Immunology in the new millennium: building on tradition.
Explore the source record for details and available documents.
Allergy and Immunology↗
Biomedical subjects
M Kemeny
Publications and source records attributed to M Kemeny.
Fusagene vectors: a novel strategy for the expression of multiple genes from a single cistron.
Transduction of cells with multiple genes, allowing their stable and co-ordinated expression, is difficult with the available methodologies. A method has been developed for expression of multiple gene products, as fusion proteins, from a single cistron. The encoded proteins are post-synthetically cleaved and processed into each of their constituent proteins as individual, biologically active factors. Specifically, linkers encoding cleavage sites for the Golgi expressed endoprotease, furin, have been incorporated between in-frame cDNA sequences encoding different secreted or membrane bound proteins. With this strategy we have developed expression vectors encoding multiple proteins (IL-2 and B7.1, IL-4 and B7.1, IL-4 and IL-2, IL-12 p40 and p35, and IL-12 p40, p35 and IL-2 ). Transduction and analysis of over 100 individual clones, derived from murine and human tumour cell lines, demonstrate the efficient expression and biological activity of each of the encoded proteins. Fusagene vectors enable the co-ordinated expression of multiple gene products from a single, monocistronic, expression cassette.
Animals↗
Breast cancer risk in relation to adipose concentrations of organochlorine pesticides and polychlorinated biphenyls in Long Island, New York.
To assess a possible etiological role of organochlorine compounds in breast cancer development on Long Island, a high-risk region of New York State, concentrations of organochlorine pesticides and polychlorinated biphenyls (PCBs) were measured in the adipose tissue of 232 women with breast cancer and 323 hospital controls admitted to surgery for benign breast disease or non-breast-related conditions. Seven pesticide residues and 14 PCB congeners were assayed via a supercritical fluid extraction method followed by gas chromatography with electron capture detection. After adjustment for age and body mass index, which were strongly correlated with organochlorine levels, adipose concentrations of 1,1-dichloro-2,2-di(4-chlorophenyl)ethylene, total pesticides, and total polychlorinated biphenyls (PCBs) did not differ significantly between cases and controls. The relative abundance of individual pesticide species and PCB congeners was similar in cases and controls. Odds ratios adjusted for age, BMI, hospital, and race gave no evidence of a dose-response for 1,1-dichloro-2,2-di(4-chlorophenyl)ethylene, total pesticides, or total PCBs, whether stratified by estrogen receptor status or not. Breast cancer risk among Long Island residents was not elevated compared with residents of the adjacent New York City borough of Queens. We did not confirm a previously reported association between breast cancer risk and levels of PCB congener 118 (2,3',4,4',5-pentachlorobiphenyl), nor did we observe an association with the most abundant congener 153 (2,2',4,4',5,5'-hexachlorobiphenyl), a strong inducer of phase I enzymes that was reported recently to have estrogenic properties. Only PCB congener 183 (2,2',3,4,4',5',6-heptachlorobiphenyl), which is also an inducer, was significantly associated with risk, with an adjusted odds ratio of 2.0 (95% confidence interval, 1.2-3.4) in women with adipose levels >5.67 ng/g; the biological importance of this observation is unclear without confirmation in additional studies. Although neither the present nor other studies have provided convincing evidence of an association between body burden of 1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane and PCBs with cancer of the breast, these compounds are rated as "possible" and "probable" human carcinogens, respectively, by the International Agency for Research on Cancer. Investigations of associations with cancer at other sites should be carried out.
Adipose Tissue↗
The prognostic significance in HIV infection of immune activation represented by cell surface antigen and plasma activation marker changes.
One hundred and eighteen HIV-infected homosexual men without AIDS and 40 control seronegative homosexual men were assessed for 23 parameters reflecting immune activation to determine prognostic significance for occurrence of AIDS. Samples cryopreserved in 1987-1989 were analyzed, with AIDS occurrence determined by mid-1992. Cell surface antigens assessed on the major lymphocyte subsets were HLA-DR, CD38, CD71, and CD25. Soluble serum molecules assessed were tumor necrosis factor alpha, soluble TNFalpha receptor II, soluble IL-2 receptor alpha, neopterin, and beta2-microglobulin. Using a proportional hazards model, prognostic markers included decreased CD4 number and percentage; increased sIL-2R, neopterin, and beta2M; increased percentage HLA-DR+ total lymphocytes and CD4+ cells; increased CD38+ total lymphocytes and CD8+ cells; increased CD71+ total lymphocytes and CD4+ cells; and decreased CD25+ total lymphocytes and CD19+ cells. After adjustment for CD4 cell levels, sIL-2R, neopterin, beta2M, and CD25+ CD19 cells remained significant, indicating that additional information about AIDS risk was provided by these markers.
