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Biomedical subjects

Y Kohno

Publications and source records attributed to Y Kohno.

At least 271 records · Page 15Linked to original sources

Enzyme-linked immunosorbent assay (ELISA) for IgG antibodies to thyroglobulin.

We used a computer programmed standard IgG curve for computer-assisted quantification of assay results for autoantibodies to thyroglobulin (Tg) by quantitative enzyme-linked immunosorbent assay (ELISA). Specific antibody levels in unknowns were quantified by comparison of their optical density readings with a standard curve of absorbance vs concentration obtained with dilutions of the reference serum. Anti-Tg antibodies were detected in 80% of the patients with chronic thyroiditis and 90% of those with Graves' disease. Anti-Tg antibodies were also detected in 14.3% of the healthy controls. The titer of anti-Tg antibodies detected by tanned red cell hemagglutination correlated well with that detected by ELISA, although, the sensitivity of the ELISA was higher. By our computer-assisted conversion method, the anti-Tg antibody can be readily and reliably quantified and low titer antibodies to Tg can be detected with adequate precision.

Adolescent↗

Comparative studies on the gastrointestinal lesions caused by several nonsteroidal anti-inflammatory agents in rats.

The gastrointestinal toxicity of a single oral administration of five nonsteroidal anti-inflammatory agents (NSAIDs) to rats was compared, by a method using 51Cr-labeled red blood cells (RBC), and by macroscopic and microscopic examination. From the profile of gastrointestinal bleeding, the NSAIDs could be divided into a group consisting of aspirin (ASA), oxaprozin (OXP) and 2-[4-(3-methyl-2-butenyl)phenyl]propionic acid (TA), which caused only a transient increase in fecal blood loss based on a gastric lesion, and another group including indomethacin (IM) and ibuprofen (IP), which produced a biphasic increase in the blood loss. The initial phase was caused not only by a gastric lesion but also an intestinal lesion, and the secondary phase originated only in the intestinal lesion. The order of potency causing blood loss was IM much greater than IP greater than ASA much greater than TA greater than OXP. The safety ratio of OXP and TA was shown to be more favorable than that of the other three drugs.

Administration, Oral↗

Effect of sofalcone on the gastric cell proliferation in the experimental gastritis of rats.

Effects of sofalcone on the morphometrical glandular structure and the generative cell proliferation in the gastric mucosa of gastritis, induced in rats by the treatment of sodium taurocholate (TCA) for 3 and 6 months, were examined by means of 3H-thymidine autoradiography. Morphometrical observation revealed that the ratios of the length of the glandular portion/the total length of the gastric gland were generally decreased in both fundic and pyloric glands with TCA treatments, which may indicate mucosal atrophy. These atrophic changes were improved to the normal levels by the administration of sofalcone for 3 weeks after the treatment of TCA. On the other hand, cell proliferative activity, indicated by the labeling indexes in the generative cell zone of gastric mucosa, was increased in TCA induced gastritis rat, which seems to be the response to replace the increased cell loss. The administration of sofalcone to the gastritis rats further increased the labeling indexes, especially in pyloric gland with statistical significance in both TCA treated rats for 3 and 6 months. From these results, it is suggested that sofalcone stimulates the compensatory increase of proliferative activity of generative cells, which would be available to repair the gastric mucosa with gastritis.

Animals↗

A case of glutaric aciduria type I with unique abnormalities in the cerebral CT findings.

A first Japanese case of glutaric aciduria type I (GA-I) was described. She was a 7-month-old girl presenting with poor head control, irritability and sleeplessness. The profile of urinary organic acids by gas chromatography mass spectrometry (GC/MS) suggesting GA-I were confirmed by no activity of glutaryl-CoA dehydrogenase in the fibroblasts. The cerebral computer tomography (CT) showed marked changes such as large fluid collections on bilateral frontotemporal regions and a slight enlargement of bilateral ventricles. The amounts of urinary glutarate excretion decreased after restriction of lysine and tryptophan in her diet and administration of carnitine improved the carnitine levels in blood and urine, while these were less effective for the neurological symptoms. On the other hand, oral administration of lioresal, an analogue of gamma-aminobutyrate (GABA), cleared her symptoms such as ill temper, irritability and sleeplessness dramatically, and the abnormalities of the CT examinations were not more deteriorative until 2 years of her age at least. The neurological manifestations of GA-I seemed to be affected by the unusual metabolism of GABA in the central nervous system.

Baclofen↗

[A case of breast cancer with pleural metastasis responding to administration of intrapleural adriamycin and systemic chemotherapy with FEMP].

A 51-year-old woman with breast cancer metastatic to the pleura was treated with intrapleural instillation of adriamycin after thoracentesis, and systemic administration of FEMP, with complete response for more than 11 months. She underwent radical mastectomy and bilateral oophorectomy for advanced breast cancer, and 18 months later presented radiological evidence of pleural fluid contralateral to the affected breast. Initially, thoracentesis for symptomatic relief was done with a positive cytology in the pleural effusion. Intrapleural instillation of adriamycin was followed by partial resolution, and administration of FEMP achieved complete disappearance of both pleural metastasis and pleural effusion.

