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Biomedical subjects

C M Balch

Publications and source records attributed to C M Balch.

At least 163 records · Page 9Linked to original sources
PubMed1983

In vitro propagation of cultured human natural killer cells expressing the HNK-1 differentiation antigen and spontaneous cytotoxic function.

Human natural killer (NK) cells expressing the HNK-1 differentiation antigen were established in long-term tissue culture for over 3 months. The fluorescence-activated cell sorter-purified HNK-1+ cells required both phytohemagglutinin and exogenous interleukin 2 to propagate in long-term culture. After 2 weeks of culture, virtually all of the growing cells exhibited the surface membrane phenotype associated with immature HNK-1+ cells, since they simultaneously expressed the HNK-1, Leu-4 and Leu-2a but lacked the M1. Leu-3a and T6 antigens, and Fc gamma receptors. They exhibited a lymphoblastoid appearance, contained cytoplasmic granules, and exhibited spontaneous cytotoxic function against a broader spectrum of target cells than did fresh HNK-1+ cells from the same donor. Cultured HNK-1+ cells lacked antibody-dependent cell-mediated cytotoxic (ADCC) function, while fresh HNK-1+ were fully capable of ADCC function. On the other hand, cultured HNK-1- cells were lymphoblasts without cytoplasmic granules or NK cytotoxic function. The cultured HNK-1+ cells gradually lost their HNK-1 antigen expression over time, although the expression of other surface antigens (e.g., Leu-4 and Leu-2a) was unchanged. With prolonged culture (greater than 2 months), they also exhibited decreasing cytotoxic function and a diminished number of cytoplasmic granules. They were eventually indistinguishable from HNK-1- cells after 3 months of culture. These observations were not influenced by adding interferon-gamma to the cultures. The results demonstrate that the immature form of NK cells (that express T cell antigens) preferentially proliferate in long-term cultures when incubated with phytohemagglutinin and interleukin 2.

Adult↗
PubMed1983

Abdominal wound closure. A randomized prospective study of 571 patients comparing continuous vs. interrupted suture techniques.

A randomized, prospective study was designed to compare a continuous with an interrupted technique for closing an abdominal incision. Five hundred seventy-one patients were randomized between the closure methods and stratified as to type of wound: clean, clean-contaminated, or contaminated. In mid-line incisions, the dehiscence rate was 2.0% (5/244) for the continuous group versus 0.9% (2/229) for the interrupted group. The difference was not statistically significant. Ventral hernias formed in 2.0% (4/201) of the continuous group vs. 0.5% (1/184) of the interrupted group. The type of wound had no influence on the results. In oblique incisions, 0% (0/39) of wounds closed continuously dehised while 2% (1/50) of incisions closed interruptedly dehised. No ventral hernias formed. Further analysis of the data indicated that dehiscence was more likely related to improper surgical technique than to the method of closure. An abdominal incision could be closed with a continuous suture in approximately half the time required for placing interrupted sutures (20 vs. 40 minutes). A continuous closure is preferred because it is more expedient and because it has the same incidence of wound disruption compared with an interrupted closure.

Abdomen↗
PubMed1983

The impact of surgical quality control in multi-institutional group trials involving adjuvant cancer treatments.

Quality control involving surgical treatment in multi-institutional cancer trials is important because the results of postoperative adjuvant therapy might be obscured by inadequate surgery or pathologic examination of the specimen. In 1975, the Southeastern Cancer Study Group (SEG) initiated a randomized clinical trial of adjuvant immunotherapy (Corynebacterium parvum vs. bacillus Calmette-Guerin) in melanoma patients with nodal metastases. During the course of reviewing the results several years later, 20 of 136 patients (15%) entered into this study were judged as surgically ineligible. The reasons were: 1) biopsy of a metastatic node only without any subsequent regional lymph node dissection (12 patients), 2) partial lymph node dissection (six patients), or 3) too few nodes surgically removed or pathologically identified in the specimen (six patients). All 20 patients were entered into the study by medical oncologists. Thirteen of these 20 surgically ineligible patients have relapsed so far; many were taken off the study as "immunotherapy failures," when, in fact, they were surgical failures. Compared to the 116 surgically eligible patients, the 20 ineligible patients had a shorter median survival (4 months vs. 25 months) and a lower 1-year disease-free survival rate (36% vs. 62%, p = 0.01). The two groups were balanced equally with respect to prognostic factors. Because of these findings, minimum surgical and pathologic guidelines were established for each adjuvant therapy protocol in the SEG. Surgical quality control was reviewed by a surgeon in each institution prior to randomization and again by a surgical investigator centrally. Pathologic criteria were also defined more precisely. The problems with surgically ineligible patients have since been virtually eliminated. Quality control measures for surgical patients entered into cooperative group trials is an essential part of the protocol design and data review. In order to evaluate properly the impact of adjuvant therapy, each clinical trial must comprise a uniform group of surgically treated patients.

