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Biomedical subjects

R Lincoln

Publications and source records attributed to R Lincoln.

At least 19 recordsLinked to original sources
PubMed2001

Linkage and association analysis of chromosome 19q13 in multiple sclerosis.

Multiple sclerosis (MS) is an autoimmune neurological disorder with a complex etiology. Sibling risk, twin, and adoption studies have demonstrated that genes play a vital role in susceptibility to MS. Numerous association and linkage studies have implicated the major histocompatibility complex (MHC) as one component of the genetic etiology, but additional loci remain to be identified. Genomic screens have suggested over 50 regions that might harbor these genes, but there has been little agreement between studies. The one region suggested by all four screens resides within chromosome 19q13. Allelic associations with several markers in this region have also been described. This region has now been examined in detail in an expanded dataset of MS families from the United States. Genetic linkage and association were tested with multiple markers in this region using both parametric and non-parametric analyses. Additional support for an MS susceptibility locus was observed, primarily in families with the MS-associated HLA-DR2 allele. While consistent, this effect appears to be modest with a maximum lambda(s) = 1.47, probably representing no more than 10% of the overall genetic effect in MS.

Chromosomes, Human, Pair 19↗
PubMed2000

Interaction between HLA-DR2 and abnormal brain MRI in optic neuritis and early MS. Optic Neuritis Study Group.

The association of the human leukocyte antigen (HLA)-DR2 allele with brain MRI signal abnormalities and with the development of MS was assessed in 178 patients enrolled in the Optic Neuritis Treatment Trial. HLA haplotype DR2 was present in 85 (48%) of the 178 patients. Its presence was associated with increased odds of probable or definite MS at 5 years (odds ratio, 1.92; 95% confidence interval, 1.01 to 3.67; p = 0.04). The association was most apparent among patients with signal abnormalities on baseline brain MRI.

Administration, Oral↗
PubMed2000

CC-chemokine receptor 5 polymorphism and age of onset in familial multiple sclerosis. Multiple Sclerosis Genetics Group.

Multiple sclerosis (MS) is a common disease of the central nervous system characterized by myelin loss and progressive neurological dysfunction. An underlying genetic susceptibility plays a clear role in the etiology of MS, likely acting in concert with an undefined environmental exposure. Full-genome screenings in multiplex MS families have identified several susceptibility regions, supporting a polygenic model for MS. Among these regions, evidence for weak linkage was observed at 3p/3cen suggesting the presence of an MS gene(s) of modest effect. Encoded here are two chemokine receptors, CCR5 and CCR2B. We examined the chromosome 3p21-24 region in 125 MS families (322 total affecteds and 200 affected sib-pairs), and performed genetic analyses of CCR5 and CCR2B loci and two nearby markers (D3S1289 and D3S1300) using both linkage- and association-based tests. No evidence of linkage to MS was observed for any of the tested markers. Affected relative-pair (SimIBD) and sib-pair analyses (ASPEX), and association testing (sib-TDT) for each locus were also not significant. However, age of onset was approximately 3 years later in patients carrying the CCR5delta32 deletion (P=0.018 after controlling for gender effects). Thus, chemokine receptor expression may be associated with differential disease onset in a subset of patients, and may provide a therapeutic target to modulate inflammatory demyelination.

Age of Onset↗
PubMed1998

Linkage of the MHC to familial multiple sclerosis suggests genetic heterogeneity. The Multiple Sclerosis Genetics Group.

Multiple sclerosis (MS) is a demyelinating autoimmune disease of the central nervous system. While its etiology is not well understood, genetic factors are clearly involved. Until recently, most genetic studies in MS have been association studies using the case-control design testing specific candidate genes and studying only sporadic cases. The only consistently replicated finding has been an association with the HLA-DR2 allele within the major histocompatibility complex (MHC) on chromosome 6. Using the genetic linkage design, however, evidence for and against linkage of the MHC to MS has been found, fostering suggestions that sporadic and familial MS have different etiologies. Most recently, two of four genomic screens demonstrated linkage to the MHC, although specific allelic associations were not tested. Here, a dataset of 98 multiplex families was studied to test for an association to the HLA-DR2 allele in familial MS and to determine if genetic linkage to the MHC was due solely to such an association. Three highly polymorphic markers (HLA-DR, D6S273 and TNFbeta) in the MHC demonstrated strong genetic linkage (parametric lod scores of 4.60, 2.20 and 1.24, respectively) and a specific association with the HLA-DR2 allele was confirmed (TDT; P < 0.001). Stratifying the results by HLA-DR2 status showed that the linkage results were limited to families segregating HLA-DR2 alleles. These results demonstrate that genetic linkage to the MHC can be explained by the HLA-DR2 allelic association. They also indicate that sporadic and familial MS share a common genetic susceptibility. In addition, preliminary calculations suggest that the MHC explains between 17 and 62% of the genetic etiology of MS. This heterogeneity is also supported by the minority of families showing no linkage or association with loci within the MHC.

