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ID PMID Title PublicationDate abstract
12471242 Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases. 2002 Dec 6 Multicellular organisms have three well-characterized subfamilies of mitogen-activated protein kinases (MAPKs) that control a vast array of physiological processes. These enzymes are regulated by a characteristic phosphorelay system in which a series of three protein kinases phosphorylate and activate one another. The extracellular signal-regulated kinases (ERKs) function in the control of cell division, and inhibitors of these enzymes are being explored as anticancer agents. The c-Jun amino-terminal kinases (JNKs) are critical regulators of transcription, and JNK inhibitors may be effective in control of rheumatoid arthritis. The p38 MAPKs are activated by inflammatory cytokines and environmental stresses and may contribute to diseases like asthma and autoimmunity.
12447630 The prevalence and significance of positive antinuclear antibodies in patients with fibrom 2002 Nov The aim of this study was to ascertain whether fibromyalgia patients with positive ANA develop other features of connective tissue disease over 2-4 years' follow-up. Patients attending our clinic with a diagnosis of fibromyalgia were identified. All ANA-positive patients (n = 12) were recruited and matched for age and sex with 12 ANA-negative FMS patients. As further control groups, patients with a diagnosis of osteoarthritis (OA) were included. A screening questionnaire for possible features of connective tissue disease was sent to all participants. Patients who had three or more positive criteria were invited for further assessment. The ANA-positive rate was 12/137 (8.8%) in FMS and 20/225 (8.9%) in OA patients. All ANA positivity was at a low titre. Fourteen out of 20 (70%) FMS patients and 17/30 (56.7%) OA patients had three or more criteria (P = 0.34). No significant differences in the number of the positive criteria were found between those who were ANA positive or negative in both groups. On full assessment we found one patient who fulfilled the criteria for SLE from the ANA-positive FMS group and one in the ANA-negative group who fulfilled the criteria for primary Sjögren's syndrome. Of the patients with OA, one who was ANA positive was diagnosed as having rheumatoid arthritis. The results from our study show that ANA (at least in low titre) is not a good predictor of the future development of connective tissue.
12439250 Results of direct exchange or debridement of the infected total knee arthroplasty. 2002 Nov In this literature review, 30 reports provided outcome data on 37 direct exchange arthroplasties, 530 open debridements, and 23 arthroscopic debridements. The average followup was approximately 4 years, but the range was broad (range, 0.02-14 years). Infection was controlled in 33 of the 37 infected total knee arthroplasties (89.2%) treated by direct exchange arthroplasty, in only 173 of the 530 infected total knee arthroplasties (32.6%) treated by open debridement and retention of the prosthetic components, and in 12 of the 23 infected total knee arthroplasties (52.2%) treated by arthroscopic debridement. There was wide variability in associated antibiotic therapy. Factors associated with successful direct exchange included infections by gram-positive organisms, absence of sinus formation, use of antibiotic-impregnated bone cement for the new prosthesis, and 12 weeks of antibiotic therapy. Direct exchange arthroplasty failed in four of 37 knees; two were in patients with rheumatoid arthritis who were taking corticosteroids. Factors associated with successful debridements included those done within 4 months of the index procedure, or in patients with less than 4 weeks of symptoms, antibiotic sensitive gram-positive organisms, well-fixed components with no radiologic evidence of osteitis, and in young healthy patients. Factors associated with the failed debridements included postoperative drainage for more than 2 weeks, sinus tracts present at the time of the debridement, a hinged prosthesis, and an immunocompromised host. Direct exchange can be successful with a sensitive organism in a healthy host with prolonged antibiotic therapy. Debridement can be successful in early infections in a healthy host.
