Search PubMed⌕ Search

Biomedical subjects

T Kotani

Publications and source records attributed to T Kotani.

At least 127 records · Page 7Linked to original sources

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↗

Radiographic and immunohistochemical analysis of leukocyte adhesion deficiency in Holstein heifers.

Radiographic and immunohistochemical analyses were performed in two Holstein heifers with leukocyte adhesion deficiency (BLAD). Severe bone resorption, osteolysis and severe progressive periodontitis in submandibula due to dysfunction of leukocytes in heifers affected with BLAD were demonstrated by radiographic examination. Immunohistochemical analysis of lymph nodes using anti-CD18 monoclonal antibody demonstrated that CD18-positive cells were not found on those from a heifer affected with BLAD, whereas CD18-positive cells were clearly present in lymph nodes from a clinically normal heifer. These characteristic findings support the importance of adherence-dependent leukocyte functions in host defense.

Animals↗

Hereditary cerebellar vermis defect in the Lewis rat.

We report a new rat model of hereditary cerebellar vermis defect. Mutant rats exhibited hind-leg paralysis from about 14 days old. Gross pathology showed the cerebellar vermis defect, fused cerebellar hemispheres and cyst formation. Ectopic dysplastic cerebellar tissues existed in the cerebello-pontine junctional zones. Mild disarrangement of lamination was also observed in the fused cerebellar hemispheres. The present mutant may serve as a valid model for studying the cerebellar vermis defect under the genetic control.

Animals↗

Antitumor effect of neocarzinostatin conjugated to human/mouse chimeric Fab fragments of the monoclonal antibody A7 on human pancreatic carcinoma.

The anticancer agent neocarzinostatin (NCS) was bound covalently to human/mouse chimeric Fab fragments of the monoclonal antibody A7 to form the conjugate chA7Fab-NCS. The antitumor effect of chA7Fab-NCS was tested by measuring the inhibition of 3H-thymidine incorporation into human pancreatic carcinoma cells. The chA7Fab-NCS was approximately 2.3 times as effective as free NCS against human pancreatic carcinoma cells which reacted with the monoclonal antibody A7. The antitumor activity of chA7Fab-NCS was inhibited by excess chA7Fab. ChA7Fab-NCS had an antitumor effect equivalent to free NCS on human pancreatic carcinoma cells which did not react with the monoclonal antibody A7. ChA7Fab-NCS appears to be a potentially useful conjugate for immunotargeting chemotherapy against pancreatic carcinoma.

Animals↗

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↗

In vitro reactivity and in vivo biodistribution of the monoclonal antibody A7 using human gastric carcinoma cell lines.

The monoclonal antibody (MAb) A7 has been used to treat patients with colorectal or pancreatic carcinoma with encouraging results. We therefore determined if MAb A7 would also react with gastric carcinoma cell lines. MAb A7 reacted with seven of eight gastric carcinoma cell lines tested. The intensity of the reaction, measured by flow cytometry, was equal to that of WiDr (colon) and HPC-YS (pancreas) cell lines. In nude mice bearing xenografts of the MAb A7-reactive gastric cancer line MKN45, the percentage injected dose of MAb A7 per g of tumour tissue on day 7 was 9.79; this value was 77% of that on day 1. The in vivo tumour-to-blood ratio of MAb A7 was 2.77 on day 7. Therefore, MAb A7 has long-term retention at binding sites as well as a high probability, high intensity and high specificity of reactivity against gastric cancer, which make it an ideal drug carrier for immunotargeted chemotherapy and immunodiagnosis.

Adenocarcinoma↗

In vivo efficacy of neocarzinostatin coupled with Fab human/mouse chimeric monoclonal antibody A7 against human colorectal cancer.

The anticancer polypeptide neocarzinostatin (NCS) was covalently coupled to a human/mouse chimeric Fab A7 monoclonal antibody (chFabA7) and the in vivo efficacy of this conjugate was examined. NCS concentration assay was carried out, and acute toxicity and tumoricidal effects were examined. The concentration assay, using anti-NCS monoclonal antibody, revealed that administration of the chA7Fab conjugate leads to a greater blood retention and a higher tumor accumulation of NCS, when compared to free NCS administration. The tumoricidal effect of chA7Fab-NCS was higher than that of either free NCS or the saline control, against antigen-positive tumors. In antigen-negative tumors there was no difference in toxic effect among the three preparations. Values of LD50, reflecting acute toxicity, were 5050 U/kg and 3600 U/kg for the chA7Fab-NCS and the free NCS, respectively. These results suggest that chFabA7-NCS may be a promising tool for targeting cancer chemotherapy.

Animals↗

Biodistribution of neocarzinostatin conjugated to chimeric Fab fragments of the monoclonal antibody A7 in nude mice bearing human pancreatic cancer xenografts.

In this study, we conjugated chimeric Fab fragments of the monoclonal antibody (MAb) A7, which reacts with pancreatic cancers, to the antitumor drug neocarzinostatin (chA7Fab-NCS) and intravenously injected 125I-labeled chA7Fab-NCS into nude mice bearing a human pancreatic cancer xenograft. We compared the tumor localization of 125I-labeled chA7Fab-NCS with that of conventional 125I-labeled A7-NCS, which was produced by conjugation of MAb A7 and NCS. 125I-Labeled chA7Fab-NCS accumulated in the tumor earlier than 125I-labeled A7-NCS, and significantly larger amounts of 125I-labeled chA7Fab-NCS had accumulated in the tumor 1 hour after injection. The results suggest that chA7Fab may be a suitable carrier for NCS in immunotargeting therapy against pancreatic cancer.

