Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Transplantation of cells and organs from pigs to human beings offers potential treatment for medical conditions such as diabetes, kidney and heart failure, and Parkinson's disease. When the antibody-mediated hyperacute rejection barrier is overcome, a xenograft may not be treated as an allograft by the human immune system. Without prior culture with porcine cells, human lymphocytes are cytotoxic to some porcine cells. Our aim was to functionally characterize this direct cytotoxic response to porcine PHA-lymphoblasts and lymphocytes. Peripheral blood mononuclear cells from seven of eight human beings were cytotoxic to porcine PHA-lymphoblasts in bulk chromium-release assays, but not to the porcine lymphocytes from which the PHA-lymphoblasts were derived. The NK cell-sensitive cell line K562 only partly blocked the response to the PHA-lymphoblasts. IL-2-expanded clones of human lymphocytes were able to discriminate between PHA-lymphoblasts from two pigs and unable to lyse K562. When using IL-2 to make the anti-porcine cells proliferate under limiting dilution conditions, the proliferation and/or function of these cells did not conform to single-hit kinetics. All the observations from experiments with cells in bulk cultures and as short-term clones suggest that the direct cytotoxic response of human lymphocytes to porcine cells is heterogeneous and composed of a small population of in vivo-activated T cells as well as NK cells.
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PMID:Direct cytotoxic response of human lymphocytes to porcine PHA-lymphoblasts and lymphocytes. 916 71

Autonomic impairment is minor in idiopathic amyotrophic lateral sclerosis (ALS) and Alzheimer's-type dementia (D) and is usually not marked in Parkinson's disease. The autonomic status of Guamanian parkinsonism (P), ALS, and parkinsonism-dementia complex (PDC) is essentially unknown. We therefore evaluated the autonomic nervous system in Guamanian D, ALS, P, and PDC. Cardiovagal, adrenergic, and postganglionic sudomotor functions were quantitated in 16 patients and 14 paired household controls. Patients comprised PDC (N = 11), D (N = 2), P (N = 2), and ALS (N = 1). Autonomic deficit was expressed on a composite autonomic scoring scale (CASS) and its subsets that corrects for the effects of age and gender. CASS severity was rated from 0 to 10 and the maximal subset scores were 3, 3, and 4 for postganglionic sudomotor, cardiovagal, and adrenergic deficits, respectively. CASS scores for mild, moderate, and severe autonomic failure are 1 to 3, 4 to 6, and 7 to 10, respectively. Symptoms were scored by an Autonomic Symptom Profile (ASP). The affected patients were older than and had a sex distribution different from paired controls (64.2 +/- 8.0 versus 53.1 +/- 13.5; p < 0.01; male/female = 9/7 versus 2/12; p = 0.045). CASS scores were markedly increased over paired controls (6.2 +/- 2.3 versus 1.9 +/- 1.3; p < 0.001), and involvement was generalized by system. There were deficits in sudomotor, cardiovagal, and adrenergic function. Orthostatic hypotension occurred in 6 of 16 patients and 2 of 14 paired controls. Guamanian patients had more autonomic dysfunction than non-Guamanian Parkinson's disease. ASP scores were higher in patients than controls and regressed with CASS. These differences persisted when corrected for the confounding effects of age, gender, and diabetes. We conclude that Guamanian patients have autonomic failure to a greater extent than non-Guamanian Parkinson's disease or ALS. This autonomic failure suggests multisystem autonomic involvement similar to but less severe than in multiple system atrophy.
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PMID:Autonomic failure in Guamanian neurodegenerative disease. 933 85

