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J Lee Nelson

Publications and source records attributed to J Lee Nelson.

24 records · Page 2Linked to original sources
PubMed2002

Human leukocyte antigen class II and cervical cancer risk: a population-based study.

The critical role of the human leukocyte antigen (HLA) system in presenting peptides to antigen-specific T cell receptors may explain why only some human papillomavirus (HPV)-infected women progress to cervical cancer. HLA class II DRB1 and DQB1 genes were examined in 315 women with invasive squamous cell cervical cancer (SCC) and 381 control subjects. Increased risks of SCC were associated with DRB1*1001, DRB1*1101, and DQB1*0301, and decreased risks were associated with DRB1*0301 and DRB1*13. Of squamous cell tumors, those containing HPV-16 were different from those not containing HPV-16 for 3 alleles: DRB1*0401, DRB1*07, and DQB1*06. Increased risks of SCC were associated with DRB1*0401-DQB1*0301 (odds ratio [OR], 1.7; 95% confidence interval [CI], 1.1-2.7) and DRB1*1101-DQB1*0301 (OR, 2.5; 95% CI, 1.4-4.5), and decreased risks were associated with DRB1*0301-DQB1*02 (OR, 0.7; 95% CI, 0.5-1.0) and DRB1*13-DQB1*06 (OR, 0.6; 95% CI, 0.4-0.9) haplotypes. These results add to the evidence that certain HLA class II alleles or allele combinations, or genes linked to them, make some women more susceptible to SCC.

Adolescent↗
PubMed2002

Male microchimerism in healthy women and women with scleroderma: cells or circulating DNA? A quantitative answer.

Male DNA, of presumed fetal origin, can be detected in the maternal circulation decades after delivery and is referred to as fetal microchimerism (FM). We previously found quantitatively greater FM in the circulation of women with the autoimmune disease scleroderma (SSc) than of healthy women. However, it is unknown whether this difference is due to intact circulating cells or free DNA released from breakdown in disease-affected tissues. To distinguish the origin of FM, we developed a real-time quantitative polymerase chain reaction (PCR) assay for the Y-chromosome-specific sequence DYS14, and tested 114 women in peripheral blood mononuclear cells (PBMCs) and/or plasma. Fifty-seven controls and 57 SSc patients were studied, 48 and 43 of whom, respectively, had given birth to at least one son. Circulating FM was quantitatively greater in PBMCs from SSc patients (n = 39; range, 0.0-12.5 male genome-equivalent cells per million maternal cells), compared with healthy women (n = 39; range, 0.0-4.4; P =.03). In contrast, there was no difference between patients (n = 25) and controls (n = 22) in plasma, and no evidence of free DNA. FM was enriched among T lymphocytes compared with PBMCs (P =.01) in controls (n = 14), but not in SSc patients (n = 14); the latter finding was most likely due to immunosuppressive medications. In conclusion, this real-time quantitative assay showed that quantitative differences in the circulation of women with SSc are due to cells and not to free DNA. As FM was not uncommon in healthy women, including among T cells, and because graft-versus-host disease has similarities to SSc, these results also suggest that FM merits investigation in pheresis products used for stem cell transplantation.

Base Sequence↗
PubMed2002

High-dose immunosuppressive therapy for severe systemic sclerosis: initial outcomes.

Systemic sclerosis (SSc) is a multisystem disease of presumed autoimmune pathogenesis for which no proven effective treatment exists. High-dose immunosuppressive therapy (HDIT) has been proposed as an investigational treatment for severe autoimmune diseases. Nineteen patients with poor-prognosis SSc underwent HDIT. The median age was 40 years (range, 23-61 years), the median modified Rodnan skin score (a measure of dermal sclerosis) was 31, and the median DLCO was 57%. Conditioning therapy involved 800 cGy total body irradiation (TBI) (+/- lung shielding to approximately 200 cGy), 120 mg/kg cyclophosphamide, and 90 mg/kg equine antithymocyte globulin. CD34-selected granulocyte-colony-stimulating factor-mobilized autologous blood stem cells provided hematopoietic rescue. With median follow-up at 14.7 months, the Kaplan-Meier estimated 2-year survival rate was 79%. Three patients died of treatment complications and one of disease progression. Two of the first 8 patients had fatal regimen-related pulmonary injury, a complication not found among 11 subsequent patients who received lung shielding for TBI. Overall, internal organ functions were stable to slightly worse after HDIT, and 4 patients had progressive or nonresponsive disease. As measured by modified Rodnan skin scores and modified health assessment questionnaire disability index (mHAQ-DI) scores, significant disease responses occurred in 12 of 12 patients evaluated at 1 year after HDIT. In conclusion, though important treatment-related toxicities occurred after HDIT for SSc, modifications of initial approaches appear to reduce treatment risks. Responses in skin and mHAQ-DI scores exceed those reported with other therapies, suggesting that HDIT is a promising new therapy for SSc that should be evaluated in prospective randomized studies.

Adult↗
PubMed2002

Microchimerism: incidental byproduct of pregnancy or active participant in human health?

It is now well recognized that cells traffic in both directions between fetus and mother during pregnancy. Moreover, fetal cells have been found to persist for years, probably for a lifetime, in the circulation of healthy women. Harboring of cells from another individual at low levels is called microchimerism. Women have a predilection to autoimmune disease, and chronic graft-versus-host disease, a condition of human chimerism, shares similarities with some autoimmune diseases. The specific HLA genes of donor and host are known to be of central importance in graft-versus-host disease, and HLA class II genes are important in autoimmune disease. Considered together, these observations led to the hypothesis that microchimerism and HLA genes of host and non-host cells are involved in autoimmune diseases. Alternative sources of microchimerism include transfer from a twin or the mother during pregnancy, or from blood transfusion. Studies of systemic sclerosis, primary biliary cirrhosis, Sjögrens syndrome, pruritic eruption of pregnancy, myositis, and thyroid disease have both lent support and raised doubts about a potential role of microchimerism in autoimmune disease.

Antigen-Presenting Cells↗