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Biomedical subjects

P Kimball

Publications and source records attributed to P Kimball.

At least 19 recordsLinked to original sources
PubMed2003

Comparison of 125I-interferon-alpha binding to peripheral blood cells from African-Americans and Caucasians with hepatitis C.

Interferon-alpha (IFN-alpha) is the major treatment for chronic hepatitis C virus (HCV) infection. Drug resistance is problematic, particularly among African-Americans who typically show poorer clinical outcomes than Caucasians. The reasons for ethnic variation in IFN-alpha sensitivity are not clear. We speculated that African-American insensitivity to IFN-alpha may be mediated by reduced density of the IFN-alpha receptor (IFN-alphaR) or reduced internalization of the IFN-alpha/IFN-alphaR complex. This speculation was evaluated by comparing binding, uptake and release of 125iodine-labelled IFN-alpha (125I-IFN-alpha) to peripheral blood cells from African-Americans and Caucasians with HCV infection and ethnically matched healthy volunteers. Under various in vitro conditions, binding of 125IFN-alpha to surface receptors was equivalent (P = ns) between African-Americans and Caucasians with HCV infection as well as healthy volunteers (P = ns). Similarly, internalization and release of the 125I-IFN-alpha/IFN-alphaR complex was equivalent (P = ns) between African-Americans and Caucasians with HCV infection and healthy volunteers (P = ns). In addition, ethnicity did not influence (P = ns) IFN-alpha suppression of phytohaemagluttinen induced proliferation. However, IFN-alpha therapy of the same patients showed that African-Americans had lower response rates than Caucasians (14%vs 54%, P < 0.0001). In summary, IFN-alpha resistance among African-Americans is not mediated by intrinsic differences in IFN-alpha receptor density or internalization.

Black People↗
PubMed2001

Ethnicity and cytokine production gauge response of patients with hepatitis C to interferon-alpha therapy.

Interferon is the primary treatment for hepatitis C virus (HCV). However, the long-term success rate is low particularly for African Americans relative to Caucasians and may be due to differential immune abilities. This study compared cytokine production from PHA-stimulated peripheral blood from 25 healthy and 40 HCV-infected African Americans and Caucasians. HCV patients were designated as IFN responders or nonresponders based on outcome after therapy. Ethnicity and genotype were associated with IFN response. IFN responders were 100% Caucasian, whereas nonresponders were 67% Caucasian and 33% African American (P = 0.01). Genotype 1 was present in 100% nonresponders and 50% responders (P < 0.05). Age, sex, liver histology, ALT, and viral titers were equivalent (ns). Cytokine production from healthy individuals showed ethnic variation in cytokine levels. Healthy African Americans produced greater amounts of IL-2 (P = 0.06), TNF-alpha (P = 0.06) and less IL-10 (P = 0.05) than healthy Caucasians. In contrast, IFN-gamma and TGF-beta levels were equivalent. Pretherapy cytokine production among HCV patients showed a similar pattern of ethnic variation. African American nonresponders produced more IL-2 (P = 0.06) and TNF-alpha (P = 0.02) than Caucasian nonresponders. Cytokine levels among Caucasian and African American nonresponders were equivalent (P = ns) to ethnically matched healthy individuals whereas Caucasian responders produced subnormal levels of IL-10 (P < 0.05) and TGF-beta (P < 0.05). Since all African Americans failed IFN therapy, cytokine production could not be compared with therapeutic outcome. However, comparison of cytokine production among Caucasians showed that responders produced less IL-10 (P < 0.001) and more TGF-beta (P = 0.06) than nonresponders and predicted Caucasian nonresponders with 83% sensitivity and 96% specificity. HCV genotype was not relevant to cytokine production (P = ns). Distribution of cytokine genetic polymorphisms (TNF-alpha, TNF-beta, IL-10, TGF-beta) was equivalent in all ethnic groups and did not predict clinical nonresponders. In summary, it appears that ethnicity may contribute to variable immune responses and therapeutic outcome. The cytokine profile among African Americans suggests a more robust immune response, which may complicate therapy with IFN. In contrast, the subnormal cytokine production among Caucasian responders may be more permissive to IFN therapy. Pretherapy cytokine production may allow prediction of drug resistance among Caucasians.

