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K Shibuya

Publications and source records attributed to K Shibuya.

At least 145 records · Page 8Linked to original sources

Effects of pegylated recombinant human megakaryocyte growth and development factor on thrombocytopenia induced by a new myelosuppressive chemotherapy regimen in mice.

Thrombopoietin, the endogenous c-Mpl ligand, is a novel lineage-specific hematopoietic factor that plays a pivotal role in the regulation of megakaryocytopoiesis and thrombopoiesis. In this study, we examined the effects of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF), a truncated molecule of recombinant human c-Mpl ligand derivatized with polyethylene glycol, on myelosuppressive chemotherapy-induced thrombocytopenia in mice. We developed a new murine model of thrombocytopenia induced by i.v. injections of mitomycin C (MMC) for two consecutive days. In control mice, platelet counts began to decrease on day 6, reached a nadir of less than 5% of basal level on day 14, and could not recover to basal level by day 26. Administration of PEG-rHuMGDF greatly enhanced recovery of the number of megakaryocyte progenitor cells and the megakaryocytes in bone marrow, and markedly reduced the severity of thrombocytopenia; it also accelerated platelet recovery in a dose-dependent manner in myelosuppressed mice. Mice receiving consecutive administration of higher doses of PEG-rHuMGDF showed no thrombocytopenia but rather had platelet counts being increased over basal level. Although absolute neutrophil counts and red cell counts also were decreased following MMC treatment, administration of PEG-rHuMGDF also improved neutropenia and anemia. Administration of PEG-rHuMGDF on alternate days or once a week after chemotherapy was almost as effective as consecutive administration in improving thrombocytopenia. Combined administration of PEG-rHuMGDF and rHuG-CSF had an additive effect on improvement of thrombocytopenia and neutropenia. These results suggest that PEG-rHuMGDF is a therapeutically effective agent in the treatment of thrombocytopenia associated with chemotherapy.

Animals↗

Effects of recombinant human granulocyte colony-stimulating factor on the growth potential of two murine myeloid leukemias.

We investigated the in vitro and in vivo effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on the proliferation of two murine leukemic cell lines. The rhG-CSF stimulated leukemic colony formation of the promyelocytic leukemic cell line L-8801 in methylcellulose culture and increased the number of L-8801 cells in liquid culture. However, rhG-CSF treatment prolonged the median survival period of mice implanted with L-8801 cells and the emergence of the leukemic blast cells in peripheral blood. Meanwhile, rhG-CSF had no influence on that of the megakaryoblastic leukemic cells L-8057 and failed to prolong the median survival period of L-8057 leukemic mice. Receptor binding analysis revealed that L-8801 cells expressed a G-CSF receptor (Kd=125 pM, 479 binding sites/cell) and L-8057 cells had no G-CSF receptors. Then, we examined the growth potential of these cells. The median survival period was longer for mice implanted with L-8801 cells cultured with rhG-CSF for 72 h in vitro than for cells grown without rhG-CSF. Furthermore, the median survival period of mice implanted with spleen cells from L-8801 leukemic mice treated with rhG-CSF was prolonged compared with those from leukemic mice without rhG-CSF. In contrast, there was no effect of rhG-CSF on the growth potential of the spleen from L-8057 leukemic mice. The results of our present study demonstrate that rhG-CSF reduced the growth of L-8801 leukemic cells in vitro and in vivo mediated through G-CSF receptors, thereby suppressing the development of leukemia.

Animals↗

Effect of recombinant human thrombopoietin in nonhuman primates with chemotherapy-induced thrombocytopenia.

We examined the effects of recombinant human thrombopoietin (rhTPO) on myelosuppressive chemotherapy-induced thrombocytopenia in cynomolgus monkeys. After treatment with nimustine (ACNU) on day 0, the monkeys intravenously received rhTPO at a dose of 0.04, 0.2 or 1 microgram/kg/d or monkey's serum once each day from day 1 to day 28. Administration of rhTPO reduced the severity of thrombocytopenia and accelerated the rate of platelet recovery in a dose-dependent fashion. Treatment with the highest rhTPO dose completely prevented thrombocytopenia and stimulated a marked increase in platelet counts over the normal values. Animals treated with ACNU also became neutropenic and slightly anaemic. Administration of rhTPO following ACNU treatment significantly improved neutropenia with increasing doses of rhTPO, but had no effect on anaemia. Compared to the control animals, rhTPO-treated animals exhibited no significant changes in several serum parameters. C-reactive protein concentration and some blood coagulation profiles within the study period. These results suggest a therapeutic efficacy of rhTPO in improving chemotherapy-induced thrombocytopenia.

