Biomedical subjects
Publications and source records attributed to M Chigira.
We report a case of an aneurysm of a persistent sciatic artery which caused buttock pain. Preoperative diagnosis is very difficult. However, awareness of the presence of this rare embryonic abnormality is important, especially in elderly persons with atherosclerotic changes. Sagittal magnetic resonance imaging (MRI) was very useful in reaching this diagnosis.
The differences in the protein expression of cyclins, cyclin-dependent kinases (cdks), and their inhibitors and cdk kinase activities were examined in serum dependent (SD) and independent (PF) clones of the murine fibrosarcoma cell line, Gc-4. The expression of cyclin A in SD was minimal in contrast to PF. Furthermore, cdk2 kinase activity in PF was remarkably lower than that in SD, yet the G1/S transition in PF appeared normal. PF was also resistant against the selective inhibitor of cdk2, butyrolactone I. These findings suggest that tumor cell proliferation and tumor progression can be promoted by the activation of a molecule(s) downstream of cdk2.
Transplantation can be considered as an artificial reconstitution of symbiosis called chimera, since the donor and recipient carry different DNAs. In successful transplantation, engrafted tissues and cells should be recognized as self by the immune system, as shown in external pathogens. The external milieu introduced by transplantation and infection can only be immunologically recognized as self when it forms a symbiotic relationship with somatic cell society. Immunological identity is a posteriori educated recognizing immunological self and genetic self may be ignored in self-recognition. For example, transplanted bone marrow immunocytes recognize somatic cell society which is selected previously by other immunological standards as self. Dissociation between genetic self and immunological self originates in the development and differentiation of multicellular organisms a priori, since alteration of DNA sequences is necessary in the development and differentiation of multicellular organisms and symbiosis is the essential nature of it.
Self-recognition by the immune system is a basic mechanism of vertebrates. Mechanisms of antigen presentation by somatic cells are based on the coupling of small peptides produced in cytoplasm and major histocompatibility complex major histocompatibility complex. The antigen pumps, including major histocompatibility complex, can present various internal molecules which are possible targets of autoimmunity, using a peptide binding mechanism. The antigen pump can transfer external signals by autoantibody and cellular immunity without a specific receptor system. This self-declaration mechanism continuously presents 'self' rather than 'non-self'. It is qualitatively impossible to differentiate self antigens from non-self antigens in this process at all. Somatic cell society is non-self for germ line DNA, since germ line DNA is symbiotic with somatic cell society. Consequently, non-self can be recognized through self-declaration.
Normal immunocytes including T and B cells are equilibrated by a reciprocal attacking mechanism called a network. Continuous disequilibrium of this network results in general immunodeficiency with oligo- and polyclonal hyperimmunity, for example, T-cell activation due to spontaneous reticuloendotheliosis, paraneoplastic autoimmune syndromes, and human immunodeficiency virus infection. In these disorders, reciprocal self-reactivity, including autologous graft-versus-host reaction, plays a role in the immunodeficiency. A priori self-targeting immunity is a key mechanism to explain autoimmunity in the acquired immunodeficiency syndrome. In the treatment of the immunodeficiency due to hyperimmunity, I propose immunological suppression by agents and reconstitution of the network by bone-marrow transplantation.
In bending, the mechanical strength of tubular bone can be estimated by the area moment of inertia (I) = 1/4 x pi x (R4 - r4) (R: external radius, and r: internal radius). Mechanical strength of bone is dissociated from bone density, since radiological density is different from inertia. When the cross-sectional area is constant (C = R2 - r2) in this equation, inertia can be expressed by the equation of (I) = 1/4 x pi x (2Cr2 + C2). Inertia increases with increases of the external and internal radii. According to the above equation, increase of inertia depending on the expansion of radii is inevitable 'optimization' of bone mass. Expansion of the radii of tubular bone with the decrease of wall thickness is an adaptation process rather than the 'decompensation' called osteoporosis. Senescence of individuals as manifested in conditions such as osteoporosis is a stampede of adaptations rather than decompensation of it.
Blood-group antigens have been developed as a self-declaration mechanism in higher organisms, since blood cells carry different DNA from that of germ-line cells, and their selfishness must be strictly limited. If not, symbiosis between somatic DNA and germ-line DNA cannot be maintained since blood cells can express autonomy programmed within themselves. For the sake of maintenance of symbiosis, this self-declaration is not limited to blood cells and all somatic cells need a self-plural declaration mechanism such as blood-group antigens. Differentiation and development including induction and inhibition also depend on the self-declaration--recognition mechanism.
We treated 23 simple bone cysts by the multiple drill-hole method and reviewed them a mean of 5 (2-10) years later. 11 cysts were located in the humerus, 9 in the femur, 2 in the tibia, and 1 in the pubis. The cysts recurred in 15 cases after the initial operation. 12 recurrent cysts were treated with reoperations. At the follow-up, good bone formation with no sign of recurrence was seen in 15 cases. A residual cyst was found in 8 cases, but further treatment was not considered necessary.
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.
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.
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.
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.
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.
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.
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.
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Preincubation of Dunn osteosarcoma cells for 1 h with both 100 nM of staurosporine and 10 micrograms/ml of genistein resulted in a significant decrease in the motility stimulated by autocrine motility factor (AMF), whereas these reagents did not affect the basal motility and proliferation at these concentrations. The effect of the agents on the stimulated motility was both dose- and time-dependent. The motility stimulated by the anti-AMF receptor mAb was also inhibited. In contrast, H-8 had a negligible effect upon the stimulated motility. These data suggest that both kinase C and tyrosine kinase play a role in AMF-stimulated cell motility, while protein kinase A, which is selectively associated with the adenylate cyclase pathway, may not be required for the stimulation.
We describe a simple bone cyst in a patient who had an osteoblastic lesion which had been discovered 1 1/2 years earlier. Curettage and drilling proved effective treatment. We suggest that increased regional blood flow, in association with bone formation, produces a hydrodynamic disorder followed by venous obstruction leading to the formation of a bone cyst.