Apoptosis, often synonymously used with the term 'programmed cell death', is an active, genetically controlled process that removes unwanted or damaged cells. Suppression, overexpression or mutation of a number of genes which orchestrate the apoptotic process are associated with disease. The diseases in which apoptosis has been implicated can be grouped into 2 broad groups: those in which there is increased cell survival (i.e. associated with inhibition of apoptosis) and those in which there is excess cell death (where apoptosis is overactive). Diseases in which there is an excessive accumulation of cells include cancer, autoimmune disorders and viral infections. Deprivation of trophic factors is known to induce apoptosis in cells dependent on them for survival. This fact has been exploited in the use of antiandrogens or antiestrogens in the management of prostate or breast cancer. Haemopoietic growth factors like granulocyte-macrophage colony stimulating factor (GM-CSF) or interleukin-3 prevent apoptosis in target cells and modulation of levels of these factors has been tried in the prevention of chemotherapy-induced myelosuppression. Until recently, it was thought that cytotoxic drugs killed target cells directly by interfering with some life-maintaining function. However, of late, it has been shown that exposure to several cytotoxic drugs with disparate mechanisms of action induces apoptosis in both malignant and normal cells. Physiological regulation of cell death is essential for the removal of potentially autoreactive lymphocytes during development and the removal of excess cells after the completion of an immune response. Recent work has clearly demonstrated that dysregulation of apoptosis may underlie the pathogenesis of autoimmune diseases by allowing abnormal autoreactive lymphocytes to survive. AIDS and neurodegenerative disorders like Alzheimer's or Parkinson's disease represent the most widely studied group of disorders where an excess of apoptosis has been implicated. Amyotrophic lateral sclerosis, retinitis pigmentosa, epilepsy and alcoholic brain damage are other neurological disorders in which apoptosis has been implicated. Apoptosis has been reported to occur in conditions characterised by ischaemia, e.g. myocardial infarction and stroke. The liver is a site where apoptosis occurs normally. This process has also been implicated in a number of liver disorders including obstructive jaundice. Hepatic damage due to toxins and drugs is also associated with apoptosis in hepatocytes. Apoptosis has also been identified as a key phenomenon in some diseases of the kidney, i.e. polycystic kidney, as well as in disorders of the pancreas like alcohol-induced pancreatitis and diabetes.
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PMID:Apoptosis: clinical relevance and pharmacological manipulation. 933 59

A follow-up study was conducted among men and women aged 55 years and over living in the community in order to estimate the incidence of initiation of antidepressant drug use and the association with chronic diseases. The study population consisted of 7,812 individuals. Overall, the incidence density for starting therapy with an antidepressant drug was 13.5 per 1000 person-years. The cumulative incidences after 1, 2 and 3 years were 1.3, 2.7 and 4.0%, respectively. The incidence in women was almost twice that in men and slightly higher in participants older than 70 years than in those younger than 70 years. The majority of the antidepressants prescribed were tricyclic antidepressants (65%), followed by selective serotonin reuptake inhibitors (23%) and other (12%) antidepressants. Only a minority (23%) received a dose considered effective for the indication of depression. Selective serotonin reuptake inhibitors were more often prescribed in an adequate dosage (68%) than were tricyclic antidepressants (12%) and other antidepressants (8%). Of the chronic diseases studied, only osteoarthritis and a history of stroke were predictors of initiation of antidepressant drug use after adjustment for age, sex and medical consumption. Hypertension, history of myocardial infarction, diabetes mellitus, rheumatoid arthritis, glaucoma, cognitive impairment and Parkinson's disease were not associated with future antidepressant drug use. No relevant differences were observed with respect to the choice of type of antidepressant drug among patients with chronic diseases. The present study indicates that each year antidepressant drug therapy is initiated in approximately 1.3% of the elderly. In general, the presence of chronic somatic diseases was not predictive of initiation of antidepressant drugs. Tricyclic antidepressants in this age group and in patients with certain chronic diseases may not be the optimal choice given their side-effects profile and drug-drug and drug-disease interactions. The predominance of these agents in the present study calls for further attention.
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PMID:Incidence of antidepressant drug use in older adults and association with chronic diseases: the Rotterdam Study. 934 83