Biopsy↗
PubMed1983

Depressed levels of granular lymphocytes with natural killer (NK) cell function in 247 cancer patients.

The HNK-1 (Leu-7) monoclonal antibody was used to enumerate and characterize the level of blood granular lymphocytes in 247 cancer patients. The results were compared to 146 control individuals. A fluorescence-activated cell sorter was used to purify blood HNK-1+ cells from cancer patients. The monoclonal antibody identified a homogeneous population of granular lymphocytes with greater than 95% purity. Conversely, virtually 100% of HNK-1- cells from cancer patients were agranular lymphocytes. These results were the same as previously observed in normal individuals, where the HNK-1+ cell fraction contained all the lymphocytes with spontaneous cytotoxicity in natural killer (NK) and killer (K) cell assays. The level of HNK-1+ cells in cancer patients correlated significantly with the patient's age and sex, with older individuals having higher levels and male patients containing a higher proportion than female patients. The levels in the cancer patients were significantly lower than normal controls (p = 0.04). When the results were subdivided by the histologic type of cancer, additional differences were noted. Compared to age and sex-matched controls, significantly depressed levels of HNK-1+ granular lymphocytes were observed in 49 patients with colon cancer (9.7% vs. 15.8%, p = 0.0001), 18 patients with lung carcinoma (11.7% vs. 27.0%, p = 0.0001), 24 patients with breast carcinoma (12.0% vs. 15.5%, p = 0.04) and 64 patients with head and neck carcinoma (15.9% vs. 19.1%, p = 0.05). However, there were no significant differences overall in the average HNK-1+ cell level of 66 patients with melanoma (13.0% vs. 13.5%, p = 0.75) and nine patients with sarcomas (15.8% vs. 14.3%, p = 0.71). Thus, this important subpopulation of granular lymphocytes with NK and K cell function was significantly depressed in most cancer patients. Accounting for the patient's age and sex and the histologic type of cancer was critical to interpreting the results.

Adult↗
PubMed1983

A randomized prospective trial of radical (Halsted) mastectomy versus modified radical mastectomy in 311 breast cancer patients.

This study reports the results of a prospectively randomized trial for treatment of carcinoma of the breast comparing standard (Halsted) radical mastectomy to a modified radical mastectomy. Three hundred eleven patients with primary operable carcinoma of the breast were entered in a surgical and adjunctive chemotherapy trial in Alabama between 1975 and 1978. A total of 91 surgeons participated (all Diplomats of the American Board of Surgery and Members of the American College of Surgeons). All operative reports, pathology and therapy were reviewed by referees. Histologically node positive patients were randomized after operation to receive melphalan or C.M.F.(cytoxan, methotrexate, and 5-FU) for 1 year. After a median follow-up of 5.5 years, there was no significant difference in disease-free survival or in overall survival between the two groups. There was a trend toward improved 5-year survival rates in the radical mastectomy group compared to the modified radical mastectomy group (84% vs. 76%, p = 0.14). There was also an increased incidence of local wound recurrence in those patients receiving modified radical mastectomy, but the differences were not statistically significant (p = 0.09). Longer follow-up will be necessary to evaluate these results more fully.

Breast Neoplasms↗
PubMed1983

A prospective phase II clinical trial of continuous FUDR regional chemotherapy for colorectal metastases to the liver using a totally implantable drug infusion pump.

