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1.
Brain Res ; 921(1-2): 219-25, 2001 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-11720729

RESUMO

It has been reported that bone morphogenetic proteins (BMPs) are involved in the generation of the central nervous system during development. However, the roles of BMPs in mature spinal cord have not been clarified. We examined the expression of BMP7 mRNA before and after traumatic injury of the adult rat spinal cord. BMP7 mRNA was already detectable at a relatively low level in uninjured spinal cord, but was dramatically increased after injury. Semiquantitative RT-PCR study further confirmed upregulation of BMP7 mRNA in injured spinal cord. In situ hybridization indicated that expression of BMP7 mRNA was present only in glial cells in uninjured spinal cord. After injury, the number of BMP7-expressing glial cells was increased, BMP7 expression also became apparent in motor neurons. It has been suggested that BMPs promote survival of subventricular zone cells in adult rats. Thus, our results suggest that increase in the expression of BMP7 promotes survival of neurons and glial cells after acute traumatic injury. In contrast, there is increasing evidence that BMPs inhibit neurogenesis and alternatively promote gliogenesis of neural progenitors, which are also present in adult spinal cord, suggesting that injury-upregulated BMP7 may regulate differentiation of glial cells from neural progenitors and may induce gliosis after central nervous system injury.


Assuntos
Proteínas Morfogenéticas Ósseas/genética , Neuroglia/metabolismo , Neurônios/metabolismo , RNA Mensageiro/metabolismo , Traumatismos da Medula Espinal/metabolismo , Medula Espinal/metabolismo , Fator de Crescimento Transformador beta , Regulação para Cima/genética , Fatores Etários , Processamento Alternativo/genética , Animais , Proteína Morfogenética Óssea 7 , Divisão Celular/genética , Sobrevivência Celular/genética , Gliceraldeído-3-Fosfato Desidrogenases/genética , Masculino , Regeneração Nervosa/genética , Neuroglia/citologia , Neurônios/citologia , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Medula Espinal/citologia , Traumatismos da Medula Espinal/genética , Traumatismos da Medula Espinal/fisiopatologia , Células-Tronco/citologia , Células-Tronco/metabolismo
2.
J Bone Miner Res ; 16(5): 948-57, 2001 May.
Artigo em Inglês | MEDLINE | ID: mdl-11341341

RESUMO

Ossification of the posterior longitudinal ligament (OPLL) of the spine is the leading cause of myelopathy in Japan. In earlier studies, we provided genetic linkage and allelic association evidence of distinct differences in the human collagen alpha2(XI) gene (COL11A2) that might constitute inherited predisposition to OPLL. In the present study, a strong allelic association with non-OPLL (p = 0.0003) was observed with an intron 6 polymorphism [intron 6 (-4A)], in which the intron 6 (-4A) allele is more frequently observed in non-OPLL subjects than in OPLL patients. In addition, a newly identified polymorphism in exon 6 [exon 6 (+28A)] was in linkage disequilibrium with the intron 6 (-4A). The functional impact of the polymorphisms was analyzed by comparing the differences in messenger RNA (mRNA) splicing by reverse-transcription polymerase chain reaction (RT-PCR) analysis in cultured cells from the interspinous ligament and an in vitro exon trapping study. The intron 6 (-4A) allele resulted in skipping exon 6 and retaining exon 7, while the exon 6 (+28A) allele was not associated with alteration in mRNA splicing. Similar mRNA species were observed in undifferentiated osteoblast (Ob) cells and in cells from posterior longitudinal ligament of non-OPLL subjects. The region containing exons 6-8 is an acidic subdomain presumably exposed to the surface that could interact with molecules of the extracellular matrix. Accordingly, retaining exon 7 together with removal of exon 6 observed in intron 6 (-4A) could play a protective role in the ectopic ossification process because the same pattern was observed in undifferentiated Ob cells and nonossified posterior longitudinal ligament cells.


Assuntos
Colágeno/genética , Ossificação do Ligamento Longitudinal Posterior/patologia , Polimorfismo Genético , Coluna Vertebral/patologia , Processamento Alternativo , Sequência de Aminoácidos , Técnicas de Cultura de Células , Diferenciação Celular , Células Cultivadas , Colágeno/fisiologia , Éxons , Humanos , Íntrons , Desequilíbrio de Ligação , Dados de Sequência Molecular , Ossificação do Ligamento Longitudinal Posterior/genética , Osteoblastos/citologia , RNA Mensageiro
3.
J Hum Genet ; 46(1): 1-4, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11289713

RESUMO

Among Japanese, ossification of the posterior longitudinal ligament of the spine (OPLL) is a leading cause of myelopathy, showing ectopic bone formation in the paravertebral ligament. We have provided genetic evidence that the collagen alpha2 (XI) (COL11A2) locus of chromosome 6 constitutes susceptibility for OPLL. Five distinct single nucleotide polymorphisms (SNPs), identified in COL11A2, were combined to construct possible haplotypes by the use of a maximum likelihood program. Estimated haplotype frequency was compared in OPLL patients and non-OPLL controls. We report a gender-specific association of the COL11AA2 haplotvpe with OPLL. The frequency of the most commonly observed haplotype was significantly higher in male patients (P = 0.0003) compared with controls, but not in female patients (P = 0.21). OPLL is predominantly observed in males. with a prevalence ratio of 2:1, and our gender-specific associations indicate that genetic factors involving COL11A2 play a specific role in the etiology of OPLL exclusively in males.