Adult↗
PubMed2000

Influenza vaccination does not promote cellular or humoral activation among heart transplant recipients.

BACKGROUND: The impact of influenza vaccination on in vitro parameters of cellular and humoral immunity, anti-viral titers, and clinical outcome was evaluated among cardiac transplant recipients. METHODS: Blood was collected from 29 patients before and 3-4 weeks after influenza vaccination and tested for phenotypic changes in lymphoid subpopulations and generation of antibodies against the allograft and vaccine. RESULTS: Vaccination did not change the percentage of lymphoid subpopulations and did not induce generation of anti-HLA alloantibodies. Anti-vaccine response was detected in 12 of 29 patients and did not correlate with rejection history, length of graft survival, or immunosuppressive therapy. Vaccination did not change the frequency of rejection. Flu-like symptoms were reported in one patient but not confirmed microbiologically. CONCLUSION: Despite the small number of patients in the study, influenza vaccination did not induce undesirable side effects, such as graft rejection or allo-sensitization. Generation of a positive anti-vaccine response was lower among the transplant recipients than healthy volunteers (41% vs. 80%). Clinical efficacy of the vaccine among the responders was not evaluated.

Aged↗
PubMed2000

Frequency, potential risk and therapeutic intervention in end-stage renal disease patients with antiphospholipid antibody syndrome: a multicenter study.

BACKGROUND: Antiphospholipid antibody syndrome (APAS) is characterized by the presence of anticardiolipin antibodies (ACA) in association with thrombotic disorders of arterial and/or venus systems, spontaneous abortion(s) or thrombocytopenia. METHODS: In this multicenter study, 502 end-stage renal disease (ESRD) patients awaiting renal transplants were screened to determine the frequency of APAS, the potential risk associated with APAS, and strategies for therapeutic intervention. Ninety-three patients (19%) had high titers of ACA. Twenty-three patients had documented evidence of one or more of the thrombotic disorders such as lupus, frequent abortions, frequent thrombosis of arteriovenous shunts, biopsy-proven microrenal angiopathy, or thrombocytopenia and thus were diagnosed with APAS. Of these 23 patients, 11 received kidney transplants either with (4 patients) or without (7 patients), concomitant anticoagulation therapy. RESULTS: All seven of the patients with APAS not treated with anticoagulation therapy lost their allografts within 1 week as a result of renal thrombosis. In contrast, three out of four transplant patients with APAS treated with anticoagulation therapy maintained their allografts for over 2 years. The fourth patient lost his graft within a week because of thrombosis. Of the remaining 70 patients with high titers of ACA but no evidence of thrombotic disorders, 37 received kidney transplants. None lost their allografts as a result of thrombosis. Our data suggest that, although 19% of our ESRD patients exhibit high titer of ACA, only 5% of the patients have APAS. CONCLUSION: In conclusion, our data suggest that the patients with APAS are at high risk of posttransplant renal thrombosis. Anticoagulation therapy could prevent patients from posttransplant thrombosis in patients with APAS.

Antibodies, Anticardiolipin↗
PubMed1998

Flow cross-matching identifies patients at risk for postoperative elaboration of cytotoxic antibodies.

