Search PubMed⌕ Search

Biomedical subjects

Y Ohtsuka

Publications and source records attributed to Y Ohtsuka.

At least 235 records · Page 13Linked to original sources

Synergistic cytotoxicity of recombinant human TNF and various anti-cancer drugs.

A synergistic increase in the cytotoxic effects of recombinant human tumor necrosis factor (rH-TNF) and anti-cancer drugs was demonstrated in vitro. The cytotoxicity of rH-TNF against L-M cells in combination with Mitomycin C (MMC), Adriamycin (ADM), Cytosine arabinoside (Ara-C), Actinomycin D (ACD), Daunomycin (DM), Cisplatin (CDDP), Vincristine (VCR), and 5-Fluorouracil (5FU), based on the concentration necessary for 50% inhibition of cell growth (IC50), was 4 to 347 times as high as that of rH-TNF alone. The results suggest that combination therapy including rH-TNF and anti-cancer drugs may be of value in the treatment of malignancy in human patients.

Antineoplastic Agents↗

Swelling of the cauda equina in patients who have herniation of a lumbar disc. A possible pathogenesis of sciatica.

Morphological changes in the cauda equina in patients who have herniation of a lumbar disc have not been previously reported, to our knowledge. Using computed tomographic myelography, we found swelling of nerve-root elements in the cauda equina that corresponded to the affected root in seventeen of twenty-eight patients who had proved herniation of a lumbar disc. All seventeen patients had severe sciatica. The swelling of the nerve-root elements gradually returned to normal after surgical decompression, which was also associated with improvement of the sciatica. Patients who did not have severe sciatica did not show swollen nerve-root elements. These findings may be an important clue to the mechanism of sciatic pain in patients who have herniation of a lumbar disc.

Adolescent↗

Fracture of the posterior margin of a lumbar vertebral body.

Using computed tomography, we studied twenty-nine patients who had thirty-one fractures of the posterior margin of a vertebra in the lumbar spine. Based on our findings, these fractures were classified morphologically into three types: a simple separation of the entire margin; an avulsion fracture of some of the substance of the vertebral body, including the margin; and a more localized fracture. In this series, twenty-two of the thirty-one fractures were associated with a defect involving the affected end-plate. This fact suggests that the pathogenesis of these fractures may be the fragility of the end-plate.

Adolescent↗

Estimation and characterization of glycosylated carbonic anhydrase I in erythrocytes from patients with diabetes mellitus.

Glycosylated form of carbonic anhydrase isozyme I was found in human erythrocytes. The percent of glycosylated enzyme of the total erythrocyte carbonic anhydrase I of patients with diabetes mellitus was significantly higher than that from normal controls. Characterization of the glycosylated carbonic anhydrase I was studied using an enzyme purified from diabetic patients. The glycosylated enzyme showed a slightly acidic isoelectric point in comparison with that of a nonglycosylated enzyme. The specific activity of the glycosylated enzyme was approximately 40% of that of the normal enzyme, and the immunological activity decreased to 52% of that of the normal enzyme. Estimation of carbohydrates which may form a ketoamine linkage with the enzyme was studied using [3H]-labelled glycosylated enzyme synthesized by incubation of the enzyme with [3H]-D-glucose in vitro, and it was found that one mol of glucose binds to one mol of enzyme. Exposure of red cells to a higher concentration of glucose in diabetics brought about glycosylation of carbonic anhydrase, which is associated with its low activity enzymatically and immunologically.

Adult↗

Erythrocyte-oxidized glutathione transport in pyrimidine 5'-nucleotidase deficiency.

