Biomedical subjects
Publications and source records attributed to M Chigira.
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.
We describe a 53-year-old Japanese woman with absence of the posterior arch of the atlas. Computed tomography revealed that the residual posterior fragment which was displaced to the right side does not correspond to a rare ossification center in the midline and that there was no clear mass of the posterior arch except for a small fragment. Moreover, the midline center was not demonstrated as a soft tissue mass. Easy tilting of the posterior fragment on flexion-extension movement suggests that the cartilaginous arch was not present between the lateral masses and the posterior fragment of the atlas. These observations support the hypothesis that hypoplastic development of the arch plays a major role in the pathogenesis of this anomaly rather than incomplete ossification. Abnormal segmentation of the vertebrae may be implicated in the etiology of this condition, since fusion of the anterior vertebral masses between the C5-6 levels, as shown in Klippel-Feil syndrome, is also observed.
We have previously shown that a protein-independent growing fibrosarcoma, Gc-4 PF has a high motile response to its cultured medium, which is associated with an increase in expression of gp78, a cell surface receptor for autocrine motility factor (AMF). Here we show that the cultured medium contains two motile activities, acidic and basic AMFs with regard to binding features on ion exchange chromatography. These two AMFs were purified by sequential DEAE anion exchange, CM cation exchange, and gel filtration chromatographies. However, both acidic and basic AMFs have a similar size of 55 kDa and 65 kDa under non-reducing and reducing conditions, respectively, with the same pI of 6.5. The stimulated motility of both AMFs was inhibited by the pertussis toxin (PT), but not by Streptomyces hyaluronidase. These two AMFs significantly stimulated the lung colonizing properties of the self-producing cells by 1.5-fold. These results suggest that both acidic and basic AMFs may correspond to the previously reported AMF and confirm directly that the AMF-gp78 signaling pathway is involved in cell motility associated with metastatic property.
From the viewpoint of evolution, mammalian immunity has been developed to prevent invasion by foreign bodies including parasites and microorganisms and not to survey oncogenesis. The surveillance system on oncogenesis has been lost in the evolutionary process from amphibians to mammals. The essential duality between developmental antigens and tumor specific antigens is important in explaining what the target of self-defense mechanisms is. This duality between self-defense and defense against foreign bodies originated from invertebrates as shown in insects. Immunity has been developed to survey retrodifferentiation of somatic cells and to drive the developmental process in organogenesis. Under these conditions, the clonal deletion theory of immunocyte differentiation will lose its teleological meaning. Also, the hypothesis explaining self reactivity of immunity by the immune system recognizing only an 'internal image' composed of an idio-antiidio network of immunocytes and antibodies is overly pedantic.
Preservation of the identity of DNA is the ultimate goal of multicellular organisms. An abnormal DNA sequence in cells within an individual means its parasitic nature in cell society as shown in tumors. Somatic gene arrangement and gene mutation in development may be considered as de novo formation of parasites. It is likely that the developmental process with genetic alterations means symbiosis between altered cells and germ line cells preserving genetic information without alterations, when somatic alteration of DNA sequence is a major mechanism of differentiation. According to the selfish gene theory of Dawkins, germ line cells permit symbiosis when somatic cell society derives clear profit for the replication of original DNA copies.
Organ- and tissue-specific metastases have been proposed as an alteration of invasion, translocation through vascular channels, lodgment, and local proliferation. However, experimental metastasis without tumor formation at the primary site can not be explained by these hypotheses. We hypothesize here that tumor cells heterotopically express homeobox genes as a marker of their location, and that they translocate elsewhere according to positional information encoded in these genes.
Transient osteoporosis is observed regionally in several disorders including demineralization of femoral head, migratory osteolysis, and sympathetic osteodystrophy. Predominant radiologic feature of these disorders is widening of medullary cavity without increase of external diameter of bone. Although, the exact mechanism of loss of bone mass in these disorders is not clearly demonstrated, it is suggested that sympathetic nerve, hormonal imbalance, arterial blood supply, and venous congestion play important roles in the pathogenesis of these disorders. It may be necessary to demonstrate these local causes of transient osteoporosis in order to show the exact mechanism of systemic osteoporosis.