BACKGROUND: Cytotoxic IgG against class I antigens can contribute to renal dysfunction or failure after transplantation. However, the clinical relevance of IgG measured by flow cytometric cross-matching is controversial. This study correlated pre- and postoperative flow reactivity with clinical outcome among renal transplant patients with negative preoperative cytotoxic cross-matches. METHODS: Nonsensitized primary renal allograft patients (n = 157) with negative preoperative cytotoxic cross-matches (complement-dependent lymphocytotoxicity assays) were stratified on the basis of IgG reactivity measured by flow cytometric cross-matching (FCXM) as FCXM negative (Neg) or positive against class I (T-pos FCXM) or class II (B-pos FCXM) antigens. The groups were compared in terms of frequency of early rejection and 1-year graft survival. RESULTS: Patient distribution was 67% Neg, 14% T-pos FCXM, 14% B-pos FCXM, and 5% IgM FCXM. The incidence of early rejection was 25+/-3% for Neg and 51+/-3% for T- and B-pos FCXM (P < 0.05). One-year graft survival for Neg versus T-pos and B-pos FCXM was 97+/-3% versus 44+/-10% (P < 0.05) and 77+/-5% (P = 0.06), respectively. Rejections requiring plasmapheresis were found only among patients with T-pos FCXM. Among 29 patients, FCXM and complement-dependent lymphocytotoxicity assays were performed 10+/-2 and 28+/-4 days after transplantation. Pre- and posttransplant antibody levels were relatively unchanged among Neg and B-pos FCXM patient groups. In contrast, patients with T-pos FCXM produced cytotoxic IgG against class I after transplantation, which may have contributed to the severe graft dysfunction experienced by this group. CONCLUSIONS: FCXM is a useful tool to stratify primary renal transplant candidates in terms of potential risk for severe rejection. Furthermore, demonstration of preoperative flow reactivity against class I may identify a subgroup of patients at risk for early elaboration of cytotoxic alloantibody.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1997

Lethal graft-versus-host disease after simultaneous kidney-pancreas transplantation.

BACKGROUND: This case report is the first documentation of the occurrence and potential source of lethal graft-versus-host disease (GVHD) after simultaneous kidney-pancreas transplantation. The patient was a 27-year-old African-American male who received an ABO-compatible, five HLA antigen-mismatched kidney-pancreas transplant from a 17-year-old African-American female donor, who died after childbirth. METHODS: Preoperative crossmatches using lymphocytotoxicity and flow cytometry were negative. The patient received four blood transfusions within 10 days of transplantation. Immunosuppression consisted of OKT3 induction, and then cyclosporine, azathioprine, and corticosteroids. RESULTS: On postoperative day (POD) 9, the patient became febrile, and leukocytopenia and pancytopenia developed. Immunosuppression was reduced and granulocyte colony-stimulating factor was begun. Cultures were negative, interleukin 6 and interleukin 8 levels were elevated, and a cutaneous rash appeared on POD 18. A skin biopsy demonstrated dermatitis with focal epidermal necrosis consistent with GVHD. In an attempt to identify the source of GVHD, variable-number tandem repeat analysis fingerprinting was performed with DNA from donor splenocytes, from the skin biopsy, as well as from the patient's buccal mucosa. The skin biopsy showed a mixed variable-number tandem repeat analysis type containing DNA fragments matching the recipient and donor. Blood donors were excluded as a source because they were serologically different from the organ donor. The patient developed liver abnormalities and died from multiorgan failure on POD 22. CONCLUSIONS: We speculate that carryover of passenger donor lymphocytes within the transplanted organ were responsible for GVHD. Furthermore, donor traits such as sexual mismatching, African-American race, and alloimmune status may be important potential risk factors for GVHD.

Adolescent↗
PubMed1996

Early results of infrageniculate arterial reconstruction using cryopreserved homograft saphenous conduit (CADVEIN) and combination low-dose systemic immunosuppression.

