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Biomedical subjects

K Ohya

Publications and source records attributed to K Ohya.

At least 19 recordsLinked to original sources

Cutaneous leiomyosarcoma.

A child's head-sized tumor on the upper back developed in a 43-year-old man. In spite of an extensive operation for the tumor, he died of multiple metastasis 15 months after the operation. Histologically, tumor cells proliferated throughout the dermal and subcutaneous regions, and a boxed-in appearance was noted with silver staining. Because electron microscopic observations strongly suggested a smooth muscle origin, we diagnosed this case as cutaneous and subcutaneous leiomyosarcoma.

Adult

Palm carotene inhibits tumor-promoting activity of bile acids and intestinal carcinogenesis.

The effects of palm carotene on chemical carcinogenesis was studied. Palm carotene suppressed mouse epidermal ornithine decarboxylase activity induced by glycocholic acid. In a two-stage mouse epidermal carcinogenesis experiment using 7,12-dimethylbenz(a)anthracene as the initiator, glycocholic acid as the 1st stage promoter, and mezerein as the 2nd stage promoter, palm carotene inhibited the promoting activity of glycocholic acid. Furthermore, in N-ethyl-N'-nitro-N-nitrosoguanidine-induced mouse duodenal carcinogenesis, 0.05% of palm carotene given in drinking water decreased the percentage of tumor-bearing mice significantly.

9,10-Dimethyl-1,2-benzanthracene

Syntheses of 2-(3,4-dimethoxyphenyl)ethylamine derivatives and their antiulcer activities.

A series of acyl derivatives of 2-(3,4-dimethoxyphenyl)ethylamine (4) were synthesized and evaluated for their effectiveness to prevent water-immersion stress-induced gastric ulceration when given intraperitoneally to rats. Among them N-[2-(3,4-dimethoxyphenyl)ethyl]-2-phenylaminoacetamide hydrochloride (15) had significant antiulcer activity. Further modification of the four parts of 15 revealed that only the introduction of a carbamoyl group into 2- or 3-position of the phenylamino part gave compounds (49-51, 54 and 55) which retained antiulcer activity comparable to the lead compound. However, the compounds (49-51 and 54) did not exert a prophylactic effect when administered orally except for the 3-substituted bezamide derivative 55. Alkyl substitution on the nitrogen of benzamide gave 3-[[[2-(3,4-dimethoxyphenyl)ethyl]carbamoyl]methyl] amino-N-methylbenzamide (66, DQ-2511) and the related compounds (67, 70, 74 and 77) which all had potent antiulcer activities at oral doses of 50-400 mg/kg.

Animals

The effect of dietary safflower phospholipid on steroids in gastrointestinal tract of rats fed a hypercholesterolemic diet.

The effect of dietary safflower phospholipid (Saf-PL) on the postprandial changes of steroids in the small intestinal and cecal contents was examined in rats fed a hypercholesterolemic diet. The triglyceride mixture (SP-Oil) containing a comparable amount of linoleic acid to Saf-PL was used as a reference fat source. Saf-PL suppressed the elevation of plasma cholesterol levels at all times after meal intake, when compared to SP-Oil. The reduction of plasma cholesterol in rats fed the Saf-PL diet was exclusively observed both in chylomicron plus very low density lipoprotein (VLDL) and low density lipoprotein (LDL) fractions. The rate of gastric emptying was not modified by the Saf-PL diet. The level of neutral steroids in the small intestinal contents was almost comparable in both groups, but in the cecal contents and feces it was significantly higher in rats fed the Saf-PL diet. On the other hand, the level of acidic steroids in the small intestinal contents tended to be higher in rats fed the Saf-PL diet than in those fed the SP-Oil diet, whereas in the cecal contents and feces it was comparable in the two diets. These results suggest that Saf-PL causes the accumulation of neutral steroids in the cecum due to the rapid transit through the small intestine.

Animals

[Alveolar bone resorption process in molar tooth region in calcium-deficient rats].