12418438 Rheumatologic diseases in the intensive care unit: epidemiology, clinical approach, manage 2002 Oct Patients with systemic rheumatic diseases may be admitted to the ICU because of worsening of or development of a new manifestation of the rheumatic disease, infections caused by immunosuppression, or adverse effects of drugs used to treat rheumatic diseases. Sometimes an unrelated, acute disorder may become life threatening because of the underlying rheumatic disorder. Rheumatoid arthritis is the most common rheumatic disease seen in ICU patients, followed by systemic lupus erythematosus and scleroderma. These three conditions together account for up to 75% of rheumatic cases admitted to the ICU. The respiratory system is the organ system most commonly affected in the acute process, followed by the renal, gastrointestinal, and nervous systems. More than 50% of admissions result from infections, and 25% to 35% result from exacerbation of the underlying rheumatic condition. In about 20% of patients, the rheumatic disorder may be diagnosed for the first time in the ICU. An aggressive approach should be pursued to establish the diagnosis of either disease exacerbation or infection. Delay in instituting appropriate immunosuppressive or antimicrobial therapy may result in multiple organ system failure and a poor outcome. The mortality rate in patients with rheumatic disease exceeds that predicted by the APACHE II or SAPS II scores and is higher than that in nonrheumatologic ICU admissions. The mortality may exceed 50% in patients admitted for infection; the prognosis is comparatively better for patients with exacerbations of disease activity. Renal failure, coma, and acute abdomen are predictors of poor outcome. Early recognition of abdominal complications requiring surgical intervention may help reduce mortality.
12401861 A retrospective analysis for aetiology and clinical findings of 287 secondary amyloidosis 2002 Nov BACKGROUND: Secondary amyloidosis is the most frequent of the various types of systemic amyloidosis, the epidemiology of which is not yet fully known. The aim of our study was to evaluate retrospectively the collective data for the aetiological distribution, clinical findings and approaches to the management of secondary amyloidosis in Turkey. METHODS: Data from a simple questionnaire addressing aetiology, and demographic and clinical characteristics of patients with biopsy-proven secondary amyloidosis was retrospectively analysed. Eleven nephrology clinics contributed data for this study. RESULTS: The 11 contributing centres provided a total of 287 cases (102 female, 185 male). The aetiological distribution was as follows: familial Mediterranean fever (FMF) 64%, tuberculosis 10%, bronchiectasis and chronic obstructive lung disease 6%, rheumatoid arthritis 4%, spondylarthropathy 3%, chronic osteomyelitis 2%, miscellaneous 4%, unknown 7%. Oedema accompanied by proteinuria was present in 88% of the cases, hepatomegaly in 17%, and splenomegaly in 11%. The mean systolic and diastolic blood pressures were 115+/-26 and 73+/-15 mmHg respectively. The family history was positive in 16%; 73% of the cases were on colchicine treatment when the questionnaire was administered. Thirty-eight per cent of the cases had progressed to ESRD and were on renal replacement therapy. CONCLUSIONS: FMF is the leading cause of secondary amyloidosis in Turkey, followed by tuberculosis. Oedema accompanied by proteinuria is the most prominent presenting finding, and hypotension seems to be common among these patients.
12220670 Chemokine receptor inhibition by AMD3100 is strictly confined to CXCR4. 2002 Sep 11 This study was undertaken to demonstrate the unique specificity of the chemokine receptor CXCR4 antagonist AMD3100. Calcium flux assays with selected chemokine/cell combinations, affording distinct chemokine receptor specificities, revealed no interaction of AMD3100 with any of the chemokine receptors CXCR1 through CXCR3, or CCR1 through CCR9. In contrast, AMD3100 potently inhibited CXCR4-mediated calcium signaling and chemotaxis in a concentration-dependent manner in different cell types. Also, AMD3100 inhibited stromal cell-derived factor (SDF)-1-induced endocytosis of CXCR4, but did not affect phorbol ester-induced receptor internalization. Importantly, AMD3100 by itself was unable to elicit intracellular calcium fluxes, to induce chemotaxis, or to trigger CXCR4 internalization, indicating that the compound does not act as a CXCR4 agonist. Specific small-molecule CXCR4 antagonists such as AMD3100 may play an important role in the treatment of human immunodeficiency virus infections and many other pathological processes that are dependent on SDF-1/CXCR4 interactions (e.g. rheumatoid arthritis, atherosclerosis, asthma and breast cancer metastasis).
