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Biomedical subjects

J L Nelson

Publications and source records attributed to J L Nelson.

At least 55 records · Page 3Linked to original sources
PubMed1999

Microchimerism of maternal origin persists into adult life.

Recent studies indicate that fetal cells persist in maternal blood for decades after pregnancy. Maternal cells are known to engraft and persist in infants with immunodeficiency, but whether maternal cells persist long-term in immunocompetent offspring has not specifically been investigated. We developed sensitive human leukocyte antigen-specific (HLA-specific) PCR assays and targeted nonshared maternal HLA genes to test for persistent maternal microchimerism in subjects with scleroderma and in healthy normal subjects. Nonshared maternal-specific DNA was found in 6 of 9 scleroderma patients. In situ hybridization with double labeling for X and Y chromosome-specific sequences revealed female cells in peripheral blood samples from 2 male scleroderma patients. HLA-specific PCR also frequently revealed persistent maternal microchimerism in healthy control subjects. The mean age of all subjects with maternal microchimerism was 28 years (range: 9-49 years). With few exceptions, mothers of subjects with persistent maternal microchimerism were HLA incompatible with subjects for class I and class II alleles. These results clearly indicate that HLA-disparate maternal cells can persist in immunocompetent offspring well into adult life. The biological significance of maternal microchimerism and whether it might contribute to autoimmune disease requires further investigation.

Adolescent↗
PubMed1999

Microchimerism: implications for autoimmune disease.

Recent studies indicate cells traffic between the fetus and mother during normal human pregnancy and that fetal cells persist in maternal peripheral blood for decades after childbirth. The long-term persistence of fetal cells, when considered together with clinical similarities of chronic graft-vs-host disease and autoimmune disease and the female predilection to autoimmunity, led to the hypothesis that microchimerism is involved in some autoimmune diseases. Sources of engraftment applicable to men and to women who have never been pregnant include from a blood transfusion, a twin sibling, or mother. Initial studies lend support to the hypothesis. A role in disease pathogenesis has not been demonstrated, however, and microchimerism is also common in healthy normals. If microchimerism is involved in the pathogenesis of some autoimmune diseases further understanding potentially may lead to new therapeutic strategies.

Adult↗
PubMed1999

Comorbid affective disorders and personality traits in alcohol abuse inpatients at an Air Force Medical Center.

A retrospective chart review of 2 years of admissions (1995-1996) for alcohol abuse and alcohol dependence patients on an inpatient substance abuse unit showed the prevalence of comorbid affective disorders, personality disorders/subsyndromal personality traits, and the combination of all three diagnoses to be 8.2, 17.5, and 9.6%, respectively. The available literature on these additional diagnoses in substance abusers is reviewed and compared with the findings of the current study. Patients identified for inpatient substance abuse treatment need full psychiatric evaluation for other Axis I and Axis II comorbidity that may greatly affect their treatment plans and clinical prognoses.

Adult↗
PubMed1998

Microchimerism and HLA-compatible relationships of pregnancy in scleroderma.

BACKGROUND: Fetal cells can be found in the maternal circulation in most pregnancies. Fetal progenitor cells have been found to persist in the circulation of women many years after childbirth. We tested the hypothesis that microchimerism is involved in the pathogenesis of scleroderma. Scleroderma is of interest because of a strong female predilection, an increased incidence in the years after childbearing, and clinical similarities between scleroderma and chronic graft-versus-host disease after allogeneic bone-marrow transplantation. We also investigated whether HLA-compatibility of a child was associated with later development of scleroderma in the mother. METHODS: We enrolled 40 women who had previously given birth to at least one son--16 healthy controls, 17 scleroderma patients, and seven healthy sisters of patients. We used quantitative PCR to amplify a Y-chromosome-specific sequence in whole peripheral blood from these women. Also 32 controls with 58 children, and 21 scleroderma patients with 47 children were HLA genotyped. FINDINGS: The mean number of male cell DNA equivalents among controls was 0.38 cells per 16 mL whole blood (median 0 [range 0-2]) and 11.1 (6.0 [0-61]) among scleroderma patients (p = 0.0007). Controls' youngest sons were born a mean of 15.4 years previously, and scleroderma patients' sons 18.5 years previously. Some scleroderma patients had concentrations of male DNA higher than those found in most pregnant women. HLA-class II compatibility of a child from the mother's perspective was more common among scleroderma patients than among controls, but was not essential for persistence of male DNA in maternal peripheral blood. INTERPRETATION: Low concentrations of male DNA can be detected in healthy women decades after the birth of a son. Microchimerism in scleroderma patients could be secondary to the underlying disease. However, the finding that HLA class II compatibility of a child was more common for scleroderma patients than for controls, supports the possibility that microchimerism may be involved in the pathogenesis of scleroderma.