Xenotransplantation is a potential solution to the current donor shortage for allotransplantation. Likewise it is being investigated for a number of other disease states such as Parkinson's disease, diabetes, and acquired immunodeficiency disease. Infections are a concern with the use of any biologic agent and as such have proved to be a substantial cause of morbidity and mortality after allotransplantation. Similarly, infections will likely cause disease after xenotransplantation. Public debate on the ethics of whether the field of xenotransplantation should move forward has focused on the concern of novel infections, xenozoonoses. Accordingly, the role of animal microbes must be critically examined. This article reviews mechanisms for xenogeneic infections and details what is known and what still needs to be learned as the field of xenotransplantation progresses. Emphasis is placed on microbial agents of baboons and swine, as they are currently the most common species considered as donor sources for xenotransplantation.
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PMID:Infectious concerns of cross-species transplantation: xenozoonoses. 936 13

Many efforts have been made to trace the causes of Alzheimer's disease (AD). There are, however, many points of controversy among reports from the same country as well as among reports from different countries. The current study is a case-control study to determine the risk factors in the development of AD in Greece. Sixty-five patients with AD and 69 age-matched controls were examined. All patients with AD fulfilled the DSM-IV criteria for AD and NINCDS-ADRDA criteria for probable AD. Demographic characteristics such as gender, current marital status, who he/she is living with, education, main place of residence in childhood, adulthood, and late life, occupational hazards, patient's medical history (history of diabetes mellitus and hypertension), life habits like alcohol consumption and smoking, and a history of head trauma, heart attack, stroke, parkinsonism, or depression were collected from the subject or from an informant. A family history of selected diseases (hypertension, diabetes mellitus, dementia, Parkinson's disease, Down's syndrome, stroke) was also elicited. Ages of father and mother at birth were also recorded. Chi-square test, Kruskal-Wallis analysis of variance, cluster analysis, and logistic regression analysis were used for statistical analysis. The results (chi-square test) showed a statistically significant difference between patients with dementia of the Alzheimer type and controls as far as marital status (p = .04), the subject's history of major depressive episode (p = .02), and family history of dementia (p = .002) were concerned. Logistic regression analysis results produced a complex model of family aggregation of dementia, with patients with a history of depression and family history of dementia having an up to seven times higher risk of developing AD. These findings, especially a family history of dementia, are consistent with most of the literature.
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PMID:Risk factors for clinically diagnosed Alzheimer's disease: a case-control study of a Greek population. 951 31

Mitochondrial DNA mutations have been implicated in a great variety of diseases, including such common ones as diabetes, Parkinson's disease and Alzheimer's, but the pathophysiological pathway leading from a specific mutation to a specific phenotype has remained elusive. Individuals with the same mutation can fall along a clinical spectrum ranging from asymptomatic to severely affected, and can even have completely different diseases. Much of this phenotypic heterogeneity has been attributed to the heteroplasmic nature of mitochondrial mutations, with both normal and mutated mitochondrial chromosomes being present in different proportions and tissue distributions. Isolated hearing loss is one of the only mitochondrial disorders that can be caused by homoplasmic mutations (e.g., only mutated mitochondrial mutations are present in all tissues). This review will outline the relationship between mitochondrial mutations and hearing loss while showing that even in a homoplasmic model, the two basic questions of mitochondrial genetics, penetrance and tissue specificity, remain unanswered: Why does the same mutation cause severe hearing loss in some family members but not in others, and why is the ear the only organ affected?
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PMID:Mitochondrial genetics and hearing loss: the missing link between genotype and phenotype. 957 47

Overt copper deficiency is not believed to be a widespread public health concern for most population groups. However, a variety of case studies suggest that under certain circumstances, clinical conditions may predispose individuals to the risk of copper deficiency or copper excess. Acquired copper deficiency has been documented in conditions predisposing to inadequate copper intakes, in prematurity, in malabsorption syndromes, and in conditions predisposing to excessive copper losses. In contrast, increases in copper concentrations have been reported in response to stress, inflammation, and infection; in Parkinson disease and diabetes mellitus; and in conditions involving an obstruction to bile flow.
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PMID:Clinical conditions altering copper metabolism in humans. 958 45