ADP-ribosyl Cyclase↗
Economic implications of hepatic arterial infusion versus intravenous chemotherapy or symptom palliation in the treatment of nonresectable colorectal liver metastases. Meta-Analysis Group In Cancer.
Explore the source record for details and available documents.
Antineoplastic Agents↗
Recent advances. Immunology.
Explore the source record for details and available documents.
Allergy and Immunology↗
Relative abundance of organochlorine pesticides and polychlorinated biphenyls in adipose tissue and serum of women in Long Island, New York.
Some organochlorine pesticides (OCPs) and PCBs are under investigation as possible risk factors for breast cancer because of their estrogenic properties and widespread presence in the environment. It is important to know whether adipose tissue used by some investigators and serum assays used by others can provide comparable information on body burden. Concentrations of seven OCPs or their breakdown products as well as 14 PCB congeners were measured in the adipose tissue and serum of 293 women enrolled as controls in a case-control study of environmental factors for breast cancer in Long Island, New York, a high-risk region. Adipose OCP/PCB levels were measured using a supercritical fluid extraction method developed by the authors. 1,1-Dichloro-2,2-di(4-chlorophenyl)ethylene (p,p'-DDE) was detected in all adipose and serum samples; two chlordane derivatives, beta-hexachlorocyclohexane (a lindane isomer) and hexachlorobenzene, were detected in at least 92% of adipose samples. The di-ortho hexachlorinated PCB congeners 2,4,5,2',4',5'-hexachlorobiphenyl and 2,3,4,2',4',5'-hexachlorobiphenyl were detected in all adipose and over 98% of serum samples. 1,1-Dichloro-2,2-di(4-chlorophenyl)ethylene comprised 77% of total pesticide residues in adipose and 71% in serum. 2,4,5,2',4',5'-Hexachlorobiphenyl comprised 24% of adipose and 21% of serum PCBs. The relative concentration patterns of the 14 PCB congeners were similar to those reported in other human studies and were also typical of patterns reported in environmental samples from various biota, including mammals and birds, but differed substantially from patterns reported in occupationally exposed workers. All adipose-serum correlations for pesticides and most PCBs were statistically significant. Either serum or adipose OCP/PCB levels of a variety of environmental organochlorine compounds may serve as useful biomarkers of body burden.
Adipose Tissue↗
Relation of impaired lymphocyte proliferative function to other major human immunodeficiency virus type 1-induced immunological changes.
Human immunodeficiency virus (HIV) type 1 (HIV-1) induces impairment of immune function reflected in reduced lymphocyte proliferative responses. Many other immune changes are induced by HIV-1, but their relationship to lymphocyte functional defects is not known. The present study was designed to correlate functional defects with other HIV disease parameters. Cryopreserved samples from 118 HIV-1-positive subjects and 40 seronegative individuals were examined. The main findings were that impaired proliferative responses to mitogens correlated with (i) decreased cell surface expression of the interleukin-2 receptor (CD25), (ii) increased expression of HLA-DR antigens on CD4 cells, (iii) reduced CD4 and increased CD8 cell numbers, and (iv) increased levels of serum immune complex dissociated p24 antigen. However, impaired function was not associated with increased serum neopterin, beta2-microglobulin, or soluble interleukin-2 receptor or with CD38 antigen expression on lymphocytes. In summary, proliferative functional impairment correlated with some, but not all, immunological changes associated with HIV-1 infection. Most of the phenotypic markers that correlated with altered function are cell surface molecules with significant roles in lymphocyte proliferation and were associated primarily with CD4 cells, compatible with the view that dysregulation of CD4 cells is responsible for impaired function.
Antigen-Antibody Complex↗
Patterns of breast cancer care in the elderly.
