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Biomedical subjects

J L Nelson

Publications and source records attributed to J L Nelson.

At least 19 recordsLinked to original sources
PubMed1996

The effects of pregnancy on autoimmune diseases.

Despite a now reasonable large body of developed information, critical gaps are apparent. Pregnancy is the only naturally occurring event in which an individual is exposed to nonself HLA. How the HLA mismatched fetus escapes rejection remains a biologic enigma. More definitive evidence is needed to determine if TH2 bias occurs in normal human pregnancy and how this impacts on established autoimmune diseases. With regard to specific autoantibody-associated placental and fetal disease, why aren't all pregnancies affected when the putative maternal antibodies are present? Future studies of maternal-fetal immunology, inclusive of information on cytokine regulation, should yield insights not only into the maintenance of normal pregnancy but also into the disproportionate increase of autoimmune diseases in females and the variable course of these diseases during pregnancy.

Autoimmune Diseases↗
PubMed1996

High protein diets are associated with increased bacterial translocation in septic guinea pigs.

During sepsis, body protein stores are decreased due to an increase in protein catabolism. The utilization of nutritional support with high-protein diets has been used as a solution to the problem of sepsis-induced protein loss. Work from our laboratory, however, has shown that diets low in protein (5% of total calories) improve survival in septic animals as compared to high protein (20%) diets. The present study investigated the relationship between low-protein diets and improved survival by determining whether septic animals receiving high-protein diets have increased bacterial translocation. Sepsis was induced in guinea pigs by the implantation of an osmotic minipump into the peritoneal cavity containing an equal mixture of Escherichia coli (10(8)) and Staphylococcus aureus (10(8)) or saline. On Day 3 postlaparotomy, the animals were randomized to one of four groups. The groups consisted of septic and nonseptic animals that received a diet with 5 or 20% of total calories as protein. Following 4 days of diet all animals received an instillation of 14C labeled E. coli (10(10)). Four hours later the animals were sacrificed and blood, mesenteric lymph nodes, spleen, lungs, and liver were removed for determination of radionuclide counts. Results indicated that the septic animals that received the high protein diet had more bacterial translocation, as indexed by higher radionuclide counts in the MLN, liver, lung and blood. These findings suggest that a low protein, enterally fed diet may improve survival in septic patients by decreasing the incidence of bacterial translocation.

Animals↗
PubMed1996

Diet and rheumatoid arthritis in women: a possible protective effect of fish consumption.

Some researchers have hypothesized that omega-3 fatty acids, found primarily in fish oils, may protect against the development of rheumatoid arthritis. We conducted a population-based case-control study in women, comparing 324 incident rheumatoid arthritis cases with 1,245 controls. We used a food frequency questionnaire to ascertain diet during a 1-year period 5 years before a reference date (first physician visit for joint-symptoms). Consumption of broiled or baked fish, but not of other types of fish, was associated with a decreased risk of rheumatoid arthritis. The adjusted odds ratios (OR) for 1- < 2 servings and > or = 2 servings of broiled or baked fish per week, compared with < 1 serving, were 0.78 [95% confidence interval (CI) = 0.53-1.14] and 0.57 (95% CI = 0.35-0.93). Other analyses showed associations with protein as a percentage of calories (adjusted OR for the top quartile as compared with the bottom quartile = 0.65; 95% CI = 0.46-0.94) and total calories (adjusted OR for the top quartile = 1.62; 95% CI = 1.15-2.28). The associations with broiled or baked fish, protein, and calories became stronger when we restricted our analysis to cases positive for rheumatoid factor. These results support the hypothesis that omega-3 fatty acids may help prevent rheumatoid arthritis.

Adolescent↗
PubMed1996

Six new DR52-associated DRB1 alleles, three of DR8, two of DR11, and one of DR6, reflect a variety of mechanisms which generate polymorphism in the MHC.

