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Biomedical subjects

M Chigira

Publications and source records attributed to M Chigira.

At least 19 recordsLinked to original sources

Apoptosis of a fibrosarcoma induced by protein-free culture involves DNA cleavage to large fragments but not internucleosomal fragmentation.

A murine fibrosarcoma clone, Gc-4 SD, grows depending on fetal calf serum. In MTT assay, protein-free cultivation resulted in a reduction of the viable cell number time-dependently. Electron-microscopic and flow-cytometric analyses revealed that the reduction in growth was accompanied by the appearance of apoptotic cells. However, no internucleosomal fragmentation was observed even after SI-nuclease treatment. On the other hand, pulse field gel electrophoresis revealed that cleavage of DNA into high-molecular-weight fragments estimated as 50 to 150 kilobase pairs (kbp), with a peak of 100 kbp, was found in the serum-deprived cells. Large fragments disappeared from the DNA extracts when the smaller cells with high blue fluorescence with Hoechst 33342 were removed by flow cytometry, suggesting direct correlation between the large DNA fragmentation and apoptosis. The addition of aurintricarboxylic acid neither abolished the large DNA fragmentation nor inhibited the reduction in the number of viable cells. Both cycloheximide and actinomycin D enhanced the reduction in the number of viable cells as well as the large DNA fragmentation. These results suggest that apoptosis of a fibrosarcoma induced by protein-free culture involves a specific endogenous endonuclease, which may be distinct from and independent of the ATA-sensitive endonuclease producing internucleosomal DNA fragmentation.

Animals

Amino acid phosphatase activity of alkaline phosphatase. A possible role of protein phosphatase.

Alkaline phosphatase (ALP) hydrolyzed phosvitin and amino acid phosphates demonstrating nonisotropy at different pH. Orthovanadate, a protein phosphatase inhibitor, more specifically inhibited the serine and tyrosine phosphatase activities of ALP than that of threonine phosphatase at concentrations > 0.1 mM or 0.01 mM, respectively. Calyculin A and okadaic acid at increased concentrations increased ALP amino acid phosphatase activity. Bisphosphonates, such as disodium-1-hydroxy-1-aminopropylidine-1,1-diphosphonate (APD) and ethane-1-hydroxy-1,1-diphosphonate (HEBP), at increased concentrations, inhibited ALP amino acid phosphatase activity. These results suggest that ALP may function as a protein phosphatase. In terms of protein kinase inhibitors, N-[2-(methylamino)ethyl]-5-isoquinolinesulfonamide, N-(6-aminoheyxl)-5-chloro-1-naphthalenesulfomide hydrochloride and 4',5,7-trihydroxyisoflavone had little effect on ALP amino acid phosphatase activity. Staurosporine slightly enhanced ALP serine and threonine phosphatase activities at a concentration of 0.1 mM. These results suggest that protein phosphatase activity does not depend on the protein kinase activity of ALP, since duality between the former and the latter is not supported. ALP may function less as a protein kinase than as a protein phosphatase. The coupling mechanism of phosphate dynamics may be regulated indirectly.

Alkaline Phosphatase

Multiple neurilemmoma in both legs. A case report.

A Japanese man, who was 61 years of age, presented with multiple neurilemmoma in both legs which had arisen from different levels of both sciatic nerves. There were no clinical findings relating to von Recklinghausen's disease in the patient or his siblings. Multiple neurilemmoma may be the result of embryonic metameric anomalies. The condition may be distinguished from von Recklinghausen's disease by the distribution of the lesions and genetic analysis.

Humans

Possible cardiac side effects of granisetron, an antiemetic agent, in patients with bone and soft-tissue sarcomas receiving cytotoxic chemotherapy.

The cardiac effect of granisetron, a selective 5-hydroxytryptamine3 receptor antagonist, on 12 patients with bone and soft-tissue sarcomas treated by cytotoxic chemotherapy consisting of multiple courses was examined. Of the 12 patients, 4 showed significant electrocardiographical changes, including sinus bradycardia, integral change of P-waves, junctional escape beat, and atrioventricular (AV) block with Wenckebach phenomenon, indicating stimulatory regulation of the vagus nerve. These changes were observed in each patient after several courses of chemotherapy but not in the first course. There was no correlation between the electrocardiographical changes and the chemotherapeutic agents used or the type of tumor present. A patient with osteosarcoma showed persistent bradycardia in three courses, all protocols of which contained high-dose methotrexate. From these findings we conclude that the cardiac responses may be due to stimulated activity of the vagal efferent nerve, which is regulated reflexly by afferent nerve activity suppressed by granisetron. On the other hand, the antiemetic efficacy of granisetron was satisfactory. These results suggest that careful observation of the heart is necessary when granisetron is used, especially for chemotherapy consisting of repeated multiple courses.