BACKGROUND: The search continues for the ideal conduit for infrageniculate arterial reconstructions when the autogenous vein is unsuitable or unavailable. Based on experimental observations in our laboratory demonstrating improvement in canine cryopreserved allograft vein patency using systemic immunosuppression (Imsup), and the remarkable clinical success achieved in older (greater than 60 years of age) solid organ transplant recipients using combination low-dose Imsup, we studied the effects of Imsup on patency of cryopreserved homograft saphenous vein (CADVEIN) used for infrageniculate arterial reconstructions. STUDY DESIGN: Under the Institutional Review Board protocol, 21 infrageniculate CADVEIN grafts were placed in 19 patients between July 1993 and August 1994 for limb salvage when autogenous veins were unavailable. An immunopharmacologic protocol consisting of low-dose cyclosporine A, azathioprine, prednisone, warfarin, aspirin, and vasodilators given orally was instituted. For various reasons, 15 patients in group 1 received Imsup; five patients never received Imsup, and one patient in group 2 received Imsup briefly. Follow-up examinations were completed using the time range of six to 18 months (mean, eight plus or minus one month). RESULTS: One patient died (5.3 percent) 30 days after emergency combined venous graft and bilateral CADVEIN bypass. The actuarial 12-month primary patency in group 1 was 59.4 percent compared with 16.7 percent in group 2 (p < 0.015, log-rank test). Cellular rejection was typically seen in explanted CADVEIN. Systemic morbidity related to Imsup was minimal. The CADVEIN morbidity rate was significant: three graft aneurysms and four early graft ruptures. Major amputations were necessary in eight of 12 patients with graft closure. CONCLUSIONS: The data suggest that Imsup significantly improves CADVEIN patency with limited systemic morbidity; however, complications related to the conduit itself occurred with greater frequency and cause greater morbidity than when the autogenous veins were used. Much has yet to be learned regarding the preservation characteristics of CADVEIN and the immunologic interactions in patients receiving CADVEIN grafts, before further clinical use of this conduit can be recommended.

Adult↗
PubMed1995

Effect of IgM-positive crossmatches on survival in heart transplant recipients.

To determine whether an IgM-positive crossmatch adversely affects the results of heart transplantation, we conducted a retrospective study of 125 orthotopic heart transplant recipients. A direct donor-recipient crossmatch was performed retrospectively on sera from all patients by the standard National Institutes of Health (NIH) method and the antihuman globulin (AHG) procedure. The patients were then divided into 3 groups as follows. Group 1 comprised 110 patients with a negative NIH and AHG crossmatch (control group). Group 2 comprised 5 patients with a positive NIH crossmatch and a negative AHG crossmatch. Group 3 comprised 10 patients with positive NIH and AHG crossmatches. All positive crossmatches in group 3 patients converted to negative after treatment of sera with dithioerythritol, indicating that the initial result was due to IgM antibodies. All patients received standard immunosuppressive treatment. An IgM-positive crossmatch did not affect the number or severity of rejection episodes among the 3 groups, nor did it have an effect on the incidence of infection. Whereas coronary artery disease was detected by angiography in 16 of 110 patients (14.6%) in group 1 and in 1 of 10 patients (10%) in group 3 (P = NS), no patient in group 2 was affected. Actuarial survival at 1 and 2 years post-transplant was significantly better for patients with an IgM-positive crossmatch (group 2) (100% survival at 2 years) than for patients with a negative crossmatch (group 1) (73% at 1 year and 71% at 2 years, P < 0.05). Based on our study, the effect of an IgM-positive crossmatch on survival is difficult to interpret because of the small sample size. An IgM-positive crossmatch, however;did not appear to have a deleterious effect on survival. It may be that the IgM antibody has an immunoregulatory role. A larger series of patients with positive crossmatches and longer follow-up will be necessary to evaluate the importance of these results.

Actuarial Analysis↗
PubMed1994

The relationship among donor-recipient HLA mismatches, rejection, and death from coronary artery disease in cardiac transplant recipients.