Assuntos
Colágeno/genética , Haplótipos , Ossificação do Ligamento Longitudinal Posterior/genética , Fatores Sexuais , Coluna Vertebral/patologia , Idoso , Mapeamento Cromossômico , Cromossomos Humanos Par 6 , Feminino , Humanos , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-Idade
4.
J Rheumatol ; 28(3): 554-9, 2001 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11296958

RESUMO

OBJECTIVE: The Japan Ankylosing Spondylitis Society conducted a nationwide questionnaire survey of spondyloarthropathies (SpA) in 1990 and 1997, (1) to estimate the prevalence and incidence, and (2) to validate the criteria of Amor and the European Spondylarthropathy Study Group (ESSG) in Japan. METHODS: Japan was divided into 9 districts, to each of which a survey supervisor was assigned. According to unified criteria, each supervisor selected all the clinics and hospitals with potential for SpA patients in the district. The study population consisted of all patients with SpA seen at these institutes during a 5 year period (1985-89) for the 1st survey and a 7 year period (1990-96) for the 2nd survey. RESULTS: The 1st survey recruited 426 and the 2nd survey 638 cases, 74 of which were registered in both studies. The total number of patients with SpA identified 1985-96 was 990 (760 men, 227 women). They consisted of patients with ankylosing spondylitis (68.3%), psoriatic arthritis (12.7%), reactive arthritis (4.0%), undifferentiated SpA (5.4%), inflammatory bowel disease (2.2%), pustulosis palmaris et plantaris (4.7%), and others (polyenthesitis, etc.) (0.8%). The maximum onset number per year was 49. With the assumption that at least one-tenth of the Japanese population with SpA was recruited, incidence and prevalence were estimated not to exceed 0.48/100,000 and 9.5/100,000 person-years, respectively. The sensitivity was 84.0% for Amor criteria and 84.6 for ESSG criteria. CONCLUSION: The incidence and prevalence of SpA in Japanese were estimated to be less than 1/10 and 1/200, respectively, of those among Caucasians. The adaptability of the Amor and ESSG criteria was validated for the Japanese population.


Assuntos
Artrite Psoriásica/epidemiologia , Espondilite Anquilosante/epidemiologia , Inquéritos e Questionários/normas , Adulto , Artrite Reativa/epidemiologia , Dor nas Costas/epidemiologia , Feminino , Saúde Global , Humanos , Incidência , Doenças Inflamatórias Intestinais/epidemiologia , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Psoríase/epidemiologia , Reprodutibilidade dos Testes , Sociedades Médicas
5.
Spine (Phila Pa 1976) ; 26(5): 494-8, 2001 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-11242376

RESUMO

STUDY DESIGN: A longitudinal cohort study of 216 elderly patients with ossification of the posterior longitudinal ligament for an average of 13 years was performed. OBJECTIVE: To know the quality of life experienced by patients after treatment. SUMMARY OF BACKGROUND DATA: No report is available on the quality of life experienced by elderly patients with ossification of the posterior longitudinal ligament. Because the life prognosis of patients with this condition is relatively good, the quality of life experienced by elderly patients with this disease is an important subject. METHODS: The study participants were 216 elderly patients with ossification of the posterior longitudinal ligament. Conservative therapy was performed for 126 patients, and surgical therapy for 90 patients. Surgery was basically indicated for patients with myelopathy, who were classified using Nurick's grading system. The cumulative survival rate of these patients and their disabilities in daily living were reviewed. The occurrence of fracture resulting from osteoporosis was surveyed, and the relation of such fractures to bone mineral density was examined. RESULTS: The cumulative survival rate of 70-year-old patients exhibiting Nurick Grade 5 severe myelopathy before treatment was 20%, whereas that of patients without myelopathy or those with Grades 1, 2, 3, or 4 myelopathy before treatment was 80%. Patients who underwent surgical therapy for Grade 3 or 4 myelopathy were statistically more likely to be independent of assistance with activities of daily living than those with similar degrees of myelopathy who underwent conservative therapy. The final quality of life was poor for patients with Grade 5 myelopathy at the first examination, regardless of therapeutic method. The prevalence of complication by fracture in patients with ossification of the posterior longitudinal ligament was 1.4% for men and 8.6% for women. The bone mineral density in these patients without myelopathy was significantly higher than in healthy subjects of the same age. CONCLUSION: The study data suggest that surgical treatment should be chosen for patients exhibiting moderate myelopathy to obtain satisfactory quality of life for them over a long period.


