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Biomedical subjects

J L Clayton

Publications and source records attributed to J L Clayton.

11 recordsLinked to original sources
PubMed2001

Genetic ablation of interferon-gamma up-regulates interleukin-1beta expression and enables the elicitation of collagen-induced arthritis in a nonsusceptible mouse strain.

OBJECTIVE: To determine whether the lack of interferon-gamma (IFNgamma) alters resistance to collagen-induced arthritis (CIA) in a nonsusceptible mouse strain, and if so, to identify changes in the antibody, cellular type II collagen (CII)-specific immune responses, and cytokine gene expression that might account for the altered susceptibility. METHODS: CIA-resistant C57BL/6 and C57BL/6 IFNgamma-/- mice were immunized with bovine CII in Freund's complete adjuvant (CFA) or in CFA alone. Animals were monitored for signs of arthritis for up to 80 days; arthritis severity was assessed visually and histologically. Sera were collected at various time points after immunization for measurement of anti-CII antibody levels. T cell responses to bovine CII were assessed in proliferation assays. Cytokine messenger RNA (mRNA) expression in lymph node cells and in synovial cells from arthritic paws was measured by RNase protection assays, and levels of cytokine protein production were determined by enzyme-linked immunosorbent assay. RESULTS: IFNgamma-/- mice developed a severe autoimmune arthritis that was dependent on immunization with CII. IFNgamma-/- mice produced significantly higher amounts of IgG1 and IgG2b antibody to the autoantigen, murine CII, compared with wild-type C57BL/6 mice and had an enhanced T cell proliferative response to bovine CII. Enhanced production of mature interleukin-1/beta (IL-1beta) protein was observed, but no significant changes in Th1 or Th2 cytokines. Although IL-6 and tumor necrosis factor alpha transcripts were clearly evident in the synovial cells from the arthritic paws of IFNgamma-/- mice, neither message was elevated to the levels measured for IL-1beta expression. Treatment of IFNgamma-/- mice with anti-IL-1beta significantly reduced the incidence and severity of the inflammation. CONCLUSION: Endogenous IFNgamma plays a role in the regulation of IL-1beta, in this model of autoimmune arthritis.

Animals↗
PubMed2001

NF-kappa B-mediated chemoresistance in breast cancer cells.

BACKGROUND: Nuclear factor-kappa B (NF-kappa B) is a known survival pathway, and it may explain differential sensitivity to tumor necrosis factor-alpha (TNF-alpha) and chemotherapeutic-induced apoptosis in apoptotically sensitive (APO+) and apoptotically resistant (APO-) Michigan Cancer Foundation-7 breast cancer cells. METHODS: Crystal violet viability and luciferase reporter gene assays were used to determine the inhibitory concentration of viability at 50% (IC(50)) and the inhibitory concentration of activity at 50% (EC(50)) values in APO- and APO+ cells with the selective NF-kappa B inhibitor, BAY 11-7082 (BAY). The apoptotic reporter assay was used to determine the effects of the transfection of the inhibitory kappa B-dominant negative (I kappa B-DN) construct in conjunction with TNF, paclitaxel, or doxorubicin treatments in these cells. RESULTS: The concentrations at which 50% of cell viability is inhibited (IC(50)) and at which 50% of NF-kappa B activity is inhibited (EC(50)) for BAY in APO- and APO+ cells were 95.24 micromol/L and 1.53 micromol/L, respectively, and 7.62 micromol/L and 2.64 micromol/L, respectively. The IC(50) and the EC(50) values were equivalent for the APO+ cells (P =.665), but not for the APO- cells (P =.025). I kappa B-DN--transfection alone, or with TNF, doxorubicin, or paclitaxel treatments resulted in cell death of both APO- and APO+ cells as compared with vector-control; however, greater cytotoxicity was seen in the APO+ cells. Direct comparison of the APO+ cells versus the APO- cells revealed that these differences were significant (P =.05). CONCLUSIONS: Pharmacologic or molecular inhibition of the NF-kappa B pathway blocked cell survival in MCF-7 APO+ cells, while only molecular inhibition induced cytotoxicity in the APO- cells. Selective manipulation of the NF-kappa B pathway in combination with standard chemotherapeutic agents may lead to an increased potency and efficacy of these agents.