The oxidized form of glutathione transport was studied in human erythrocytes in pyrimidine 5'-nucleotidase (P5N) deficiency, a disorder in which the amounts of CTP and UTP in the erythrocytes are elevated. The inhibition of ATP-requiring oxidized glutathione (GSSG) transport by CTP and UTP is believed to play a role in elevating the levels of the reduced form of glutathione (GSH) in the erythrocytes of patients with P5N deficiency. The current investigation was undertaken to determine if GSSG transport actually decreases in the erythrocytes of such patients. Erythrocytes from a 17-year-old patient and a 13-year-old patient with P5N deficiency hemolytic anemia and from ten normal subjects were used as materials for the experiment. Erythrocytes, which had been previously incubated with [3H]glycine, were incubated at 37 degrees C, and the rate of [3H]GSSG transported by the cells was estimated. The velocity of GSSG transport out of the erythrocytes was quite low in the patients, 3.17-3.65 nmol GSSG/ml erythrocytes/hr at 37 degrees C in one case, and 3.30 nmol GSSG/ml erythrocytes/hr in the other case, vs that in the normal controls (6.00 +/- 0.80 nmol GSSG/ml erythrocytes/hr; mean +/- SD). The activity of gamma-glutamylcysteine synthetase and glutathione synthetase did not decrease in the patients. Decreased transport activity of GSSG in addition to a normal synthesis rate for GSH may explain the increased concentration of erythrocyte GSH in P5N deficiency.

5'-Nucleotidase↗

The early-infantile epileptic encephalopathy with suppression-burst: developmental aspects.

A clinico-electroencephalographic study on 14 cases of the early-infantile epileptic encephalopathy with suppression-burst (EIEE) including long-term follow-up studies for one year 8 months to 12 years 2 months disclosed the specificity of EIEE in its developmental aspects. With age, clinical evolution from EIEE to the West syndrome was observed in as many as 10 cases, among which two cases showed further transition to the Lennox-Gastaut syndrome. Electroencephalographically, suppression-burst pattern gradually began to disappear from age of 3 months and disappeared by 6 months in all the cases, transforming to hypsarhythmia in 10 cases from 2 to 6 months of age, showing further transition to diffuse slow spike-and-waves in 2 cases at one year and one month and at 3 years and one month of age, respectively. Changing pattern of EEG were classifiable into two types which strongly related to the prognosis. These findings indicated EIEE to be an independent epileptic syndrome as the earliest form of the age-dependent epileptic encephalopathy.

Electroencephalography↗

Treatment of the West syndrome with high-dose pyridoxal phosphate.

Fifteen (12.7%) among 118 cases of the West syndrome were effectively treated by high-dose pyridoxal phosphate (PAL-P). 1) Clinical seizures were completely suppressed in 12 cases with PAL-P alone, and in 3 cases by an addition of PAL-P to the previously poorly-effective regimen. At the follow-up, 12 cases have continued to be free from seizures, while two cases relapsed into the Lennox-Gastaut syndrome, and one died. 2) Electroencephalographically hypsarhythmia disappeared by PAL-P in all 15 effective cases. 3) Effective daily dose of PAL-P was 30 to 400 mg. 4) Notably, PAL-P was effective even in the cases with obvious organic brain pathology, such as tuberous sclerosis, porencephaly, holoprosencephaly, postmeningitis, besides 5 idiopathic cases. 5) Efficacy of PAL-P was significantly higher in idiopathic cases than symptomatic cases; 35.7% vs 9.6%. 6) Response to PAL-P was not predictable by any laboratory data nor clinical features. 7) Prognosis of PAL-P responsive cases was favorable; as many as 6 cases developed normally among 14 cases followed-up. Treatment with a high-dose PAL-P should be tried in all cases of the West syndrome at first.

Administration, Oral↗

Erythrocyte insulin receptor in insulin autoimmune syndrome: effects of corticosteroid therapy.

Changes in the erythrocyte insulin receptors were studied in a patient with insulin autoimmune syndrome before and after corticosteroid therapy. In this case, despite a quite low fasting plasma glucose value (29 mg/100 ml), a 75 g oral glucose tolerance test (OGTT) showed a diabetic curve and extremely high immunoreactive insulin (IRI) levels were observed. After 6 months duration of the disease, corticosteroid was given to the patient and hypoglycemic attacks disappeared with an improvement of the levels of plasma glucose. The number of insulin receptors decreased from 58 to 29 sites/erythrocyte and an increase in binding affinity or maximal binding ability were observed after the treatment with corticosteroid. These receptor changes, for the most part, might be derived from the steroid effects, since there were similar results when we administered steroid for a long term to a certain disease. There was a 20% reduction in the amount of insulin binding IgG purified from the serum one month after treatment with corticosteroid as compared with that purified from the serum before the treatment. The results suggest the usefulness of corticosteroid therapy in treatment of the insulin autoimmune syndrome.