Animals↗

Phenotypic modulation in cisplatin-resistant cloned cells derived from transplantable rat malignant fibrous histiocytoma.

The histogenesis of malignant fibrous histiocytoma (MFH) was studied using cisplatin (CDDP)-resistant MT-R8 and MT-R9 cells derived from cloned undifferentiated MT-8 and fibrohistiocytic MT-9 cells, respectively, which had been established from transplantable rat MFH. CDDP concentrations required for 50% suppression of proliferation of MT-R8 and MT-R9 cells were 5.4- and 3.3-fold greater than those of parental MT-8 and MT-9, respectively. MT-R8 and MT-R9 showed the higher positive rates to histiocytic lysosomal/ antigenic (ED1 and ED2) markers. The number of alpha-smooth muscle actin (SMA)-positive cells significantly increased in MT-R8; SMA-positive cells were also observed in MT-R9, but no difference was seen between MT-9 and MT-R9. MT-R8 and MT-R9 expressed both histiocytic and myofibroblastic phenotypes. However, the histology of subcutaneous tumors induced in syngeneic rats by MT-R8 and MR-R9 did not always reflect their in vitro nature. MT-R8 developed undifferentiated sarcomas similar to parental MT-8 tumors. In contrast, MT-R9 induced tumors with polytypic histologies such as the storiform growth pattern, neoplastic growth of granular cells and myofibroblasts, osteosarcoma-like areas, collagen-rich areas containing well-developed fibroblasts and areas involving many lipoblasts. These in vivo observations suggest the multidirectional differentiation of MT-R9 cells. Phenotypic modulation of rat MFH cells seemed to be easily induced by CDDP. A possible histogenesis of MFH was discussed based on the data collected.

Animals↗

Neurally mediated syncope complicated with paroxysmal atrial fibrillation.

Recently, it has come to be accepted that the result of the tilt test is specific to neurally mediated syncope (vasovagal syncope). Only rarely is a case of paroxysmal atrial fibrillation without any organic diseases in childhood reported. A case reported here of a 14-year-old boy with neurally mediated syncope; which was complicated by paroxysmal atrial fibrillation, and which was diagnosed by performing the tilt test. Atrial fibrillation can be induced by the extraordinary stimulation of the vagal nerve during syncope. In a child, neurally mediated syncope complicated with paroxysmal atrial fibrillation has not been previously reported.

Adolescent↗

Phenotypic changes in lipopolysaccharide-treated cloned cells derived from transplantable rat malignant fibrous histiocytoma.

To investigate a possible phenotypic modulation, MT-8L and MT-9L cells were induced by in vitro culture of undifferentiated MT-8 and fibrohistiocytic MT-9 cells, which had been established from a rat malignant fibrous histiocytoma (MFH), in the medium containing 10 micrograms lipopolysaccharide (LPS)/ml. MT-8L and MT-9L gave greater positive reactions for histiocytic lysosomal markers and showed ultrastructures of histiocytic natures. In MT-8L, alpha-smooth muscle actin-positive myofibroblastic cells also significantly increased in number. MT-8L expressed both histiocytic and myofibroblastic phenotypes. MT-8L-induced tumors consisted mainly of storiform type MFH, differing from undifferentiated sarcoma type induced by MT-8. MT-9L and MT-9 tumors showed a storiform pattern. A phenotypic modulation of MFH cells was easily induced by LPS treatment.

Animals↗

Heterogeneity in the origin and immunophenotypes of "histiocytic" cells in transplantable rat malignant fibrous histiocytoma.