Antineoplastic Agents↗
PubMed2000

Comparison of three assays for cytomegalovirus detection in AIDS patients at risk for retinitis.

The purpose of this study was to determine the sensitivity and specificity of three different methods of cytomegalovirus (CMV) detection for AIDS patients at risk for CMV retinitis. Patients with CD4(+) counts of <100/microl and negative baseline screening eye examinations were tested for CMV infection by (i) pp65 antigenemia expression in leukocytes, (ii) the Digene Hybrid Capture CMV DNA System, and (iii) the Roche Amplicor Qualitative PCR Test. The incidence of CMV retinitis in our study of 296 patients at the Medical Center of Louisiana-New Orleans HIV Outpatient Clinic was 7. 2 per 100 person-years (a total of 20 episodes in 18 patients from April 1997 to February 1999). Receiver operating characteristic curves were calculated for each assay to determine optimal cutoff points which maximized the sensitivity and specificity of each assay. The sensitivities of the assays compared to the eye examinations were 80% for the pp65 antigenemia assay (cutoff, >0 cell per 1.5 x 10(5) leukocytes), 85% for the Digene assay (cutoff, 1,400 genome copies/ml of whole blood), and 60% for the Amplicor assay. The specificities of the assays were 84, 84, and 87%, respectively. The Digene assay with a cutoff of >/=1,400 genome copies/ml gave optimal sensitivity and specificity and was found to have predictive values equal to those of the more technically cumbersome antigenemia assay.

AIDS-Related Opportunistic Infections↗
PubMed1996

Decontamination, sterilization, and disinfection.

Creating and maintaining a sterile environment before and during the surgical procedure minimizes the patient's risk of acquiring a postoperative wound infection. The most important measure in preventing postoperative wound infection is the application of flawless aseptic technique principles. It is important that everyone understands their role in reducing the risk of infection to the surgical patient. Prevention of infection begins in central supply with the decontamination, assembly, preparation, and sterilization of surgical items and continues with the surgical team as it monitors the implementation of aseptic technique principles in the operating suite.

Animals↗
PubMed1989

Large volume lipoplasty.

As experience accumulates, previously held beliefs about the risks and dangers of large scale lipoplasty are being challenged. We present our experience with over 300 patients who underwent large scale suctions ranging in volume from 2500 to 8000 cc. We have found that the incidence of postoperative complications does not correlate directly with the volume of fat extracted. Preoperative fluid loading, adequate intraoperative fluid management, and the liberal use of autologous whole blood transfusions appear to reduce the risks of large scale suctions. It is the belief of the author that, when indicated, single stage lipoplasty of greater than 2500 cc is an appropriate alternative to staged procedures, and can be safely undertaken when adequate provisions are made for blood replacement.

Abdomen↗
PubMed1985

Infections acquired in clinical laboratories in Utah.

We reviewed laboratory-acquired infections occurring in Utah from 1978 through 1982. Written and telephone interviews of supervisors of 1,191 laboratorians revealed an estimated annual incidence of 3 laboratory-acquired infections per 1,000 employees. Infections, in order of frequency, included hepatitis B (clinical cases), shigellosis, pharyngitis, cellulitis, tuberculosis (skin test conversion), conjunctivitis, and non-A, non-B hepatitis. One-half of large laboratories (over 25 employees), but only 12% of smaller laboratories, reported infections. The annual incidence, however, at smaller laboratories was more than three times greater than at large laboratories (5.0 versus 1.5 per 1,000; P less than 0.05, chi-square test). Microbiologists were at greatest risk of infection, with an incidence of almost 1%, followed by generalists and phlebotomists. Shigellosis was acquired only by microbiologists and accounted for more than half of their infections. The most common laboratory-acquired infection, hepatitis B, affected a microbiologist, a hematologist, a phlebotomist, a pulmonary blood gas technician, and a blood bank technologist who died from her illness. Clinical cases of hepatitis B occurred at a rate 10 times higher than the rate in the general U.S. population. The incidence of tuberculosis skin test conversion was intermediate between rates reported for hospital employees and for the state of Utah.

Aerosols↗