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1. |
Does Parkinson's Disease Have an Immunological Basis?The Evidence and its Therapeutic Implications |
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BioDrugs,
Volume 15,
Issue 6,
2001,
Page 351-355
Urszula Fiszer,
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摘要:
Parkinson's disease (PD) is an age-related neurodegenerative movement disorder of unknown aetiology. Immune abnormalities have been described in PD including the occurrence of autoantibodies against neuronal structures and high numbers of microglia cells expressing the histocompatibility glycoprotein human leucocyte antigen-DR in the substantia nigra. An infectious cause for PD has been discussed for years. Disturbed cellular and humoral immune functions in peripheral blood of patients with PD have been also reported. An elevated gd+T cell population and increased immunoglobulin G immunity in CSF to heat shock proteins have been found in PD. Cytokines and apoptosis-related proteins were elevated in the striatum in patients with PD. Activated glial cells may participate in neuronal cell death in PD by providing toxic substances. We may conclude that the immune system is involved in the pathogenesis of PD. However, we are not able to determine whether the disturbances described above constitute a primary or secondary phenomenon. Immunomodulatory agents may have important applications in the development of new therapies for PD.
ISSN:1173-8804
出版商:ADIS
年代:2001
数据来源: ADIS
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2. |
Gene Therapy for Colorectal CancerTherapeutic Potential |
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BioDrugs,
Volume 15,
Issue 6,
2001,
Page 357-367
Ming-Jen Chen,
Guy A. Chung-Faye,
Peter F. Searle,
Lawrence S. Young,
David J. Kerr,
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摘要:
Colorectal cancer is a leading cause of cancer mortality in Western countries. Gene therapy has been proposed as a potential novel treatment modality for colorectal cancer, but it is still in an early stage of development. The preclinical data have been promising and numerous clinical trials are underway. This brief review aims to summarise the current status of clinical trials of different gene therapy strategies, including immune stimulation, mutant gene correction, prodrug activation and oncolytic virus therapy, for patients with colorectal cancer. Data from phase I trials have proven the safety of the reagents but have not yet demonstrated significant therapeutic benefit. In order to achieve this and extend the scope of the treatment, continuing efforts should be made to improve the antitumour potency, efficiency of gene delivery and accuracy of gene targeting.
ISSN:1173-8804
出版商:ADIS
年代:2001
数据来源: ADIS
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3. |
Immunosuppressive Treatment of Ocular Myasthenia Gravis |
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BioDrugs,
Volume 15,
Issue 6,
2001,
Page 369-378
Björn Tackenberg,
Bernhard Hemmer,
Wolfgang H. Oertel,
Norbert Sommer,
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摘要:
Myasthenia gravis (MG) is caused by autoantibodies against proteins at the neuromuscular junction. This autoimmune process leads to abnormal fatiguability and weakness of striated muscle. Ptosis and diplopia are among the most common manifestations of MG. The term ‘ocular MG’ (OMG) as opposed to ‘generalised MG’ (GMG) is used to define the clinical subtype of MG with isolated eye muscle weakness. Although OMG may appear to cause only moderate disability, it can significantly impair the patient's activities of daily living and progress to generalised myasthenia. Therefore, a clear management plan should be installed early in these patients. Since prospective treatment trials have not been performed, basic management strategies for OMG have to be deduced from retrospective studies, trials in GMG, and generally accepted clinical experience. Cholinesterase inhibitors are used in all types of MG, but are often less helpful in OMG. In the absence of thymoma, thymectomy is usually not considered in OMG, although a few studies have described histological abnormalities in thymuses from patients with OMG. Corticosteroids are of great short term benefit in most patients with OMG but potential adverse effects limit their long term use. Azathioprine is needed to reduce long term corticosteroid adverse effects, but this agent requires about 6 months to be effective. In summary, OMG has a good prognosis in most patients, with corticosteroids and azathioprine being the major treatment options. The challenges for the clinician are to recognise the condition despite the large number of differential diagnoses, to minimise the patient's symptoms using the therapies available and to carefully limit potentially hazardous therapeutic efforts, especially in mild or even uncertain cases.
ISSN:1173-8804
出版商:ADIS
年代:2001
数据来源: ADIS
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4. |
New Therapeutic Approaches to the Management of Rheumatoid Arthritis |
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BioDrugs,
Volume 15,
Issue 6,
2001,
Page 379-393
Laura B. Hughes,
Larry W. Moreland,
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摘要:
Rheumatoid arthritis (RA) is a common disease that affects up to 1% of the population, and causes significant morbidity and early mortality. The aetiology of RA is unknown; however, in the last 10 to 15 years significant advances in molecular technology have provided a greater understanding of the pathogenesis of the disease. This has led to the development of new approaches to the treatment of RA. The disease modifying antirheumatic oral agent leflunomide inhibits the proliferation of activated T cells that are important in the inflammation and degradation of synovial tissues. The 2 biological agents approved for the treatment of RA, infliximab and etanercept, are inhibitors of the pro-inflammatory cytokine, tumour necrosis factor-α (TNFα). Infliximab is a chimeric human/mouse monoclonal antibody which is administered by intravenous infusion and binds with high affinity to TNFα, thereby neutralising its effects. Etanercept is a recombinant, soluble TNF receptor molecule which is administered subcutaneously and binds to TNFα in the serum rendering it biologically inactive. The protein A immunoadsorption column is a medical device that in conjunction with plasmapheresis can be used in patients with refractory RA. These agents have provided new and effective therapies for the treatment of patients with RA.
