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Biomedical subjects

C M Balch

Publications and source records attributed to C M Balch.

At least 199 records · Page 11Linked to original sources

Recent advances in human cellular immunobiology.

Several recent advances in human cellular immunology will have increasing impact on surgical science. First, lymphocytes are composed of diverse subpopulations with different biological properties. Second, lymphocytes and phagocytes expressed distinctive cell surface markers that reflect the specialized function of each cell. Third, different subpopulations of lymphocytes probably have one or only a few specific functions rather than being multipotential. Despite the seemingly complex heterogeneity of the immune system, the component parts collaborate in a highly integrated fashion. The recent elucidation of suppressor cells and their interaction with effector cells, for example, is a major conceptual advance. Fourth, the technology of immunologic science has advanced significantly. More discriminating methods for detecting lymphocyte markers and the ability to physically separate and analyze lymphocyte subpopulations will permit increasingly more refined insights into normal and abnormal immune responses. A number of important advances at the molecular level involving the disciplines of immunogenetics and immunochemistry have also been described but are beyond the scope of this review. Much work remains, however, in correlating these in vitro observations in the laboratory with in viro activity in the patient. It is now evident that the outcome of an immune response (or lack of it) represents a net balance of different components in the immunologic network that determine the time course, intensity of response, and the actual mechanisms of antigen elimination. A better understanding of these component parts of a normal immune response, and their deviations in disease states, is essential for designing more sophisticated therapeutic manipulations of the immune system. Attempts at "immune manipulation" aimed at stimulating or depleting the entire system are no more likely to be successful or reproducible than are attempts to "manipulate" the entire endocrine system. More meaningful results will occur when one can deal with individual components of an immune response (such as suppression or killing) and can precisely monitor the consequences of altering them.

Animals↗

The preparation and immunosuppressive properties of equine antihuman thymocyte membrane immunoglobulin G.

Human thymocytes separated by a Ficoll gradient produced a cell population that was 99% pure thymocytes and free of platelets, leukocytes, and epithelial cells. These cells, disrupted by a nitrogen bomb, produced a membrane-ribosome antigen fraction confirmed by enzyme analysis. Equine antithymocyte membrane-immunoglobulin G (ATM-IgC) prepared against this antigen in four of five horses contained immunosuppressive properties capable of prolonging monkey skin allograft survival longer than 21 days. No adverse effects were noted by the intramuscular and intravenous administration of this antisera to primates, and autopsy examination showed marked depletion of paracortical lymphocytes in the spleen and mesenteric lymph nodes. A moderate thrombocytopenia occurred during a 4 hour intravenous administration of ATM-IgG to primates with a marked decrease in the peripheral lymphocyte count. The deposition of ATM-IgG upon monkey glomerular basement membrane could not be demonstrated by immunofluorescent techniques. The specificity of this globulin to contain anti-T-cell antibody was confirmed by an immunofluorescent assay in that ATM-IgG reacted with both human thymocytes and peripheral blood thymus-dependent cells, but was nonreactive when tested against a panel of human cells free of thymus-dependent antigens.

Animals↗

A multifactorial analysis of melanoma. II. Prognostic factors in patients with stage I (localized) melanoma.

Stage I melanoma encompasses an extraordinary diversity of biologic behavior. In such a setting where numerous parameters appear to influence survival, a multifactorial analysis using Cox's regression model is a valuable statistical model. Using a computerized data base of 394 clinical stage I melanoma patients treated at this institution during the past 20 years, a multifactorial analysis was used to compare the relative prognostic strength of 11 parameters. Two pathological factors (tumor thickness and ulceration) and two clinial factors (initial surgical treatment and anatomic location) were identified as the dominant prognostic variables. Other factors examined simultaneously that did not provide additional predictive influence on survival included the level of invasion, pigmentation, growth pattern, lymphocyte infiltration, pathological state, sex, and age. Melanoma thickness was the most important factor for predicting survival in patients with stage I melanoma (P less than 10(-8). This parameter is easy to measure and provides a quantitative estimate of clinically occult regional and distant metastases. Contrary to other reports using single factor analysis, the type of initial surgical treatment, in fact, did influence survival after other variables were taken into consideration. Thus the multifactorial analysis supports the observation that patients with intermediate thickness melanoma thickness of 1.5 to 3.99 mm had a 78% 8-year survival rate with wide excision of the melanoma and elective node dissection, while none survived more than 8 years if a melanoma of the same thickness was only widely excised. Multifactorial analysis is a useful and important statistical method when comparing treatment alternatives and prognostic factors in patients with melanoma.

Adult↗

A methodological approach to the prediction of anticancer drug effect in humans.

Tumor cells from animals and humans were treated with drugs under tissue culture conditions. Tumor cells from the sensitive L1210 model were studied first. A dose-response curve was derived between drug exposure and subsequent cytotoxicity in L1210. The concentration of drug and duration of exposure were factors critical to the subsequent development of in vitro cytotoxicity. The in vitro dosage which effected 50% leukemic cell death in L1210 cells correlated with reported in vivo drug levels. Other tumor models and human neoplastic cells were studied at this dosage level. A good correlation was noted in these studies between the in vivo responsiveness and the in vitro chemotherapy results in both animals and humans. It was suggested by these results that it may be possible to predict cancericidal drug activity for individual neoplasms by assaying the tumor cells in vitro for drug sensitivity.