12139733 DNA microarray analysis of T cell-type lymphoproliferative disease of granular lymphocytes 2002 Aug Lymphoproliferative disease of granular lymphocytes (LDGL) is characterized by the clonal proliferation of large granular lymphocytes of either T- or natural killer cell origin. To better understand the nature of T cell-type LDGL, we purified the CD4-CD8+ proliferative fractions from LDGL patients (n=4) and the surface marker-matched T cells isolated from healthy volunteers (n=4), and compared the expression profiles of 3456 genes using DNA microarray. Through this analysis, we identified a total of six genes whose expression was active in the LDGL T cells, but silent in the normal ones. Interestingly, expression of the gene for interleukin (IL) 1beta was specific to LDGL T cells, which was further confirmed by the examination of the serum level of IL-1beta protein. Given its important role in inflammatory reactions, the disease-specific expression of IL-1beta may have a causative relationship with the LDGL-associated rheumatoid arthritis. Spectratyping analysis of the T-cell receptor repertoire also proved the monoclonal or oligoclonal nature of LDGL cells. These data have shown that microarray analysis with a purified T-cell subset is an efficient approach to investigate the pathological condition of Tcell-type LDGL.
12052219 Recent advances in PDE4 inhibitors as immunoregulators and anti-inflammatory drugs. 2002 The phosphodiesterases (PDEs) are responsible for the hydrolysis of intracellular cyclic adenosine and guanosine monophosphate (cAMP and cGMP, respectively). They are classified into 11 major families (PDE1-11) and the type 4 phosphodiesterase (PDE4) is a cAMP-specific enzyme localized in airway smooth muscle cells as well as in immune and inflammatory cells. The PDE4 activity is associated with a wide variety of diseases some of which have been related to an inflammatory state, (e.g. asthma, chronic obstructive pulmonary disease (COPD), rheumatoid arthritis (RA)) while others have recently been connected to autoimmune pathology. Therefore, an intense effort toward the development of PDE4 inhibitors has been generated for the last decade. Unfortunately, the effects of prototype PDE4 inhibitors have been compromised by side effects such as nausea and emesis and the clinical use of those compounds is still limited. Several companies have focused on the design of a new generation of PDE4 inhibitors dissociating beneficial activity and adverse effects. This review highlights the recent data of the most advanced clinical candidates, the design and structure activity relationships of the recent structural series reported in the literature over the last two years, as well as recent advances in the multiple therapeutic indications of PDE4 inhibitors (a review with 375 references).
12037402 Immune profiles of patients with chronic idiopathic urticaria. 2002 May BACKGROUND: The immunologic characterization of chronic idiopathic urticaria (CIU) is still incomplete. In particular, it is not known if positivity to the intradermal autologous serum skin test (ASST) identifies an immunologic subset of CIU patients. METHODS: Nineteen CIU patients and 15 healthy controls were enrolled in the study. A diagnostic flowchart was designed to select CIU patients, who were then analyzed by ASST. Cytokine and chemokine production and the expression of adhesion molecules was measured in patients and controls. RESULTS: In CIU patients compared to controls, it was found that (1) TNF-alpha, IL-10, MIP-1alpha and RANTES production was augmented and IL-2 and INF-gamma reduced, and (2) CD44, CD11a and CD62L expression on CD4 and CD8 cells was augmented. Additionally, TNF-alpha and chemokine production was significantly increased in CIU patients with a negative ASST (p-; n = 10) compared to patients with a positive response to the test. CONCLUSIONS: The presence of an inflammatory process in CIU patients is suggested by the findings that the production of both TNF-alpha and chemokines as well as the expression of adhesion molecules is increased in these patients. Similarly to what is seen in rheumatoid arthritis, augmented IL-10 production might be secondary to the attempt to hamper the inflammatory milieu. Immune profiles are particularly altered in CIU p- patients, in whom a more aggressive therapeutic strategy might be considered.