We have sequenced DNA from six new DR52-associated DRB1 alleles initially detected by PCR/SSOP analysis. Three DR8 associated alleles differed from previously known alleles by single nucleotide substitutions. DRB1*0807 and DRB1*0811 both vary from DRB1*08021 at codon 57 resulting in two different amino acids at this residue. DRB1*0807 was identified in samples of Brazilian origin while *0811 was identified among samples from the Tlingit Native American population of Southeast Alaska. DRB1*0814, identified in a family of Chinese origin, differed from DRB1*08032 at codon 12 at both the nucleotide and the amino acid level. In addition, two alleles of DR11, DRB1*1113 and *1119, were each detected in Caucasian individuals. DRB1*1113 differs from other DR11 alleles at codons 37, 67, 70 and 74, while DRB1*1119 differs from *1101 by a single nucleotide substitution at codon 67. Finally, DRB1*1418 was detected in a sample from an Asian or Pacific Islander and shares sequences with several other DR52-associated DRB1 alleles. These six DRB1 alleles appear to have been generated by either gene conversion events, DRB1*1113 and *1418, or by point mutations, DRB1*0814, *0807, *0811 and *1119, although the single nucleotide substitutions found in the latter three alleles are also present in at least one other DRB1 allele and, therefore, could have been the product of gene conversions.

Base Sequence↗
PubMed1995

Positive selection in autoimmunity: abnormal immune responses to a bacterial dnaJ antigenic determinant in patients with early rheumatoid arthritis.

A novel 'multistep molecular mimicry' mechanism for induction of rheumatoid arthritis (RA) by bacterial antigens that activate T lymphocytes previously 'educated' by peptides derived from a class of human histocompatibility antigens is reported here. These antigens have the amino acid sequence QKRAA, which is also present on the Escherichia coli heat-shock protein dnaJ. Synovial fluid cells of early RA patients have strong immune responses to the bacterial antigen, but cells from normal subjects or controls with other autoimmune diseases do not. The activated T cells may cross-react with autologous dnaJ heat-shock proteins that are expressed at synovial sites of inflammation. Our findings may have direct relevance to new strategies for the immune therapy of RA.

Amino Acid Sequence↗
PubMed1995

Anabolic impact of cimaterol in conjunction with enteral nutrition following burn trauma.

Burn injury is characterized by increased energy expenditure, weight loss, and muscle protein wasting. Studies have shown that beta 2-adrenergic agonists have anabolic properties in the presence of increased metabolism. This study investigated the effects of the beta 2-agonist cimaterol in burned animals receiving enteral nutrition. Guinea pigs with gastrostomies were given a 30% total body surface area burn and fed for 14 days. Animals received saline or cimaterol (0.15 mg/kg, SC) twice daily. Energy expenditure was determined before burn and on postburn days 3, 6, 9, and 12. On day 14, the soleus, gastrocnemius muscles, and heart were excised and weighed as a measure of muscle catabolism and anabolism. Carcass weight was determined to measure muscle catabolism. Cimaterol increased (p < 0.05) total protein content, gastrocnemius muscle, and carcass weights. The soleus muscle and heart weights, and resting metabolic rates showed no significant differences. Results suggest enteral nutrition with cimaterol decreases burn-induced muscle catabolism.

Adrenergic beta-Agonists↗
PubMed1994

Rheumatoid factor, HLA-DR4, and allelic variants of DRB1 in women with recent-onset rheumatoid arthritis.

OBJECTIVE: To examine the relationship of rheumatoid factor (RF) to HLA-DR4 and alleles of DRB1 in women with recent-onset rheumatoid arthritis (RA). METHODS: Incident cases of RA were identified as part of a prospective, population-based case-control study. HLA typing was completed for 246 cases meeting criteria for definite or classic RA. RESULTS: One hundred thirty-six patients (55%) were positive for DR4, and 130 (53%) were RF positive. DR4 was found to be strongly associated with seropositivity (odds ratio 4.1, P < 0.0001). Patients with a shorter interval from RA onset to RF testing had a higher frequency of seropositivity than those with a longer interval (< or = 18 months 60%, > 18 months 33%). Further analysis of patients who had RF testing within 18 months of RA onset showed that the frequency of seropositivity was significantly greater among DR4-positive patients who had the shared sequence stretch of DR beta 1 associated with RA susceptibility (76% RF positive) than among DR1-positive patients who had this sequence (45% RF positive) (odds ratio 3.8, P = 0.01). Moreover, the frequency of seropositivity among DR1-positive patients with the sequence did not differ from that among all patients without the shared sequence (47%) (odds ratio 0.9, P = 0.8). CONCLUSION: HLA-DR4 is strongly associated with seropositivity in women with recent-onset RA. The amino acid sequence of DR beta 1 that is associated with susceptibility to RA and is shared between DR4 and DR1 appears not to be the primary determinant of seropositivity in these women.