To clarify the origin and nature of "histiocytic" cells in malignant fibrous histiocytoma (MFH), immunoreactivities to rat macrophage/histiocyte-specific monoclonal antibodies (ED1 and ED2) and monocyte chemoattractant protein-1 (MCP-1) production were investigated using rat transplantable MFH-derived cloned cells (undifferentiated MT-8 and fibrohistiocytic MT-9). In different cultures, the positive rates for ED1 and ED2 ranged from 2.5% to 26.0% in MT-8, and from 6.0% to 40.0% in MT-9. In homotransplants, ED1-positive cells were frequently observed in MT-9 tumors, but barely seen in MT-8 tumors. In both MT-8 and MT-9 tumors, ED2-positive cells were not detected within tumors. Immunophenotypic characteristics of MT-8 and MT-9 to these antibodies seemed to be easily altered depending on in vitro and in vivo conditions. By ELISA, MCP-1 was hardly detected in culture supernatants of MT-8 and MT-9, but its level was very high in sera of MT-8- and MT-9-tumor-bearing rats. In rats with these tumors, the number of circulating monocytes was significantly increased and the presence of factors stimulating macrophage proliferation was demonstrated by the colony formation assay using rat bone marrow cells. Histiocytic cells in MT-8 and MT-9 tumors that were produced in nude mice reacted only with antibody to mouse macrophage-associated antigen. This suggests the existence of non-neoplastic, infiltrated macrophages of host origin that were induced probably by MCP-1 and factors stimulating macrophage proliferation. The present studies indicate the presence of heterogeneities in the origin and immunophenotypes of "histiocytic" cells in rat MFH.

Animals↗

Establishment and characterization of cell lines, MeMS and MeFS, derived from spontaneous rat mesotheliomas.

New cell lines, designated MeMS and MeFS, were established from the epithelial type of mesotheliomas occurring spontaneously in aged male and female Fischer 344 rats, respectively. Morphologically, MeMS and MeFS expressed the epithelial phenotype. Coexpression of keratin and vimentin in both cell lines was confirmed by the immunocytochemistry, one-dimensional gel electrophoresis and immunoblotting for intermediate filament proteins. Hyaluronic acid synthesis of both MeMS and MeFS was demonstrated by the analysis using high-performance liquid chromatography. MeMS and MeFS seem to be useful models for studying the biological nature of rat mesotheliomas.

Aging↗

Analysis of the derangement of the pancreatic microcirculation in a rat caerulein pancreatitis model using an intravital microscope system.

In order to clarify the derangement of the pancreatic microcirculation in acute pancreatitis, the pancreatic microcirculation in caerulein pancreatitis was monitored intravitally and the roles of bradykinin and nitric oxide were examined using bradkykinin B2 receptor antagonist, HOE140. Under an intravital microscope, the pancreatic microcirculation was observed 2 or 6 hr after the induction of acute pancreatitis. HOE140 was administered 30 min before the induction of acute pancreatitis. The videoimages were taken into the computer, and the value of grayscale was measured with imaging software to quantify the degree of extravasation. Extravasation in the postcapillary venules was remarkable and the velocity in pancreatic terminal arterioles decreased significantly. However, the adherence of leukocytes was not observed until 6 hr after the induction. Both the extension of extravasation and the decrease of velocity were prevented by HOE140. The levels of nitric oxides in the pancreatic tissue declined and this decline was not influenced by HOE140. Bradykinin participates mainly in the regulation of vascular permeability in the early stage of caerulein pancreatitis. Further, the impairment of pancreatic microcirculation may play a key role in the onset and development of acute pancreatitis.

Acute Disease↗

[A patient with parkinsonism presenting hyperintensity in the globus pallidus on T1-weighted MR images: the correlation with manganese poisoning].

We report a 55-year-old woman who developed symptoms resembling parkinsonism. Her psychiatric symptoms in the early stage, cervical dystonia and tremor increasing on movement were consistent with manganese poisoning. Manganese levels were elevated to 1.5 micrograms/l in the serum (normal; 0.3-1.1 micrograms/l) and to 1.4 micrograms/l in the urine (normal; less than 1.2 micrograms/l). Intravenous infusion of calcium disodium editate (CaEDTA; chelating agent) was followed by the marked excretion of manganese (27.3 micrograms/l) in the urine. These findings support manganese poisoning. Manganese poisoning is a disease which results from chronic exposure to manganese, but the source of manganese exposure remained obscure in this patient. T1-weighted MRI of the brain showed symmetric high signal intensity in the globus pallidus without any abnormality on T2-weighted images. There is a report that manganese induced brain lesions in Macaca fascicularis as revealed by MRI and the fascicularis developed signs of unsteady gait and hypoactivity. The patient responded to treatment with CaEDTA and the second MRI demonstrated regression of abnormal signal intensity. This may be due to enhanced manganese excretion. To our knowledge, this is the first case of probable manganese-induced human parkinsonism whom changes in MRI were noted after treatment with CaEDTA.