Transplantation has become a successful method for the management of functional failure of a variety of tissues or organs. However, the majority of clinical transplantations use non-autologous allogeneic donor tissue implanted from one human to another. In order to prevent rejection of the allogeneic tissue, methods to overcome the immune barrier are necessary. Although prevention of organ rejection is currently achieved with pharmacological immune suppression, the undesirable side effects of this method have incited interest in novel methods to overcome the immune barrier. One such novel method of preventing immune reaction is immuno-isolation, in which the non-autologous tissues are physically isolated from the host tissues by placement in devices with perm-selective membranes. The membranes of these devices allow release of the therapeutic product required from the transplanted tissues, as well as diffusion of nutrients and waste necessary for survival of the non-autologous tissues. The membranes also prevent host immune mediators from contacting the non-autologous cells, thus preventing immune rejection. This technology has been tested for efficacy in large animal models, and is currently in the process of clinical trials in humans. This review will discuss the progress made in using immuno-isolation of non-autologous tissues in large animals. Immuno-isolation can be subdivided into two major areas of interest based on whether the non-autologous tissue used in the immuno-isolation device is genetically altered (gene therapy) or not. Studies using non-genetically altered non-autologous cells for immune-isolation have been dominated by the use of pancreatic islet cells for the treatment of diabetes. This work has been tested in large animal models of diabetes, including canine and primate model animals, and human clinical trials are underway. As well, there has also been work on treatment of neurological disorders such as Parkinson's disease or chronic pain using non-autologous immuno-isolated adrenal chromaffin cells or dopaminergic PC12 cells in large animals such as sheep and primates. This work will be reviewed in detail as to the types of disorders, immuno-isolation devices used and the type of large animals involved. Immune-isolation for gene therapy is a more recently developed field of research. In this case, the non-autologous cells used are first genetically altered to secrete a recombinant therapeutic product before placement in the immune-isolation devices. Genetic engineering of the non-autologous cells is beneficial, as it allows the use of a cell type that tolerates well the environment of the immune-isolation device, while still delivering the therapeutic product of interest. This form of gene therapy has been tested in our laboratory for delivery of marker products such as human growth hormone to canines. As several large animal models of human genetic disorders are available, such as canines affected with hemophilia or the lysosomal storage disease mucopolysaccharidosis, testing the efficacy of immuno-isolation for gene therapy in large animal models is an important prelude to human clinical trials. This review will discuss the topics outlined above, as well as some further considerations of the usefulness of large animal models in studying immune-isolation for non-autologous transplantation. Large animals may be more appropriate model organisms than rodents in which to study immune-isolation, as issues such as biocompatibility and immune response in a larger animal can be addressed. As well, large animal studies of immune isolation may provide data that are more relevant than rodent studies to the eventual application to human clinical trials.
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PMID:Non-autologous transplantation with immuno-isolation in large animals--a review. 961 31

The potential therapeutic applications of encapsulated cells are enormous. In the US alone, it has been estimated that nearly half-a-trillion dollars are spent each year to care for patients who suffer tissue loss or dysfunction. Over 6 million patients suffer from neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease, over 14 million patients suffer from diabetes, and millions more from liver failure, hemophilia, and other diseases caused by the loss of specific vital cellular functions. It appears likely that by the end of the decade clinical trials of encapsulated cells to treat many of these diseases will become a reality. The Food and Drug Administration has already authorized studies to evaluate the safety and biological activity of several types of systems. A number of issues will have to be addressed, including the sourcing of raw materials, the design and building of manufacturing facilities, the scale-up and optimization process, storage and distribution of the product, and quality control.
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PMID:Encapsulated cell technology. 963 Oct 60


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