The present study was carried out to investigate the alveolar bone resorption in the molar tooth region in the rats fed a low calcium diet. Male Wistar rats (70-85g in body weight) were either fed a low calcium diet (0.05% Ca, 0.35% P) or a control diet (0.5% Ca, 0.35% P) by using a pair feeding technique. The rats were sacrificed at intervals of 3, 6, 9 and 20 days during the experimental period. Contact microradiograph of the second molar region of the mandible showed that the cancellus bone as well as the endosteal surface of the cortical bone were progressively resorbed soon after the start of low calcium feeding. At day 9, the amount of bone was reduced to about half of the control rats and 80% of the bone was diminished at day 20. In spite of the severe bone resorption, the alveolar bone proper that surrounds the molar sockets and a few cancellus bone were seen remaining and the occlusal function of the molar tooth seemed to be maintained. These results suggest that the alveolar bone quickly responded to the low calcium diet resulting in bone resorption and that the bone in the supporting tissues of the molar tooth seems to be not affected by the calcium deficiency.

Alveolar Bone Loss

[Asymptomatic multilocular cystic renal cell carcinoma].

From January 1982 to December 1989, we experienced seven multilocular cystic renal cell carcinomas (MLCRCCs) in 36 asymptomatic renal cancers incidentally diagnosed, and none in 23 symptomatic renal cancers (p less than 0.05). No multiocular cystic nephromas (MLCNs) appeared in either group. Though MLCRCCs have been considered to be, in general, extremely rare, they do occur in asymptomatic renal cancers. A multiloculated renal mass with thick septum discovered in an adult by ultrasonography or CT scan should be suspected as being a MLCRCC rather than a MLCN.

Adult

[Neoadjuvant intra-arterial chemotherapy followed by partial cystectomy for invasive bladder cancer].

From January, 1987 through January, 1990, partial cystectomy was performed for 4 (18%) of 22 patients with invasive bladder cancer who had received neoadjuvant intra-arterial chemotherapy. The criteria of patient selection for partial cystectomy were: 1) invasive bladder cancer showing good response (greater than or equal to PR) to neoadjuvant chemotherapy, 2) solitary or localized tumor that can be eradicated by segmental resection, and 3) tumor of stage T3 or less. As a rule, cisplatinum (100 mg/m2) and THP-adriamycin (40 mg/m2) were administered selectively to the internal iliac artery by one-shot infusion. Concurrently, sodium thiosulfate (10 g/m2), a neutralizing agent against cisplatinum, was administered intravenously. All four patients had achieved clinical complete responses by one or two courses of intra-arterial chemotherapy, and then underwent partial cystectomy with pelvic lymphadenectomy. Pathological examination revealed pTONO in two patients, and the remains were pT3aNO and pT3bN1. After the mean follow-up of 24 months, three of them are alive with no evidence of disease, and also with normal bladder and sexual functions. However, one with pT3bN1 tumor underwent total cystectomy 5 months later for local recurrence (pT4b) and had died of cancer 18 months later. Neoadjuvant intra-arterial chemotherapy followed by partial cystectomy should be the most applicable conservative therapy with high radicality for invasive bladder cancer, when: 1) the patient has localized invasive cancer showing good response (greater than or equal to PR) to neoadjuvant chemotherapy, 2) the tumor is stage T3a or less and without findings of tentacular invasion (INF gamma) by pre-operative biopsy, and 3) pre-operative multiple biopsy is performed as deeply as possible along the prearranged incision line.

Aged

Human monoclonal antibodies to human cytomegalovirus derived from peripheral blood lymphocytes of healthy adults.

Immunoglobulin G class human monoclonal antibodies to human cytomegalovirus (HCMV) were produced by the fusion of Epstein-Barr virus-transformed B cells and a murine myeloma cell line. The B cells were derived from the peripheral blood lymphocytes of healthy adult volunteers. Four hybridomas producing HCMV-specific monoclonal antibodies were established and each of four antibodies immunoprecipitated an HCMV-specific protein with a molecular weight of 68 kDa. However, the antibodies differed in some of their properties as characterized by indirect immunofluorescence assay and immunoblotting studies, due to the detection of different epitopes on the reacting antigen. None of the four antibodies had any virus neutralizing activity.

Adult

Incidence and properties of renal masses and asymptomatic renal cell carcinoma detected by abdominal ultrasonography.

