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Biomedical subjects

C M Balch

Publications and source records attributed to C M Balch.

At least 181 records · Page 10Linked to original sources
PubMed1982

Associations of properdin factor B with melanoma.

We investigated 98 melanoma patients and 135 normal controls for differences in phenotype and genotype frequencies at the properdin factor B locus. A significant negative association with the Bf-F allele and melanoma was found, resulting in an estimated relative risk of 0.5. The estimated relative risk for developing melanoma among people with the Bf-FF genotype is 0.07. The Bf-S phenotype was significantly increased among the melanoma sample, with an estimated risk of 6.5. The data suggest association of the Bf locus with a melanoma protection and/or susceptibility gene(s).

Complement Factor B↗
PubMed1982

Excessive prostaglandin E2 production by suppressor monocytes in head and neck cancer patients.

The proliferative response of peripheral blood mononuclear cells (PBMC) to the mitogens PHA and Con A significantly depressed in 86% of 45 head and neck cancer patients compared with 44 normal controls. This depression of immune competence was greatest in older patients and in those with more advanced disease stages. The abnormal mitogen responses could be restored toward normal (especially with Con A stimulation) by incubating the cells with either of two prostaglandin synthetase inhibitors (indomethacin or RO-205720). This augmentation of immune response was independent of other factors, including the primary tumor site, disease stage, treatment (surgery, radiation therapy, or chemotherapy) or the patients's age or race. The most likely explanation for this depressed level of immunocompetence was an excessive production of PGE2 by suppressor cells. This was confirmed by the finding that PBMC from patients produced more PGE2 than PBMC from normal individuals (8.4 ng/ml vs. 5.2 ng/ml, p=0.002). This difference was greatest among patients less than 60 years of age whose cultured PBMC produced 91% more PGE2 than controls (p less than 0.0007). Virtually all of the PGE2 was produced by a population of monocytes defined by a monoclonal antibody and purified with a fluorescence-activated cell sorter. Patients with epidermoid cancer of the head and neck thus have an abnormality of immunoregulatory monocytes that can contribute significantly to their depression of cellular immunity by elaborating prostaglandin E2. This abnormality could be partially corrected in vitro by incubating their PMBC with a prostaglandin synthetase inhibitor.

Adult↗
PubMed1982

A comparison of prognostic factors and surgical results in 1,786 patients with localized (stage I) melanoma treated in Alabama, USA, and New South Wales, Australia.

Twelve clinical and pathologic parameters were compared in two series of Stage I melanoma patients treated at the University of Alabama in Birmingham, USA (676 patients) and at the University of Sydney in New South Wales, Australia (1,110 patients). Actuarial survival rates were virtually the same at the two institutions over a 25-year follow-up period. The incidence of thin melanomas (less than 0.76 mm) was also similar at both geographic locations (25% vs. 26%). Other similarities of these two patient populations included the following: 1) tumor thickness (Breslow Microstaging). 2) level of invasion (Clark Microstaging), 3) surgical results, 4) sex distribution, and 5) age distribution. The greatest differences between the two patient populations were their 1) anatomic distribution, 2) growth pattern, and 3) incidence of ulceration. The trunk was the most common site of melanoma, and occurred more frequently among Australian patients (37% vs. 28%). A multifactorial analysis (Cox's regression model) was then performed that included a comparison of the two institutions as a variable (Alabama vs. Australia). The dominant prognostic factors (p less than 0.0001) were 1) ulceration, 2) tumor thickness, 3) initial surgical management (wide excision +/- node dissection), 4) anatomic location, 5) pathologic stage (I vs. II), and 6) level of invasion. The benefit of elective lymph node dissection was demonstrated in both series for patients with intermediate thickness melanoma (0.76 to 3.99 mm.) For melanomas ranging from 0.76 to 1.5 mm in thickness, the benefit of node dissection was primarily in male patients. Survival rates for melanoma at the two institutions were not significantly different in the multifactorial analysis, even after adjusting for all other variable. Thus, the biologic behavior of melanoma in these two different parts of the world was virtually the same, with only minor differences that did not significantly influence survival rates. Long-term follow-up exceeding eight to ten years after surgery is critical in the interpretation of these prognostic factors and the surgical results.