Adolescent↗
PubMed1998

Diets and infection: composition and consequences.

This brief review focuses on the effects of nutrient composition of enteral diets on the outcome of surgical patients and experimental models of infection. Complete enteral diets containing combinations of immunonutrients (arginine, glutamine, RNA, omega-3 fatty acids), when given postoperatively or after trauma to surgical patients, can reduce hospital stay, overall costs, and the incidence of wound complications and acquired infections. Immunonutrient diets can also reduce the length of hospital stay when given to patients admitted to the surgical intensive care unit. A high protein diet is usually required for optimal benefit, although administration of high protein immunoenhancing diets may have adverse effects in animals with severe untreated peritonitis because of a sustained overproduction of cytokines.

Animals↗
PubMed1998

Microchimerism and the causation of scleroderma.

The application of molecular techniques to the study of human pregnancy has resulted in the recognition that there is bi-directional cell traffic during pregnancy. Recent studies indicate fetal progenitor cells can persist in the maternal peripheral blood for decades after childbirth. Scleroderma is increased in women, has a peak incidence following childbearing years, and has clinical similarities to chronic graft-versus-host disease that occurs after allogeneic stem cell transplantation. This paper explores the idea that microchimerism is involved in scleroderma and considers insights gained from transplantation biology in seeking to understand how microchimerism might contribute to the pathogenesis of scleroderma. Chimerism means that a body contains cell populations derived from different individuals and microchimerism low levels of chimerism. Although highlighted in the study of scleroderma, microchimerism is also implicated in selected other autoimmune disorders.

Chimera↗
PubMed1998

Microchimerism and the pathogenesis of systemic sclerosis.

The application of molecular biological techniques to the study of human pregnancy has resulted in the recognition of bidirectional cell traffic at the fetal-maternal interface. Fetal progenitor cells have been found to persist in the maternal peripheral blood for decades after childbirth. Scleroderma has a strong predilection for women, a peak incidence in women following childbearing years, and clinical similarities to chronic graft-versus-host disease that occurs after allogeneic stem cell transplantation. This article explores the hypothesis that microchimerism contributes to the pathogenesis of scleroderma and reviews early studies that lend support to this hypothesis. Chimerism is used to indicate a body that contains cell populations derived from different individuals; microchimerism indicates low levels of chimerism. A mechanism by which microchimerism might contribute to the pathogenesis of scleroderma is unknown, but insights can be gained through knowledge garnered in studies of microchimerism in transplantation biology. Although high-lighted in the study of scleroderma, microchimerism is also implicated in selected other autoimmune disorders.

Autoimmune Diseases↗
PubMed1998

Pregnancy, persistent microchimerism, and autoimmune disease.

Fetal cells have been detected in maternal peripheral blood in the majority of normal pregnancies, and the influx of fetal cells into the maternal circulation increases during parturition. Recently, fetal progenitor cells have been found to persist in maternal peripheral blood for decades after childbirth--which has potential implications for some autoimmune diseases in women, such as scleroderma. Scleroderma has a strong female predominance, a steep increase in incidence in women following the childbearing years, and clinical similarity to the chronic graft-versus-host disease that occurs after allogenic bone marrow transplantation. This article explores the hypothesis that microchimerism (nonhost cells) contributes to the pathogenesis of scleroderma and certain other autoimmune disorders.

Autoimmune Diseases↗
PubMed1998

Pregnancy immunology and autoimmune disease.