Aged↗

[Clinical evaluation of MMC-mc-chemoembolization therapy and its combination with UFT in hepatocellular carcinoma].

A retrospective comparative study was done on the management of hepatoma: MMC-mc-chemoembolization therapy (group A; 9 patients) vs. the same therapy in combination with UFT as a maintenance therapy (group B; 8 patients). The six-month survival rate was 44.4% for group A, and 87.5% for group B. Generalized Wilcoxon test for the whole period revealed that the survival was favorable for group B as compared with A (P = 0.048). For adverse reactions in UFT therapy, no subjective signs occurred, but objective ones appeared such as one case of leukocytopenia, one of thrombocytopenia and 3 of increased GOT. However, no cessation of UFT therapy was necessary in these patients. These findings suggested that maintenance therapy with UFT may be favorable in this type of treatment for hepatoma.

Adult↗

[Analysis of the signalling pathway of TNF in normal cells and tumor cells].

The internalization process and intracellular distribution of 125I-labeled TNF, in L-M (murine tumorigenic fibroblasts, highly sensitive to TNF cytotoxicity) cells and in HEL (human embryonic lung cells, non-sensitive to TNF cytotoxicity) cells bearing TNF receptor, were elucidated by pulse-chasing and by Percoll density gradient centrifugation. Effect of TNF treatment on the RNA and protein synthesis of target cells was also studied using 3H-UDR and 35S-methionine incorporation. In both L-M and HEL cells, receptor-bound 125I-TNF was rapidly internalized and delivered to lysosomes within 15-30 min, followed by degradation and release into the culture medium. RNA synthesis and protein synthesis were not affected by TNF treatment in HEL cells, but marked stimulation (3.5 times and 4.2 times, respectively) was observed in L-M cells.

Animals↗

[Anti-tumor effect and mechanism of action of the tumor necrosis factor (TNF)].

TNF is cytokine derived from macrophages and shows much promise for use in cancer therapy because of its marked antitumor effects and its high specificity to tumors. The clinical application (Phase I-II) of TNF has been started because human recombinant TNF (rH-TNF) can be produced on a large scale. In spite of notable antitumor effects, little is known concerning the mechanism of its cytotoxic action. In this article, the antitumor effects of rH-TNF against human and murine tumors, the mechanism of its action and the synergistic effects of rH-TNF in combination with IFN-gamma, various anticancer drugs or with hyperthermia are reviewed.

Cell Line↗

[The synergistic effect of human recombinant TNF in combination with various anti-cancer drugs].

The synergistic effect of human recombinant TNF in combination with various anti-cancer drugs was examined in vitro. In vitro treatment of L-M cells with TNF and mitomycin C (MMC), adriamycin (ADM), cytosine arabinoside (Ara-C), actinomycin D (ACD), daunorubicin (DM), cisplatin (CDDP), vincristine (VCR), or 5-fluorouracil (5-FU) revealed a synergistic cytotoxicity. However, the combination of TNF with bleomycin (BLM) failed to show such a synergistic effect.

Animals↗

Phagocytosis of latex particles by leucocytes. I. Dependence of phagocytosis on the size and surface potential of particles.

A series of latex particles, having different sizes and surface structures, were prepared and the dependence of phagocytosis of latex particles by leucocytes on the particle size and surface potential was investigated by measuring the oxygen consumption of leucocytes. Most of the phagocytic behaviour in the initial stages can be explained by susceptibility of particles to heterocoagulation i.e. attachment of small particles (latex particles) onto large particles (leucocytes) by the colloidal attractive force between the two kinds of particles. Specific behaviour for fine particles seems to be attributed to the contribution of steric stabilization by the hydrated layer on the particle surface and to the inability for the leucocytes to recognize very fine particles as foreign materials.

Humans↗