Assuntos
Ossificação do Ligamento Longitudinal Posterior/psicologia , Qualidade de Vida , Absorciometria de Fóton , Idoso , Idoso de 80 Anos ou mais , Densidade Óssea , Vértebras Cervicais/lesões , Vértebras Cervicais/metabolismo , Avaliação da Deficiência , Feminino , Seguimentos , Fraturas Espontâneas , Humanos , Masculino , Pessoa de Meia-Idade , Ossificação do Ligamento Longitudinal Posterior/complicações , Ossificação do Ligamento Longitudinal Posterior/mortalidade , Ossificação do Ligamento Longitudinal Posterior/cirurgia , Prevalência , Prognóstico , Índice de Gravidade de Doença , Compressão da Medula Espinal/etiologia , Compressão da Medula Espinal/mortalidade , Compressão da Medula Espinal/psicologia , Compressão da Medula Espinal/reabilitação , Fraturas da Coluna Vertebral/epidemiologia , Fraturas da Coluna Vertebral/etiologia , Fraturas da Coluna Vertebral/psicologia , Fraturas da Coluna Vertebral/reabilitação , Taxa de Sobrevida
6.
Spine (Phila Pa 1976) ; 26(2): 161-5, 2001 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-11154536

RESUMO

STUDY DESIGN: The significance of occipitoaxial angle in the development of subaxial subluxation after occipitocervical fusion was determined in a minimum 5-year follow-up study performed retrospectively. OBJECTIVE: To clarify the association between the position of the fixed occipital bone and axis and the development of subaxial subluxation. SUMMARY OF BACKGROUND DATA: There have been few reports describing the association between the position of fixation of the occipital bone and axis and subaxial lesion in occipitocervical fusion. MATERIALS AND METHODS: Thirty-eight patients with rheumatoid arthritis who underwent occipitocervical fusion for irreducible atlantoaxial dislocation were reviewed. The angle between the McGregor line and the inferior surface of the axis (O-C2) was measured in healthy volunteers and patients who had undergone occipitocervical fusion. The association between any changes in the alignment of the cervical vertebrae and the development of subaxial subluxation during follow-up periods was studied. RESULTS: The number of the patients in whom postoperative kyphosis and swan neck deformity developed was only five, but in four (80%) of them, retroversion of the occipital bone was used to increase the O-C2 angle. In 14 patients, in whom anteversion of the occipital bone against the axis was excessive, 12 (86%) patients experienced subaxial subluxation after surgery. In the patients in whom fixed O-C2 angles were in normal range, only one patient developed such abnormal changes in the middle and lower cervical vertebrae. CONCLUSION: It is necessary to give attention to the position of the fixed occipital bone and axis during procedures of occipitoaxial fusion for patients with rheumatoid arthritis.


Assuntos
Artrite Reumatoide/cirurgia , Articulação Atlantoaxial/cirurgia , Articulação Atlantoccipital/cirurgia , Luxações Articulares/etiologia , Complicações Pós-Operatórias/etiologia , Fusão Vertebral/efeitos adversos , Fusão Vertebral/métodos , Adulto , Idoso , Artrite Reumatoide/complicações , Artrite Reumatoide/patologia , Articulação Atlantoaxial/diagnóstico por imagem , Articulação Atlantoaxial/patologia , Articulação Atlantoccipital/diagnóstico por imagem , Articulação Atlantoccipital/patologia , Fenômenos Biomecânicos , Causalidade , Feminino , Humanos , Fixadores Internos/efeitos adversos , Luxações Articulares/diagnóstico por imagem , Luxações Articulares/prevenção & controle , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/diagnóstico por imagem , Complicações Pós-Operatórias/prevenção & controle , Radiografia , Fusão Vertebral/instrumentação , Resultado do Tratamento
7.
J Orthop Sci ; 5(3): 310-5, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-10982675

RESUMO

The pathogenesis of ossification of the posterior longitudinal ligament (OPLL) is still unknown. Gene analysis and molecular biology have been introduced in recent years, and etiologic and pathological clarifications are being achieved. An important role of the genetic background in the development of this disease was demonstrated by pedigree survey, twin survey, and HLA haplotype study. The results of gene linkage study showed that patients with OPLL have a significantly higher incidence of genetic abnormalities found in the XI collagen (alpha)2 gene (COL11A2) region. From the gene mapping of this abnormality, the abnormal N-propeptide of the COL11A2 gene was found to be responsible. We are planning to undertake genetic analysis of the whole of chromosome VI to find the pathogenic genes responsible for OPLL in addition to COL11A2. A cell biological approach is also necessary to make clear the relationship between abnormalities of the COL11A2 gene and ossification of the ligament. In future, identification of the susceptible gene, elucidation of its function, and study toward the development of preventive and therapeutic drugs will advance.


Assuntos
Colágeno/genética , Ossificação do Ligamento Longitudinal Posterior/genética , Peptídeos/genética , Pró-Colágeno/genética , Mapeamento Cromossômico , Predisposição Genética para Doença/genética , Humanos
8.
Anticancer Res ; 20(6C): 4681-6, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-11205200

RESUMO

PURPOSE: To investigate the optimal duration of oral HCFU administration for minimization of side effects induced by long-term administration. PATIENTS AND METHODS: In total, 155 patients allocated to two groups of different duration of the therapy were reviewed: twice or three times per day doses of oral HCFU (8 mg/Kg body weight/day) for 3 months vs. 12 months. RESULTS: Though statistically significant difference was not found in cumulative survival and disease-free rates between the groups due to so many violations of duration of therapy, when reanalyzing the variables in order of real duration of therapy, those rates were significantly higher in patients treated for 300 and more days than less than 300 days (g-Wilcoxon test: p < 0.04). No significant difference was observed in the background factors between the groups. CONCLUSION: At least 300 days is suggested to be necessary to obtain the optimal effectiveness of adjuvant chemotherapy for curatively resected colorectal cancer.


