid tissue specimens of various thyroid diseases. On Northern blot analysis, all 16 differentiated carcinomas (12 papillary and 4 follicular carcinomas) overexpressed CD26/DPP IV mRNA, whereas all 14 benign tissue specimens (4 normal thyroid, 4 Graves' disease, 2 adenomatous goiters and 4 follicular adenomas) showed faint expression of CD26/DPP IV mRNA. All 14 benign tissues expressed high levels of TPO mRNA, whereas all 12 papillary carcinomas strongly underexpressed TPO mRNA. A medullary carcinoma did not show any mRNA expression of either enzyme. TPO mRNA expression in differentiated carcinomas did not always correlate with mRNA expression of thyroglobulin, thyroid stimulating hormone receptor, and thyroid transcription factor-1. Northern blot analysis also revealed that CD26/DPP IV is a more specific marker of differentiated carcinoma than three proto-oncogenes previously reported to increase mRNA expression in thyroid carcinomas: c-met, c-erbB-2, and EGF-R. Histochemically, all 14 benign tissues were CD26/DPP IV negative and strongly TPO positive, while all 12 papillary carcinomas were strongly CD26/DPP IV positive and TPO negative. Three of 4 follicular carcinomas were histochemically positive for the two enzymes. These findings suggest that the differential expression of these two enzymes can be applied to study the thyroid tumorigenesis.

Adenocarcinoma, Follicular↗

CD26 (dipeptidyl peptidase IV/DPP IV) as a novel molecular marker for differentiated thyroid carcinoma.

In this report we show that CD26 (dipeptidyl peptidase IV/DPP IV) is a novel molecular marker for differentiated thyroid carcinoma. Northern-blot analysis of 22 various thyroid tissues revealed that CD26 is a more specific marker of differentiated thyroid carcinoma than 3 proto-oncogenes previously reported to increase mRNA expression in thyroid carcinomas: c-met, c-erbB-2 and EGF-R. A comparative study of 3 CD26 assays, Northern blotting, immunohistochemical staining and activity staining clearly showed that CD26 enzyme activity staining is the most specific assay for differentiated thyroid carcinoma, yet the easiest to perform. Activity staining of 216 thyroid tissues detected CD26 in all 52 papillary carcinomas and all 5 follicular carcinomas, while all 58 cases of Graves' disease were CD26-negative. Among benign neoplasms, 54 of 55 adenomatous goiters and 29 of 33 follicular adenomas were CD26 negative. Staining intensity of the enzyme activity was relative to the degree of CD26 mRNA expression. Southern-blot study showed no gene amplification or major translocation of the CD26 gene in 7 papillary carcinomas examined. Based on this study, ectopic expression of CD26 in differentiated thyroid carcinomas is thought to be mainly caused by increased CD26 mRNA expression. In conclusion, CD26 activity staining is a simple, specific assay which should be added to the usual pathological examinations in order to distinguish differentiated thyroid carcinomas from benign thyroid diseases.

Adolescent↗

Experience with laparoscopic double gallbladder removal.

Double gallbladder is a rare congenital anomaly and an encounter with it while performing cholecystectomy laparoscopically is a challenge to the laparoscopic surgeon. A 28-year-old man complaining of epigastric pain was evaluated at Teikyo University Hospital, Mizonokuchi, Japan. There were no abnormal laboratory findings. Ultrasonography revealed an acoustic shadow in each compartment without any inflammatory changes in the gallbladder. No lesions were endoscopically noted in the stomach. CT scan could not demonstrate the anomaly. ERCP revealed a duplication of the gallbladder shadow with a stone in each vesicle and also the confluence of two cystic ducts from both the gallbladders draining into the common bile duct (CBD). Laparoscopic cholecystectomy was performed successfully in this case. This paper presents this particular case because of double gallbladder's rarity in the literature and to emphasize the importance of preoperative cholangiographic evaluation for double gallbladder. The laparoscopic surgeon is given an idea of the meticulous dissection at the "hepatocystic triangle" due to the various other vascular and other congenital anomalies associated with it. An account of the classification of this congenital abnormality and its various types is also discussed here.