ISSN:1173-8804
出版商:ADIS
年代:2001
数据来源: ADIS
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5. |
The Potential of Monoclonal Antibodies to Reduce Reperfusion Injury in Myocardial Infarction |
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BioDrugs,
Volume 15,
Issue 6,
2001,
Page 395-404
Marcus E. McKenzie,
Paul A. Gurbel,
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摘要:
Reperfusion injury is mediated, in part, by the accumulation of platelets and leucocytes in the microvasculature after reflow. These components of the blood pool form aggregates that can obstruct flow in small vessels. In addition, mediators released from leucocytes and platelets further damage the reperfused myocardium. A strategy to limit reperfusion injury exploits the important role of membrane-bound adhesion molecules that attach platelets and leucocytes to themselves and to the vascular endothelium. Monoclonal antibodies against specific adhesion receptors effectively eliminate the function of the receptor. The most widely investigated receptors are P-selectin, present on platelets and the endothelium, CD11/CD18, present on leucocytes, and the fibrinogen receptor on platelets. Numerous animal studies have strongly supported the use of these monoclonal antibodies to block adhesion receptors as adjunctive reperfusion therapy. However, recent human trials have yielded disappointing results.
ISSN:1173-8804
出版商:ADIS
年代:2001
数据来源: ADIS
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6. |
Systemic Availability of Inhaled Budesonide and Fluticasone PropionateHealthy versus Asthmatic Lungs |
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BioDrugs,
Volume 15,
Issue 6,
2001,
Page 405-411
Timothy Ward Harrison,
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摘要:
Inhaled corticosteroids are now recommended for the majority of patients with asthma. Although their therapeutic ratio is superior to that of oral corticosteroids, their long term use is associated with several potentially important adverse effects. A number of studies have compared the efficacy and/or systemic activity of the currently available inhaled corticosteroids, but the results of many of these studies have been conflicting. Although there are a number of factors that may explain these conflicting results, there is evidence that the type of individuals being studied is important. Extrapolation of the findings from healthy individuals to patients with asthma appears to be misleading because the systemic effects of some, but not all, inhaled corticosteroids are greater in healthy individuals than in patients with asthma.
ISSN:1173-8804
出版商:ADIS
年代:2001
数据来源: ADIS
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7. |
Antibody Responses of Healthy Infants to Concurrent Administration of a BivalentHaemophilus influenzaeType b-Hepatitis B Vaccine with Diphtheria-Tetanus-Pertussis, Polio and Measles-Mumps-Rubella Vaccines |
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BioDrugs,
Volume 15,
Issue 6,
2001,
Page 413-418
David J. West,
Gerard P. Rabalais,
Barbara Watson,
Harry L. Keyserling,
Holly Matthews,
Teresa M. Hesley,
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摘要:
ObjectiveTo confirm that children given a bivalentHaemophilus influenzaetype b-hepatitis B vaccine (bivalent Hib-HB vaccine; COMVAX™) concurrently with priming doses of diphtheria-tetanus-pertussis vaccine (DTP), a booster dose of diphtheria-tetanus-acellular pertussis vaccine (DTaP), inactivated or oral polio vaccine (IPV or OPV) and measles-mumps-rubella vaccine (M-M-R®II) have satisfactory antibody responses to all antigens.Design126 healthy 2-month-old infants were scheduled to receive bivalent Hib-HB vaccine concurrently with DTP (2 and 4 months of age), OPV or IPV (random allocation to OPV or IPV at 2 months of age; OPV at 4 and 14 to 15 months of age), DTaP and M-M-R®II(14 to 15 months of age). A response was judged ‘adequate’ if the lower bound of the 95% confidence interval on the proportion of vaccinees having a critical antibody level was <10 percentage points below prediction.ResultsAntibodies to hepatitis B virus surface antigen,H. influenzaepolysaccharide, diphtheria toxin, tetanus toxin, pertussis agglutinogens, pertussis toxin (as measured by enzyme immunoassay but not by Chinese hamster ovary cell assay), pertussis filamentous haemagglutinin after a booster dose of DTaP, poliovirus type 2, measles virus, and mumps virus all equalled or exceeded expected levels. Antibodies to rubella virus and pertussis filamentous haemagglutinin (after priming doses of DTP) fell slightly, and in the case of rubella significantly, below predicted levels. Antibodies to poliovirus types 1 and 3 were also below expectation after 2 doses of polio vaccine but were adequate following a third dose of vaccine.ConclusionConcurrent administration of bivalent Hib-HB vaccine with priming doses of DTP, a booster dose of DTaP, OPV, IPV, or M-M-R®IIwas well tolerated and, with the possible exception of rubella, did not substantially impair the antibody response to any antigen.
ISSN:1173-8804
出版商:ADIS
年代:2001
数据来源: ADIS
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