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Biomedical subjects

T Taguchi

Publications and source records attributed to T Taguchi.

At least 811 records · Page 45Linked to original sources

[Subrenal capsule assay for chemosensitivity test (II)--Sequential changes in the implanted tumor tissue and histological findings].

We carried out fundamental subrenal capsule assay methodology, using tumor specimens of human cancer xenografts (breast cancer and colon cancer) serially transplanted into nude mice. With regard to sequential changes in the tumor grafts implanted under the renal space of immunocompetent mice, tumor size was largest macroscopically around day 6 after inoculation, and later involuted gradually. Histological findings showed that implanted tumor tissues were preserved to a moderate extent until day 4 after inoculation, but leukocyte infiltration by host reaction had begun by day 4, and tumor tissues were almost replaced by host reactive tissues on day 6. Labeling index scoring did not indicate growth of implanted tumor cells. We found that macroscopic tumor size was largest around day 6 because we measured tumor size with involved leukocyte infiltration, and the macroscopic tumor did not represent the true extent of the tumor tissue.

Animals↗

[Fundamental evaluation of the subrenal capsule assay as an in vivo chemosensitivity test].

Histological analyses of the subrenal capsule assay (SRCA) carried out with modification of Bogden's original method revealed that the major portion of cancer tissue implanted were almost replaced by the host immune cells and reactive tissue by day 6. For the purpose to find a more improved condition, the following experiments were performed using human cancer lines xenografted in nude mice. No prominent differences in the host reaction to xenograft were found between 3 kinds of immunocompetent mice. Subrenal space of the athymic nude mice allowed cancer tissue to grow well until 15 days after inoculation, and then chemosensitivity test to judge the growth inhibition rates. The similar condition as in nude mice was achieved in CDF1 mice by daily injection of 60 mg/kg of cyclosporin A.

Animals↗

Long-term prognosis and prognostic indices of IgA nephropathy in juvenile and in adult Japanese.

For a comparative study of IgA nephropathy occurring in Japanese adolescents and adults, the clinical and histological findings and prognosis (follow-up period; 12 +/- 6 years for children and 10 +/- 5 years for adults) were compared. The subjects studied included 98 children and 86 adults. Development into renal failure occurred in 9 children (9.2%) and in 20 adults (23.3%), (p less than 0.01). The actuarial renal survival rate at year 10 after the onset of glomerulonephritis in children and adults was 95% and 80%, respectively, and at year 20, 82% and 50%, respectively. The prognosis was definitely better in the children and this was attributable to the observation that (1) the glomerular injury at the initial biopsy in children was less extensive than in adults; (2) the frequency of complication with hypertension was lower in children (27.6%) than in adults (41.9%), (p less than 0.05); (3) hypertension was one prognostic indice, even in children, after age 30; (4) after age 40, aging and arteriosclerosis were more contributory than hypertension to the progress of IgA nephropathy; and (5) the quantity of intraglomerular immune deposits and the period of deposition were not related of prognostic indices. Thus, in the long-term prognosis of IgA nephropathy in both children and adults, immunological disorders seem to have little influence while factors such as hypertension, arteriosclerosis and aging play important roles.

Adolescent↗

[Subrenal capsule (SRC) assay as a chemosensitivity test (IV)--Evaluation of the SRC assay method as a system for growing implanted tumor-xenografts].

Using tumor specimens of human cancer serially transplanted in nude mice, we examined fundamentally the subrenal capsule assay method in order to improve the subrenal space as an area where implanted tumor-xenografts persistently grow. Host reaction in immunocompetent mice treated with cyclosporin A (CsA) (60 mg/kg subcutaneously, daily) was suppressed almost completely, and tumor-xenografts persistently grew similarly to those implanted under the renal capsule of BALB/c-nu/nu mice. CsA treatment, 30 mg/kg given subcutaneously; daily, or 60 mg/kg subcutaneously; every other day, could not suppress the host reaction. Bredinin treatment, 200 mg/kg subcutaneously; every other day, or 100 mg/kg subcutaneously; daily, could not suppress the host reaction also, and tumor-xenografts implanted under the renal capsule were rejected.

Animals↗

Structural-functional correlations in serial biopsies from patients with glomerulonephritis.