Adult↗
PubMed1982

Natural killer (HNK-1+) cells in Chediak-Higashi patients are present in normal numbers but are abnormal in function and morphology.

Children with the Chediak-Higashi (CH) syndrome are known to have abnormalities of natural killer (NK) cell function. We used the HNK-1 monoclonal antibody that reacts specifically with human NK and K cells to distinguish whether this abnormality was due either to a numerical deficiency of NK cells or a defect in their ability to function. In eight CH patients, a significant proportion of their blood mononuclear cells (10--19%) expressed the HNK-1 differentiation antigen. The level of NK cells in the five children with CH syndrome was higher than for age-matched normal controls (15.8% vs. 5.8%, P less than 0.001). When HNK-1+ cells were isolated with a fluorescence-activated cell sorter, the NK cells from CH patients were a homogeneous population of lymphocytes with a single large granule rather than the multiple small granules seen in Nk cells from normal individuals. The purified HNK-1+ cells from the CH patients had minimal NK or K cell function. The CH syndrome thus includes a functionally defective population of NK cells that retain the capability of expressing the HNK-1 differentiation antigen.

Adolescent↗
PubMed1982

Immune modulatory effects of indomethacin in melanoma patients are not related to prostaglandin E2-mediated suppression.

Indomethacin significantly enhances the depressed levels of lymphocyte proliferation to the mitogens phytohemagglutinin and concanavalin A in melanoma patients. We postulated that these results were related to an abnormality in prostaglandin E2 (PGE2)-mediated suppression, since this mechanism has previously has previously been demonstrated in patients with Hodgkin's lymphoma and with head and neck carcinoma. However, the results of three experimental approaches did not support this hypothesis. First, in vitro PGE2 production by cultured blood mononuclear cells was the same in 16 melanoma patients as in 45 normal controls (4.9 versus 4.7 ng/ml). Second, lymphocyte sensitivity to PGE2 for melanoma patients was essentially the same as that for normal controls, since exogenous doses of PGE2 inhibited the mitogen responses to the same degree. Third, another prostaglandin synthetase inhibitor (RO-205720), which is structurally unrelated to indomethacin, did not augment the mitogen response in these patients. Thus PGE2 cannot be implicated as a mediator of immunosuppression in melanoma patients. To further examine the immunomodulatory mechanism of indomethacin, we preincubated the drug with purified populations of either lymphocytes or monocytes, which were then recombined and tested for mitogen response. The results suggested that indomethacin had a direct effect on the responding T lymphocytes rather than an indirect effect on monocytes. These are the first studies demonstrating that indomethacin can act directly as a modulator of cellular immune function, independent of PGE2-mediated suppression.

Adult↗
PubMed1982

Characterization of HNK-1+ (Leu-7) human lymphocytes. I. Two distinct phenotypes of human NK cells with different cytotoxic capability.

Human lymphocytes with NK and K cell activities can be identified by the HNK-1 (Leu-7) monoclonal antibody. In these experiments, subsets of HNK-1+ cells from blood and bone marrow were distinguished by their expression of other cell surface antigens, their morphology, and their NK functional capability. Two-color immunofluorescence analysis revealed that subpopulations of HNK-1+ cells in blood expressed antigens found on mature T cells (e.g., T1, T3, T4, T8), but none expressed antigens characteristic of immature T cells (T6, T9). The majority of HNK-1+ cells (greater than 60%) also expressed a myeloid antigen (M1), whereas a minority (less than 25%) expressed HLA-DR. HNK-1+ cells were separated into T3- and T3+ subsets with the fluorescence-activated cell sorter and analyzed for their morphology and NK cell function. HNK+T3- cells exhibited a high level of NK activity against K562 target cells and contained many cytoplasmic granules. On the other hand, HNK+T3+ cells had low NK activity and a paucity of cytoplasmic granules. The cell sizes of HNK+T3- and HNK+T3+ cells were indistinguishable by light-scatter analysis. When these cell fractions were analyzed further, a reciprocal relationship between T3 and M1 antigen expression was observed. These results thus delineate two distinct subsets of human HNK-1+ cells in blood with different cytotoxic capability: HNK+T3-M1+ and HNK+T3+M1- cells. Analysis of bone marrow cells demonstrated that only 0.7% of the nucleated cells expressed the HNK-1 antigen; virtually all of these cells expressed both the T3 and T8 antigens but lacked the M1 antigen. Thus, a majority of HNK-1+ cell population in blood were T3-M1+, whereas almost all bone marrow HNK-1+ cells were T3+M1-. We propose that these subsets of cells represent different stages in NK cells differentiation.