Renal ultrasonography was performed in 45,905 adults, including 41,364 without any signs suggesting urinary tract malignancies, 1,667 with microscopic hematuria only and 2,874 with some signs of malignancy. Renal lesions were found in 355 adults (0.858%) in the asymptomatic, 39 (2.3%) in the microscopic hematuria and 75 (2.6%) in the symptomatic groups, respectively. Renal cell carcinoma was found in 35 (7.5%) lesions: 19 (5.4%) in the asymptomatic, none in the microscopic hematuria and 16 (21.3%) in the symptomatic groups. A total of 47 patients, including 12 other renal cell carcinoma patients transferred from related hospitals, was grouped into 28 without and 19 with symptoms. Primary tumor size and clinical stages were significantly smaller and lower, respectively, in the asymptomatic group than in the symptomatic group. Radical nephrectomy was performed in all but 2 asymptomatic patients. The 5-year survival rates after nephrectomy were 94.7 and 60.9% for the asymptomatic and symptomatic groups, respectively (p less than 0.01). The results indicate that ultrasonography is a useful tool to detect low stage asymptomatic renal cell carcinoma at low cost.

Carcinoma, Renal Cell

[Continuous arterial infusion chemotherapy in cancer cases followed as outpatients].

Continuous arterial infusion chemotherapy is associated with a significantly greater tumor response rate, though patients must be hospitalized for a long time. This paper describes techniques and our experience with arterial continuous infusion chemotherapy for outpatients using implantable port and ambulatory pump. Eleven patients (liver metastasis of colorectal cancer, hepatocellular carcinoma and local recurrence of rectal cancer) were treated with continuous arterial infusion chemotherapy at our outpatient clinic. The chemotherapy infusions were carried out repeatedly for 5.7 months on average (10-2 months) with 5-FU or CDDP. Total periods of infusions were 64.8 days on the average (136-24 days). The infusion dose and frequency of drug refilling were limited by pump quality. A major complication occurred only in one patient who developed arterial thrombosis. Minor complications were mainly gastrointestinal symptoms (nausea, vomiting) and abdominal pain, which were easily corrected with drugs. The tumor responses were as follows: PR 1 case, MR 1 case, NC 7 cases and PD 2 cases. Home arterial continuous infusion chemotherapy reduced the hospitalized period and helped patients return to work. Therefore it may well contribute to improve the quality of life of cancer patients.

Ambulatory Care

Production of calcification inhibitors by rat calvaria and bone cells in culture.

Inhibition of calcium phosphate crystal formation was assessed in conditioned medium from cultured rat calvaria and rat calvaria cells. The amount of inhibitor activity was measured by determining the amount of hydroxyapatite needed to induce calcium phosphate precipitation in a solution with a constant calcium phosphate supersaturation. Rat calvaria in culture released inhibitor activity. This activity was separated by chromatography on a Bio-Gel P4 column into a high molecular weight (HMW) fraction and a low molecular weight (LMW) fraction. The latter contained, among others, citrate and pyrophosphate (PPi), but the concentration of these was too low to account for the total activity observed. The identity of the HMW and the remaining LMW inhibitors are at present unknown. Various populations of calvaria cells also produced these two types of inhibitors, 20% of the LMW being due to PPi. Fibroblasts produced only the HMW type of inhibitors. These results suggest that cells might control the process of biologic calcification by regulating the amount of inhibitors they produce.

Animals

Detection of cross-reactive antibody to BLV p24 in sera of human patients infected with HTLV.