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/cirurgia , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/cirurgia , Fluoruracila/uso terapêutico , Neoplasias Retais/tratamento farmacológico , Neoplasias Retais/cirurgia , Administração Oral , Adulto , Idoso , Antimetabólitos Antineoplásicos/administração & dosagem , Neoplasias do Colo/mortalidade , Neoplasias do Colo/patologia , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Intervalo Livre de Doença , Esquema de Medicação , Feminino , Fluoruracila/administração & dosagem , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Retais/mortalidade , Neoplasias Retais/patologia , Estudos Retrospectivos , Taxa de Sobrevida , Fatores de Tempo
9.
J Bone Miner Metab ; 17(4): 296-300, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-10575595

RESUMO

Bone mineral density (BMD) has not been clearly determined in patients with ossification of the posterior longitudinal ligament (OPLL) in the cervical spine. BMD in patients with OPLL was measured in the third vertebral body in the lateral projection and in the distal part of the radius in the anteroposterior projection using dual-energy X-ray absorptiometry (DXA). Patients with OPLL had significantly higher BMD than healthy controls in both the lumbar spine and radius. Observing BMD by gender and age group, high BMD was recognized especially in female patients over 60 years of age. Significantly increased BMD was observed in patients with ankylosing spinal hyperostosis (ASH) in addition to OPLL. These findings suggest that patients with OPLL may tend to develop systemic hyperostosis, leading to the pathological ectopic ossification observed in OPLL.


Assuntos
Vértebras Cervicais/fisiopatologia , Ossificação do Ligamento Longitudinal Posterior/fisiopatologia , Absorciometria de Fóton , Adulto , Idoso , Densidade Óssea , Feminino , Humanos , Ligamentos Longitudinais , Vértebras Lombares/fisiopatologia , Masculino , Pessoa de Meia-Idade
10.
Calcif Tissue Int ; 65(4): 285-9, 1999 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-10485979

RESUMO

This study was designed to assess the effect of vitamin K and D supplementation on ovariectomy-induced bone loss. Female Sprague-Dawley rats aged 8-9 months were ovariectomized (OVX) or sham operated and divided into five experimental groups: (1) ovariectomy (OVX), (2) OVX plus vitamin K supplementation, (3) OVX plus vitamin D supplementation, (4) OVX plus vitamin K and vitamin D supplementation, and (5) sham operation. The trabecular bone area was estimated by bone histomorphometry by microradiography and histological examination. Bone loss in OVX plus vitamin K and vitamin D group was significantly reduced at both 7 and 14 weeks compared with the OVX group. No significant bone loss in OVX plus vitamin K or OVX plus vitamin D groups was found. A similar effect of vitamin K and D supplementation on ovariectomy-induced bone loss was recognized in histological examination. Our findings indicate that vitamins K and D may have a synergistic effect on reducing bone loss. This is valuable information for the treatment of bone loss in postmenopausal women with osteoporosis.


Assuntos
Suplementos Nutricionais , Hidroxicolecalciferóis/farmacologia , Osteoporose/tratamento farmacológico , Vitamina K/farmacologia , Animais , Feminino , Hidroxicolecalciferóis/administração & dosagem , Osteoporose/patologia , Ovariectomia , Ratos , Ratos Sprague-Dawley , Tíbia , Vitamina K/administração & dosagem
11.
Spine (Phila Pa 1976) ; 24(14): 1397-401, 1999 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-10423782

RESUMO

STUDY DESIGN: Immunohistochemical study of expression and localization of bone morphogenetic protein (BMP)-2/4 and type I and II receptors on intervertebral disc. OBJECTIVES: To determine the biologic functions of BMPs and their receptors in the process of degeneration of the intervertebral disc. SUMMARY OF BACKGROUND DATA: Biologic and pathologic processes in the cell during the degeneration of the intervertebral disc are as yet poorly understood. METHODS: The cervical spines of 15 male senescence-accelerated mice aged 8, 24, or 50 weeks were used for histologic and immunohistochemical examination of BMP-2/4 and BMP receptors IA, IB, and II. Immunostaining was performed with the avidin-biotin-peroxidase complex method. RESULTS: Degenerative change was recognized within intervertebral discs of senescence-accelerated mice aged 50 weeks. BMP-2/4 and its receptors were abundant in hyaline cartilaginous cells within the endplate of the vertebrae at 8 and 24 weeks of age. However, the expression of BMP-2/4 and its receptors moved from the hyaline cartilage of the endplate of the vertebrae to fibrous cells within the anulus and to the calcified cartilage at the site of enthesis of mice aged 50 weeks. CONCLUSIONS: BMP-2/4 and its receptors may play roles in degenerative change of intervertebral disc.