A prospective phase II evaluation of regional FUDR chemotherapy using a totally implantable drug infusion pump was conducted in 81 patients with colorectal metastases to the liver. The survival results were compared to a historical control group of 129 patients with isolated liver metastases. The two groups were comparable with respect to their dominant prognostic factors. The pump patients received their continuous chemotherapy on an outpatient basis and had an 88% response rate, as evidenced by a fall in their serum CEA levels by one-third or greater after two cycles of chemotherapy. By four criteria, the regional chemotherapy patients had an improved survival rate compared to the control series. First, the 1 year survival and median survival was better for the entire group of pump patients vs. controls (82% vs. 36%, 26 months vs. 8 months, p less than 0.0001). The survival for the regional chemotherapy patients was not influenced by the extent of tumor involvement, whether previous systemic 5-FU was given, or whether the patient had symptomatic disease. Second, the entire group of regional chemotherapy patients (including nonresponders) had a greater 1 year survival compared to the most favorable subgroup of control patients with the following characteristics: normal liver function tests, no symptoms, and only one lobe involved (82% vs. 66%, p = 0.009). Third, a subgroup of 49 pump patients, whose initial treatment for metastatic disease was regional chemotherapy (within 3 months of diagnosis) had a better 1 year survival than an exactly matched group of 49 control patients (67% vs. 30%, p = 0.000003). Fourth, the actuarial survival for all 81 pump patients was significantly better than predicted by a mathematical model constructed to predict the patient's clinical course based upon the seven dominant prognostic variables identified in a multifactorial analysis (82% survival at 1 year vs. 33% predicted survival). While liver metastases could be controlled in most patients, the major cause of death was tumor progression in extrahepatic sites, particularly lung metastases and abdominal carcinomatosis. Although it appears that regional chemotherapy with an implantable pump appears to prolong life by 12 to 18 months more than matched historical controls, these results must be confirmed by a randomized (phase III) prospective clinical trial.

Clinical Trials as Topic↗
PubMed1983

A multifactorial analysis of prognostic factors in patients with liver metastases from colorectal carcinoma.

A multifactorial analysis was used to identify the dominant prognostic variables predicting survival rates of 175 patients with hepatic metastases from colorectal carcinoma. Seven of 22 parameters examined simultaneously were found to independently influence the median survival rate in these patients: (1) elevated alkaline phosphatase (p = 0.0004), (2) elevated serum bilirubin level (p = 0.0005), (3) location of hepatic metastases (unilateral or bilateral, p = 0.0022), (4) number of metastatic nodes involved (0, 1-5, greater than 5; p = 0.0148), (5) depressed serum albumin (p = 0.0217), (6) whether or not the primary colorectal tumor was resected (p = 0.0013), and (7) chemotherapy (given or withheld, p = 0.0439). The prothrombin time, serum lactic dehydrogenase, and the number of hepatic metastases also correlated with survival, but they did not independently predict survival rates after other more dominant factors were accounted for. A mathematical equation for predicting an individual patient's clinical course once they developed hepatic metastases was derived from this statistical analysis. In addition, a simple and clinically useful guide for predicting outcome was developed that integrated the two most important risk factors, alkaline phosphatase and bilirubin.

Aged↗
PubMed1983

A multifactorial analysis of melanoma. IV. Prognostic factors in 200 melanoma patients with distant metastases (stage III).

A multifactorial analysis of 200 cutaneous melanoma patients with distant metastasis (stage III) was performed on 13 clinical and pathological factors using the Cox regression analysis. There were only three dominant prognostic variables that independently predicted the patient's clinical course: (1) number of metastatic sites (1 vs. 2 vs. greater than or equal to 3, p less than 0.00001), (2) remission duration (less than 12 mo vs. greater than or equal to 12 mo, p = 0.0186), and (3) the location of the metastases (visceral vs. nonvisceral vs. combined, p = 0.0192). Factors that were not significant in the multifactorial analysis included the patients' age and sex, the site of the primary melanoma, the sequence of metastases, and all histopathological features of the primary melanoma (thickness, level of invasion, ulceration, growth pattern, pigmentation, and lymphocyte infiltration). For a single metastatic site, the 1-yr survival rate was 36%, while it was only 13% for 2 sites, and 0% for greater than or equal to 3 sites (p less than 0.00001). The 1-yr survival for patients was 40% for nonvisceral sites (skin, subcutaneous, distant lymph nodes) compared to only 11% for visceral metastases and 8% for combined sites (p less than 0.00001). Pulmonary metastases were associated with a significantly higher survival rate than metastatic melanoma in any other visceral site. The most common first site of distant metastases (either alone or in combination) was skin (38%), lung (36%), liver (20%), and brain (20%). The skin, subcutaneous and distant lymph node group was the first site of metastases in 59% of patients. This finding emphasizes the importance of careful physical exams in routine metastatic evaluations. Only a minority (25%) of stage I patients progressed to stage III disease after a median interval of 2.8 years. In contrast, the majority (75%) of melanoma patients with nodal metastases (stage II) progressed to stage III disease after a median duration of only 11 mo. Of the patients who eventually developed stage III disease, 95% of those who initially presented with stage II disease progressed within 3 yr, while stage I patients who progressed to stage III did not reach a 95% cumulative incidence until 8 yr.

Actuarial Analysis↗
PubMed1983

Suppressor cell function of human granular lymphocytes identified by the HNK-1 (Leu 7) monoclonal antibody.