Adult↗

Prevention of laparoscopic surgeon's thumb.

Laparoscopic surgery is being used in an increasing number of operations today. We have been performing various types of laparoscopic techniques in our department. A problem we sometimes have encountered involves a ring of pressure that develops around the surgeon's thumb at the end of the procedure, which is accompanied by an area of paresthesia in the distribution of the lateral digital nerve. We report our own experience and a small review of the literature.

Humans↗

High-density-lipoprotein-independent killing of Trypanosoma brucei by human serum.

The cattle pathogen Trypanosoma brucei brucei is morphologically indistinguishable from the human pathogens T.b. rhodesiense and T.b. gambiense. However, unlike the human pathogens, T.b. brucei is lysed by normal human serum (NHS). The trypanolytic factor in NHS co-purifies with high-density lipoproteins (HDL), but its precise nature is unknown. Using a new fluorescence-based viability assay to assess T.b. brucei killing, we find that the HDL-deficient sera from two patients with Tangier disease are as trypanolytic as NHS. Fractionation of the Tangier sera by density ultracentrifugation revealed that the activity resides only in lipoprotein-depleted fractions. Tangier and NHS were also subjected to molecular sieving chromatography, and the activity profiles were identical. Lytic fractions to T. brucei (but not to T. rhodesiense) appeared under two distinct peaks of 100-600 kDa and > 1000 kDa. Neither peak coincided with the position of the major serum lipoproteins, as determined by cholesterol titrations. The high-molecular-mass peak did not contain the HDL-associated apolipoprotein-A1. Further, we did not find that purified apolipoproteins A1 or J are lytic for the trypanosomes. We conclude that the killing of T. brucei by human serum can be independent of HDL.

Animals↗

Identification of biclonal (duplex) leukaemic cells expressing either CD4+/CD8- or CD4-/CD8+ from a patient with adult T-cell leukaemia/lymphoma.

A 24-year-old Japanese woman was admitted to our hospital in 1987 with a chief complaint of skin eruptions, and was diagnosed as having chronic ATLL. In 1993 the leucocyte count increased gradually to 126.0 x 10(9)/l with 91.5% abnormal lymphocytes expressing two different types of antigenicity, either CD+/CD8- or CD4-/CD8+. Monoclonal integration of human T-cell lymphotropic virus type-I proviral DNA was detected at different sites of the genomic DNA in each cell type. These studies clearly indicate that CD4+/CD8- and CD4-/CD8+ leukaemic cells originated from two independent clones.

Adult↗

c-Kit proto-oncogene is more likely to lose expression in differentiated thyroid carcinoma than three thyroid-specific genes: thyroid peroxidase, thyroglobulin, and thyroid stimulating hormone receptor.

Although c-kit proto-oncogene product is known to be weakly expressed on normal thyrocytes, its function is unclear. In order to investigate the significance of thyroid c-kit, c-kit gene expression in 37 various thyroid tissues was analyzed by comparing c-kit gene expression with the mRNA expression of three thyroid-specific genes: thyroid peroxidase, thyroglobulin, and thyroid stimulating hormone receptor, c-kit mRNA was hardly detected by the usual northern blot method in 2 of 7 follicular carcinomas, 11 of 12 papillary carcinomas, and a medullary carcinoma. On the other hand, a high level of c-kit mRNA expression was found in all 17 benign thyroid tissues (4 normal thyroid tissues, 4 Graves' disease, 2 adenomatous goiters, and 7 follicular adenomas). This study found that c-kit proto-oncogene is more likely to lose expression in differentiated thyroid carcinoma than any thyroid-specific gene. Decreased c-kit gene expression may serve as an indicator for the de-differentiation of thyrocytes.

Blotting, Northern↗

Apoptosis in thyroid tissue from patients with Hashimoto's thyroiditis.