Assuntos
Proteínas Morfogenéticas Ósseas/fisiologia , Deslocamento do Disco Intervertebral/metabolismo , Envelhecimento , Animais , Proteína Morfogenética Óssea 2 , Proteína Morfogenética Óssea 4 , Receptores de Proteínas Morfogenéticas Ósseas Tipo I , Receptores de Proteínas Morfogenéticas Ósseas Tipo II , Proteínas Morfogenéticas Ósseas/metabolismo , Vértebras Cervicais/química , Técnicas Imunoenzimáticas , Disco Intervertebral/química , Deslocamento do Disco Intervertebral/etiologia , Masculino , Camundongos , Camundongos Mutantes , Proteínas Serina-Treonina Quinases/análise , Receptores de Superfície Celular/análise , Receptores de Fatores de Crescimento/análise , Fator de Crescimento Transformador beta/fisiologia
12.
J Bone Miner Res ; 14(7): 1145-52, 1999 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-10404014

RESUMO

Members of the transforming growth factor-beta (TGF-beta) family transduce signals from the cell membrane to the nucleus via specific type I and type II receptors and Smad proteins. Smad1 and Smad5 mediate intracellular signaling of bone morphogenetic protein (BMP), whereas Smad2 and Smad3 transduce TGF-beta signaling. Smad4 is a common mediator required for both pathways. Smad6 and Smad7 inhibit signaling by members of the TGF-beta superfamily. Here, we examined the expression of Smad1 to Smad7 proteins during endochondral ossification of epiphyseal plate of growing rats using immunohistochemical techniques. The expression of Smad proteins was correlated with the expression of TGF-beta1 and its receptors, and BMP-2/4 and BMP receptors. The results show that TGF-beta1 and BMP-2/4 were actively expressed in chondrocytes that are undergoing proliferation and maturation, which overlaps with expression of their corresponding type I and type II receptors. The Smads, however, exhibited a distinct expression pattern, respectively. For example, Smad1 and Smad5 were highly expressed in proliferating chondrocytes and in those chondrocytes that are undergoing maturation. The TGF-beta/activin-restricted Smads were also expressed in a nearly complementary fashion; Smad2 was strongly expressed in proliferating chondrocytes, whereas Smad3 was strongly observed in maturing chondrocytes. Smad4 was broadly expressed in all zones of epiphyseal plate. Inhibitory Smads, Smad6 and Smad7, were strongly expressed in the zone of cartilage that contained mature chondrocytes. Our findings show a colocalization of the pathway-restricted and inhibitory Smads with activating ligands or ligands whose action they antagonize and their receptors in various zones of epiphyseal growth plate, suggesting that TGF-beta superfamily Smad signaling pathways plays a morphogenic role during endochondral bone formation.


Assuntos
Receptores de Ativinas Tipo I , Proteínas de Ligação a DNA/metabolismo , Lâmina de Crescimento/metabolismo , Osteogênese/fisiologia , Sistemas do Segundo Mensageiro/fisiologia , Transativadores/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Animais , Proteína Morfogenética Óssea 2 , Proteína Morfogenética Óssea 4 , Receptores de Proteínas Morfogenéticas Ósseas Tipo I , Receptores de Proteínas Morfogenéticas Ósseas Tipo II , Proteínas Morfogenéticas Ósseas/metabolismo , Núcleo Celular/metabolismo , Condrócitos/metabolismo , Lâmina de Crescimento/fisiologia , Imuno-Histoquímica , Proteínas Serina-Treonina Quinases/metabolismo , Ratos , Ratos Wistar , Receptor do Fator de Crescimento Transformador beta Tipo I , Receptor do Fator de Crescimento Transformador beta Tipo II , Receptores de Fatores de Crescimento/metabolismo , Receptores de Fatores de Crescimento Transformadores beta/metabolismo
13.
J Neurosurg ; 91(1 Suppl): 98-104, 1999 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-10419375

RESUMO

OBJECT: The aims of this study were to clarify the histological and histochemical changes associated with cell death in the spinal cord after acute traumatic injury and to examine the role of excitatory amino acid release mediated by N-methyl-D-aspartate (NMDA) receptors. METHODS: Following laminectomy, the spinal cord in 70 rats was injured at the T-9 level by applying extradural static weight-compression, in which a cylindrical compressor was used to induce complete and irreversible transverse spinal cord injury (SCI) with paralysis of the lower extremities. The injured rats were killed between 30 minutes and 14 days after injury, and the injured cord was removed en bloc. Rats that received NMDA receptor antagonist (MK-801) were killed at the same time points as those that received saline. The specimens were stained with hematoxylin and eosin, Nissl, and Klüver-Barrera Luxol fast blue and subjected to in situ nick-end labeling, a specific in situ method used to allow visualization of apoptosis. Thirty minutes post-SCI, a large hematoma was observed at the compressed segment. Six hours after injury, large numbers of dead cells that were not stained by in situ nick-end labeling were observed. Between 12 hours and 14 days postinjury, nuclei stained by using the in situ nick-end labeling technique were observed not only at the injury site but also in adjoining segments that had not undergone mechanical compression, suggesting that the delayed cell death was due to apoptosis. The number of cells stained by in situ nick-end labeling was maximum at 3 days postinjury. The results of electron microscopic examination were also consistent with apoptosis. In the MK-801-treated rats, the number of cells stained by in situ nick-end labeling was smaller than in nontreated rats at both 24 hours and 7 days after injury. CONCLUSIONS: These findings suggest that NMDA-receptor activation promotes delayed neuronal and glial cell death due to apoptosis.