Alleles↗
PubMed1998

"A satellite primer on tuberculosis:" a collaboration in distance education.

"A Satellite Primer on Tuberculosis" was offered as a distance-based certificate course on tuberculosis (TB) fundamentals to a national audience of over 5,000 individuals. The course was a collaborative effort of a school of public health, a state health department, and the Centers for Disease Control and Prevention. Instruction was provided through print-based self-study modules that were complemented by live, interactive satellite conferences. Course completers, over 70 percent of whom were nurses and employees of public health departments, scored significantly higher on a course posttest than on a pretest, and the vast majority felt the course provided valuable training.

Curriculum↗
PubMed1996

Tumor necrosis factor (TNF) microsatellite haplotypes in relation to extended haplotypes, susceptibility to diseases associated with the major histocompatibility complex and TNF secretion.

TNFabc microsatellite haplotypes were determined on normal, type I diabetes and multiple sclerosis Caucasian MHC haplotypes in family studies. Although independent examples of conserved extended haplotypes usually had the same TNFabc haplotypes, there were a number of exceptions, suggesting that these loci are more mutable than most loci in the human MHC. Some TNFabc haplotypes were characteristic of only one extended haplotype, whereas others were shared by several different extended haplotypes. From the analysis of TNFabc on extended haplotype fragments, and assuming that the fragments arose by ancient homologous crossing over, it was possible to "map" TNF and how that it was somewhat closer to HLA-B than the complement region, corresponding to the physical map of this region. TNF haplotype associations with type I diabetes and multiple sclerosis were attributable to the known extended haplotype associations of these diseases. There was also a trend for higher TNF-alpha secretion by peripheral blood mononuclear cells from individuals homozygous for [HLA-B8, SC01, DR3] than from individuals homozygous for [HLA-B7, SC31, DR2].

Alleles↗
PubMed1996

A complete genomic screen for multiple sclerosis underscores a role for the major histocompatability complex. The Multiple Sclerosis Genetics Group.

Multiple sclerosis (MS), an inflammatory autoimmune demyelinating disorder of the central nervous system, is the most common cause of acquired neurological dysfunction arising in the second to fourth decades of life. A genetic component to MS is indicated by an increased relative risk of 20-40 to siblings compared to the general population (lambda s), and an increased concordance rate in monozygotic compared to dizygotic twins. Association and/or linkage studies to candidate genes have produced many reports of significant genetic effects including those for the major histocompatability complex (MHC; particularly the HLA-DR2 allele), immunoglobulin heavy chain (IgH), T-cell receptor (TCR) and myelin basic protein (MBP) loci. With the exception of the MHC, however, these results have been difficult to replicate and/or apply beyond isolated populations. We have therefore conducted a two-stage, multi-analytical genomic screen to identify genomic regions potentially harbouring MS susceptibility genes. We genotyped 443 markers and 19 such regions were identified. These included the MHC region on 6p, the only region with a consistently reported genetic effect. However, no single locus generated overwhelming evidence of linkage. Our results suggest that a multifactorial aetiology, including both environmental and multiple genetic factors of moderate effect, is more likely than an aetiology consisting of simple mendelian disease gene(s).

Chromosome Mapping↗
PubMed1995

Elevated mast cell tryptase in cerebrospinal fluid of multiple sclerosis patients.