11950250 Characterization of infiltrating T cells and Th1/Th2-type cytokines in the synovium of pat 2002 Apr OBJECTIVE: It has been suggested that osteoarthritis (OA) is induced by mechanical stress followed by cartilage destruction, and it is generally accepted that there is little involvement of an immune response in OA compared with that in rheumatoid arthritis (RA). We have previously found clonally expanded transcripts of Vbeta chain of the T cell receptor (TCR) in the synovium of patients with OA. To test the hypothesis that an immune response is involved in OA, we determined: (a) whether CD3+, CD4+, and CD8+ T-cells were infiltrating the synovial membrane of patients with OA; (b) the Th1/Th2-type cytokines produced at the protein level in the synovium of patients with OA. METHODS: Immunohistochemical analysis was performed to identify T-cells that infiltrated the synovium of patients with OA using specific antibodies against CD3+, CD4+, and CD8+ T-cell differential antigens, interferon-gamma (IFN-gamma as a marker for Th1 cells, and interleukin-4 (IL-4) as a marker for Th2 cells. RESULTS: CD4+ T-cells were strongly detected in the sublining layer of the synovium of patients with OA compared with the number detected in the same synovial layer of normal subjects. The number of IFN-gamma+ cells was significantly higher than that of IL-4+ cells in the synovium of patients with OA (P< 0.05). CONCLUSION: These observations suggest that Th1 cells predominate in the synovium of patients with OA, which clearly indicates that immune regulation occurs and may play critical roles in inflammation and cartilage destruction in patients with OA.
11922232 Inhibition of membrane Na+-K+ ATPase activity: a common pathway in central nervous system 2002 Mar OBJECTIVES: The study was conducted to assess the role of hypothalamic digoxin in neuropsychiatric and systemic disorders. A hypothesis regarding the central role of hypothalamic digoxin in neuroimmunoendocrine integration is proposed. METHODOLOGY: Blood samples from patients of CNS glioma, multiple sclerosis, systemic lupus erythematosis, subacute sclerosing panencephalitis, primary generalized epilepsy, Parkinson's disease, Down syndrome, AIDS dementia with neuropsychiatric features, syndrome X with multiple lacunar state, senile dementia, familial group (a family with familial coexistence of schizophrenia, Parkinson's disease, primary generalized epilepsy, malignant neoplasia, rheumatoid arthritis and syndrome X over three generations), schizophrenia and manic depressive psychosis were analysed for RBC membrane Na+-K+ ATPase, levels of digoxin and Mg++. RESULTS: Inhibition of RBC membrane Na+-K+ ATPase activity was observed in most cases along with increase in the levels of serum digoxin and decrease in the level of serum Mg++. CONCLUSION: The decreased Na+-K+ ATPase activity can be due to increased digoxin, which is a potent inhibitor of this enzyme. The inhibition of Na+-K+ ATPase can contribute to increase in intracellular calcium and decrease in magnesium, which can result in 1) defective neurotransmitter transport mechanism, 2) neuronal degeneration and apoptosis, 3) mitochondrial dysfunction, 4) defective golgi body function and protein processing dysfunction, 5) immune dysfunction and oncogenesis. The mechanism of how increased intracellular calcium and decreased magnesium can contribute to the above effects is discussed.
11916167 Heterogeneity of HLA-DRB1*04 and its associated haplotypes in the North Indian population. 2002 Jan HLA-DR4 has been implicated in several diseases including rheumatoid arthritis (RA) and type I diabetes, the strength of associations being ethnically variable. Unusually high level of heterogeneity in DR4-DQB1 haplotypes has been reported in the Indian population. The present study is an attempt to determine the genetic diversity of the HLA-DR4 allelic family and its associated DQA1-DQBI haplotypic combinations in the healthy North Indian population. Using PCR-SSP and PCR-SSOP techniques, nine subtypes of DR4 were encountered of which DRB1*0403 was the most predominant allele (34.8%) followed by *0404 (27%), *0401 (14.6%), and *0405 (11%). No examples of *0402, *0409, *0411, *0413-*0417, and *0419-23 were encountered, although a few other subtypes, *0410 (three examples), *0406 and *0418 (two examples each), and *0407, *0408, and *0412 (single example each) occurred infrequently in a cohort of 85 HLA-DR4 positive samples studied. Most of these subtypes occurred in combination with DQA1*03-DQB1*0302 (69.5%). DRB1*0403 and *0404 exhibited maximum heterogeneity of DQB1 combinations. Haplotype data revealed the presence of 15 different DR4-DQ haplotypes, four of which were found to be "unique" to Asian Indians, not reported in any other population. These results help to explain the observed variability in DR4 associations in autoimmune diseases in Asian Indians and provide support for scientific and historical documentation of extensive admixture in the Indian subcontinent.