Administration, Oral↗

[On the lymphatics of the cardia--with special reference to the study of using endoscopic lymphoscintigraphy with SPECT].

Endoscopic lymphoscintigraphy was performed on 29 patients. In 15 of 29 cases, Single Photon Emission Computed Tomography (SPECT) was performed to observe the lymphatics of the cardia. The rate of detection of paraaortic lymph nodes by SPECT was 66.6%, and in particular the paraaortic lymph nodes in the upper portion of the left renal vein were detected at a rate of 58.3%. The ascending lymph flow from the cardia to the mediastinum could be depicted by SPECT. The SPECT images and the distribution of accumulation of Tc-99m Rhenium colloid into the regional lymph nodes indicated a similar tendency to the actual metastatic rate of carcinoma of the cardia. Endoscopic lymphoscintigraphy with SPECT is considered to be useful for imaging the lymph flow from the cardia to the regional lymph nodes. On the other hand, the conventional planar image was poor in depicting lymph nodes, and was impossible in dynamic analysis. In the early stage of carcinoma of the cardia, if the area limited, proximal gastrectomy seems reasonable, but in progressive and deepseated cancer, it is suggested that it is necessary to remove the lymph nodes in a wide area, including the paraaortic lymph nodes, in addition to performing total gastrectomy.

Adenocarcinoma↗

Bone in the marmoset: a resemblance to vitamin D-dependent rickets, type II.

The common marmoset, a New World monkey, requires a large amount of vitamin D3 to maintain its normal growth. This monkey is reported to have an end-organ resistance to 1 alpha,25-dihydroxyvitamin D3 (1 alpha,25(OH)2D3). In this study, the bone morphology of marmosets fed a high vitamin D3 diet (intake of vitamin D3, 110 IU/day/100 g of body weight) was compared by X-ray and histological examinations with that of rhesus monkeys (Old World monkey) fed a normal diet (intake of vitamin D3, 5 IU/day/100 g of body weight). Three of 20 marmosets were found by X-ray examination to have osteomalacic changes in their bones despite the high daily intake of vitamin D3, whereas none of the 5 rhesus monkeys showed any signs of osteomalacia. Osteomalacic marmosets had distinct increases in osteoid surface, relative osteoid volume, and active osteoclastic bone resorption, whereas non-osteomalacic marmosets had no increase in osteoid tissues in their bones. None of the marmosets, either osteomalacic or non-osteomalacic, was hypercalcemic despite the extremely high circulating levels of 1 alpha,25(OH)2D3. However, the serum 25-hydroxyvitamin D3 (25OHD3) and 24R,25-dihydroxyvitamin D3 (24R,25(OH)2D3) levels were significantly lower in the osteomalacic than in the non-osteomalacic marmosets. These results suggest that the marmoset is likely to exhibit osteomalacic bone changes despite the high daily intake of vitamin D3. These changes resemble those in vitamin D-dependent rickets, type II.

24,25-Dihydroxyvitamin D 3↗

In vitro early changes in intercellular junctions by treatment with a chemical carcinogen.

To examine early intercellular junction changes caused by treatment with 9,10-dimethyl-1,2-benzanthracene (DMBA), rat lingual epithelium was cultivated in isolation and observed by electrophysiological, freeze-fracture and whole-mount electron microscopy. Electrophysiological measurements showed a transient decrease in membrane potential of -10.2 mV 6 h after the treatment. It returned to almost the same level as that of the control group 1 day later. Six hours after treatment, input resistance decreased rapidly to 5.3 M omega but increased to 18.0 M omega 12 h after treatment. Transient reduction of input resistance and membrane potential occurred prior to the decrease in the coupling ratio 6 h after treatment with DMBA. In freeze-fracture replicas, the number of gap junctions decreased by approximately 45% of the control value 6 h after treatment with DMBA. At 12 h and thereafter, the number and area of gap junctions subsequently decreased by 60-80% of the control value. Alterations in the number and area of desmosomes were similar to those of the gap junctions. The formation of epithelial cytoskeletons, partially devoid of the 2-4 and 5-8 nm filaments was also observed. A decrease in the density of filament networks beneath the plasma membranes was especially apparent. Treatment with a carcinogen brought about morphological cellular changes as early as 6 h after treatment, and such early changes might trigger metabolic cellular abnormalities. Affected cells appear to move away from normal cells in a process of repeated destruction and revision of intercellular junctions, and cytoskeletons.

9,10-Dimethyl-1,2-benzanthracene↗

Cerebro-oculo-hepato-renal syndrome (Arima' syndrome): a distinct clinicopathological entity.