OBJECTIVE: To examine whether a cytokine, autocrine motility factor (AMF), plays a role in rheumatoid arthritis (RA). METHODS: We investigated the chemokinetic activity of synovial fluids (SF) obtained from patients using a unique protein-free culture fibrosarcoma Gc-4 PF, the motility of which is specifically dependent on the cytokine. RESULTS: Treatment of the cells with the SF stimulated their phagokinetic motility by 1.4, 1.8, and 2.1-fold at protein concentrations of 100, 250 and 500 micrograms/ml, respectively. This dose dependent response was observed in all 3 patients with classical or definite RA. In contrast with Gc-4 PF cells, the SF did not stimulate the motility of Gc-4 SD cells that have little response to AMF. The ability of this chemokinetic activity to block binding of the monoclonal antibody to the receptor for AMF was demonstrated on immunoblots. CONCLUSION: Based on these results, it is suggested that the motile activity may be AMF. The possible role of the cytokine in the pathogenesis of RA is discussed.
The motile response of serum-dependent (Gc-4 SD) and protein-independent (Gc-4 PF) murine fibrosarcoma cells to monoclonal antibody (MAb) that binds to gp78 a cell-surface receptor (M(r) 78,000) for an autocrine motility factor (AMF) was analyzed. The Gc-4 PF cells responded to the anti-gp78 by increased motility in vitro (3-fold) and increased lung colonization in vivo (8- to 20-fold), while the serum-dependent counterpart failed to respond to motile stimulation both in vitro and in vivo. Immuno-analysis of cell-surface expression and cell extracts revealed a smaller amount of gp78 in Gc-4 SD cells than in Gc-4 PF cells. Both cell lines secrete an equal amount of AMF to the culture media. Our results suggest that protein-free culture of Gc-4 PF cells is associated with high response to AMF and with high expression of its receptor, and that autonomous motile regulation may play a role in tumor dissemination.
We report five cases of irregularity of the apophysis of the ischial tuberosity (Kremser's disease). In four, plain radiographs showed that the density of the radiolucent area increased within several months of a minor injury. Serial computerised tomography demonstrated new bone formation across the widened apophyseal plate, although there was no change in the shape or density of the apophysis itself. The separation repaired and remodelled spontaneously within a year. In one case, CT showed that the apophyseal ossification centre was smaller than that on the opposite side. Our findings showed that in four cases the irregularity of the apophysis of the ischial tuberosity may have been caused by an avulsion fracture, but the appearance in the fifth case was a normal variant of the ossification centre.
We report a case of sternal segment dislocation in a child. Although the segment was rotated 90 degrees it was completely remodeled. We now believe that no surgical treatment is necessary for this condition.
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.
Carcinogenesis is functionally a deletion alteration rather than addition of genetic information. Repressor genes may be more sensitive to 'neutral' mutations of DNA than those of structural genes, since selection pressure for deletion of repressors is extremely low in multicellular organisms. Dysfunction of repressors caused by genomic mutation induces autonomic expression of structural genes which is programmed a priori in each cell. Tumor progression can be explained by this deletion model with abnormal DNA repair. Alteration of DNA repairing units may be the initial mutation in carcinogenesis.
So-called 'limited life span' of diploid cells does not depend on their unresponsiveness to growth factors from the data obtained by complete protein-free culture of tumor cells. Limited proliferation (called limited life span) of diploid cells is one of the 'ad-hoc' negative regulatory mechanisms in animals, and can not be differentiated from other inhibitory mechanisms called 'tumor suppression' and 'terminal differentiation'. Metabolic imbalance induced by proliferation-dependent time-bomb mechanisms including infidelity of DNA repair is suggested to explain limited proliferation of cells. After maturation, autonomic progression of negative regulators in cells is induced by no prohibition of terminal differentiation, since organisms prepare no programs to stop development and differentiation. It is an attractive hypothesis that a proliferation-dependent time-bomb has been developed to control organogenesis for maturation and to determine body size. It is true that limited proliferation of cells can not explain longevity of individuals, although the so-called longevity genes play roles in ageing. Teleologically, longevity of individuals has been developed to produce genetic heterogeneity according to the selfish gene theory. This inter- and intra-species genetic heterogeneity increases the probability of selfish gene replication in germ cell line. After maturation and reproduction of DNA in germ cell line, individuals as vehicles for the DNA can be discarded by the 'selfish' genes.
Locomotion of tumor cells and its regulation are thought to be crucial for metastasis. Autocrine motility factor (AMF) is a cytokine which stimulates in vitro motility and in vivo lung-colonizing ability of tumor cells via a receptor, a cell surface glycoprotein of 78kD (gp78)-mediated signaling pathway. AMF induces gp78 internalization to intracellular tubulovesicles including lysosome and transport to the leading edge. The AMF-gp78 complex internalization from the cell surface is involved in control of cell motility during metastasis.
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.
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.
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.