Assuntos
Apoptose , Maleato de Dizocilpina/uso terapêutico , Antagonistas de Aminoácidos Excitatórios/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Traumatismos da Medula Espinal/patologia , Animais , Apoptose/efeitos dos fármacos , Contagem de Células , Morte Celular , Núcleo Celular/ultraestrutura , Corantes , Doenças Desmielinizantes/tratamento farmacológico , Doenças Desmielinizantes/patologia , Maleato de Dizocilpina/administração & dosagem , Antagonistas de Aminoácidos Excitatórios/administração & dosagem , Corantes Fluorescentes , Hematoma/patologia , Marcação In Situ das Extremidades Cortadas , Laminectomia , Masculino , Microscopia Eletrônica , N-Metilaspartato/antagonistas & inibidores , Fibras Nervosas Mielinizadas/efeitos dos fármacos , Fibras Nervosas Mielinizadas/patologia , Neurônios/ultraestrutura , Fármacos Neuroprotetores/administração & dosagem , Paralisia/tratamento farmacológico , Paralisia/patologia , Ratos , Ratos Wistar , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Compressão da Medula Espinal/patologia , Traumatismos da Medula Espinal/tratamento farmacológico
14.
J Neuropathol Exp Neurol ; 58(5): 442-50, 1999 May.
Artigo em Inglês | MEDLINE | ID: mdl-10331432

RESUMO

The aims of this study were to clarify the mechanism of cell death by apoptosis in the spinal cord after traumatic injury, and to examine the role of the mitogen-activated protein kinase (MAPK) pathways in the transmission of apoptosis signals. The rat spinal cord, experimentally injured by extradural static weight-compression, was studied by hematoxylin and eosin staining, Nissl-staining, terminal deoxynucleotidyl transferase (TdT) mediated dUTP nick-end labeling (TUNEL) staining, and immunostaining using polyclonal antibodies against Apoptosis Signal-regulating Kinase 1 (ASK1), c-Jun N-terminal kinase (JNK), and p38 MAPK. TUNEL-positive cells were present at all stages studied until 7 days after injury, and percentage positivity for these cells was maximal at 3 days after injury. Electron microscopic analysis revealed the occurrence of apoptosis in both neuronal cells and glial cells. TUNEL-positive glial cells were stained by oligodendrocyte-specific maker. Expression of ASK1 was maximal at 24 h after injury in the gray matter and at 3 days after injury in the white matter. Following the expression of ASK1, activated forms of JNK and p38 were observed in apoptotic cells detected by the TUNEL method. Colocalization of ASK1 and activated JNK or activated p38 was observed in the same cell. These findings suggest the involvement of the stress-activated MAPK pathways including ASK1 in the transmission of apoptosis signals after spinal cord injury.


Assuntos
Apoptose/fisiologia , Proteínas Quinases Dependentes de Cálcio-Calmodulina/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno , Quinases de Proteína Quinase Ativadas por Mitógeno , Proteínas Quinases Ativadas por Mitógeno , Proteínas Quinases/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Traumatismos da Medula Espinal/metabolismo , Animais , Anticorpos , Proteínas Quinases Dependentes de Cálcio-Calmodulina/análise , Proteínas Quinases Dependentes de Cálcio-Calmodulina/imunologia , Marcação In Situ das Extremidades Cortadas , MAP Quinase Quinase 4 , MAP Quinase Quinase Quinases , Masculino , Microscopia Eletrônica , Neurônios/citologia , Neurônios/enzimologia , Neurônios/ultraestrutura , Proteínas Quinases/análise , Proteínas Quinases/imunologia , Proteínas Serina-Treonina Quinases/análise , Proteínas Serina-Treonina Quinases/imunologia , Ratos , Ratos Wistar , Transdução de Sinais/fisiologia , Proteínas Quinases p38 Ativadas por Mitógeno
15.
Spinal Cord ; 37(4): 269-74, 1999 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-10338347

RESUMO

STUDY DESIGN: Myeloscopic examination was performed to observe the cauda equina in patients with lumbar spinal canal stenosis before and after treatment with Lipo prostaglandin E1, a strong peripheral vasodilator. OBJECTIVES: The purpose of this study was to clarify the effects of Lipo prostaglandin E1 on blood flow in the cauda equina in patients with lumbar spinal canal stenosis. SETTING: Japan, Kagoshima METHODS: We performed myeloscopic observations of morphological changes in blood vessels running along the cauda equina in 11 patients with lumbar spinal canal stenosis before and after treatment with Lipo prostaglandin E1. RESULTS: In six of these patients, dilation of the running blood vessels was observed immediately after administration. In all of the patients who exhibited a dilation of vessels on the surface of the cauda equina, intermittent claudication and lower extremity pain and/or numbness lessened immediately after examination. However, none of the patients who exhibited no morphological changes in the vessels along the cauda equina after administration of Lipo prostaglandin E1 experienced any improvement of symptoms at the time of examination. CONCLUSION: Results of this study suggest that Lipo prostaglandin E1 may enhance blood flow in the cauda equina and improve clinical symptoms in some patients with lumbar spinal stenosis.