The HNK-1 (Leu 7) differentiation antigen defines a subpopulation of human granular lymphocytes with natural killer (NK) and K cell function. In this study, we investigated whether HNK-1+ cells, identified with the monoclonal antibody and purified with a fluorescence-activated cell sorter (FACS), could function as suppressor cells. The results demonstrated that purified HNK-1+ cells efficiently suppressed both PWM-induced IgG production by B cells and T cell proliferation in mixed lymphocyte reactions (MLR). Manifestation of this suppressor cell activity required immune complex activation and was partially sensitive to 2000 rad irradiation. This suppressor cell activity was predominantly mediated by a subset of HNK-1+ cells that have previously been shown to have maximum NK function and lack expression of the E rosette (ER) receptor and T cell antigens (e.g., T3 and T8). Thus, HNK-1+ER- cells suppressed a MLR by an average 52%; HNK-1+ER+ were one-half as efficient, causing an average 23% suppression. For comparison, we also examined the characteristics of Leu 2a+ suppressor T lymphocytes. In contrast to HNK-1+ cells, unactivated Leu 2a+ cells suppressed both B and T cell responses. This suppressor activity was not augmented by immune complex activation and was absolutely radio-sensitive in PWM assays. HNK-1+ cells, especially the HNK+ER- subset, can therefore mediate suppressor cell function in addition to their spontaneous cytotoxic function. Furthermore, some of their suppressor cell properties are distinct from those attributed to other types of suppressor lymphocytes.

Antibodies, Monoclonal↗
PubMed1983

Involvement of the cytotoxic/suppressor T-cell subset in liver tissue injury of patients with acute and chronic liver diseases.

So far, phenotypic and functional analyses of cytotoxic lymphocytes in viral hepatitis, as well as in primary biliary cirrhosis, have focused on circulating lymphocyte subpopulations, whereas their occurrence and distribution at the involved site, namely the liver, remain largely unknown. In the present study, monoclonal antibodies were used to characterize both circulating and liver-tissue-infiltrating lymphocyte subsets in acute cytomegalovirus hepatitis, in chronic B-virus hepatitis, and in primary biliary cirrhosis. Special emphasis was laid on the cytotoxic/suppressor T-cell subset. Total T cells were identified by the monoclonal antibody T411. The monoclonal antibody T811 was used to identify the cytotoxic/suppressor T-cell subset, which comprises virus-specific, altered self, and alloreactive cytolytic T lymphocytes and their precursors, a fraction of killer and natural killer cells. Furthermore, killer and natural killer cells were identified more specifically by the monoclonal antibody. HNK1. Irrespective of the number of cytotoxic/suppressor T cells in peripheral blood, these cells (T811 phenotype) were accumulated in the liver at the site of tissue injury. The preponderance of this lymphocyte subset at the site of tissue injury suggests an important role for these cells in the mechanism leading to tissue injury.

Adult↗
PubMed1983

Interleukin 2 receptor expression by activated HNK-1+ granular lymphocytes: a requirement for their proliferation.

A subpopulation of HNK-1+ cells was found to express interleukin 2 receptor (IL 2R) as monitored by the anti-Tac monoclonal antibody after lectin or allogeneic cell stimulation. When blood mononuclear cells were stimulated with phytohemagglutinin (PHA) or concanavalin A for 3 days, or with pokeweed mitogen or allogeneic mononuclear cells for 6 days, virtually all of the HNK-1+ cells remained as small resting lymphocytes. One-fourth of these HNK-1+ cells expressed IL 2R, however, usually within 18 hr after stimulation. Neither circulating HNK-1+ cells nor unstimulated HNK-1+ cells in short-term culture expressed IL 2R. Only the subset of HNK-1+ cells that expressed T cell surface markers, such as the sheep erythrocyte receptor and Leu-4 antigen, could be induced to express IL 2R. When long-term cultures of HNK-1+ cells were established with initial PHA stimulation and the continued presence of IL 2, a majority of the cells was found to express the IL 2R. When anti-Tac antibody was added to the long-term cultures, proliferation of the HNK-1+ cells was completely inhibited. These results suggest that entry into growth cycle by this subpopulation of HNK-1+ granular lymphocytes may require two signals: a relatively nonspecific ligand interaction with cell surface glycoprotein(s) to induce expression of IL 2R, and subsequent IL 2 interaction with these specific cell surface receptors.

Adult↗
PubMed1982

A randomized prospective clinical trial of adjuvant C. parvum immunotherapy in 260 patients with clinically localized melanoma (Stage I): prognostic factors analysis and preliminary results of immunotherapy.