The advent of molecular biologic techniques has resulted in the recognition of bidirectional traffic of cells at the maternal-fetal interface. In this light, and because women are preferentially affected by a wide variety of autoimmune diseases, the subject of pregnancy immunology is of special interest. That pregnancy often induces remission of rheumatoid arthritis is an intriguing biologic observation for which further understanding may yield insights into disease pathogenesis. Another important question is the effect of pregnancy on susceptibility to autoimmune diseases. This question is highlighted by the recent finding that chimeric cells can persist for many years after pregnancy completion. At present, the biologic significance of microchimerism from pregnancy is an area of research that is for the most part unexplored.

Arthritis, Rheumatoid↗
PubMed1997

Genetic bias in immune responses to a cassette shared by different microorganisms in patients with rheumatoid arthritis.

Rheumatoid arthritis (RA) is an autoimmune disease associated with HLA-DRbeta1 alleles which contain the QKRAA amino acid sequence in their third hypervariable region(s). The QKRAA sequence is also expressed by several human pathogens. We have shown previously that an Escherichia coli peptide encompassing QKRAA is a target of immune responses in RA patients. Here we address two questions: first, whether QKRAA may function as an "immunological cassette" with similar, RA-associated, immunogenic properties when expressed by other common human pathogens; and second, what is the influence of genetic background in the generation of these responses. We find that early RA patients have enhanced humoral and cellular immune responses to Epstein-Barr virus and Brucella ovis and Lactobacillus lactis antigens which contain the QKRAA sequence. These results suggest that the QKRAA sequence is an antigenic epitope on several different microbial proteins, and that RA patients recognize the immunological cassette on different backgrounds. ANOVA of immune responses to "shared epitope" antigens in monozygotic twin couples shows that, despite significantly elevated responses in affected individuals, a similarity between pairs is retained, thus suggesting a role played either by hereditary or shared environmental factors in the genesis or maintenance of these responses.

Antigen Presentation↗
PubMed1997

Pregnancy and rheumatoid arthritis.

Amelioration of rheumatoid arthritis (RA) occurs in about three quarters of pregnancies. Most women who improve experience initial relief in the first trimester. RA almost invariably recurs within 3 to 4 months of delivery. The effect of pregnancy upon the risk of first developing RA is similar in some respects but also differs from that observed in women with established disease. Analogous to women with established disease, the chance of a woman first developing RA is significantly reduced during pregnancy but increased in the first year post partum; thereafter risk is decreased. There is no indication of any adverse effects of RA on pregnancy outcome. Although limited, some medications can be used during pregnancy and during lactation without jeopardizing the well-being of the fetus.

Arthritis, Juvenile↗
PubMed1997

Pre-existing autoimmune disease in patients with long-term survival after allogeneic bone marrow transplantation.

We reviewed the experience with allogeneic bone marrow transplantation (BMT) at Fred Hutchinson Cancer Research Center and affiliated Seattle hospitals for patients with preexisting autoimmune diseases. The review was limited to patients who received transplants between 1969 and 1989 from a related donor and who had at least 3 years of relapse-free survival. Of 901 evaluable patients, 11 were identified with a preexisting autoimmune disease and 2 with diseases that were possibly autoimmune in nature. Pretransplant diseases identified in this review included rheumatoid arthritis (n = 1), discoid or systemic lupus (n = 2), insulin dependent Type 1 diabetes (n = 3), hyperthyroidism (n = 4), dermatitis herpetiformis (n = 1), vasculitis (n = 1), and Crohn's disease (n = 1). All 13 patients survive with a median followup of 14 (range, 7-20) years after transplantation from an HLA identical sibling (n = 10), parent (n = 1) or identical twin (n = 2). Pre and post-transplant histories are presented. Variables to be considered in the assessment of any beneficial effect of BMT are discussed, including consideration of different patterns of activity that describe the natural history of various autoimmune diseases. Although autoimmune disease did not recur after allogeneic BMT in these 13 patients, disease and post-transplant variables may confound the interpretation of results from retrospective analysis.

Adolescent↗