Assuntos
Alprostadil/uso terapêutico , Cauda Equina/irrigação sanguínea , Estenose Espinal/tratamento farmacológico , Vasodilatadores/uso terapêutico , Idoso , Aracnoidite/complicações , Cauda Equina/efeitos dos fármacos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fluxo Sanguíneo Regional/efeitos dos fármacos , Estenose Espinal/fisiopatologia
16.
Spine (Phila Pa 1976) ; 24(10): 937-8; discussion 939, 1999 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-10332781

RESUMO

STUDY DESIGN: The human leukocyte antigen (HLA) haplotypes in families of patients with known ossification of the posterior longitudinal ligament (OPLL) were reviewed. OBJECTIVE: To clarify how genetic factors relate to the development of OPLL. SUMMARY OF BACKGROUND DATA: The association between genetic factors and the development of OPLL is still unknown. MATERIALS AND METHODS: The association between HLA haplotypes and OPLL was studied in families of 24 patients with OPLL. RESULTS: The prevalence of OPLL was higher in the siblings showing a higher share of identical HLA haplotypes: 10 (53%) of 19 with concurrence of two strands, and 5 (24%) of 21 with concurrence of one strand. Of 21 subjects who had no HLA haplotype identical with that in OPLL patients, only one showed evidence of OPLL. CONCLUSION: Genetic factors predispose toward the development of OPLL.


Assuntos
Antígenos HLA/genética , Ossificação do Ligamento Longitudinal Posterior/genética , Idoso , Feminino , Predisposição Genética para Doença/genética , Antígenos HLA/sangue , Haplótipos , Teste de Histocompatibilidade , Humanos , Masculino , Pessoa de Meia-Idade , Ossificação do Ligamento Longitudinal Posterior/sangue , Ossificação do Ligamento Longitudinal Posterior/diagnóstico por imagem , Tomografia Computadorizada por Raios X
17.
J Bone Miner Res ; 14(4): 500-8, 1999 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-10234570

RESUMO

Ossification of the posterior longitudinal ligament of the spine (OPLL) is characterized by ectopic bone formation in the ligament. OPLL is a very common disorder, in fact it constitutes the leading cause of myelopathy among Japanese. In the previous report, we provided the genetic linkage evidence that the genetic susceptibility of OPLL mapped to HLA complex of chromosome 6. As a candidate gene approach, retinoic X receptor beta (RXR beta), assigned to chromosome 6p21.3 adjacent to HLA class II, was analyzed for a possible causality. To start screening for the molecular variants of RXR beta in OPLL subjects, we first obtained P1 phage genomic clones containing the entire human RXR beta and elucidated the genomic organization of the gene. The human RXR beta is composed of 10 exons spanning over 6.2 kb of genomic DNA. Sequence analysis of the promoter region revealed a GC-rich sequence without TATA motif. We have identified three distinct molecular variants, one was in exon 10 and two were in the intergenic region between RXR beta and collagen 11A2 (COL11A2). Two variants in the intergenic region, 3' end + 140 and 3' end + 561, exhibit statistically significant associations with OPLL in case-control study (p = 0.0028 for 3' end + 140 and p = 0.034 for 3' end + 561). These results indicate that the genetic causality of OPLL lies within or close to the RXR beta/COL11A2 locus.


Assuntos
Mutação , Ossificação do Ligamento Longitudinal Posterior/genética , Receptores do Ácido Retinoico/genética , Fatores de Transcrição/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Sequência de Bases , Estudos de Casos e Controles , Células Cultivadas , Análise Mutacional de DNA , Primers do DNA/genética , Éxons , Feminino , Frequência do Gene , Variação Genética , Haplótipos , Humanos , Íntrons , Ligamentos/metabolismo , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Regiões Promotoras Genéticas , Receptores X de Retinoides
18.
Spine (Phila Pa 1976) ; 24(7): 670-5, 1999 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-10209796

RESUMO

STUDY DESIGN: An analysis of the change in strain distribution of intervertebral discs present after anterior cervical decompression and fusion by an original method. The analytical results were compared to occurrence of herniation of the intervertebral disc on magnetic resonance imaging. OBJECTIVES: To elucidate the influence of anterior cervical decompression and fusion on the unfused segments of the spine. SUMMARY OF BACKGROUND DATA: There is no consensus regarding the exact significance of the biomechanical change in the unfused segment present after surgery. METHODS: Ninety-six patients subjected to anterior cervical decompression and fusion for herniation of intervertebral discs were examined. Shear strain and longitudinal strain of intervertebral discs were analyzed on pre- and postoperative lateral dynamic routine radiography of the cervical spine. Thirty of the 96 patients were examined by magnetic resonance imaging before and after surgery, and the relation between alteration in strains and postsurgical occurrence of disc herniation was examined. RESULTS: In the cases of double- or triple-level fusion, shear strain of adjacent segments had increased 20% on average 1 year after surgery. Thirteen intervertebral discs that had an abnormally high degree of strain showed an increase in longitudinal strain after surgery. Eleven (85%) of the 13 discs that showed an abnormal increase in longitudinal strain had herniation in the same intervertebral discs with compression of the spinal cord during the follow-up period. Relief of symptoms was significantly poor in the patients with recent herniation. CONCLUSIONS: Close attention should be paid to long-term biomechanical changes in the unfused segment.