Review of 448 cyclosporine-treated heart transplant recipients was undertaken to examine the relationship of donor-recipient HLA compatibility to patient survival, rejection, and death from coronary artery disease (CAD). Pre-Tx crossmatching and panel-reactive antibody (PRA) were correlated to survival as well. Overall patient survivals were 78%, 70%, and 65% at 1,3, and 5 years post-Tx, respectively. Matching of donor-recipient HLA did not improve outcome in that 1,3, and 5 years survivals for well-matched (< or = 2 A, B, or 0-1 DR mismatches [MMs]) vs. poorly matched (> 2 A, B, or 2 DR MMs) recipients were comparable and not significantly different. Well-matched recipients, however, experienced significantly fewer rejections (1.06 +/- 1.2 vs. 1.96 +/- 1.0, P < 0.01 for < or = 2 A, BMMs vs. > 2 A, B MMs and 1.1 +/- 0.9 vs. 2.0 +/- 1.1 for 0-1 DR MMs vs. 2 DR MMs, P < 0.01). Moreover, HLA-DR, but not HLA A, B was a significant (P < 0.01) predictor of early rejection (<30 days) in that 65% (165/254) of poorly matched vs. only 40% (95/194) of well-matched HLA-DR recipients experienced early rejections. Interestingly, an inverse relationship was found between HLA A and B MM, but not HLA-DR MM, and death from coronary artery disease in that 17% (19/11) of well matched vs 9% (32/327) of poorly matched patients died from CAD. Pre-Tx PRA did not impact patient survival or rejection. Donor-recipient crossmatching was performed utilizing the NIH and/or antiglobulin (AHG) procedures. No survival differences were observed at 1, 2, and 3 years post-Tx when comparing outcome for the 24 NIH crossmatch (XM)-positive (+) with the 424 NIH-XM-negative displayed a positive AHG recipient antidonor displayed a positive AHG recipient antidonor reactivity. When these 10 AHG-XM (+) sera were treated with dithioerythritol (to inactivate IgM) all 10 converted to a negative reactivity, indicating that a positive crossmatch due to IgM reactivity should not be considered a contraindication to cardiac transplantation. These data also suggest that the reactivity of the 24 NIH-XM(+) sera were most likely due to IgM, and that poorly matched heart recipients may benefit from a more aggressive immunosuppressive regimen to prevent early rejections.

Adolescent↗
PubMed1994

A follow-up of a media-based, worksite smoking cessation program.

Described an examination of data collected 2 years following the onset of a media-based, worksite smoking cessation intervention. Thirty-eight companies in Chicago were randomly assigned to one of two experimental conditions. In the initial 3-week phase, all participants in both conditions received self-help manuals and were instructed to watch a 20-day televised series designed to accompany the manual. In addition, participants in the group (G) condition received six sessions emphasizing quitting techniques and social support. In the second phase, which continued for 12 months, employees in G participated in monthly peer-led support groups and received incentives, while participants in the nongroup (NG) condition received no further treatment. Twenty-four months after pretest, 30% of employees in G were abstinent compared to only 19.5% in NG. This study is one of the few experimentally controlled worksite smoking cessation interventions to demonstrate significant program differences 2 years following the initial intervention.

Employment↗
PubMed1993

Stability of renal allograft glomerular filtration rate associated with long-term use of cyclosporine A.

Renal allograft glomerular filtration rate (GFR) was measured at 4-month intervals for up to 1 year in 43 CsA-treated patients using x-ray fluorescence determination of plasma iohexol clearance. Study patients were divided into cohorts based on time (years) after transplantation at study entry (0-1; 1-2; 2-3; and > 3 years) and entry GFR levels (20-29; 30-39; 40-49; and > or = 50 ml/min/1.73 m2). GFR at study entry was 42 +/- 2 and was comparable in CAD (n = 31) versus LRD (n = 12) allografts (42 +/- 2 and 44 +/- 4 ml/min/1.73 m2, respectively). Range of entry GFR levels was similar in each of the "time at entry" cohorts defined above. Serum creatinine concentrations of 1.5-2.5 mg% were associated with GFR levels of 20-60 ml/min/1.73 m2. Serial GFR levels obtained at 4-month intervals for 1 year (n = 34 patients) were not consistent with a pattern of progressively declining GFR occurring as a function of either time after transplantation or absolute GFR level at study entry (intraindividual coefficient of variation 10.3 +/- 1.0%). Patients in the lower quartile of "entry GFR" levels (< 34 ml/min/1.73 m2) were more likely than their counterparts to have had a history of acute rejection. Results are consistent with retrospective population studies of aggregate serum creatinine levels, indicating that long-term CsA use is not uniformly associated with accelerated loss of renal allograft function consequent to a progressive, toxic nephropathy. The data also suggest that neither absolute GFR level nor time after transplantation represent indications for routine dose reduction or conversion to AZA.

