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Biomedical subjects

T Todoroki

Publications and source records attributed to T Todoroki.

At least 109 records · Page 6Linked to original sources
PubMed1986

Effect of fractionated irradiation prior to conservative and radical surgery on therapeutic gain in a spontaneous fibrosarcoma of the C3H mouse.

The efficacy of fractionated irradiation given preoperatively was examined using early generation isotransplants of a spontaneous fibrosarcoma (FSaII) growing in the right leg of syngeneic C3Hf/Sed mice and employing as endpoints local tumor control probability, normal tissue damage (5 mm leg shortening), and distant metastasis. Complete dose response assays have been performed on small (4-5 mm) and large (8 mm) tumors. TCD50s (the dose that on average would be expected to control half the irradiated tumors) for radiation given in five equal doses (1 day between treatments) were 93.6 and 111.8 Gy for the 4-5 and 8-mm tumors, respectively. Surgery was performed under a dissecting (8X) microscope at 5-6 days after the completion of irradiation. For small tumors, radical (en bloc) and conservative (local) resection alone achieved 69.8 (30/43) and 21.9% (7/32) tumor control, respectively. The corresponding figures for large tumors were 25 (8/32) and 6.1% (2/33), respectively. Preoperative irradiation increased tumor control rate up to 100% at dose levels much lower than TCD50 for radiation alone. Enhancement ratios (ER) were computed for preoperative radiation as follows: TCD50 for radiation alone/TCD50 for radiation and surgery. ERs were computed for local and en bloc resection for tumor control and for leg shortening. From these ER values, therapeutic gain factors (TGF) were then computed for local and en bloc resection for tumor control and for leg shortening. From these ER values, therapeutic gain factors (TGF) were then computed as ER tumor response/ER leg shortening. In small tumors, the TGFs (TCD80 and leg shortening of 5 mm) were 2.1 and 2.0 for conservative and radical resection, respectively. Corresponding figures for large tumors were 1.5 and 1.5. In this experimental system for small and large tumors, radiation treatment prior to conservative surgery achieved a comparable therapeutic gain to that by combining radiation with radical surgery. No effect of preoperative fractionation on the frequency of distant metastasis was observed.

Animals↗
PubMed1986

Superoxide generation by synovial fluid neutrophils enhanced by immune complexes and suppressed by rheumatoid factor in synovial fluid.

Synovial fluid (SF) from patients with rheumatoid arthritis (RA) enhanced superoxide generation by neutrophils isolated from RA SF, in contrast to SF from patients with osteoarthritis. These superoxide generation-enhancing substances may be intermediate-sized immune complexes and a complement C5-derived fragment. Rheumatoid factor (RF) isolated from RA SF suppressed superoxide generation-enhancing activity of aggregated IgG. Therefore, biologically active RF may block the interaction of the immune complexes with neutrophils accumulating in RA SF, and protect the joint tissue from the effects of oxygen radicals or proteases.

Antigen-Antibody Complex↗
PubMed1986

Conversion to adipocytes of a clonal bone marrow preadipocyte line (H-1/A) and fatty acid composition of the resultant adipocytes.

Conversion to adipocytes and fatty acid composition were investigated in a clonal bone marrow preadipocyte line (H-1/A). The growing cells exhibited a fibroblastic appearance. After the cessation of growth, triacylglyceride (TG) synthesis in the cells increased as they incorporated precursor from the growth medium and became adipocytes. Hydrocortisone and insulin accelerated the TG synthesis in H-1/A cells in a dose-dependent manner when they were cultured in the growth medium containing 10% horse serum. The rate of conversion to adipocytes was reduced as the concentration of horse serum was decreased, and this reduction was not influenced by the addition of insulin and/or hydrocortisone. These results suggest that conversion to adipocytes of H-1/A cells is primarily dependent on some component(s) of the serum. Conversion to adipocytes of the cells may involve a process of differentiation since the conversion was completely inhibited when the cells were cultured in the presence of bromodeoxyuridine. Fatty acid composition was significantly different between adipose H-1/A cells and adipocytes derived from other marrow preadipocyte line MC3T3-G2/PA6 cells. Unsaturated fatty acids accounted for 76% of the fatty acid composition of adipose H-1/A cells; in contrast, saturated fatty acids constituted 65% of the fatty acid composition of the adipose MC3T3-G2/PA6 cells. These results suggest that there is a heterogeneity of preadipocytes in bone marrow. These two preadipocyte lines thus provide a useful tool for the study of marrow adipocytes and can also be used to analyze the hematopoietic microenvironment through studies of the effect of these cells on hematopoietic cell proliferation.

Adipose Tissue↗
PubMed1986

Surgical treatment for carcinoma at the confluence of the major hepatic ducts.