11914667 Multiple hepatic adenomas: Tc-99m RBC liver SPECT findings with pathologic correlation. 2002 Apr A 24-year-old man with multiple hepatic masses incidentally detected by ultrasonography underwent Tc-99m RBC liver SPECT. SPECT images showed increased blood pooling mimicking hemangiomas in two of four masses or activity similar to normal liver in the others. The patient had a 3-year history of steroid therapy for rheumatoid arthritis. Computed tomography and magnetic resonance imaging showed multiple liver lesions. Angiography revealed three hypervascular and one hypovascular mass. Microscopic examination of the enucleated specimens disclosed hepatic adenomas with many dilated sinusoids in the masses showing blood pooling and fatty change, and adenomas without dilated sinusoids in the masses not showing blood pooling. This case report shows that the appearance of hepatic adenomas can vary on Tc-99m RBC liver SPECT, depending on whether dilated sinusoid and hepatic adenomas show blood pooling. This is one of the few examples of false-positive findings that can be mistaken for hemangioma.
11785833 Immunosurveillance, immunodeficiency and lymphoproliferations. 2002 The incidence of malignant lymphomas is significantly higher in patients who have congenital or acquired immunodeficiencies. Although there are some differences between these immunodeficiency-associated lymphoproliferative disorders (IALD), they share several features: a tendency to present in extranodal sites, particularly the central nervous system and gastrointestinal tract, rapid clinical progression when untreated, diffuse large cell histology, B-cell origin and association with the Epstein-Barr virus (EBV). In the presence of disturbed T-cell function EBV may induce not only prolonged proliferation but also transformation of B-cells. In patients with primary, congenital immunodeficiency the incidence of IALD ranges from 0.7% for patients with X-linked agammaglobulinemia to 12-15% in patients with ataxia telangiectasia. In patients with post-transplant lymphoproliferative disorders (PT-LPD) the incidence varies from 0.5% after bone marrow transplantation to 10% after heart-lung transplantation. PT-LPD are often characterized by a polymorphic cell population. Recent studies identified three categories: plasmacytic hyperplasia, polymorphic lymphoproliferation and B-cell non-Hodgkin's lymphoma (NHL). The plasmacytic hyperplasias are of polyclonal composition, while polymorphic lymphoproliferations and NHL are monoclonal. The precise risk of lymphoma development in HIV infection is not defined, but estimates suggest a prevalence of 3-4%. HIV-related NHLs are divisible by site of manifestation into systemic, primary central nervous system and body-cavity lymphomas, and by pathology into Burkitt's and Burkitt's-like lymphoma, and diffuse large cell lymphoma (DLCL). In about 90% of cases these lymphomas are of monoclonal B-cell composition. Recent experiences suggest a link between therapy with immunosuppressive drugs (methotrexate, azathioprine, cyclophospamide, etc.) and development of IALD, best supported by the increased rate of IALD in patients with rheumatoid arthritis who receive methotrexate therapy. The occurrence of IALD demonstrates the importance of competent immunosurveillance in the development of lymphoid neoplasias, which may have therapeutic relevance too.