It has been proposed that interstitial fibrosis is causally related to a progressive decrease in glomerular filtration rate (GFR), in patients with various renal diseases. We examined the relationship between morphological and functional parameters in 200 samples from 74 patients with mesangial proliferative glomerulonephritis. The glomerular lesion was semiquantitatively analyzed using the Glomerular Index (GI). Interstitial volume (IV) was determined by the point-counting method. Both GI and IV showed a significant negative correlation with Ccr and a positive correlation with serum creatinine. The serial change in IV from the first to the last biopsy (delta IV) showed a weak but significant negative correlation with those in Ccr, over the same period (delta Ccr). The serial change in GI (delta GI) did not correlate with delta Ccr. There was a significant positive correlation between GI and IV and between delta GI and delta IV. These data confirmed a cause-and-effect relationship between interstitial damage and GFR and also showed that the glomerular lesion as well as the interstitial change play an important role in the deterioration of renal function. Thus, the interstitial lesion alone should not be emphasized as a determinant of renal function, as we noted a close correlation between the interstitial and glomerular lesion. Interstitial damage is apparently secondary to the glomerular lesion in patients with mesangial proliferative glomerulonephritis.

Adolescent↗

[Damaging action of human recombinant TNF on tumor vessels as an aspect of its anti-neoplastic action against Meth A sarcoma in mice].

Effect of human recombinant TNF (rHu-TNF) on tumor blood vessels was investigated in relation to its mode of anti-neoplastic action against Meth A sarcoma in BALB/c mice. The extent of the blood vessel lesion was evaluated by measuring the degrees of blueing and hemorrhage after intravenous injection of Evan's blue. When injected intravenously into mice bearing Meth A cells in the abdominal skin transplanted 8 days previously, rHu-TNF, at doses of 3000 and 10,000 units/mouse produced dose-related lesioning of blood vessels in the sarcoma and the adjacent skin but not in the skin distant from the sarcoma. Similar lesioning of blood vessels in the adjacent skin was seen after intravenous administration of 10,000 units/mouse of rHu-TNF in mice with the sarcoma in which the cells had been selectively killed by intratumoral injection of acetic acid (20%, 0.01 ml). On the other hand, rHu-TNF (10,000 units/mouse, i.v.) produced weak lesioning of blood vessels in the granuloma tissue caused by subcutaneous implantation of felt pellets and in the adjacent skin but not in the operation wound in mice with the sarcoma. These results suggest that rHu-TNF damages newly formed blood vessels, particularly those connected with the sarcoma, without influencing blood vessels in normal skin and healing wounds in mice with Meth A sarcoma.

Animals↗

[Blocking factors in human blood which inhibit the cytotoxicity of lymphocytes].

The cytotoxicity of human peripheral blood lymphocytes against malignant tumor cell lines was significantly inhibited by human plasma or sera. In addition to so-called blocking factors such as antigens, antibodies, antigen-antibody complexes, IAP and ferritin, some substances which could be removed by heat or centrifugation were considered to play a significant role.

Antibody-Dependent Cell Cytotoxicity↗

[Inhibitory effect of human plasma on 17-1A-dependent cellular cytotoxicity].

Mouse monoclonal antibody 17-1A-dependent cellular cytotoxicity hardly revealed any killer activity in the presence of human plasma, nor did 17-1A show complement-dependent cytotoxicity. ADCC of 17-1A-armed effector cells was also inhibited by human plasma. These results were caused by the inhibition of 17-1A binding to the Fc receptors of effector cells.

Antibodies, Monoclonal↗

[A phase II study of 590-S (1-phthalidyl-5-fluorouracil) in patients with breast cancer--multi-center cooperative study--Cooperative Study Group of 590-S in Breast Cancer].

A phase II clinical study involving 16 institutions was performed for the treatment of breast cancer with 590-S, a new masked fluoropyrimidine derivative. A dose of 900 mg/day was administered orally for more than 4 weeks. Out of 33 cases enrolled, 18 were completely recorded and evaluable. The response rate was 33.3%: 2 CR and 4 PR. It was noteworthy that, out of 12 cases previously treated with other 5-FU derivatives, 5 cases (41.7%) were judged as effective. Of 26 cases, side effects were observed in 8 (30.8%). All of these were gastrointestinal disorders such as nausea, vomiting, and loss of appetite. 590-S is considered to be a useful antitumor agent. However, further investigation will be required.

Administration, Oral↗

Mass screening for colorectal cancer by testing fecal occult blood.

The validity of screening for colorectal cancer by testing for occult blood on 2 successive days was evaluated over a 2-year period beginning April 1980 by testing 9449 individuals without symptoms. The Shionogi slide (Shionogi Pharmaceutical Co., Osaka, Japan), a commercial guaiac-impregnated slide with moderate sensitivity, was used for screening subjects under dietary restriction. Of the 1401 persons (14.8%) who had a positive reaction for occult blood, 858 (61.2%) received further diagnostic examinations, and 265 of them proved to have one or more abnormalities of the gastrointestinal tract. Colorectal cancer was detected in 11 persons and polyps in 91 persons. Eight of the cancers were in an early stage. This screening method was found to be suitable for large-scale mass screening, and appears to have high diagnostic value.