Animals↗

A multifactorial analysis of melanoma: prognostic histopathological features comparing Clark's and Breslow's staging methods.

A multifactorial analysis was used to identify the dominant prognostic variables affecting survival from a computerized data base of 339 melanoma patients treated at this institution during the past 17 years. Five of the 13 parameters examined simultaneously were found to independently influence five year survival rates: 1) pathological stage (I vs II, p = 0.0014), 2) lesion ulceration (present vs absent, p = 0.006), 3) surgical treatment (wide excision vs wide excision plus lymphadenectomy, p = 0.024), 4) melanoma thickness (p = 0.032), and 5) location (upper extremity vs lower extremity vs trunk vs head and neck, p = 0.038). Additional factors considered that had either indirect or no influence on survival rates were clinical stage of disease, age, sex, level of invasion, pigmentation, lymphocyte infiltration, growth pattern, and regression. Most of these latter variables derived their prognostic value from correlation with melanoma thickness, except sex which correlated with location (extremity lesions were more frequent on females, trunk lesions on males). This statistical analysis enabled us to derive a mathematical equation for predicting an individual patient's probability of five year survival. Three categories of risk were delineated by measuring tumor thickness (Breslow microstaging) in Stage I patients: 1) thin melanomas (<0.76 mm) were associated with localized disease and a 100% cure rate: 2) intermediate thickness melanomas (0.76-4.00 mm) had an increasing risk (up to 80%) of harboring regional and/or distant metastases and 3) thick melanomas (>/=4.00 mm) had a 80% risk of occult distant metastases at the time of initial presentation. The level of invasion (Clark's microstaging) correlated with survival, but was less predictive than measuring tumor thickness. Within each of Clark's Level II, III and IV groups, there were gradations of thickness with statistically different survival rates. Both microstaging methods (Breslow and Clark) were less predictive factors in patients with lymph node or distant metastases. Clinical trials evaluating alternative surgical treatments or adjunctive therapy modalities for melanoma patients should incorporate these parameters into their assessment, especially in Stage I (localized) disease where tumor thickness and the anatomical site of the primary melanoma are dominant prognostic factors.

Aged↗

The logic of adjunctive therapy in surgical patients with resectable cancer.

The principles and rationale of using multiple modalities (surgery, chemotherapy, radiotherapy, and immunotherapy) to treat solid malignancies is reviewed. Animal models of human tumors have clearly demonstrated the superiority of combining local treatment (eg, surgery) with systemic treatment (eg, chemotherapy). Although the results of many trials of adjunctive therapy in man are still preliminary, they warrant the caustious generalization that multiple modality therapy will increasingly become more effective than surgery alone for most types of solid tumors. Although the strategy of employing adjunctive therapy is rational, it must be emphasized that the therapeutic efficacy of specific drugs or agents for particular patients or tumor types has not always been satisfactory. Clinical trials now in progress may demonstrate more effective regimens. In the meantime, physicians should be cautious about using adjunctive therapy as standard treatment until long-term benefits and safety have been demonstrated. Participation in clinical trials is encouraged to verify the validity and application of this therapeutic approach.

Animals↗

A new B cell differentiation antigen (BDA) on normal and leukemic human B lymphocytes that is distinct from known DR (Ia-like) antigens.

A newly defined human B cell differentiation antigen, designated as BDA, has been defined and partially characterized. BDA is expressed on normal human B cells and lymphocytic leukemia cells at all stages of known differentiation (pre-B cells to plasma cells). It is distinct from DR (Ia-like) determinants and other known B cell surface constituents.

Animals↗

Expression of two differentiation antigens on normal and cultured human T cells.

An antiserum specific for human T lymphocytes (AMT) was used to examine patterns of T cell surface antigen expression and to isolate their reactive membrane antigens. By a quantitative adsorption assay, different plateaus of AMT reactivity with blood T cells were observed after serial adsorptions with individual T cell lines. MOLT-3 cells removed 95% of AMT activity to blood T cells whereas MOLT-4 removed 70% and HSB-2 removed only 30%. A cross-adsorption analysis demonstrated that each of the three cell lines differed in their adsorbing efficiency to remove AMT antibodies reactive with the reciprocal cell lines. Radiolabeled membrane proteins were solubilized with either sodium deoxycholate (DOC) or NP-40 detergents, precipitated with AMT, and Staphylococcus aureus Cowan strain I, and analyzed by sodium dodecyl sulfate-polyacrylamide disc gel electrophoresis (SDS-PAGE). Two distinct T lymphocyte antigens of approximately 25,000 daltons (p25) and 16,000 (p16) were identified on MOLT-3 cells. Similar relative quantities of p25 and p16 were detected on human peripheral T cells and thymocytes. MOLT-4 cells contained less of the p25 peak than did MOLT-3. HSB-2 cells gave a small peak in the same general location as the MOLT-3 p25 peak, and a relatively large p16 peak. Adsorption of AMT with HSB-2 removed the capacity of the antiserum to precipitate p16 from MOLT-3, but did not eliminate reactivity with p25.

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