BACKGROUND: The elderly represent a large proportion of the women with breast cancer. However, there is a lack of information regarding breast cancer care in the elderly. METHODS: A patient care evaluation survey for breast carcinoma was conducted by the Commission on Cancer of the American College of Surgeons for 1983 and 1990. Data were obtained from hospital tumor registries from all 50 states, Puerto Rico, and Canada. Information regarding presentation, diagnostics, staging, treatment, recurrence, and survival were analyzed. Comparisons were made between women 75 years and older and those younger than 75 years. RESULTS: Included were 17,029 diagnosed with breast carcinoma during 1983 and 24,004 diagnosed during 1990. In 1983 and 1990, 20.4% and 23.4% of women, respectively, were 75 years or older. Fewer cancers were detected mammographically and needle localized biopsies were performed less often in the elderly. There was no difference in tumor location or histology. Stage at diagnosis appeared more advanced in the elderly. Most women regardless of age, underwent modified radical mastectomy. Of the elderly who did undergo breast conserving surgery in 1983 and 1990, 72% and 39%, respectively, did not receive radiation therapy. No difference was found in the local recurrence rates between the elderly and younger groups. In the elderly, 20% of deaths occurred from causes other than breast cancer. Overall disease specific survival was worse in the elderly but, when analyzed by stage, was significantly different for only certain stages. CONCLUSIONS: There are several differences in the detection, diagnostic methods, stage at diagnosis, treatment approaches, and outcome of breast cancer in elderly women compared with younger women.
Age Factors↗
Reappraisal of hepatic arterial infusion in the treatment of nonresectable liver metastases from colorectal cancer.
BACKGROUND: Metastases confined to the liver cause substantial morbidity and mortality for patients with colorectal cancer. The results of several randomized clinical trials conducted to study the effectiveness of hepatic arterial infusion (HAI) of fluoropyrimidines for the treatment of such patients have suggested that this treatment, as compared with systemic administration of fluoropyrimidines, increases the likelihood of tumor response. However, the impact of HAI on survival is unclear. PURPOSE: A meta-analysis was carried out to provide an objective and quantitative appraisal of the benefits of HAI in terms of tumor response rate and overall patient survival. METHODS: The meta-analysis was based on individual data provided by the principal investigators of six individual trials and on summary data for one trial. Of the seven trials, five compared HAI with floxuridine (5-fluoro-2'-deoxyuridine; FUDR) and intravenous chemotherapy (IVC) with FUDR (three trials) or fluorouracil (5-FU) (two-trials), and two compared HAI with FUDR and an ad libitum control group in which some patients could be left untreated. Response data were analyzed by use of a Mantel-Haenszel test on all randomized patients. Survival data were analyzed by the use of stratified logrank test. Multivariate analyses were performed with use of the logistic regression model for tumor response and the Cox regression model for survival. All P values resulted from two-sided statistical tests. The analyses were performed by an independent secretariat and were reviewed by the collaborators. RESULTS: The tumor response rate was 41% for patients allocated to HAI with FUDR or 5-FU (CR, 2%; PR, 12%). This difference was highly significant, with a response odds ratio of 0.25 (95% confidence interval = 0.16-0.40; P < 10 (-10)). Survival analyses showed a statistically significant advantage for HAI with FUDR compared with control when trials were taken into account (P = .0009) but not when the survival analysis was restricted to trials comparing HAI with FUDR and IVC with FUDR or 5-FU (P = .14). CONCLUSION: These results confirm that HAI can achieve much higher tumor response rates than systemic chemotherapy in patients with liver metastases from colorectal cancer. IMPLICATIONS: The therapeutic benefit of use of HAI with FUDR in these patients should be judged together, with an overall evaluation of this therapy in terms of convenience, toxicity, and costs. These end points should be considered in addition to tumor response and survival in further trials involving HAI.
Antimetabolites, Antineoplastic↗
The multidimensional nature of received social support in gay men at risk of HIV infection and AIDS.
This article concerns received social support in gay men at risk of HIV and AIDS. Distinctions are made between three types of support (informational, tangible, emotional), four sources of support (friends, relatives, partner, organizations), and three dimensions of support (amount, satisfaction, reciprocity). A 24-item inventory reflecting these distinctions was administered to a sample of 587 gay men at two points in time. The psychometric properties of the instrument were determined, and the factor structure of the items varying sources and types of social support were tested. This was done by exploratory as well as by confirmatory factor analyses. The hypothesized structure was confirmed in both waves separately. Results corroborated the assumption that enacted or received social support is a highly differentiated construct and requires assessment tools that are designed according. Descriptive results on the support perceptions in this sample are also presented. Implications for the study of support in men at risk of HIV and AIDS are discussed.
Acquired Immunodeficiency Syndrome↗
Bilateral brachial plexus palsy after immediate breast reconstruction with TRAM flaps.