Edetic Acid↗

Improvement of thrombocytopenia following bone marrow transplantation by pegylated recombinant human megakaryocyte growth and development factor in mice.

We examined whether pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) is capable of improving thrombocytopenia and promoting thrombopoietic reconstitution following lethal irradiation and bone marrow transplantation (BMT) in mice. Immediately after receiving 10 Gy whole body irradiation (day 0), male C3H/HeN mice were inoculated with 10(6) bone marrow cells obtained from syngeneic mice. Circulating platelet counts decreased to below 4% of the normal counts with a nadir on day 10, and then returned to the normal level on day 28 in the control mice undergoing BMT. Subcutaneous consecutive treatment with PEG-rHuMGDF at doses from 10 to 300 micrograms/kg/day from day 1 for 13 days significantly improved the platelet nadir and promoted platelet recovery. The white blood cell counts and hemoglobin concentration following BMT were not influenced by the PEG-rHuMGDF. PEG-rHuMGDF-injection starting from day 5 did not improve the platelet nadir following BMT. Furthermore, administration with PEG-rHuMGDF on alternate days at 55.7 micrograms/kg/day for 7 days or at an interval of 3 days at 78 micrograms/kg/day for 4 days (twice a week for 2 weeks) had a significant efficacy, but these administration regimens had less efficacy than consecutive administration at 30 micrograms/kg/day for 13 days. The numbers of megakaryocytes and megakaryocyte progenitor cells decreased to 5 and 0.2% of normal level, respectively, in the control mice. Consecutive administration of PEG-rHuMGDF enhanced the recovery of the mean number of these cells compared to those in vehicle-treated mice, although such effects were not statistically significant except for the number of megakaryocyte progenitors on day 12. These results suggest that consecutive treatment with PEG-rHuMGDF beginning from the day after BMT may be effective in improving thrombocytopenia following BMT.

Animals↗

Solution structure of a human cystatin A variant, cystatin A2-98 M65L, by NMR spectroscopy. A possible role of the interactions between the N- and C-termini to maintain the inhibitory active form of cystatin A.

The solution structure of a human cystatin A variant, cystatin A2-98 M65L, which maintains the full inhibitory activity of the wild-type protein, was determined at pH 3.8 by sD/3D heteronuclear double- and triple-resonance NMR spectroscopy. The structure is based on a total of 1343 experimental restraints, comprising 1139 distance, 154 phi and chi 1 torsion angle restraints, and 50 distance constraints for 25 backbone hydrogen bonds. A total of 15 structures was calculated using the YASAP protocol with X-PLOR, and the atomic rms distribution about the mean coordinate positions for residues 8-93 was 0.55 +/- 0.10 A for the backbone atoms and 1.05 +/- 0.11 A for all heavy atoms. The structure consists of five antiparallel beta-sheets and two short alpha-helices. Comparison with the X-ray structure of cystatin B in the papain complex shows that the conformation of the first binding loop is quite similar to that of cystatin A, with an rms deviation of 0.78 A for the backbone atoms in the 43-53 region (cystatin A numbering). The second binding loop, however, is significantly different in the two structures, with an rms deviation greater than 2 A. There are some other significant differences, especially for the N-terminal and alpha-helix regions. The overall structure of cystatin A is also compared with the recently reported NMR structure of the wild-type cystatin A (stefin A) at pH 5.5 (Martin et al., 1995) and reveals the following features. that differ in our structure from the previous one: (1) the N-terminal segment, which was unstructured in the previous report, folds over in close vicinity to the C-terminus, as revealed by the distinctive NOEs between those segments; (2) two discrete short alpha-helices linked by a type II reverse turn were found, instead of the continuous single alpha-helix with a slight kink shown in the previous structure; (3) the second binding loop, which was not well converged in the previous study at pH 5.5, is determined very well in our structure. The effect of the N-terminal truncation on the cystatin A structure was examined by comparing the 1H-15N HSQC spectrum of cystatin A2-98 with that of the cystatin A5-98 variant, which lacks the anti-papain activity, revealing significant chemical shift differences in the residual N-terminal segment and the first binding loop, together with small shifts in the other parts.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗

The effect of antigen dose on CD4+ T helper cell phenotype development in a T cell receptor-alpha beta-transgenic model.