During the period of November 1976 through October 1984, we have treated 46 patients with carcinoma at the confluence of the major hepatic ducts. Curative resection of the tumor (where no carcinoma cells at the margin of the resected portion were found macroscopically and microscopially), was performed upon ten patients, palliative resections were done in 11, palliative resection and intraoperative radiotherapy (IOR) in ten, bile duct drainage and IOR in three, and percutaneous transhepatic cholangiodrainage in 12. Among the ten patients who underwent curative operation, five are living six to 104 months after operation while the remaining five died four to 72 months postoperatively. Of the 11 patients who underwent palliative resection, five are alive two to 22 months after operation and six died between four and 20 months after operation. For the ten patients with carcinoma in the advanced stages, palliative resection with IOR was performed. Eight patients died 20 days to 16 months after operation while two patients are alive 13 and 14 months after the procedure. Of the three patients who underwent drainage of the bile duct and IOR, two died three months after operation and one patient survived 34 months. Twelve patients underwent drainage of the bile duct only and all died after 13 months. To perform a curative operation for carcinoma located at the confluence of major hepatic ducts, it is necessary to resect the right or left lobe, including the caudate lobe, in many instances. For the patients with carcinoma in the advanced stages, the possibility of long term survival period after operation exists through the use of the combined techniques of IOR and palliative resection of the tumor.

Adult↗
PubMed1985

Rationale for combining surgery and radiation therapy.

The combination of radiation and surgery is being employed increasingly in preference to radical surgery alone or high radiation dose alone in the treatment of malignant epithelial and mesenchymal neoplasms. The basis for this interest is that the scope of the surgery and/or the radiation dose level are less than if either were employed alone. A reduction in treatment related morbidity, improved cosmetic and functional status, and in some instances a lower local failure rate may be achieved by this approach. The rationale for combining radiation and surgery is that radiation at moderate dose levels is effective in the eradication of microscopic extensions of tumor beyond the clearly obvious mass while the surgery (usually more conservative) removes the principal mass.

Combined Modality Therapy↗
PubMed1985

Cell cycle analysis using numerical simulation of bivariate DNA/bromodeoxyuridine distributions.

This report describes a mathematical model of cell proliferation for simulation of bivariate DNA/bromodeoxyuridine (BrdUrd) distributions. The model formulates the change with time in the frequency of cells with any DNA content and in the amount of incorporated BrdUrd, according to given cytokinetic parameters, i.e., durations and dispersions of cell cycle phases and DNA synthesis rate during S-phase. We have applied this model to sequential DNA/BrdUrd distributions measured for Chinese hamster ovary cells asynchronously grown in vitro, 1) for 30 min in 10 microM BrdUrd followed by growth in BrdUrd-free medium for 0 to 24 h, or 2) during continuous incubation in 3 microM BrdUrd plus 30 microM thymidine for 2 to 24 h. The matches between the experimental and simulated distributions give the G1, S, G2M, and total cell cycle durations (and coefficients of variation) of 5.6 h (0.08), 7.0 h (0.07), 1.4 h (0.16), and 14.0 h (0.05), respectively. The model is shown to be useful for quantitative interpretation of the bivariate distributions.

Animals↗
PubMed1985

Therapeutic advantage in preoperative single-dose radiation combined with conservative and radical surgery in different-size murine fibrosarcomas.

The efficacy of surgery alone or combined with preoperative radiation was examined using isotransplants of the spontaneous fibrosarcoma (FSaII) growing in the right leg of syngeneic C3Hf/Sed mice and employing as end-points both local tumor control probability and normal tissue damage. Complete assays have been performed on small (4-5 mm) and large (8 mm) tumors. The TCD50s (the dose required to control half the irradiated tumors) for radiation alone were 63.2 and 82.7 Gy for small and large tumors, respectively. Surgery was performed 4 days after the radiation treatment. Surgical resections were performed under an 8 X dissecting microscope. In small tumors, radical (enbloc resection) and conservative (local resection) surgery alone achieved 69.8% (30/43) and 21.9% (7/32) tumor control. The corresponding figures for large tumor were 25% (8/32) and 6.1% (2/33), respectively. The combination of radiation and surgery increased tumor control frequency up to 100% with doses lower than TCD50 for radiation alone. The TGF is expressed as therapeutic gain factor for conservative and for radical surgery for 4-5-mm and for 8-mm tumors from analyses of dose response curves for tumor control and leg shortening. In small tumors, the TGFs at the 80% tumor control (TCD80) and leg shortening of 5 mm were 1.4 and 1.8 for radical and conservative resection, respectively. The TGFs at the TCD50 level for large tumors were 1.4 and 1.7 in respective resections. In this particular experimental system, conservative surgery yielded higher TGFs than radical surgery for both tumor sizes. No effect of preoperative treatment on the frequency of distant metastasis was observed.

Amputation, Surgical↗
PubMed1985

Mouse lymphoma L1210 cells can be arrested in the G1 phase by adjusting cellular cysteine and glutathione.