Antigens, Surface↗
PubMed1982

Characterization of HNK-1+ (Leu-7) human lymphocytes. II. Distinguishing phenotypic and functional properties of natural killer cells from activated NK-like cells.

HNK-1+ and HNK-1- lymphocytes from human blood were sorted with a fluorescence-activated cell sorter and compared for their phenotypic and functional properties. The HNK-1+ cells exhibited virtually no response to either mitogens (PHA, Con A, and PWM) or allogeneic cells, because the 3H-thymidine uptake for HNK-1+ cells was only 1 to 3% of that for HNK-1- cells. On the other hand, the HNK-1- cells responded efficiently to these stimuli and acquired a potent killing activity against K562 and other target cells after stimulation. The proliferating lymphoblasts did not acquire the HNK-1 antigen. These activated HNK-1- cells had a wider spectrum of spontaneous cytotoxicity than did HNK-1+ cells against 12 different target cells. Two distinct populations of effector cells for spontaneous killing can thus be distinguished on the basis of HNK-1 antigen expression. The classically defined NK cells are HNK-1+, whereas effector cells activated by either mitogens or allogeneic cells are HNK-1-. The HNK-1+ cells were not generated from the pool of HNK-1- cells under any of the culture conditions tested. The NK cells defined by the HNK-1 antibody are thus a functionally distinct population of cells. Although some HNK-1+ cells may also express T cell-associated antigens and sheep erythrocyte receptors, they lack some important functional properties ascribed to T cells.

Antigens, Surface↗
PubMed1981

Polypoid melanoma, a virulent variant of the nodular growth pattern.

Thirty-two patients who had polypoid melanoma were identified in a registry of 552 melanoma patients. The tumor is regarded as a variant of nodular melanoma and is associated with an increased thickness, more frequent ulceration than the nodular variant of melanoma, younger patient age, and higher probability of occult metastasis. Polypoid melanomas were most frequently present on the trunk, and were also encountered in unusual sites, such as the mucosa of the nose, hard palate, and anorectal junction. In terms of survival, the patients with the polypoid nodular variant fared significantly worse than those with nonpolypoid nodular (P = 0.05) and those with superficial spreading (P = 0.003) melanomas. The five-year survival rate for polypoid variant was 42%, in contrast to 57% for the nonpolypoid nodular and 77% for the superficial spreading melanomas. The poor prognosis of patients who have polypoid melanoma is most likely due to its being the type of melanoma with the deepest penetration at the time of surgical excision.

Acute Disease↗
PubMed1981

A multifactorial analysis of melanoma: III. Prognostic factors in melanoma patients with lymph node metastases (stage II).

Twelve prognostic features of melanoma were examined in a series of 185 patients with nodal metastases (Stage II), who underwent surgical treatment at our institution during the past 20 years. Forty-four per cent of the patients presented with synchronous nodal metastases (substage IIA), 44% of the patients had delayed nodal metastases (substage IIB), and 12% of the patients had nodal metastases from an unknown primary site (substage IIC). The patients with IIB (delayed) metastases had a better overall survival rate than patients with IIA (synchronous) metastases, when calculated from the time of diagnosis. These differences could be explained on the basis of tumor burden at the time of initial diagnosis (microscopic for IIB patients versus macroscopic for IIA patients). Once nodal metastases became evident in IIB patients, their survival rates were the same as for substage IIA patients, when calculated from the onset of nodal metastases. The survival rates for both subgroups was 28% at five years and 15% for ten years. Substage IIC patients (unknown 1 degrees site) had better five-year survival rates (39%), but the sample size was small and the differences were not statistically significant. A multifactorial analysis was used to identify the dominant prognostic variables from among 12 clinical and pathologic parameters. Only two factors were found to independently influence survival rates: 1) the number of metastatic nodes (p = 0.005), and the presence or absence of ulceration (p = 0.0019). Additional factors considered that had either indirect or no influence on survival rates (p > 0.10) were: anatomic location, age, sex, remission duration, substage of disease, tumor thickness, level of invasion, pigmentation, and lymphocyte infiltration. All combinations of nodal metastases were analyzed from survival differences. The combination that showed the greatest differences was one versus two to four versus more than four nodes. Their five-year survival rates were 58%, 27% and 10%, respectively (p < 0.001). Ulceration of the primary cutaneous melanoma was associated with a <15% five-year survival rate, while nonulcerative melanomas had a 30% five-year survival rate (p < 0.001). The combination of ulceration and multiple metastatic nodes had a profound adverse effect on survival rates. While tumor thickness was the most important factor in predicting the risk of nodal metastases in Stage I patients (p < 10(-8)), it had no predictive value on the patient's clinical course once nodal metastases had occurred (p = 0.507). The number of metastatic nodes and the presence of ulceration are important factors to account for when comparing surgical results, and when analyzing the efficacy of adjunctive systemic treatments.