Adolescent

Morpho-densitometry of bone using a trigonometric function.

When long bone is considered to be a tube-like structure filled up with a homogenous material, single-directional densitometry of it separately shows cortical and medullary bone mass using a trigonometric function at any given section. Both bone masses can be differentiated from each other using the values of peak bone density and central bone density. This densitometry is based on the two-dimensional structure of long bone. This principle can be universally applied to skeletal disorders including osteoporosis, metabolic bone disorders, and bone tumors in which the mineral content is altered. Dynamic changes in calcium metabolism can be analyzed serially without any invasion at low cost.

Absorptiometry, Photon

Irregularity of the apophysis of the ischial tuberosity evaluated by magnetic resonance imaging.

OBJECTIVE: To report the findings of magnetic resonance imaging (MRI) in two cases of apophyseal irregularity of the ischial tuberosity. PATIENTS AND METHODS: The authors describe the MRI findings for two males who presented with pain of sudden onset in the buttock. Both patients were examined by radiography, MRI and computed tomography, and one underwent bone scanning. RESULTS: On T1-weighted images, signal intensity was decreased in both the apophysis and the body adjacent to it; however, the signal intensity on T2-weighted images was increased. These findings are consistent with avulsion fracture of the apophysis. CONCLUSION: The MRI findings in these cases may support the previously suggested hypothesis that apophyseal irregularity with characteristic radiographic changes over time is caused by avulsion fracture of the apophyseal line. The relation between the characteristic radiographic features and the structural changes associated with fracture in this condition is discussed.

Adolescent

[Combination effect of pirarubicin, ifosfamide, and vincristine sulfate in the treatment of advanced synovial sarcoma--report of a case].

Synovial sarcoma with pulmonary metastases appeared to be sensitive to multiagent chemotherapy of Pirarubicin, Ifosfamide, and Vincristine Sulfate. However, this chemotherapy regimen could not be continued because of severe hemorrhagic cystitis due to the toxicity of Ifosfamide. Even in the advanced stage, this multiagent chemotherapy would be useful for the treatment of synovial sarcoma, if hemorrhagic cystitis could be prevented.

Adult

Osteosarcoma with multiple skeletal metastases. A case of "nonstochastic" metastasis.

Osteosarcoma of the thoracic spine developed in a 15-year-old Japanese boy. After his first admission with paralysis, multiple skeletal metastases were demonstrated in the absence of pulmonary metastasis. This rare condition may possibly be considered as a unicentric osteosarcoma with bone metastases, since there were no precursor lesions or history of exposure to radioactive materials or chemical agents. These multiple lesions may be an example of so-called "organ-specific metastasis," although this "nonstochastic" process is rare.

Adolescent

Multivariate analysis of serum tumor markers for diagnosis of skeletal metastases.

Serum tumor markers, including carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), carbohydrate antigen 15-3 (CA 15-3), carbohydrate antigen 19-9 (CA 19-9), cancer antigen 125 (CA 125), and tissue polypeptide antigen (TPA), were measured in 26 patients with skeletal metastases and 11 patients with primary malignant bone tumors. TPA, which was elevated in 16 patients (61.5%), was the most sensitive marker for detection of skeletal metastases. Combined measurement of these markers was useful in detecting skeletal metastases from primary lesions, although tumor markers had little organ specificity. In addition, skeletal metastases could be completely differentiated from primary lesions by the use of multivariate discriminant analysis of markers. The most and least powerful discriminating factors were AFP and CA 19-9, respectively. On multidimensional scaling, the distance between AFP and CEA was longest, with the other markers scattered between them. Expression of individual markers can not be linked to that of other markers.

Antigens, Neoplasm

Remodeling of large bone defects in the treatment of space-occupying lesions. Curettage without bone graft for treating benign bone tumors.

Curettage without bone graft was performed in 17 patients with benign bone tumors and tumor-like lesions. New bone formation with uniformly increased radiodensity appeared in serial plain radiographs within 3 months after the operation. The average period before full weight could be borne on the lower extremities was 14 weeks. Computed tomography revealed that the central part of the bone lesions persisted without bone formation. The thickening of cortical bone was predominant. These data indicate that enough mechanical strength for daily activity will be recovered by bone within 4 months after curettage without any filler, although remodeling continues for over a year. It is suggested that bone graft and implantation of "biomaterials" are not necessary in patients, especially younger ones, with benign bone tumors or tumorous conditions.

Adolescent

Toxicity of silica-containing calcium phosphate glasses demonstrated in mice.