Animals↗

Bioassay for interleukin-1, interleukin-6, and tumor necrosis factor-like activities in canine sera.

To measure interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF)-like activities in canine serum, bioassays were conducted using human melanoma A375S1, IL-6 dependent murine hybridoma MH60.BSF2, and WEHI 164 murine sarcoma subclone 28-4. Clinically normal adult beagles were experimentally induced endotoxic shock by an intravenous injection of lipopolysaccharide or local inflammation by an intramuscular injection of turpentine oil. IL-1-like activity was detected in sera from dogs with endotoxic shock. IL-6 and TNF-like activities were detected in sera from both dogs with endotoxic shock and local inflammation. IL-1-like activity in sera from the dogs with endotoxic shock declined after dilution with either medium or serum obtained before treatment (pre-serum), but the IL-1-like activity was maintained to a greater extent in samples diluted with pre-serum compared to those diluted with medium. TNF-like activity declined equally after dilution with either medium or pre-serum. On the other hand, IL-6-like activity was inhibited at low dilution. It was, therefore, necessary to dilute the serum samples to 1:180 from dogs with endotoxic shock or 1:60 from dogs with local inflammation, in order to minimize the effect of inhibitory factors on IL-6-like activity. IL-6-like activity was neutralized by monoclonal antibody against murine IL-6 receptors. TNF-like activity was neutralized by anti-mouse TNF alpha rabbit serum. However IL-1-like activity was not neutralized by either anti-mouse or anti-human IL-1 rabbit serum.

Animals↗

The first case of equine motor neuron disease in Japan.

A 9-year-old male horse showed emaciation, weakness and trembling and was euthanatized. Histopathological examinations revealed loss, swelling and chromatolysis of motor neurons throughout the spinal ventral horns, axonal degeneration of the ventral spinal roots. Eosinophilic cytoplasmic inclusions were distributed in degenerated spinal ventral neurons. Ultrastructurally, the inclusions consisted of aggregations of granular dense material and a few vesicles. They reacted positively with polyclonal antibody against ubiquitin. The present case was diagnosed as equine motor neuron disease, which has recently been reported in North America and the United Kingdom.

Animals↗

Canine acute phase response: relationship between serum cytokine activity and acute phase protein in dogs.

The changes in serum activity of interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF) were studied in dogs with acute inflammation. Dogs with local inflammation induced by an intramuscular injection of turpentine oil showed clinically a typical progression in the inflammatory response, recovering on day 14 after the treatment. Serum concentrations of C-reactive protein (CRP) and alpha 1 acid glycoprotein (alpha 1AG) increased, and the albumin concentration decreased in all dogs during the acute phase response. These values each returned to the normal range from day 14 to 21. Serum IL-6-like activity was detected from 2 hr to day 6 after treatment. Serum TNF-like activity in the treatment group was detected at a low level from 3 to 24 hr after treatment, but there was no statistically significant difference compared with the control group. The temporal changes in serum IL-6 and TNF-like activities preceded those in serum concentrations of CRP, alpha 1 AG, and albumin. No dogs showed a detectable rise in serum IL-1-like activity after treatment.

Acute-Phase Proteins↗

Myocardiopathy and expression of atrial natriuretic peptide in rats with monocrotaline-induced pulmonary hypertension.

Myocardiopathy in rats with monocrotaline (MCT)-induced pulmonary hypertension was investigated morphologically and immunohistochemically. A single subcutaneous injection of MCT (60 mg/kg body weight) to SD rats produced progressive cardiac lesions. Histologically, the lesions were characterized by myocardial hypertrophy and myocardial degeneration followed by mononuclear cell infiltration and fibroblast proliferation in the right atrium and ventricle. Such histological changes began to be seen 3 weeks after injection and thereafter progressively developed in rats killed 4 and 5 weeks after injection. These findings indicate progressive hypertrophic myocardiopathy, due probably to pulmonary hypertension induced by MCT. Immunohistochemically, atrial natriuretic peptide (ANP)-positive myocardial cells were frequently observed in the left and right ventricle in MCT-treated rats killed 4 and 5 weeks after injection. The intensive immunopositive reaction was observed mainly in hypertrophic myocardial cells in the subendocardium of the right ventricle and also present in hypertrophic myocardial cells around injured areas consisting of degenerated myocardial cells, mononuclear cell infiltration and fibrosis. These findings suggest a close relationship between the ANP expression and cardiac hypertrophy in MCT-treated rats.

Animals↗

[Adrenal ganglioneuroma: report of a case].

A 52-year-old man was hospitalized for a right adrenal tumor which had been incidentally found by abdominal CT scan for examination of colon cancer. Laboratory and endocrine findings were within the normal limits except for increased urinary concentrations of noradrenaline and dopamine. Adrenal angiography revealed that the feeding artery of the tumor was the inferior suprarenal artery. Adrenal venous blood sampling studies detected no abnormalities in the concentrations of catecholamine, cortisol or aldosterone. Right adrenalectomy was performed and the tumor was histologically diagnosed as ganglioneuroma. Ganglioneuroma is a benign tumor originating from the sympathetic nerve ganglion. The adrenal origin of the tumor is relatively rare and 60 cases of adrenal ganglioneuroma including our case have been reported in Japan.

Adrenal Gland Neoplasms↗

[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↗