Adult↗
PubMed1981

A differentiation antigen of human NK and K cells identified by a monoclonal antibody (HNK-1).

A monoclonal IgM antibody (HNK-1) was produced against a membrane antigen from the cultured T cell line, HSB-2. By indirect immunofluorescence, this antibody reacted with certain human cultured T cell lines (HSB-2 and MOLT-4 but not MOLT-3) but not with other lines of B cell or phagocytic cell origin. HNK-1 reacted with 15.1 +/- 7.1% of normal blood lymphocytes but was unreactive with monocytes, granulocytes, erythrocytes, and platelets. HNK-1+ cells separated by a fluorescence-activated cell sorter (FACS) were a homogeneous population of medium sized lymphocytes with abundant neutrophilic cytoplasm containing azurophilic granules. HNK-1+ cells were nonadherent, surface Ig-, mostly FcIgG receptor+ and both positive and negative for demonstrable sheep erythrocyte (E) rosetting capability. Cell suspensions enriched for E-rosetting T cells and depleted of FcIgG receptor+ cells contained few (6%) HNK-1+ cells. Depletion of HNK-1+ cells from blood mononuclear cell populations by complement (C) mediated lysis greatly reduced NK activity against K-562 target cells and K cell lytic activity against antibody-coated chicken red blood cells. Treatment with HNK-1 alone or C alone did not affect these activities. When the FACS was utilized to separate HNK-1+ and HNK-1- cells from 6 individuals, the HNK-1+ cell population contained almost all of the NK and K cell function. The monoclonal antibody HNK-1 thus defines the first differentiation antigen shown to be selectively expressed on human NK and K cells.

Animals↗
PubMed1981

Indomethacin enhancement of immunocompetence in melanoma patients.

Lymphocyte responses to the mitogens concanavalin A (Con A) and phytohemagglutinin (PHA) are important in vitro parameters of immunocompetence in cancer patients. The tempo and intensity of this response is regulated by monocytes. We found that the blood lymphocyte response to one or both of these mitogens was significantly depressed in 32 of 33 melanoma patients compared to 29 normal control subjects. However, these responses were significantly enhanced when the drug indomethacin, a prostaglandin synthetase inhibitor, was added to cultures of peripheral blood mononuclear cells (PBMCs) from the melanoma patients, but not from the normal control subjects. For example, at a 1 microgram/ml dose of Con A, the mean response of melanoma patients increased from 56% to 81% of the normal mean response, whereas at 20 micrograms/ml PHA the mitogen response increased from 57% to 77% of normal when PMBC were incubated with indomethacin (P less than 0.001). Overall, indomethacin enhanced the mitogen responses of melanoma patients by 35% to 85%, whereas indomethacin increased the response in normal subjects by only 5% to 15%. The mitogen response of monocyte-depleted ER+ lymphocytes for melanoma patients was equivalent to that of normal control subjects, and there was no enhancement of this response in the presence of indomethacin. This suggests that the abnormality was due to an altered function of immunoregulatory monocytes. The enhancement by indomethacin in melanoma patients was not significantly influenced by their stage of disease, age, or the proportion of blood monocytes. The decreased levels of cellular immunocompetence in these melanoma patients, as measured by their lymphocyte proliferative responses to mitogens, therefore appears to be associated with an abnormality in monocyte function that is partially corrected by indomethacin.