To clarify whether apoptosis of thyroid follicular epithelial cells occurs at the tissue level in autoimmune thyroiditis, 17 specimens of thyroid tissues with Hashimoto's thyroiditis were stained for fragmented DNA. Almost all nuclei of follicular epithelial cells forming atrophic thyroid follicles surrounded by mononuclear cell infiltration and fibrosis showed positive staining. With increasing distance from lymphoid cell follicles, the percentage of follicular epithelial cells with DNA fragmentation-positive nuclei decreased (30-80%). Electron microscopic study revealed the existence of epithelial cells with shrunk and condensed nuclei. The frequency of those cells in different areas was almost compatible with that of cells with fragmentation-positive nuclei. These findings suggest that apoptosis plays an important role in the thyroid tissue injury in autoimmune thyroiditis.

Adult↗

[Tissue concentration of 5-FU after intra-operative arterial infusion].

The aim of this study was to measure the tissue concentration of anti-cancer agents administered by arterial infusion. After the abdominal cavity was opened, 250 mg of 5-FU diluted in 20 ml saline was infused into the feeding artery in 16 patients with colonic cancer. After the affected lesion was resected, specimens were obtained at the tumor, at sites 5 and 10 cm from the center of the tumor, and at the adjacent nodes. The concentration of 5-FU was higher in the tumor and the adjacent lymph nodes than in the normal colon near the lesion. This suggests that 5-FU has a more favorable distribution profile in tumor tissue than in normal tissue. Patients with a high concentration of 5-FU in the tumor also demonstrated high levels in the other tissue. Blood flow volume and the length of time between the injection of 5-FU and harvest of the specimen may account for differences in the tissue concentration of the agent after administration of the same dose.

Colonic Neoplasms↗

Expression of functional Fas antigen on adult T-cell leukemia.

The expression of Fas antigen was analyzed in the peripheral blood mononuclear cells of 12 patients with adult T-cell leukemia (ATL) by flow cytometry. The induction of apoptosis in these cells by adding an anti-Fas antibody and the expression of activated T-cell surface antigens, CD25 and CD26, were also studied. It appears that the cells in ATL expressed a significantly larger number of Fas antigens than those in normal subjects (p < 0.01) and their fluorescent intensity was also shown to be much stronger in ATL (p < 0.01). The large number of ATL cells showed apoptosis in a short-term culture in the presence of the anti-Fas antibody. There was no difference in the expression of Fas antigen among ATL cells with different phenotypes of CD4+/CD8-, CD4-/CD8- and CD4+/CD8+ as well as with clinical subtypes of ATL. Interestingly, the expression of Fas and CD26 antigens showed a negative correlation (p < 0.01, r = 0.78). The strong expression of functional Fas antigen in ATL leads to the impression that anti-Fas antibody could be one of the treatment modalities for ATL which is known to be a very difficult disease to cope with.

Antigens, Differentiation, T-Lymphocyte↗

[Measurement of human thyroid peroxidase autoantibodies by enzyme immunoassay using recombinant human TPO].

An EIA for measuring anti-TPO autoantibodies (rhTPO-EIA) was developed using recombinant human TPO expressed in CHO cells and was compared with MC-HA generally used in laboratory routine work. rhTPO-EIA showed a satisfactory reproducibility in the intra-assay test and did not have an accidental error of lots. Almost equal number of healthy females and males were measured for their IgG binding to TPO to define a normal range of anti-TPO autoantibodies. After setting 20 IU/ml as an upper limit of normal range, sera from patient with thyroid disorders were measured for their anti-TPO autoantibodies. Chronic thyroiditis and Graves' disease were highly positive, while adenoma, thyroid cancer, SLE, and RA were low in their positivity. The positive rate of anti-TPO autoantibodies was compatible to those of previous reports in each disorder. Seventy-two sera from patients with chronic thyroiditis or Graves' disease were measured for their autoantibodies by both rhTPO-EIA and MC-HA and the results were compared between both methods. A correlation coefficient was 0.486. Following absorption with thyroglobulin, sera were measured again and as the results, the correlation coefficient increased to 0.723. Therefore, MC-HA was thought to be influenced in the presence of anti-thyroglobulin autoantibodies. Since rhTPO-EIA is excellent in quality and not affected by anti-thyroglobulin antibodies, it is useful and applicable to clinical diagnosis and observation of thyroid disorders.

Autoantibodies↗