Biomedical subjects
Publications and source records attributed to S Tsuchiya.
Spurious methotrexate (MTX) concentrations in sera and cerebrospinal fluids from leukemia patients who were given trimethoprim (TMP) were estimated using an MTX assay kit which is based on its inhibition of dihydrofolate reductase. The interference of TMP with MTX was confirmed in the assay system. A concentration of 0.17 microgram/ml of TMP gave a value for an apparent MTX of 10 microM.
Acute toxicity, eye irritation, primary skin irritation, skin sensitization, phototoxicity, photosensitization and mutagenicity of sophorolipid derivatives were studied in rats, mice, rabbits, guinea pigs and Salmonella typhimurium strains. The acute oral toxicity of sophorolipid (SL) which Torulopsis bombicola produces, and its derivatives (PSL, Ethyl-SL and Oleyl-SL) were shown to be very low. The LD50 values of PSL ranged from 10 g/kg to 16 g/kg on oral administration in rats and mice, and from 5.8 g/kg to 6.6 g/kg on subcutaneous administration in mice. The oral LD50 values of Ethyl-SL and Oleyl-SL were estimated to be greater than 15 g/kg and that of SL was 12.5 g/kg. In eye irritation study, PSL failed to produce any reactions at 50% concentration even when the rabbit eye was not subsequently washed. SL, Ethyl-SL, Oleyl-SL and Tween 20 were "no irritant" or "slight irritant" to the rabbit eye at 20% concentration. PSL showed no irritancy to both the intact and abraded guinea pig skin at 50% concentration. And in other examinations, it was also indicated that PSL had no potentials of skin sensitization, phototoxicity and photosensitization in guinea pigs and had no potentials of mutagenicity in Salmonella typhimurium TA98 and TA100.
The patient was a 48-year-old woman who had undergone radical surgery for gastric carcinoma in 1981. Seventeen months after the operation, recurrence of gastric carcinoma at the anastomotic stoma was found, and total gastrectomy was performed. Fourteen months after the second operation, she was revealed to have bilateral breast tumors and underwent exploratory excision. Histological examination suggested primary malignant tumor of the breast. Bilateral standard radical mastectomy was done seven days after the excision. Final histological examination revealed metastatic breast cancer originating from the stomach. She died from general metastasis seven months after the radical mastectomy in spite of adjuvant immunochemotherapy.
Twenty-three patients with inoperable non-small cell lung cancer were treated with a combination chemotherapy of CDDP 100 mg/m2, ADM 30 mg/m2 and MMC 8 mg/m2 (PAM). Ten cases were adenocarcinoma, 9 cases were squamous cell carcinoma and 4 cases were large cell carcinoma. In 21 evaluable cases, partial response was obtained in 47.6%. (The response rates were 40.0% in patients with adenocarcinoma, 50.0% in those with squamous cell carcinoma and 66.7% in those with large cell carcinoma.) Leukocytopenia of less than 4,000/mm3 occurred in 100% of cases, thrombocytopenia of less than 100,000/mm3 occurred in 81.0%, and anemia(fall in hemoglobin over 2.0 g/dl) occurred in 66.7%. A transient elevation of Cr (over 1.5 mg/dl) and/or BUN (over 30 mg/dl) was observed in 23.8%. Nausea and vomiting occurred in almost all patients. No death occurred due to toxicity of PAM. These results demonstrate that PAM is an effective combination chemotherapy in patients with non-small cell carcinoma of the lung.
The anticancer agent, Nimustine, which is a derivative of Nimustine hydrochloride (Sankyo CC, Ltd), was suspended in an oil, Lipiodol, using an ultrasonic suspender and used in experimental animals and human subjects with malignant tumor. The use of Lipiodol facilitates the fluoroscopic demonstration of the site into which the suspension has been injected. The Nimustine-Lipiodol suspension was almost stable in room air over 7 days and diffusion of suspended Nimustine into saline in vitro was still noted 4 weeks later. Remarkable regression of tumor size was observed when the Nimustine-Lipiodol suspension was locally injected into the lesion of Lewis lung cancer subcutaneously inoculated into mice. Moreover, a marked regression of tumor size and improvement of CEA level in serum were also obtained when arterial injection of the Nimustine-Lipiodol suspension was carried out in patients with metastatic liver cancer. Therefore, local or arterial injection of Nimustine-Lipiodol suspension is considered to be effective as a method of cancer targeting therapy.
The effect of cefmenoxime (CMX) was evaluated in the abdominal surgery at 18 hospitals on the prevention and the treatment of postoperative infections. The results were summarized as follows. In 179 patients with prophylactic use of 2-4 g of CMX a day, no postoperative infection was observed in 94.4%. Using fever index to judge the effect of CMX in prevention of postoperative infections, the value of fever index was higher in the infected group than in the non-infected group. A significant difference was also observed in mean fever index value between the groups given CMX in 2 g and 4 g daily, being 15.4 degree hours and 1.7 degree hours. The incidence of postoperative infections was higher in cases with intraoperative bleeding of more than 500 ml than in cases with less bleeding. Postoperative infection and peritonitis subsided after the administration of 2-4 g of CMX/day for more than 8 days in 77.1% of cases. Very few side effects were noted due to CMX. These results suggest that CMX is safe and effective in the field of abdominal surgery for the prevention of postoperative infections and in the treatment of postoperative infections.