15607128 Inhibitors of mast cell tryptase beta as therapeutics for the treatment of asthma and infl 2005 A survey of the available biological data on tryptase inhibitors suggests that there is considerable interest in tryptase as a therapeutic target particularly for the treatment of allergic asthma and inflammatory disorders. This interest was driven primarily by data from studies carried out on the cellular and in vivo actions of this serine protease over the past decade, all of which have suggested a pro-inflammatory role for tryptase. Tryptase beta is the form of interest in allergic asthma and the data from numerous studies have shown that tryptase cannot only contribute to airway bronchoconstriction and hyperresponsiveness, but may have a key role in fibrosis and ECM turnover, hallmarks of the remodeling process. Hence, inhibitors of tryptase have the potential to make an impact on fibrosis and airway wall remodelling. However, few studies, if any, have been carried out to determine the effect of tryptase inhibitors on airway remodeling and this is an area that warrants further investigation with the appropriate models because the eventual positioning of tryptase inhibitors in asthma therapy will be strengthened by data supporting an impact on airway remodeling in addition to effects on bronchial hyperresponsiveness. This review has focused on tryptase inhibitors in the pipeline and it is clear that with a few exceptions, the majority of these compounds are targeted for inhaled delivery. Finally, judging by the interest from numerous pharmaceutical companies, it appears the stage is set for tryptase inhibitors to make their mark as drugs of the future for allergic asthma and the results from clinical trials is awaited with eager anticipation.
15605695 [Atlanto-axial subluxation posssibly due to eosinophilic granuloma of the axis: a case rep 2004 Dec A 29-year-old male presented with symptoms of acute severe neck pain with no other neurological symptoms. He had noticed lymph node swelling with pain in his neck about 2 months before admission and had been treated by the transoral administration of antibiotics for about 10 days. His neck was protected with a neck collar and an evaluation of any possible neck lesion was performed. Plain X-ray film and CT scans of the cervical spine showed an anterior subluxation of the atlas and an anterior declination and erosion of the dens. The MRI findings showed long T1 and T2 values in many parts of the bone marrow of the body of the axis and the dens, and both the bone marrow and thickend soft tissue between the pharynx and the axis were slightly enhanced. Inflammatory disease, tuberculosis, rheumatoid arthritis, malignant lymphoma, and leukemia were all ruled out based on the laboratory data, Ga schintigrams and other examinations. Almost no changes in the lesion were observed on MRI at about 6 weeks after admission. As a result, we presumed that this lesion was not likely to be malignant, but might be some kind of granuloma, especially an eosinophilic granuloma. A laminectomy of the atlas and a resection of the posterior margin of the foramen magnum and upper portion of the lamina of the axis was performed to achieve decompression of the craniovertebral junction, and posterior fusion was performed with a rod betweeen the occipital bone and the C4 lamina. The rod was fixed with screws and wires to the occipital bone and with lamina hooks to the axis and C4 laminas. At 14 months postoperatively, the patient is doing well and the axis and the dens have been reconstructed without any need to resect the lesion, or perform either chemothrapy or radiotherapy. Our clinical findings of this case correlate with the opinion that an immobilization of the lesion is a sufficient treatment for many cases of eosinophilic granuloma. Although a biopsy or histological examination of the lesion was not performed, the clinical course of this case strongly suggests that this lesion was indeed an eosinophilic granuloma.
15578912 Extracellular tropomyosin: a novel common pathway target for anti-angiogenic therapy. 2004 Nov Angiogenesis is characterized by the development of new vasculature from pre-existing vessels and plays a central role in physiological processes such as embryogenesis, wound healing and female reproductive function, as well as pathophysiologic events including cancer, rheumatoid arthritis and diabetic retinopathy. The growth and metastasis of tumors is critically dependent upon angiogenesis. Although targeting angiogenesis as a therapeutic strategy has to date met with limited success in the clinic, the recent FDA approval of the anti-VEGF antibody Avastin has validated the use of anti-angiogenic therapeutic strategies for cancer treatment. We have recently identified several plasma proteins having anti-angiogenic properties, including Histidine-Proline-Rich Glycoprotein (HPRG) and activated high-molecular-weight kininogen (HKa). Both of these proteins are able to induce apoptosis in endothelial cells in vitro and can inhibit angiogenesis in vivo. Recent studies from our laboratories have also identified a novel cell-surface binding protein for HKa that mediates its anti-angiogenic activity. This protein, tropomyosin, is normally found inside the cell and is associated with the actin cytoskeleton, where it plays a critical role in stabilizing actin filaments in a variety of cell types. However, in angiogenic endothelial cells, tropomyosin appears to have extracellular localization. Previous studies have also suggested the involvement of tropomyosin in the anti-angiogenic activity of endostatin, and our recent work indicates that tropomyosin may mediate the antiangiogenic activity of HPRG as well. In this review, we summarize data describing extracellular tropomyosin as a novel receptor for multiple anti-angiogenic proteins. Extracellular tropomyosin may therefore represent a previously undescribed central target for the development of anti-angiogenic therapy.