The dose of foreign antigen can influence whether a cell-mediated or humoral class of immune response is elicited, and this may be largely accounted for by the development of CD4+ T helper cells (Th) producing distinct sets of cytokines. The ability of antigen dose to direct the development of a Th1 or Th2 phenotype from naive CD4+ T cells, however, has not been demonstrated. In this report, we show that the antigen dose used in primary cultures could directly affect Th phenotype development from naive DO11.10 TCR-alpha beta-transgenic CD4+ T cells when dendritic cells or activated B cells were used as the antigen-presenting cells. Consistent with our previous findings, midrange peptide doses (0.3-0.6 microM) directed the development of Th0/Th1-like cells, which produced moderate amounts of interferon gamma (IFN-gamma). As the peptide dose was increased, development of Th1-like cells producing increased amounts of IFN-gamma was initially observed. At very high (> 10 microM) and very low (< 0.05 microM) doses of antigenic peptide, however, a dramatic switch to development of Th2-like cells that produced increasing amounts of interleukin 4 (IL-4) and diminishing levels of IFN-gamma was observed. This was true even when highly purified naive, high buoyant density CD4+ LECAM-1hi T cells were used, ruling out a possible contribution from contaminating "memory" phenotype CD4+ T cells. Neutralizing anti-IL-4 antibodies completely inhibited the development of this Th2-like phenotype at both high and low antigen doses, demonstrating a requirement for endogenous IL-4. Our findings suggest that the antigen dose may affect the levels of endogenous cytokines such as IL-4 in primary cultures, resulting in the development of distinct Th cell phenotypes.

Animals↗

Human cystatin A is inactivated by engineered truncation. The NH2-terminal region of the cysteine proteinase inhibitor is essential for expression of its inhibitory activity.

A series of NH2-terminal truncated forms of human cysteine proteinase inhibitor, cystatin A, was prepared by genetic engineering using Escherichia coli harboring mutated genes. Each variant of cystatin A was efficiently expressed as a fused protein with porcine adenylate kinase and released by CNBr degradation after exchange of the sole inner Met to Leu. The mutant cystatin A lacking an amino-terminal Met residue (called standard variant starting from Ile2, CystA2-98(M65L) showed the same inhibitory activity as authentic one isolated from human epidermis. Two-residue truncation scarcely influenced the activity, but further truncations deleting Pro3 and beyond conservative Gly4 and Gly5 caused a remarkable decrease of their inhibitory activity. But little effect was observed by a substitution of Pro3 with Leu. The loss of the activity by amino-terminal truncation was compensated slightly by engineered substitution of Gly75 with His on a second loop. In the two-dimensional 15N-1H HSQC NMR spectrum, four-residue truncation was found to cause changes in the chemical shifts of Val47 and Val48, which locate on a first loop and consist of a conservative QVVAG sequence. Furthermore, the truncation led to a change in fluorescence spectroscopic behavior of Trp75, which was introduced as a probe on the second loop. Fluorescence intensity of the Trp of the truncated (5-98) form was more affected by heating than the active standard variant. Conversely, fluorescence of Trp75 in 2-98 form was more quenched by acrylamide than the 5-98 variant. Thus, the amino-terminal region of cystatin A is essential for the expression of its inhibitory activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

Tyrosine phosphorylation and activation of STAT5, STAT3, and Janus kinases by interleukins 2 and 15.