A total of 260 patients with clinically localized melanoma (Stage I) from 18 medical institutions in the Southeastern Cancer Study Group were randomized to receive either surgical treatment alone, or surgery plus Corynebacterium parvum immunotherapy. A multivariant analysis (Cox regression model) of nine prognostic factors was performed on 110 patients with a minimum of two years follow-up. The dominant prognostic variables were thickness (P = 0.0007) and anatomic location of the melanoma (trunk versus other, P = 0.015). Disease-free survival curves were then calculated for 204 surgically evaluable patients. Overall, there was no significant difference in three-year survival for the two-treatment arms, which was 81% for the adjuvant immunotherapy group compared to 67% for the surgical control group (P = 0.10). The median follow-up period was 24 months (range, 1-60 months). However, when the data was subgrouped by tumor thickness, an apparent benefit of immunotherapy was observed in 49 patients with melanomas greater than 3 mm in thickness. Only five of 23 such patients relapsed after receiving C. parvum. Their three-year disease-free survival was 73%. In contrast, 13 of 26 patients who did not receive immunotherapy have relapsed so far and their three-year disease-free survival was only 33% (P = 0.01). In the 175 patients with melanomas less than 3 mm in thickness, both treatment arms had identical three-year disease-free survival rates of 83%. No significant differences between the treatment arms were observed using other prognostic variables, including the level of invasion. Toxicity to C. parvum injections was minimal in most patients. It is concluded that a prognostic factor analysis is critically important in adjunctive trials of melanoma to determine which dominant variables should be used for analyzing patient subgroups; that C. parvum immunotherapy appears to be associated with an improved disease-free survival rate in the subgroup of patients with melanomas greater than 3 mm thickness (this early encouraging data must still be confirmed with continued patients accrual and a longer observation period); and that patients with melanomas less than 3 mm thickness have a relatively favorable prognosis after appropriate surgical treatment, and immunotherapy does not improve their survival rates.

Adolescent↗
PubMed1982

Postnatal expansion of the natural killer and keller cell population in humans identified by the monoclonal HNK-1 antibody.

Human natural killer (NK) and killer (K) cells were directly enumerated using a monoclonal antibody (HNK-1) and an immunofluorescence assay. The frequency of cells bearing surface HNK-1 antigen was very low in the newborn (less than 1.0%) and increased progressively through childhood and into adult life. This was correlated with an age-related increase in functional NK and K cell activities. Males had a slightly higher proportion of HNK-1+ cells than females. In addition to HNK-1 expression on the surface membrane, a prominent cytoplasmic expression of HNK-1 antigen was found in some but not all surface HNK-1+ cells. The cytoplasmic accumulation of HNK-1 molecules appeared to occur in more mature cells of this lineage.

Adolescent↗
PubMed1982

Prophylactic lymph node dissection in clinical stage I cutaneous malignant melanoma: results of surgical treatment in 1319 patients.

A retrospective study was made of 1319 patients with cutaneous primary malignant melanoma and regional lymph nodes clinically free of disease, whose first definitive surgical treatment was either (a) wide excision of the primary lesion (WE) or (b) wide excision of the primary lesion plus a prophylactic lymph node dissection (PLND). Patients were stratified according to three dominant prognostic factors, as revealed by multifactorial analyses: sex of patient, the anatomical site and thickness of the primary lesion. Of 380 patients who underwent PLND for lymph nodes clinically free of disease, there was microscopic evidence of nodal metastases in 5 per cent. Despite this, prognosis in these patients was nearly twice as good as in those patients undergoing lymph node dissection for clinically involved nodes. Five-year survival rates for all those clinical stage I patients with lesions less than 0.8 mm thick were high irrespective of initial surgical treatment. In men with lesions of intermediate thickness (particularly 1.6-3.0 mm), survival rates for those undergoing PLND were considerably higher than for those undergoing WE. There were no survival benefits of PLND in men with lesions thicker than 3.0 mm. This was in contrast to the situation in women, where PLND was indicated for patients with the thickest lesions. This study has defined three parameters which can serve as useful practical guides for selecting alternative surgical procedures in the management of clinical stage I cutaneous malignant melanoma.

Adult↗
PubMed1982

Molecular comparison of mouse Thy-1 and its human homologue.

Physicochemical techniques were used to verify previous immunochemical studies showing homology of the human Thy-1 (formerly p25) antigen and the murine Thy-1 or theta antigen. Peptide maps and amino acid compositions showed close similarity between these two proteins; however, they were not identical. These data confirm that the p25 antigen is the human homologue of mouse Thy-1.

Alanine↗