Although most postoperative upper extremity neuropathies are caused by extremes of position or intraoperative manipulation of the arm, nerve injury is possible without either of these. Pedicled TRAM flap surgery, during which no axillary retraction or hyperabduction of the arm is used, is not free of risk for neural injury. More studies are needed to specifically define risk-related maneuvers for these and other anesthetized patients.
Adult↗
Differential effect of beta-endorphin on three human cytotoxic cell populations.
We have examined in vitro the effect of the proopiomelanocortin gene product, beta-endorphin (bE), on the cytotoxic activity of natural killer (NK) cells, lymphokine activated killer (LAK) cells and cytotoxic T-lymphocytes (CTL). Our studies show that bE reproducibly suppressed LAK cytotoxic activity in all donors tested. The effect of bE on the generation of CTL varied, and was negligible on CTL cytotoxic function. Our study also confirms the variable nature of the effects of bE on NK cytotoxicity. In all instances, the effects of bE were generally small, but could be blocked by opioid receptor antagonists, or by prior heat-inactivation of the peptide. The magnitude of the effects was greatest at low effector:target ratios in all of the three systems studied. These results support the emerging body of evidence that the neuroendocrine system may influence host defense mechanisms mediated by cytotoxic cells.
Adolescent↗
Limbal vernal keratoconjunctivitis: clinical characteristics and immunoglobulin E expression compared with palpebral vernal.
Limbal and palpebral vernal keratoconjunctivitis (VKC) are usually considered to be different expressions of the same disease. This single centre population of 120 patients with VKC had 32 patients with limbal VKC, 54 with palpebral VKC and 34 with mixed palpebral and limbal VKC. There were higher proportions of females (p = 0.015) blacks, Indians and Asians (p = 0.0001) in the limbal group and fewer limbal patients had other atopic diseases (p = 0.03). The age of presentation was similar for all groups; 87/112 (78 per cent) presenting before the age of 16. The follow-up period was shorter in the limbal VKC patients (p = 0.004) suggesting a shorter disease course. Only one limbal VKC patient developed corneal opacities compared to fifty (47 per cent) with palpebral or mixed VKC, 24 (27 per cent) of whom lost vision. Tear and serum levels of total IgE and specific IgE to the major inhalent allergens cat, house dust mite and grass pollen were compared in 17 patients with palpebral or mixed VKC and ten with limbal VKC; no statistically significant differences were shown. However the significant variations in sex, racial distribution and associated atopic disease suggest that limbal VKC may be a different disease from palpebral VKC although this is not expressed in terms of IgE production.
Adolescent↗
Regional chemotherapy for hepatic tumors--new hope on the horizon.
Explore the source record for details and available documents.
Embolization, Therapeutic↗
Immediate hypersensitivity to ovalbumin in children with hen's egg white allergy.
Serum concentrations of IgE, IgG1 and IgG4 antibodies to ovalbumin and basophil sensitivity to ovalbumin were compared with the results of a titrated oral provocation test with ovalbumin in 27 children sensitive to hen's egg white, of whom 17 responded with an immediate hypersensitivity reaction. Neither the serum level of IgE, IgG1 and IgG4 antibodies to ovalbumin nor a positive histamine release test predicted the clinical relevance of ovalbumin sensitivity. The children with a positive challenge test had a significantly higher IgE/IgE4 ratio and tended to be younger and to have higher serum IgE levels and a higher IgG1/IgG4 ratio than those with a negative challenge test. We conclude that an oral provocation test is necessary to confirm the diagnosis of food allergy.
Child↗
Enhanced ELISA: how to measure less than 10 picograms of a specific protein (immunoglobulin) in less than 8 hours.
In this paper we outline a flexible and rapid method to measure picogram quantities of isotype-specific immunoglobulin (Ig), including IgE. Only readily or commercially available reagents are required: isotype-specific, anti-human Ig murine monoclonal antibodies (Mab) to coat microtiter plates, polyclonal alkaline phosphatase-coupled isotype-specific F(ab)'2 or Fab' fragments as second antibodies, and an enhanced developing system that amplifies the signal-to-noise ratio of the quantitatively bound second antibody. The procedure is detailed in the appendix to enable easy application, even if one has no previous experience with ELISAs. This system can be used to detect less than 10 picograms of Ig in cultures supernatants of cells that contain mixtures of various Igs and it can be used to detect the product of a single cell producing Ig. This method also will be applicable to measurement of the minute quantities of lymphokines and other biologically active molecules produced in vitro and found in various fluids in vivo.
Antibodies, Monoclonal↗