Biology of articular cartilage repair--present status and prospects

The cartilage response to injury differs from the classic wound healing because of two important features of the cartilage structure; lack of vascular system and rich matrix preventing chondrocyte from migration to the injury site. Three distinct types of cartilage injuries can be identified based on the depth of injury and the repair response: microdamage, chondral injury, and osteochondral injury. There have been numerous attempts to repair cartilage injury, however their results have reinforced that articular cartilage has limited potential to repair itself. However, current research is helping to clarify the mechanism of cartilage injury and repair based on its gene expression. Biology, gene therapy, and tissue engineering may provide a breakthrough to treat cartilage injury.     

Graves' disease accompanied by anti-myeloperoxidase antibody-related nephropathy and autoimmune hepatitis

A 17-year-old woman was admitted because of proteinuria, microhematuria and liver dysfunction with increased antinuclear antibody and anti-myeloperoxidase antibody (MPO-ANCA). Fourteen months' previously, urinalysis and liver function showed normal range. At that time she suffered from tachycardia and weight reduction, diagnosed as Graves' disease, she was given propylthiouracil for treatment of her Graves' disease. The histological finding of renal biopsy was compatible with minor glomerular abnormalities. Liver biopsy finding was compatible with autoimmune hepatitis. After we had administered prednisolone, liver function returned to normal range and urine protein became negative. Then we performed subtotal thyroidectomy, and she was not given propylthiouracil. MPO-ANCA decreased gradually.     

Significant liver injury with dual positive IgM antibody to Epstein-Barr virus and cytomegalovirus as a puzzling initial manifestation of infectious mononucleosis

A 35-year-old man was admitted because of significant hepatic dysfunction with mild splenomegaly and intra-abdominal lymphadenopathy of unknown cause. Infectious mononucleosis was suggested by subsequently detected high fever, pharyngotonsillitis and cervical lymphadenopathy, but IgM to Epstein-Barr virus (EBV) and cytomegalovirus (CMV) showed dual positivity. A definite diagnosis of EBV-induced infectious mononucleosis was established 3 months later on the basis of seroconversion to Epstein-Barr nuclear antigen (EBNA)-IgG positivity and reduced CMV-IgM titer with persistently negative CMV-IgG. This case highlights the initial diagnostic difficulties of EBV-induced infectious mononucleosis particularly in older patients, due to concomitant abnormal humoral immunity and unusual initial manifestations such as significant liver injury and extensive intra-abdominal lymphadenopathy.     

Implantation of dendritic cells in injured adult spinal cord results in activation of endogenous neural stem/progenitor cells leading to de novo neurogenesis and functional recovery

We report a treatment for spinal cord injury involving implantation of dendritic cells (DCs), which act as antigen-presenting cells in the immune system. The novel mechanisms underlying this treatment produce functional recovery. Among the immune cells tested, DCs showed the strongest activity inducing proliferation and survival of neural stem/progenitor cells (NSPCs) in vitro. Furthermore, in DC-implanted adult mice, endogenous NSPCs in the injured spinal cord were activated for mitotic de novo neurogenesis. These DCs produced neurotrophin-3 and activated endogenous microglia in the injured spinal cord. Behavioral analysis revealed the locomotor functions of DC-implanted mice to have recovered significantly as compared to those of control mice. Our results suggest that DC-implantation exerts trophic effects, including activation of endogenous NSPCs, leading to repair of the injured adult spinal cord.     

Reduced expression and aberrant localization of p120catenin in human squamous cell carcinoma of the skin

BACKGROUND: p120catenin (p120ctn), a member of the Armadillo protein family, is ubiquitously expressed and binds to classical cadherins together with other catenins to participate in the adherens junction. p120ctn has numerous isoforms generated through extensive splicing and alternative usage of translation initiation codons. Although the involvement of p120ctn in cell growth control has been postulated, little has so far been known about its expression patterns in the skin and epidermal tumors. OBJECTIVE: To identify the isoforms expressed in benign and malignant keratinocytes and to analyze the expression patterns of p120ctn in epidermal tumor specimens. METHODS: HaCaT, DJM-1, BSCC-93, HSC-1, HSC-5 and A431 cells along with normal skin tissue were subjected to RT-PCR to identify the expressed isoforms. For immunofluorescence study, surgical specimens including 29 squamous cell carcinomas (SSCs), 4 basal cell carcinomas (BCCs) and 4 seborrheic keratoses as well as 3 normal skin samples were stained with specific antibodies to detect p120ctn and E-cadherin. RESULTS: RT-PCR revealed that the isoform 3A was predominantly expressed with faint expression of the isoform 4 and that there was no difference in expressed isoforms between the examined cell lines. Immunofluorescent staining indicated that the expression of p120ctn was significantly reduced in all of the examined squamous cell carcinomas and that p120ctn was frequently localized in cytoplasm. In benign tumors and normal samples, p120ctn was properly expressed in cell-cell boundaries. Furthermore, there were several SCCs where E-cadherin continued to be expressed with no expression of p120ctn. CONCLUSION: Reduced expression and aberrant localization of p120ctn are among the most common events during the development and/or progression of SCCs.     

Cognitive impairments in Machado-Joseph disease

BACKGROUND: Cognitive function of Machado-Joseph disease (MJD) patients has not been clarified. OBJECTIVES: To determine the characteristics of cognitive dysfunction in MJD patients and to assess the relationship of dysfunction to age at onset, age at examination, disease duration, education, ataxia, depression, anxiety, and CAG repeat length. DESIGN: Case-control study. SETTING: Research-oriented hospitals. PARTICIPANTS: Sixteen genetically confirmed MJD patients able to complete neuropsychological tests and 20 control subjects matched to patients by age and education. MAIN OUTCOME MEASURES: Neuropsychological tests, including general cognition, verbal and visual memory, working memory, visuospatial and constructional ability, language, executive function, depression, and anxiety. RESULTS: Machado-Joseph disease patients scored significantly lower than controls in verbal and visual memory, in visuospatial and constructional tasks, and in phonemic and semantic fluency tasks. None of these impairments correlated with CAG repeat length, age at onset, age at examination, disease duration, or education. Verbal fluency (words named in a category) correlated with the International Cooperative Ataxia Rating Scale score. CONCLUSION: Machado-Joseph disease patients have verbal and visual memory deficits, visuospatial and constructional dysfunction, and verbal fluency deficits, all unrelated to CAG repeat length.     

Single footshock attenuates c-Fos expression induced by 5-HT2A receptor agonist (+/-)-2,5-dimethoxy-4-iodoamphetamine hydrochloride in rat brain

Administration of 3 mg/kg 5-hydroxytryptamine2A/2C (5-HT2A/2C) receptor agonist (+/-)-2,5-dimethoxy-4-iodoamphetamine hydrochloride (DOI) induced c-Fos expression in all areas of the rat neocortex. The single footshock 24 h before DOI administration significantly attenuated DOI-induced c-Fos expression in layer IV of the primary somatosensory cortex. These changes in c-Fos expression suggest an adaptational change in the somatosensory cortex by acute stress.     

Correlation of neuron-specific enolase and S100B with histological cerebral damage in fetal sheep after severe asphyxia

Experimental brain damage was induced in 16 fetal sheep by umbilical cord occlusion, and the correlation of neuron-specific enolase (NSE) or S100B with the damage grade was investigated in seven fetuses. Significant correlations of damage degree with NSE (p = 0.016) and S100B (p = 0.018) in serum 2 h after insult were shown by Spearman's test. These findings suggest that they represent potentially useful markers for detecting brain damage at early stage after ischemic insult.