Adult↗
PubMed1980

The prognostic significance of ulceration of cutaneous melanoma.

Ulceration of a cutaneous melanoma on microscopic sections is an adverse prognostic finding. The five-year survival rate is reduced from 80% for non-ulcerated melanomas to 55% in the presence of ulceration for Stage I melanoma patients and from 53 to 12% for Stage II melanoma patients (P less than 0.001). As a group, ulcerated lesions are thicker and more likely to have a nodular growth pattern. However, survival rates were still worse for ulcerated melanomas when matched with nonulcerated lesions for thickness and stage of disease. The width but not the depth of surface ulceration significantly correlated with survival. The median ulcer depth was 0.08 mm (range 0.01-1.2 mm). In those few lesions with ulcer craters more than 0.2 mm in depth, the melanomas were so thick they had the same poor prognosis regardless of whether thickness was measured to the base of the ulcer or to the top of the lesion. The Breslow microstaging method of measuring thickness is therefore a valid prognostic indicator, even for ulcerated lesions. The incidence of ulceration for the entire patient group ranged from 12.5% for melanomas less than 0.76 mm thickness to 72.5% for melanomas greater than 4.0 mm thick (P of correlation = 0.0001); from 12% for Level II invasion to 63% for Level V lesions (P = 0.005); from 23% for superficial spreading growth patterns to 49% for nodular and 74% for polypoid lesions (P = 0.0001); and from 27% for lesions with a heavy lymphocyte infiltration to 60% for minimal or absent host response (P = 0.005). There was no significant correlation with anatomic location, pigmentation of the melanomas, or with the patient's age and sex. Since ulceration appears to have such an important influence on survival rates, this parameter should be considered as a stratification criterion in clinical trials and accounted for when analyzing results of melanoma treatment.

Adult↗
PubMed1980

Isolation and partial characterization of the human homologue of Thy-1.

A glycoprotein of 25,000 daltons was isolated from a human T lymphoblastoid cell line (MOLT-3). A monovalent antiserum raised against this antigen precipitated mouse Thy-1.1 antigen as well as a 25,000-dalton antigen from human blood T cells. The unabsorbed serum was also cytotoxic for both mouse and human T cells. By multiple criteria, this human T antigen appears to be homologous with mouse Thy-1.

Animals↗
PubMed1980

Surgical management of regional lymph nodes in cutaneous melanoma.

The initial evaluation of melanoma patients should include an assessment of the regional lymph nodes for metastatic disease. Clinical palpation of the nodes is an important but relatively crude index of metastatic melanoma. In clinically normal nodes, the risk of microscopic metastatic melanoma can be predicted by such prognostic factors as thickness, ulceration, and anatomic location of the melanoma. Other prognostic factors, including the level of invasion and growth pattern (nodular and superficial spreading) provided no additional predictive information after these dominant factors were accounted for. Stage I patients with intermediate thickness melanoma (0.76-4.00 mm) have an improved survival rate with elective lymphadenectomy, while those with thin (less than 0.76 mm) and thick (greater than or equal to 4.00 mm) melanomas do not benefit from elective node dissection. Stage II melanoma patients with documented nodal metastases have relatively poor survival rates because of a high risk for distant microscopic metastases. A surgical strategy for deciding about the timing, the extent, and the treatment goals of regional node dissection in melanoma patients is reviewed.

Female↗
PubMed1980

Immunochemical characterization of a human B lymphocyte differentiation antigen (p65).

A human B-cell differentiation antigen (BDA-1) with a molecular weight of 65,000 was identified by use of an anti-B-cell xenoantiserum. BDA-1 was isolated by immunoprecipitation of cell lysates from a B-lymphoblastoid cell line (SB) and from blood B lymphocytes (sIg+ER-) of four normal individuals. It was not detectable in cell membrane lysates from two T-lymphoblastoid cell lines (HSB-2 and MOLT-3) or from enriched normal T cells (sIg-ER+). BDA is single-chain molecule since its migration in SDS-PAGE gels was not altered by heating the protein to 100 degree C or by treatment with 2-mercaptoethanol. Immunodepletion experiments demonstrated that the antigen recognized by anti-BDA xenoantiserum has neither structural nor antigenic relationships with Ia-like antigen or beta 2-microglobulin.

Antibodies↗