For detection of antibody to bovine leukemia virus (BLV) major core protein of p24 and cross-reactive antibody in human patients infected with human T cell leukemia virus type I (HTLV-I), monoclonal antibody, D432 against BLV p24 was used by competitive binding enzyme-linked immunoadsorbed assay (ELISA). In sera from cattle with enzootic bovine leukosis (EBL) which were positive for BLV antibodies by immunodiffusion test, 109 out of 112 (97.3%) were positive for BLV p24 antibody by competitive binding ELISA. By using the same procedures, 21 samples from adult T cell leukemia (ATL) patients and healthy carriers with HTLV-I were tested for cross-reactive antibody to BLV p24. All 21 samples were positive for HTLV-I antibodies by immunofluorescence test and/or ELISA. By competitive binding ELISA using non-treated BLV antigens, none of these 21 samples inhibited the binding of the D432. When the BLV antigen was treated by several different denaturation procedures, several HTLV-I positive samples showed the inhibition of the D432 binding and the most effective treatment was by 2-mercaptoethanol (2-ME). Sixteen out of 21 samples showed the presence of cross-reactive antibody against 2-ME-treated BLV antigens. The cross-reactivity of human sample to BLV p24 antigen was further confirmed by Western blotting of the 2-ME-treated BLV antigens. None of the 28 samples from leukemia patients other than ATL which were negative for HTLV-I antibodies showed inhibition of the D432 by the competitive binding ELISA.

Antibodies, Viral

Identification of carpronium chloride and its metabolite in human urine by field desorption mass spectrometry using deuterium labelling.

The identification of carpronium chloride and a metabolite in human urine has been performed by means of field desorption mass spectrometry using deuterium labelling. Essential points in this study are the simultaneous administration of a deuterium labelled drug ([2H9]carpronium chloride), a purification procedure by ion pair extraction with an iodine reagent, and the use of paper electrophoresis to examine the degree of clean-up. The field desorption mass spectra of the purified extracts obtained from sample urine gave a characteristic pattern resulting from the carpronium cation (m/z 160, m/z 169) and a metabolite of the N-(3-carbohydroxypropyl)trimethyl ammonium cation (m/z 146, m/z 155).

Adult

Effects of colchicine on osteoblast in rat: an ultrastructural study.

The present study was an attempt to investigate the effects of colchicine on the ultrastructure of rat osteoblasts with special reference to the microtubular function in vivo. Rats were killed at intervals of 2, 4, 8, 12 and 24 hours after the colchicine injection (0.1 mg per 100 g of body weight, subcutaneously). At 2 and 4 hours after the injection, the secretory granules and small vesicles accumulated in the Golgi area of the osteoblasts. The dilated spherical cisterna of the rough endoplasmic reticulum and the large vacuoles appeared, being located in the periphery of the cell. Microtubules were rarely found in the cytoplasm. Small masses of microfilaments of 80 to 110 A in diameter were found also in the cytoplasm. According to the special staining for collagen, it was indicated that the contents of the secretory granules might be collagen-like materials. At 8 hours after the injection, the shape of the osteoblasts transformed to a round profile and the autophagic vacuoles increased in the cytoplasm. At 12 and 24 hours after the injection, the osteoblasts seemed to be destroyed by the breakdown of the plasma membrane and by the increase of the autophagic vacuoles. It is suggested that colchicine affects the secretory process of the bone matrix and the cytoskeletal system of the osteoblasts by interfering with the structure and the function of the microtubules and colchicine also interferes with the function of the plasma membrane followed by the destruction of the osteoblasts.

Animals

Analysis of drugs by pyrolysis. I. Selected ion monitoring combined with a pyrolysis method for the determination of carpronium chloride in biological samples.

In order to establish an analytical method for carpronium chloride, a parasympathomimetic agent, the pyrolysis reaction of carpronium chloride was examined in a g.c.m.s. system, which revealed that gamma-butyrolactone was produced directly from the drug as the main pyrolysis product. In the case of conversion of [2,2,3,3-2H4]carpronium chloride into the deuterated gamma-butyrolactone, 2H/1H scrambling was observed and confirmed to occur during the pyrolysis process of the deuterated compound. The proportion of gamma-[2H4]butyrolactone among the pyrolysis products was almost independent of the operating conditions, so [2,2,3,3-2H4]carpronium chloride was of practical use as an internal standard for selected ion monitoring. By incorporation of the pyrolysis reaction of carpronium chloride with selected ion monitoring and the use of [2,2,3,3-2H4]carpronium chloride as an internal standard, a rapid, sensitive and selective method was devised for the determination of the drug in biological samples. The method was utilized successfully for the biopharmaceutical studies of carpronium chloride in ma.

4-Butyrolactone