Adult↗
PubMed1989

A worksite smoking cessation intervention involving the media and incentives.

This study evaluated an attempt at 38 workplaces to help employees stop or reduce their levels of smoking. In past research, worksite support groups, in combination with a media smoking cessation program and self-help manuals, were found to be effective in helping employees quit smoking. Unfortunately, recidivism was found at the follow-up evaluations. The present study replicated the results of the previous worksite smoking cessation program with support groups, a television intervention, and self-help manuals. At this postpoint, 42% of employees provided groups plus incentives were abstinent compared to only 15% who were only provided self-help materials. An important difference in this study was that there were also monthly follow-up support groups and incentives. Work settings can be a source of stress and conflict, which can precipitate relapse. At a 12-month follow-up, 26% of those participants who were provided support and incentives were abstinent compared to 16% who were only provided the self-help materials.

Adult↗
PubMed1980

The threshold for binaural interaction.

The absolute sensitivity of the binaural auditory system was studied by asking subjects to discriminate tones that were truly monaural from dichotic tones that sounded monaural because of an extremely large interaural difference of intensity. Thresholds for this discrimination across the range of frequencies from 250 to 4000 Hz were achieved when the tones in the weaker channel were in the region from -45 to -50 dB relative to tones in the stronger channel. Since the monaural reference tones, as well as the stronger signals in the dichotic conditions, were chosen to be 61 dB sensation level (SL), the weakest levels for which binaural interaction could be measured appear to have been on the order of 10 to 15 dB SL.

Adult↗
PubMed1976

Sialylatin of glycoproteins of murine mammary tumor virus, murine leukemia virus, and Mason-Pfizer monkey virus.

Neuraminidase treatment of mouse mammary tumor virus, Rauscher murine leukemia virus, and Mason-Pfizer monkey virus resulted in loss of their capacity to inhibit hemagglutination of influenza virus. Hemagglutination-inhibition activity of these RNA tumor viruses could be restored by in vitro resialylation catalyzed by sialyl transferase. The major glycoprotein in the intact envelope of desialylated and, to some extent, native virions could be specificallly labeled in vitro with CMP-(14C) sialic acid. These studies further characterize the individual glycoproteins of mouse mammary tumor virus, Rauscher murine leukemia virus, and Mason-Pfizer monkey virus.

Animals↗
PubMed1975

Molecular mechanism of in vitro transformation of mammalian cells by chemical carcinogens.

BHK21 clone 13 cells transformed by dimethylnitrosamine (DMN) or nitrosomethylurea (NMU) ("alkylating" chemical carcinogens) appear to be restricted by temperature in the expression of their transformed phenotype. When grown at 38.5 degrees C, they exhibit a transformed phenotype (clonal morphology and ability to plate in agar), when grown at 32 degrees C, their phenotype is normal. Conversion from the normal to the transformed phenotype and the reverse is possible by temperature shifts. Conversely of the BHK21 clone 13 cells, of the rat fibroblasts (R111) transformed by 4-nitroquinoline-N-oxide (NQN), some exhibit a transformed phenotype restricted by temperature while others are not restricted by temperature in the expression of transformation. A working hypothesis is proposed suggesting that the phenotype of cells transformed by chemical carcinogens may be determined by the nature of the chemical reaction with the cell DNA. "Alkylating" carcinogens cause prevalently point mutation in bacteria (of the base substitution kind); in the case of transformation of mammalian cells temperature-sensitive phenotypes will be obtained. "Frameshift" carcinogens cause frameshift mutation in bacteria and cells transformed by this class of carcinogens will exhibit a transformed phenotype unrestricted by temperature.

Animals↗