Mouse lymphoma L1210 cells (NCI line) that have low ability to take up cystine became deficient in cellular cysteine and glutathione in normal culture media. The cells entered the resting state during culture when they were seeded at high cell densities. They remained viable and were mostly present in the G1 or G0 phase. In the growth-arrested state, the cellular glutathione content was one order of magnitude lower than in the exponentially growing phase in the presence of 2-mercaptoethanol. In the arrested state, DNA synthesis was almost inhibited, and RNA and protein synthesis decreased markedly. Transfer of the cells to medium containing 2-mercaptoethanol, which improves the utilization of cystine by these cells, produced the rapid recovery of RNA and protein synthesis. DNA synthesis slowly increased, reaching a maximum after a lag period.

Animals↗
PubMed1984

Improved assay for alcohol dehydrogenase activity in serum by centrifugal analysis.

We describe an improved method for determination of alcohol dehydrogenase (EC 1.1.1.1) activity in 60 microL of human serum, based on conversion of ethanol to acetaldehyde with simultaneous reduction of NAD+ in glycine NaOH buffer (pH 9.0) at 37 degrees C in a centrifugal analyzer. The final concentration of NAD+ was 10 mmol/L and ethanol was 20 mmol/L. The dilution curve was linear with enzyme activity up to 200 U/L, and results by this method correlated well with those by a manual method (N Engl J Med 279: 241-248, 1968). Within-run precision (CV) was 0.9 to 8.2% over the range of 4.5 to 88.1 U/L, and day-to-day precision was 5.4 to 5.6%. In sera from 198 healthy individuals, mean alcohol dehydrogenase activity was 1.6 (SD 1.2, range 0-5) U/L. To evaluate the clinical utility of determining alcohol dehydrogenase, we measured the activity of alanine aminotransferase and alcohol dehydrogenase in sera from 470 patients with various diseases in our hospital, and found that results for the two enzymes did not correlate well.

Adult↗
PubMed1983

Serum factors from patients with systemic lupus erythematosus enhancing superoxide generation by normal neutrophils.

It has been suggested that human neutrophils exposed to performed immune complexes or activated complement fragments generate O2- anions in extracellular medium. In vivo studies have revealed that oxygen intermediates produced by immune complex-activated neutrophils play an important role in subsequent tissue damage. Since it is difficult to obtain direct evidence that O2- is released into plasma in patients with systemic lupus erythematosus (SLE), we studied the capacities of their sera to stimulate O2- release by human neutrophils in vitro. Sera from patients with SLE significantly enhanced O2- generation by neutrophils compared to normal sera. The enhancing activity of serum in the induction of increased O2- generation correlated positively with the presence of serum immune complexes and negatively with serum complement levels. The enhancing factors were analyzed by serum fractionation on Sephadex G-200 gel filtration, and were concluded to be immune complexes of intermediate size containing an activated complement fragment.

Cytochrome c Group↗
PubMed1982

[Tissue concentration of 5-FU following pre-operative administration of FT-207].

Forty patients with gastric cancer and 30 patients with colon cancer were administered FT-207 prior to the operation. The relation between a total dose (4-88g) and tissue concentration of 5-FU was investigated and the following results were obtained. (5-FU concentration was measured with the method of Gas chromatography mas fragmentography) 1) The relation between total doses of FT-207 (x) and concentration of 5-FU in the tissue (y) was demonstrated by the formula: y = 0.00317x + 0.025 (gastric cancer) r = 0.519, p = 0.0001 y = 0.0019x + 0.043 (colon cancer) r = 0.641, p = 0.0001 2) In most of the patients with rectal cancer who received radiation therapy prior to the operation, 5-FU concentration in the tissue was extremely low. 3) 5-FU concentration showed no difference between the normal and metastatic lymph nodes, or among the lymph node groups. Administration methods (oral intake or suppository) had no influence on the concentration of 5-FU. 4) Among the organs, 5-FU concentration was higher in the following orders: liver, normal mucosa, lymph node, tumor, normal serosa. 5) In five autopsy cases, 5-FU concentration of the tissue show a great difference among them, and some cases showed 10 times as high concentration as others in the tissue of every organ.

Female↗
PubMed1982

Enhanced radiation lethality in partially synchronized solid mouse tumors.

We studied the combined effects of local irradiation on in vivo partially synchronized solid mouse tumors. Syngeneic fibrosarcoma cells were transplanted s.c. into the thighs of C3H/He mice. When the tumors grew to 179 cu mm in volume, 1-beta-D-arabinofuranosylcytosine (ara-C) was repeatedly injected i.p. followed by a single injection of vinblastine sulfate at 5 hr after the end of the ara-C treatment. The mitotic indexes increased from 4% in control to 22 to 23% at 5 hr after the ara-C treatment, and the level continued for another 5 hr. Further treatment with vinblastine sulfate after the ara-C injections resulted in more effective accumulation of mitotic cells, i.e., 30% at the sixth hr. The tumor was locally irradiated with a single dose of 3000 rads of gamma-rays at the maximum level of mitotic index. The results indicated a synergistic inhibition of tumor growth and an 84% prolongation of the 50% survival day beyond that of the nontreated control mice.

Animals↗