Adolescent↗
PubMed1994

Non-contraceptive hormones and the risk of rheumatoid arthritis in menopausal women.

BACKGROUND: Several reproductive factors appear to affect a women's risk of developing rheumatoid arthritis. This study's purpose was to determine whether use of non-contraceptive hormones is among them. METHODS: A population-based case-control study was conducted in King County, Washington and Group Health Cooperative of Puget Sound, a prepaid health plan. New cases of rheumatoid arthritis in peri- or postmenopausal women (n = 135) were verified through clinical examination and compared with 592 controls. Both groups were interviewed in person about hormone use and demographic and reproductive factors. RESULTS: The age-adjusted relative risk (RR) among women who had ever used non-contraceptive oestrogens was 1.04 (95% confidence interval [CI]: 0.70-1.55), and among women who had ever used progestins it was 0.66 (95% CI: 0.40-1.08). For current users of oestrogen only, the RR was 0.97 (95% CI: 0.62-1.53), and among current users of oestrogen plus progestin it was 0.81 (95% CI: 0.45-1.45). Multivariate analyses yielded similar results. There was little evidence of a dose-response relationship with duration of use or with frequency of progestin use. CONCLUSIONS: Use of non-contraceptive oestrogens appears to have little effect on the risk of developing rheumatoid arthritis in menopausal women. There may be a modest reduction in risk among progestin users.

Adolescent↗
PubMed1994

Publicity and pricelessness: grassroots decisionmaking and justice in rationing.

The "grassroots turn" in bioethical discussions about justice in allocation of health care resources has attracted a great deal of support; in the absence of a convincing theory of justice in rationing, democratic decisionmaking concerning priority setting emerges with a kind of inevitability. Yet there remain suspicions about this approach--most importantly, worries about the socially corrosive impact of explicit, public decisionmaking that in effect sets a price on the lives of persons. These worries have been quieted, particularly by the work of Leonard Fleck, but not altogether stilled. I explore more sympathetically the ideals to which concerns about public rationing somewhat dimly respond, and suggest constraints on priority setting discussions which might accommodate those ideals rather better.

Community Participation↗
PubMed1994

Role of early enteral feeding and acute starvation on postburn bacterial translocation and host defense: prospective, randomized trials.

OBJECTIVES: To investigate the effect of: a) starvation during the preburn period and b) immediate postburn enteral nutrition on the permeability of the gut to microorganisms and the ability of the host to kill translocated bacteria. DESIGN: Prospective, randomized, experimental trials. SETTING: Laboratory. SUBJECTS: Balb/c mice and Hartley guinea pigs. INTERVENTIONS: In the first experiment, mice were starved for 0, 6, 12, 18, or 24 hrs before receiving gavage with 10(10) 14C-labeled Escherichia coli and a 20% burn injury. In the second experiment, guinea pigs received a 40% burn injury and were randomized to receive a complete enteral diet (175 kcal/kg/day) or infusion of an equal volume of lactated Ringer's solution via a previously placed gastrostomy for 6, 24, or 48 hrs. After each feeding period, 10(10) 14C Escherichia coli were infused intragastrically. In both experiments, the animals were killed 4 hrs after gavage, and mesenteric lymph nodes, spleen, liver, lungs, peritoneal fluid, and blood were harvested aseptically. MEASUREMENTS: For each tissue or fluid, the number of viable E. coli and radionuclide counts of the 14C E. coli were measured and the percentage of translocated bacteria that remained alive was calculated. MAIN RESULTS: In mice, 18 and 24 hrs of preburn starvation increased translocation only to the mesenteric lymph nodes, but it also enhanced bacterial killing in all tested tissues. Guinea pigs that were fed enterally for 6, 24, and 48 hrs postburn had significantly lower bacterial translocation in all tissues compared with animals infused with lactated Ringer's solution. Additionally, enhanced killing of translocating organisms was observed after 24 and 48 hrs of feeding. CONCLUSIONS: Starvation preburn has different consequences than starvation postburn on translocation and bacterial killing. Postburn enteral nutrition decreases the load of viable bacteria in the tissues via a double mechanism: an initial decreased translocation and a subsequent improved ability to kill bacteria that do translocate.