The cytokines interleukin 2 (IL-2) and IL-15 have similar biological effects on T cells and bind common hematopoietin receptor subunits. Pathways that involve Janus kinases (JAKs) and signal transducers and activators of transcription (STATs) have been shown to be important for hematopoietin receptor signaling. In this study we identify the STAT proteins activated by IL-2 and IL-15 in human T cells. IL-2 and IL-15 rapidly induced the tyrosine phosphorylation of STAT3 and STAT5, and DNA-binding complexes containing STAT3 and STAT5 were rapidly activated by these cytokines in T cells. IL-4 induced tyrosine phosphorylation and activation of STAT3 but not STAT5. JAK1 and JAK3 were tyrosine-phosphorylated in response to IL-2 and IL-15. Hence, the JAK and STAT molecules that are activated in response to IL-2 and IL-15 are similar but differ from those induced by IL-4. These observations identify the STAT proteins activated by IL-2 and IL-15 and therefore define signaling pathways by which these T-cell growth factors may regulate gene transcription.

Base Sequence↗

Significance of the highly conserved Gly-4 residue in human cystatin A.

The expression system for human recombinant cystatin A has already been established to be a fusion protein with porcine adenylate kinase in Escherichia coli [Kaji et al. (1990) Biol. Chem. Hoppe-Seyler 371, Suppl., 145-150]. After cyanogen bromide cleavage of the fused protein expressed in E. coli, the cystatin portion could be readily isolated. The inhibitory activity of the obtained variant (Cyst A (2-98)) was found to be almost identical with that of the wild type, and thereafter a mutation was introduced into this variant (Ctst A(2-98)), called the standard variant. To elucidate the role of the Gly-4 residue, which is completely conserved in all cystatin species, this residue was substituted with 17 other amino acids by means of cassette mutagenesis. Thus 17 variants (Cyst A(2-98)[G4X]) obtained were examined as to their inhibitory activity towards papain. As the side chain of the substituted amino acid residue became more bulky, the inhibitory activity of the variant markedly decreased. Variants whose side chains were bulkier than a Val residue showed almost no inhibitory effect towards papain. Consequently, it was deduced that the large side chain of a substituted amino acid may cause steric hindrance, which may be responsible for the decrease in inhibitory activity. Thus, we could conclude that the 4th (Gly) residue on cystatin A must be small, because amino acids which existed on the N-terminal side of this residue could interact with a papain molecule.

Amino Acid Sequence↗

Establishment and characterization of a cell line (NB-YK) derived from a transplantable rat nephroblastoma.

A new cell line, designated NB-YK, was established from a transplantable rat nephroblastoma (NB-Y) which was derived from a spontaneous nephroblastoma in an aged Fischer 344 rat. NB-YK grew in a piling-up and noncohesive pattern on the plastic surface and formed colonies in a soft agar. The main cell type of NB-YK represented morphology of mesenchymal phenotype and most of the cells contained several secretory granules in their cytoplasm. Immunocytochemically the cells were positive for vimentin, cytokeratin, and laminin. Coexpression of vimentin and cytokeratin in the cells was confirmed by the one-dimensional gel electrophoresis and immunoblotting for intermediate filament proteins. NB-YK cells were tumorigenic and produced fibrosarcoma-like tumor when inoculated subcutaneously or intraperitoneally into syngeneic rats and nude mice. NB-YK seems to be a useful model for studying biological properties of nephroblastoma.

Animals↗

[Central cervical cord syndrome: a case report on rehabilitation, with special references to accidental falls in the elderly].

An 81-year-old man with Parkinson's disease was admitted to our hospital with impaired function of all extremities. Four weeks before his symptoms developed, he had tripped on the steps, fallen and bruised his jaw. Following this episode he experienced a few more falls inside his house. On examination his greatest weakness was in the hands and wrists. He was hyper-reflexic in all extremities and had bilateral Babinski's sign. He could not walk and needed physical assistance in most of his daily living activities. X-ray films of the cervical spine showed significant degenerative changes. The magnetic resonance images suggested central cervical cord damage at the level of the C6 vertebral body. After three months' rehabilitation treatment, he became able to walk with a cane and became independent in all the basic activities of daily living except for bathing. He never regained skillful function of his hands despite later levodopa treatment of Parkinson's disease. His clinical features were consistent with the central cervical cord syndrome, described by Schnneider and co-workers in 1954. This syndrome may occur as a result of hyperextension neck injury, occasionally associated with an accidental fall in the elderly with cervical spondylosis. Thirteen patients with cervical spinal cord injury above 65 of age were admitted to our department from 1983 to 1993. Six of them presented with the central cervical cord syndrome, and all patients had a history of accidental injuries related to falling.

Accidental Falls↗