Three children with Leber's congenital amaurosis, agenesis of the cerebellar vermis, and infantile polycystic kidneys are described. The common clinical findings of three unrelated patients (two boys and one girl) included severe visual impairment from early infancy, profound psychomotor retardation, hypotonia, nystagmus, characteristic facial appearance with blepharoptosis, and progressive chronic renal insufficiency. The two boys died of uremia at ages 13 and 12 years. The common pathological findings in these two patients consisted of minor disproportions of cerebral lobes, almost total aplasia of the cerebellar vermis, micropolygyria of the dentate nuclei, malformations of the brain stem (including pachygyria of the inferior olivary nuclei and partial absence and anomalous position of the pyramidal tracts), and infantile polycystic kidneys; there was fatty liver in one case and hepatic fibrosis in the other. The clinicopathological findings of our two patients were entirely compatible with those of patients previously reported by Arima and other Japanese authors. Therefore, these patients seem to comprise a distinct clinicopathological entity, cerebro-oculo-hepato-renal syndrome (Arima's syndrome), different from other syndromes with retinal, cerebellar, and renal abnormalities.

Blindness↗

Activated lymphocytes in patients with newly diagnosed type 1 (insulin-dependent) diabetes mellitus.

The expression of activation antigens (transferrin receptor, IL-2 receptor and Ia antigen) on circulating T lymphocytes from Japanese children with Type 1 diabetes was studied using five monoclonal antibodies (Ab), OKT9, anti-Tac Ab, OKIa1, anti-human HLA-DR Ab and OKT3. For detecting Ia positive T cells, the dual staining technique using OKT3 and anti-Ia antibody was employed. Four out of six patients (67%) with newly diagnosed Type 1 diabetes showed a raised level of either OKT9 or Tac positive cells when examined at diagnosis. These patients, however, rapidly lost these activation antigens after the insulin therapy was started. In contrast, in 32 long-standing patients, only 2 (6%) had a high percentage of OKT9 positive cells and none of them demonstrated Tac positive cells. One out of six newly diagnosed patients or three out of 21 long-standing patients had a significantly high percentage of Ia-positive T cells compared with normal subjects. In poorly controlled long-standing patients whose HbA1 value was higher than 14%, none of them had an increased number of activated lymphocytes. Therefore, it is unlikely that insulin deficiency and hyperglycemia were responsible for the changes observed in these studies. Activated lymphocytes might be related to activation of the immune system involved in pathogenesis of Type 1 diabetes.

Antibodies, Monoclonal↗

Antigenic determinants on thyroglobulin recognized by T cells in patients with chronic thyroiditis.

It was found that the proliferating cells to thyroglobulin (Tg) in patients with chronic thyroiditis are confined to a T cell subpopulation. Then, we attempted to characterize the antigenic determinants of Tg recognized by T cells from patients with chronic thyroiditis by Tg-induced DNA-synthetic response. T cells from patients could respond to Tgs from whales, pigs and chickens as well as to human Tg. These findings indicated that epitopes on Tg recognized by T cells were shared by Tgs from various species. In addition, the T cells from different individuals varied in specificity.

Adolescent↗

Autoantibodies to thyroid peroxidase in patients with chronic thyroiditis: effect of antibody binding on enzyme activities.

Using thyroid peroxidase (TPO), which was purified from the thyroid of patients with Graves' disease, we attempted to determine whether sera from patients with chronic thyroiditis contained antibodies to the enzyme. When the binding was tested by ELISA, sera from patients with chronic thyroiditis revealed high binding activities to TPO. When TPO was incubated with IgG from sera followed by treatment with protein A-Sepharose and centrifugation, the remaining TPO activities in the supernatant fraction were lower in most of the patients, as compared to normal controls. Moreover, IgG purified by DEAE-cellulose chromatography from sera in patients interfered with the TPO activities. Titres of anti-TPO antibodies correlated well with those of anti-microsome antibodies. These results indicate the presence of autoantibodies to TPO in sera of most patients with chronic thyroiditis and that TPO may be one component of microsome antigen complexes recognized by the autoantibodies. Studies on the inhibition of TPO by IgG isolated from sera of patients using guaiacol and iodide assays revealed that at least three epitopes of TPO molecule were recognized by autoantibodies and that the antigenic determinants on TPO molecule recognized by autoantibodies could be heterogeneous in patients.

Adolescent↗

[Comparative studies on immunological property of thyroglobulins obtained from the thyroid tumor and the adjacent tissue].

The immunological properties of thyroglobulins (Tg) of individual patients, obtained from a thyroid tumor and its adjacent tissue were compared, using conventional or monoclonal antibodies against human Tg. The thyroid tumors studied were non-functioning thyroid carcinomas and functioning thyroid adenomas. In contrast to non-functioning tumors, Tg from the functioning tumors was generally iodinated at a level close to that of normal tissue, and Tg from the tissue adjacent to the tumors had a very low iodine content. The conventional antiserum and monoclonal antibodies, B2F, seemed to recognize the conformation of Tg, while C6G showed a high affinity to Tg even when unfolded or denatured. In most cases, Tg isolated from the tissue adjacent to a tumor showed a higher affinity to antibodies than Tgs of the tumor tissue, as determined by the inhibitional effect of these Tgs against the binding of standard Tg and antibody. Furthermore, the Tg of the adjacent tissue was immunologically different in nature from the standard Tg obtained from a normal thyroid gland. From these results, Tgs of tumor and the adjacent tissue in individual patients were heterogeneous in immunological property, regardless of iodine content.

Adenocarcinoma↗