Assuntos
Vértebras Cervicais/cirurgia , Descompressão Cirúrgica/efeitos adversos , Disco Intervertebral/lesões , Fusão Vertebral/efeitos adversos , Entorses e Distensões/etiologia , Adulto , Idoso , Fenômenos Biomecânicos , Vértebras Cervicais/fisiopatologia , Feminino , Seguimentos , Humanos , Disco Intervertebral/diagnóstico por imagem , Disco Intervertebral/patologia , Deslocamento do Disco Intervertebral/complicações , Deslocamento do Disco Intervertebral/diagnóstico , Deslocamento do Disco Intervertebral/cirurgia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Amplitude de Movimento Articular , Recidiva , Compressão da Medula Espinal/diagnóstico , Compressão da Medula Espinal/etiologia , Compressão da Medula Espinal/cirurgia , Entorses e Distensões/diagnóstico , Entorses e Distensões/fisiopatologia , Tomografia Computadorizada por Raios X , Resultado do Tratamento
19.
J Spinal Disord ; 12(1): 40-4, 1999 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10078948

RESUMO

The aim of this study was to determine the usefulness of Posner's definition of spinal instability for selection of surgical therapy for lumbar spinal stenosis. Sixty patients with lumbar spinal stenosis were studied. Thirty-three patients were found to have instability, as defined using Posner's method. Nineteen of the 33 patients with instability underwent decompression and instrumented fusion. The 14 remaining patients with instability underwent decompression alone. Twenty-seven patients without instability were treated by decompression alone. Patients treated by decompression and fusion obtained the best results. Good results also could be obtained by decompression alone only if patients did not have instability. However, patients treated by decompression alone in the presence of instability had the worst results. The Posner's definition of instability proved useful for selecting patients with instability for fusion treatment.


Assuntos
Instabilidade Articular , Vértebras Lombares/cirurgia , Seleção de Pessoal/métodos , Doenças da Coluna Vertebral , Estenose Espinal/cirurgia , Terminologia como Assunto , Adulto , Idoso , Feminino , Humanos , Instabilidade Articular/diagnóstico , Instabilidade Articular/cirurgia , Laminectomia , Masculino , Pessoa de Meia-Idade , Doenças da Coluna Vertebral/diagnóstico , Doenças da Coluna Vertebral/cirurgia , Fusão Vertebral , Estenose Espinal/diagnóstico , Resultado do Tratamento
20.
Spinal Cord ; 37(1): 20-4, 1999 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-10025690

RESUMO

Very little detailed biomechanical examination of the alignment of the cervical spine following laminoplasty has been reported. We performed a comparative study regarding the buckling-type alignment that follows laminoplasty and laminectomy to know the mechanical changes in the alignment of the cervical spine. Lateral images of plain roentgenograms of the cervical spine were put into a computer and examined using a program we developed for analysis of the buckling-type alignment. Sixty-four patients who underwent laminoplasty and 37 patients who underwent laminectomy were reviewed retrospectively. The subjects comprised patients with cervical spondylotic myelopathy (CSM) and those with ossification of the posterior longitudinal ligament (OPLL). The postoperative observation period was 6 years and 7 months on average after laminectomy, and 5 years and 6 months on average following laminoplasty. Development of the buckling-type alignment was found in 33% of patients following laminectomy and only 6% after laminoplasty. Development of buckling-type alignment following laminoplasty appeared markedly less than following laminectomy in both CSM and OPLL patients. These results favor laminoplasty over laminectomy from the aspect of mechanics.


Assuntos
Vértebras Cervicais/patologia , Laminectomia/efeitos adversos , Curvaturas da Coluna Vertebral/patologia , Fusão Vertebral/efeitos adversos , Coluna Vertebral/patologia , Adulto , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/cirurgia , Feminino , Seguimentos , Humanos , Interpretação de Imagem Assistida por Computador , Cifose/diagnóstico por imagem , Cifose/etiologia , Cifose/patologia , Ligamentos Longitudinais/diagnóstico por imagem , Ligamentos Longitudinais/lesões , Ligamentos Longitudinais/cirurgia , Masculino , Pessoa de Meia-Idade , Radiografia , Estudos Retrospectivos , Curvaturas da Coluna Vertebral/diagnóstico por imagem , Curvaturas da Coluna Vertebral/etiologia , Osteofitose Vertebral/diagnóstico por imagem , Osteofitose Vertebral/cirurgia , Coluna Vertebral/diagnóstico por imagem , Coluna Vertebral/cirurgia , Fatores de Tempo
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