15564440 Mounting evidence for vitamin D as an environmental factor affecting autoimmune disease pr 2004 Dec Low vitamin D status has been implicated in the etiology of autoimmune diseases such as multiple sclerosis, rheumatoid arthritis, insulin-dependent diabetes mellitus, and inflammatory bowel disease. The optimal level of vitamin D intake required to support optimal immune function is not known but is likely to be at least that required for healthy bones. Experimentally, vitamin D deficiency results in the increased incidence of autoimmune disease. Mechanistically, the data point to a role for vitamin D in the development of self-tolerance. The vitamin D hormone (1,25-dihydroxy vitamin D(3)) regulates T helper cell (Th1) and dendritic cell function while inducing regulatory T-cell function. The net result is a decrease in the Th1-driven autoimmune response and decreased severity of symptoms. This review discusses the accumulating evidence pointing to a link between vitamin D and autoimmunity. Increased vitamin D intakes might decrease the incidence and severity of autoimmune diseases and the rate of bone fracture.
15555933 Purification and characterization of a recombinant version of human alpha-fetoprotein expr 2004 Dec Alpha-Fetoprotein (AFP) is a 68 kDa glycoprotein expressed at high levels by the fetal liver and yolk with transcription repressed to very low levels after birth. Transfer of fetal AFP through the placenta into the circulation of the mother is correlated with remission of rheumatoid arthritis, multiple sclerosis, and other autoimmune disorders. AFP is therefore under development as a biopharmaceutical for the treatment of autoimmune diseases. The clinical evaluation of AFP requires the production of hundreds of grams of highly purified and biologically active protein. We have produced goats that express a form of the human AFP transgene under the control of the beta-casein promoter. In this form of rhAFP, the single N-linked glycosylation site was removed by mutagenesis (N233Q). Here, we describe a purification protocol for this recombinant human (rh)AFP from the milk of these transgenic goats. A three-column procedure was developed to produce gram quantities of highly purified rhAFP. Near- and far-UV circular dichroism spectra of human umbilical cord blood AFP and rhAFP were essentially identical, suggesting that the structure is not affected by removal of the glycosylation site. Furthermore, the cell binding and pharmacokinetics of purified rhAFP were similar to human AFP isolated from cord blood. Our results demonstrate that an active form of rhAFP can be produced on industrial scale by expression in transgenic goat milk.
15497064 An evaluation of the underlying causes of fall-induced hip fractures in elderly persons. 2004 Oct BACKGROUND: Falls are the major cause of hip fractures in elderly patients. The aim of this prospective study was to investigate the underlying causes of fall-induced hip fractures in the elderly. METHODS: The study included 32 patients (18 males, 14 females; mean age 78 years; range 57 to 95 years) who had proximal femoral fractures following an unexpected and sudden fall from about a meter height at a moment of lying, sitting, or standing position. Underlying causes of falls were sought, including previous falls, stroke, polyneuropathy, motion disorders, dementia, vision problems, fainting, vestibular pathologies, and cardiac diseases. RESULTS: Eight patients (25%) had a history of previous falls and 12 patients (37.5%) had a history of stroke. Polyneuropathy, Parkinson's Disease, and dementia were diagnosed in eight (25%), three (9.4%), and five (15.6%) patients, respectively. Twenty-one patients (65.6%) had neurologic diseases, 11 patients (34.4%) had cataract or other vision problems, eight patients (25%) had osteoarthritis and rheumatoid arthritis, 10 patients (31.3%) had vestibular pathologies, and 17 patients (53.1%) had cardiac diseases such as heart failure, orthostatic hypotension, ischemic heart disease, and arrhythmia. CONCLUSION: In order to prevent recurrent falls, risk factors associated with falls should be determined and preventive treatment and measures should be put into practice in elderly patients who have fall-induced injuries.