Multiple sclerosis (MS) lesions are associated with infiltration of T lymphocytes and macrophages that appear to mediate myelin destruction and gliosis (scarring). Mast cells are located perivascularly in the brain, are juxtaposed to neurons, and have been shown to secrete vasoactive and inflammatory mediators in response to neuropeptides and direct nerve stimulation. Mast cells have been previously identified in MS lesions, are activated by myelin basic protein, and can participate in the regulation of blood-brain barrier permeability, as well as in myelin destruction. Here, cerebrospinal fluid from MS patients and controls with other neurologic diseases was assayed for histamine, its major metabolite methylhistamine, and the specific mast cell marker tryptase. Histamine and methylhistamine were not elevated in MS. However, the mast cell specific proteolytic enzyme tryptase was significantly elevated in MS, suggesting that mast cell activation may be involved in the pathophysiology of this disease.

Adult↗
PubMed1993

Unusual organization of the human T-cell receptor beta-chain gene complex is linked to recombination hotspots.

Two rare Sfi I polymorphisms of 360 kb and 280 kb present within the human T-cell antigen receptor beta-chain gene complex were revealed by pulsed-field gel electrophoresis. They represent allelic variants of the polymorphic 330- and 300-kb Sfi I fragments previously described. The 360-kb polymorphism results from duplication of the 30-kb DNA fragment responsible for the 330/300-kb insertion/deletion-related polymorphism. The 280-kb polymorphism results from a 20-kb deletion from the 300-kb SfiI allele. The rare polymorphisms also map on either side of a Sal I site located near a recombination hotspot, suggesting that germline duplications and deletions arose from nonhomologous crossover events.

Chromosomes, Human, Pair 7↗
PubMed1990

Cytokine accumulations in CSF of multiple sclerosis patients: frequent detection of interleukin-1 and tumor necrosis factor but not interleukin-6.

We identified the cytokines interleukin-1 beta (IL-1 beta), tumor necrosis factor (TNF), and interleukin-6 (IL-6) by specific radioimmunoassays in the CSF of patients with multiple sclerosis (MS) and other neurologic diseases (OND). There was a high incidence of detectable IL-1 beta in patients with active MS compared with inactive MS or OND patients. TNF was also more frequently present in active MS than in OND CSF. By contrast, most MS CSF did not contain detectable IL-6. There was no correlation between the degree of CSF pleocytosis and the level of individual cytokines, suggesting that cytokine accumulations may be derived from CNS, and not CSF, cells. As IL-1 beta and TNF experimentally induce astrogliosis, demyelination, temperature elevation, lassitude, and sleep, and results raise the possibility that these cytokines may contribute to a variety of manifestations in MS and in other disease states.

Humans↗
PubMed1990

Characteristics of alcoholics and codependents who did and did not complete treatment.

Demographic data were collected on 803 patients who were treated for dependency/codependency issues at the Center for Problem Resolution (CPR) from September 1, 1986, until December 31, 1987. Comparisons were made between patients who completed treatment and noncompleters. Results are reported on the entire sample and then broken down into three patient categories. Factors which may be associated with staying in treatment for codependents are previous counseling and health problems. Chemical dependents who tended to finish treatment were female, employed, not detoxing, and willing to commit themselves to an appropriate number of self-help meetings following treatment.

Adolescent↗
PubMed1989

Loss of libido.

Loss of libido is caused by unconscious anger and it can be restored if the feeling of anger is expressed. The common causes of such anger are classified and case histories suggest how the doctor/patient encounter can be used to help patients.

Adult↗
PubMed1989

Continence issues in acute care.

Urinary incontinence affects up to 43 per cent of acute care patients. Toileting is a function of intact bladder, sphincters, and nervous system. Five types of incontinence are stress, urge, reflex, total, and functional. Problems affecting patients in acute care are: 1. Diagnostic studies 2. Treatments--for example, intravenous fluids, hyperalimentation, medications, catheters 3. Bedrest 4. Restraints 5. Pain 6. Iatrogenic conditions 7. Environment Assessment includes a specific history and physical examination, focused on previous episodes of incontinence, functional ability, and cognitive status. Management includes scheduled fluid intake and toileting, manipulation of the environment, and attention to orientation and psychological factors. The treatment of fecal incontinence in the hospital elderly includes: 1. Assessment of incontinence and contributing factors; 2. Bowel regimen and environmental assists for persons with periodic incontinence; 3. Treatment of diarrhea or constipation; and 4. Protection of perineal skin from stool exposure.

Aged↗