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A man aged 17 had an amblyopic left eye with central fixation and lost his normal right eye by an accident. After the accident, spontaneous improvement of the visual acuity of the amblyopic left eye was rapid. Just after the accident, overall contrast sensitivity of the left eye was considerably less than that of a normal adult. Improvement of the contrast sensitivity was recorded first at low spatial frequencies and then at high spatial frequencies. However, the contrast sensitivity at medium spatial frequencies remained less than that of a normal adult. These results suggest that lateral inhibitory processes may be relatively undeveloped or receptive fields do not develop to be as small as those of normal adults.
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The distribution of five types of collagen and fibronectin in 6 normal and 9 keratoconus corneas was examined, using immunofluorescent staining and the enzyme-labeled antibody method. Types I, III and V collagens were detected in the corneal stroma. There was essentially no difference between normal and keratoconus corneas in their distribution. Type IV collagen and fibronectin were detected in the basement membrane of the normal corneal epithelium, while in the keratoconus corneas the disruption of the basement membrane as well as the excrescence of basement membrane materials was observed. The abnormal distribution of the type IV collagen and fibronectin was also observed in the anterior stromal area of keratoconus corneas.
The treatment of early colon cancer limited lamina propria mucosa is endoscopic polypectomy. If invasion into the submucosal layer is present, usual colectomy with regional lymph adenectomy is indicated. Colon cancer without distant metastasis is treated by colectomy with regional lymph adenectomy. Right hemicolectomy, transverse colectomy, left hemicolectomy, and sigmoidectomy are indicated according to the location of the cancer. Five years survival rate for curative resection in 96 personal cases was 80.8%. Palliative resection was available to prolong the survival time. Mean survival time after palliative resection was 14 months, but in unresectable case it was 4 months.
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A human cell line established from a patient of an acute monocytic leukemia (THP-1) retained an ability to synthesize and secrete plasma apolipoprotein E like protein. The protein was identified with monospecific antibody raised against human plasma apolipoprotein E. The cells also secreted lipoprotein lipase (EC 3.1.1.34). The enzyme was characterized as lipoprotein lipase on the basis of the requirement of apolipoprotein C-II as an activator and the inhibition of its activity by sodium chloride. The secretion of both apolipoprotein E and lipoprotein lipase was markedly enhanced in the process of differentiation into macrophage-like cells by the addition of 4 beta-phorbol 12 beta-myristate 13 alpha-acetate.
A successful transplantation of soybean agglutinin (SBA) and sheep red blood cell (SRBC)-fractionated, maternal marrow in a patient with severe combined immunodeficiency (SCID) is reported. The engraftment of HLA-haplotype mismatched marrow cells was obtained without apparent graft versus host disease (GVHD). With immunological reconstitution the patient recovered from a BCG infection, which might have been caused by a BCG inoculation before his bone marrow transplantation.
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The IgG2a monoclonal antibody TH-1, which reacts specifically with blood group A1 but with neither A2 nor O erythrocytes, has been established. The antibody reacted only with A1 erythrocytes in hemagglutination and antibody absorption assays; it did not react with A2 erythrocytes, even after trypsin or sialidase treatment. This antibody detected, on TLC immunostaining, a series of glycolipids from A1 erythrocytes but virtually none or very weak bands from A2 erythrocytes. It did not react with type 1 or type 2 chain A, or with globo-A. The simplest reactive component was isolated from a previously assigned Ab fraction by HPTLC of acetylated compounds. The structure of the reactive component was characterized by 1H NMR spectroscopy, methylation analysis, and enzymatic degradation, as shown below: (Formula: see text). The structure is essentially a repetitive A epitope attached to type 2 chain and is hereby called type 3 chain A. The determinant can be carried on extended and/or branched structures, but it was not detectable in glycoproteins. The structure was characteristic of A1 erythrocytes and present in only trace amounts in A2 erythrocytes. The precursor H (Fuc alpha 1----2Gal beta 1----3GalNAc alpha 1----3[Fuc alpha 1----2]Gal beta 1----4GlcNAc beta 1----R; type 3 chain H) was present in greater quantity in A2 erythrocytes than in A1 erythrocytes, but it was absent in both O and B erythrocytes. The A1 transferase apparently can transfer alpha-GalNAc to type 3 chain H, while the A2 transferase may not have this ability.
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The two spectrally distinguishable bound forms of 2-(4'-hydroxyphenylazo) benzoic acid (HABA) on bovine serum albumin (BSA), i.e, the azo and hydrazone forms, were suggested to form ion pairs with basic amino acid residues in our previous study. Arginine (Arg), lysine (Lys), tyrosine (Tyr) and tryptophan (Trp) were modified to estimate the amino acid residues participating in the formation of an ion pair with HABA. Decrease of the binding of only hydrazone form was observed following modification of Arg residues. The modification of Lys, Tyr and Trp residues caused no decrease in binding to either form. However, the induced circular dichroism (CD) spectra of HABA bound to N- and O-acetylated BSA were reversed at 360 and 440 nm, respectively. But two bands of these spectra were capable of taking on the same shape of the spectra of native BSA only by O-deacetylation. The induced CD spectra of bound HABA by Trp modified BSA changed as if the bound amounts of the azo form were increased. The binding sites of the azo form may possibly be situated in the vicinity of Trp 212 on the tertiary structure.