Adult↗

Clinical studies of recombinant interferon alfa-2a (Roferon-A) in cancer patients.

A Phase I study of interferon alfa-2a was conducted in 20 patients with disseminated cancer to establish the relationship between dose and interferon-related side effects. Fever was the most common side effect, and was not dose-related. Other side effects not related to dose included flu-like symptoms, gastrointestinal symptoms, and numbness of fingers and toes. A dose-response relationship was seen for leukopenia, thrombocytopenia, and the elevation of serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT). A Phase II study was then conducted in 641 patients to evaluate the efficacy of interferon alfa-2a in a number of disseminated malignant neoplasms. The 415 male and 226 female patients, almost all of whom had malignancies refractory to standard therapy, were treated with interferon alfa-2a at an initial daily dose of 3 X 10(6) U for 3 days. Doses were increased gradually at 3- to 7-day intervals until the therapeutic dosage was established. The daily dose could not exceed 50 X 10(6) U, and treatment was continued for at least one month. Efficacy rates, for 65 patients who achieved partial or complete responses, based on the total number of evaluable patients by cancer type were: 11/49 (22.4%), multiple myeloma; 4/21 (19%), lymphomas; 15/108 (13.8%), renal cell carcinoma; 2/30 (6.6%), bladder cancer; 4/39 (10.2%), brain tumors; 5/26 (19.2%), melanoma; 12/12 (100%), cutaneous lymphoma; 10/19 (52.6%), other skin cancers; 2/30 (6.6%), bone and soft tissue sarcomas. Overall, 65/371 (17.5%) of evaluable subjects responded.

Antibody Formation↗

Quantitative analysis of urinary glycine conjugates by high performance liquid chromatography: excretion of hippuric acid and methylhippuric acids in the urine of subjects exposed to vapours of toluene and xylenes.

A new method for the direct determination of hippuric acid (HA) and o-, m- and p-methylhippuric acids (MHAs) in the urine, metabolites of toluene and o-, m- and p-xylenes by high performance liquid chromatography (HPLC) is described. A stainless-steel column packed with silica gel having dinitrophenyl residue and a mixed solution of methanol/water/acetic acid (80/20/0.2) containing tetra-n-butylammonium bromide (0.2% w/v) as mobile phase was used. Concentrations of HA and MHAs were estimated from their peak height at a wave length of 225 nm. Urine can be analyzed directly without solvent extraction or pretreatment to obtain complete separation of HA and o-, m- and p-MHAs. Urine samples from male workers exposed to toluene or xylenes were analyzed for HA or MHAs. The urinary levels of HA and MHAs increased by exposure to toluene and xylenes in proportion to the environmental concentrations of the solvents, although there is a considerable variation in metabolite concentrations. The slope of regression line between toluene and HA and that between m-xylene and m-MHA were similar. The urinary concentrations of HA and MHAs corresponding to 100 ppm (TLV) of toluene was 2.35 g/g creatinine and that of m-MHA corresponding to 100 ppm (TLV) of m-xylene was 2.05 g/g creatinine. The warning levels of the urinary metabolite concentrations of a group of workers and that of an individual worker corresponding to TLV of organic solvent concentration is discussed.

Adult↗

Postoperative adjuvant chemotherapy for gastric cancer, the second report. Analysis of data on 2873 patients followed for five years.

The effectiveness of combination chemotherapy with mitomycin-C (MMC) plus futraful (N1-(2'-tetrahydrofuryl)-5-fluorouracil), as an adjunct to surgery for gastric cancer was investigated in a prospective randomized controlled study. Three thousand and thirty-three Japanese patients in 344 hospitals were entered and 2873 could be followed for 5 years. All patients had undergone gastrectomy from April 1977 to May 1979 and were assigned, at random, to either Groups A, B or C. In Group A, bolus MMC was administered with no further treatment. In Group C, oral futraful was given for one year, without MMC induction. In Group B, both a bolus MMC injection and oral futraful were prescribed. This randomized study showed no statistical difference in the 5 year survival rate among the three groups. However, in patients given MMC and put on oral futraful for one year, the 5 year survival rate for those with stage III gastric cancer or for those with positive lymphnode metastasis plus obvious serosal invasion seemed to be improved.

Adult↗