Suspensions of calcium phosphate glass containing various concentrations of silica (glass composition (moles): 100 Ca(PO3)2 to x SiO2,x = 0, 5, 10, 15 or 40) dispersed in normal saline were injected intraperitoneally into C57BL/6 mice to determine the mortality within 30 days. The mortality was 0/10, 3/10, 9/10, 10/10 and 10/10 at x = 0, 5, 10, 15 and 40 mol of silica, respectively. By means of inductively coupled plasma analysis, the amount of dissolved silica (Si4+) in water at 37 degrees C from the calcium phosphate glass depended on the amount of silica in the glasses. The mortality of mice was directly proportional to the silica content of the glass injected intraperitoneally. These results clearly show that the dissolved silica (Si4+) from the glass, monomeric or low molecular silicic anion, is highly toxic. The SiO2 component in biomaterials has toxic potential when dissolved in the body.

Animals

Freedom from wholism in multicellular organisms: a possible role of tumor suppressor genes.

Wholism, known as 'homeostasis' in multicellular organisms, is fundamentally expressed in the regulation of cell proliferation and of the metabolism of individual cells. Control mechanisms represent an overriding control of the autonomy of cells in multicellular organisms. Negative regulation by suppressor genes including tumor suppressor genes is essential to maintain homeostasis in these organisms. Without wholistic regulation, the cellular society of multicellular organisms would progress from bad to worse, with eventual destruction of the whole system. The enhancement of division and differentiation of cells transduced by water-soluble factors may be considered as the controlling structure on the tumor suppressor genes. In microevolution, cell killing by the immunosurveillance systems directed at the external environments has been avoided for the 'self' cells in general, since the multicellular organism may not be considered as only a crowd of single cells.

Animals

[Diagnosis of skeletal metastases by serum tumor markers].

Levels of serum tumor markers including CEA, AFP, CA 15-3, CA 19-9, CA 125 and TPA were measured in 26 patients with bone metastases and in 9 patients with primary bone tumors. TPA was the most sensitive marker to detect skeletal metastasis being elevated in 15 of the 22 patients (68.2%). High sensitivity was observed in CEA (46.1%), CA 15-3 (40%), and CA 125 (35%), and AFP showed relatively low sensitivity (4.3%). When elevation of TPA only or elevation of more than two tumor markers including TPA was used as a screening test for skeletal metastasis, over-all sensitivity, specificity, and accuracy were 73.1%, 88.9%, and 81% respectively. No definite correlation between the markers could be seen in this study. A combination of serum tumor markers was useful in the differential diagnosis of bone metastases from primary bone lesions. However, organ specificity of the markers were relatively low.

Adolescent

[Roentgenographic and computed topographic observations on benign bone tumor and tumor-like lesions treated by simple curettage without bone grafting].

Curettage without bone graft was performed in fifteen patients with benign bone tumors and tumor-like lesions. We studied the bone formation after curettage by plain radiography and computed tomography for six or more months. Average period before full-weight-bearing in thirteen patients of the lower extremities was three and a half months. We found no pathological fractures after curettage in any of the patients. Increases in radiodensity and reconstruction of the bone were observed in serial plain radiographs within three months. Computed tomography revealed that the center of the lesions persisted without bone formation, although thickening of cortex bone was predominant. From the data obtained here, it appears that bone grafts may not be necessary in patients, especially in younger ones, with benign bone tumors and tumor-like lesions.

Adolescent

Diagnostic value of serum tumor markers in skeletal metastasis of carcinomas.

Levels of serum tumor markers including tissue polypeptide antigen (TPA), CA 15-3, CA 19-9, squamous cell carcinoma antigen, carcinoembryonic antigen, alpha-fetoprotein, and PAP were measured in 26 patients with bone metastasis and in 9 patients with primary bone tumors. More than one markers was elevated in 19 of the 26 patients with bone metastasis, although there was no elevation of the markers in 3 patients with renal cell carcinoma. TPA was the most sensitive marker in the diagnosis of metastasis. CA 15-3 was also a sensitive marker in this study, since metastasis from breast carcinoma may be the most common of all metastases in the skeleton. On the other hand, alpha-fetoprotein was uniformly unresponsive except in one case of gastric cancer. Combinations of markers are valuable for metastasis screening tests. No definite correlations were found between the markers in this study. On the other hand, there was a slight elevation of the markers observed in two of the nine patients with primary bone lesions. Serum tumor markers are useful in the diagnosis of bone metastasis to differentiate it from primary bone lesions. Especially in solitary bone lesions, serum markers may be the only way to make a differential diagnosis between the two.

Antigens, Neoplasm

No correlation between tumor markers and prognosis under polygenic control systems.

Tumor markers in serum should not be correlated with the prognosis of patients with malignant tumors, although the markers indicate the presence of tumors, since marker levels and prognosis are controlled independently by poly-genes. Furthermore, prognostic factors, including incidence of pulmonary metastasis, tumor growth rate, tumor drug sensitivity and host response, vary among patients. In general, tumor markers may be used to demonstrate response of tumor to treatments only when expression of the markers does not change in a time-dependent manner.

Biomarkers, Tumor