Acute Disease↗
PubMed1994

T-cell receptor polymorphisms in Tlingit Indians with rheumatoid arthritis.

Rheumatoid arthritis (RA) develops as a result of the interaction of both genetic and environmental factors. Among the genes in humans that have been suggested as candidate susceptibility genes in RA are those encoding the T cell receptor for antigen (TCR). A high prevalence and early age of onset of RA has previously been reported in Alaskan Tlingit Indians. In this study, the frequency of seven different restriction fragment length polymorphisms (RFLPs) in the TCR alpha and beta gene complexes were measured in a population of Alaskan Tlingit Indians. No statistically significant differences were noted when the frequencies of these RFLPs were compared between Tlingits with RA and healthy controls (p > 0.05). These results do not support the hypothesis of an RA-susceptibility allele in the vicinity of these TCR alpha or beta genes. Since TCR RFLPs have not been extensively studied in native American populations, TCR polymorphism frequencies in the Tlingits were also compared to the frequencies observed in a second control group of healthy Caucasians. Statistically significant differences were observed in these comparisons implying a different distribution of individuals in these populations with different TCR repertoires.

Alleles↗
PubMed1994

Rheumatoid arthritis in Tlingit Indians: clinical characterization and HLA associations.

OBJECTIVE: To characterize the features of rheumatoid arthritis (RA) in Tlingit Indians, to identify the HLA-DR alleles associated with RA in the Tlingit, and to determine whether disease severity or specific clinical manifestations correlate with the presence of specific HLA antigens. METHOD: Thirty-seven Tlingit patients with RA and 75 controls were evaluated clinically; comparative HLA studies were carried out in 33 patients and 62 controls. RESULTS: The results of this clinical study of RA in the Tlingit confirms that the disease found in them is classical RA, characterized by an early age of onset, a high frequency of nodules, serum rheumatoid factor (RF) and antinuclear antibodies (ANA); an often severe clinical course, with a high frequency of erosive disease and frequent need for surgical joint repair, and an often positive family history. In Tlingit volunteers who did not have RA we also found an increased prevalence of RF and ANA. Neither HLA-DR1 nor DR4 was found to be associated with RA in the Tlingit. The commonest DR antigen in patients with RA was DR14. The most frequent DRB1 allele was DRB1*1402 (Dw16). CONCLUSION: The Tlingit population had a very high frequency of the DRB1*1402 allele, which shares key sequence homology with DRB1*0401 (Dw4) and DRB1*0101 (Dw1), associated with RA in other racial groups. No correlations were found between specific HLA-DRB1 alleles or combinations of alleles and specific disease features or severity.

Adult↗
PubMed1994

Smoking, obesity, alcohol consumption, and the risk of rheumatoid arthritis.

There is some evidence that sex hormones may influence the incidence of rheumatoid arthritis. Obesity has been found to increase endogenous estrogens, particularly among postmenopausal women. Although the association of endogenous hormones with smoking and alcohol use is less clear, we examined the relation of these three factors with rheumatoid arthritis in women. We conducted a population-based case-control study of rheumatoid arthritis in King County, WA, and Group Health Cooperative of Puget Sound. We compared 349 incident cases of rheumatoid arthritis with 1,457 controls selected by random digit dialing or by random selection from the enrollment files of Group Health Cooperative. We conducted personal interviews to collect data on weight, smoking, alcohol history, reproductive variables, and other demographic variables. Women with 20 or more pack-years of smoking had a relative risk of 1.5 [95% confidence interval (CI) = 1.0-2.0] compared with never-smokers. Post-menopausal women who averaged more than 14 alcoholic drinks per week had a reduced risk of rheumatoid arthritis (relative risk = 0.5; 95% CI = 0.2-1.7). Women in the highest quartile of body mass index had a risk of 1.4 (95% CI = 1.0-2.0) relative to women with lowest body mass index.

Adolescent↗