Biomedical subjects

A J Cochran

Publications and source records attributed to A J Cochran.

At least 91 records · Page 5Linked to original sources

PubMed1987

Suppressor cell activity in melanoma-draining lymph nodes.

We previously demonstrated that the cells of lymph nodes near to a melanoma respond well to stimulation by mitogens, alloantigens, and interleukin 2 than do nodes further away. In this study we examined suppressor T-cell activity in nodes at different distances from primary melanoma, using a concanavalin A (Con A) suppressor cell assay. Tumor-free regional nodes were classified as proximal, intermediate, and distal relative to primary melanoma. Lymph node lymphocytes (LNL) were stimulated with 50 micrograms/ml Con A for 48-72 h, inactivated, and then mixed with autologous peripheral blood lymphocytes. The peripheral blood lymphocyte-LNL mixtures were stimulated with phytohemagglutinin for 3 days. Proliferation was measured by [3H]thymidine uptake during the final 18 h of culture. In 13 patients, Con A-treated LNL from nodes near to tumor were more suppressive of the peripheral blood lymphocyte response to phytohemagglutinin than those from nodes located further from tumor. T-lymphocyte subset assessment before and after Con A treatment of LNL showed no significant changes in T4:T8 ratios. Con A-induced suppressor cells could be maintained in culture in the presence of recombinant interleukin 2 and retained their suppressive activity. LNL not exposed to Con A and maintained in culture with interleukin 2 did not show suppressor cell activity. Suppressor cell activity thus contributes to the weak immune reactivity of lymph nodes near to melanoma.

Concanavalin A↗

PubMed1987

Variations in functional immunocompetence of individual tumor-draining lymph nodes in humans.

In studying the histology and immunohistology of tumor-draining lymph nodes, we observed that nodes close to tumor showed reduced paracortical activity relative to those further away. To assess whether this reduction was paralleled by alterations in the functional activity of nodes, we examined the immunocompetence of individually oriented tumor-draining lymph nodes. We assessed the unstimulated activity of lymph node lymphocytes and their responses to phytohemagglutinin, interleukin 2, and one-way alloantigenic stimulation (mixed lymphocyte reaction) in vitro. Regional nodes from patients with malignant melanoma or breast cancer were classified as proximal, intermediate, or distal relative to tumor. Node groups with and without tumor metastases in them were studied. Significant variations in [3H]thymidine uptake were noted with the unstimulated and stimulated lymphocytes of different lymph nodes from the same individual. Nodes near to tumor were less responsive than those located further away; some of the latter showed relative immunostimulation. Tumor-draining node groups thus demonstrated a nonrandom variation in the strength of reaction of individual nodes. There are zones of low and high lymph node reactivity, related to the position of each node relative to tumor. Tumor-derived immunosuppressive products and/or immunoregulation down-regulates lymph node functional activity, creating conditions that may permit the survival of tumor cells and the establishment of metastases. It is suggested that immunosuppression of nodes nearest to tumor may facilitate the early establishment of metastases.

Humans↗

PubMed1987

Mononuclear cell infiltrates in bullous disease.

Mononuclear cell subset-specific monoclonal antibodies, indirect immunoperoxidase labeling, and a specific quantification technique were used to determine the constitution of mononuclear cell infiltrates associated with bullous pemphigoid (BP), pemphigus vulgaris (PV), dermatitis herpetiformis (DH), and linear IgA bullous disease, as well as those in normal skin (NS) from healthy adult volunteers. Bullous pemphigoid and PV lesions contain significantly greater numbers of T lymphocytes (p less than 0.001), including both T helper/inducer and T cytotoxic/suppressor subsets, macrophages (p less than 0.002), and Langerhans cells (p less than 0.01), than NS or lesions of DH, supporting the concept that cell-mediated immunity is involved in bulla formation and autoantigen presentation in BP and PV. The infiltrates associated with DH lesions appear to reflect a different mechanism of autoantibody production and bulla formation.

Adult↗

PubMed1987

Variations in S-100 protein expression in naevocellular naevi may be related to metabolic activity.

Significant amounts of S-100 protein were demonstrated in naevus cells by an immunoperoxidase technique. Distribution of S-100 protein was similar in the various types of naevi tested. In most lesions, the superficial A-type naevus cells stained most heavily, while staining was weaker in the deeper B- and C-type naevus cells. The intensity of staining was not, however, homogeneous in the cells of the various layers of the naevus. S-100 protein was especially abundant in giant naevus cells which occurred in the vicinity of sub-epidermal A-type naevocytes. Cells from neurocutaneous melanosis contained extremely large amounts of S-100 protein. Normal melanocytes in the epidermis over dermal naevi contained variable amounts of S-100 protein, but mainly showed weak staining. However, in the basal epidermis of traumatized naevi there were many unusually large and partly dendritic melanocytes. In this part of the epidermis, S-100 protein-positive cells lay close together, and many stained strongly. In earlier work, large amounts of metabolic enzymes were found at the same sites in traumatized naevi and giant cells. These results suggest that a high degree of expression of S-100 protein is due to metabolic activity shown, for example, by giant naevus cells and basal melanocytes of the regenerating epidermis over traumatized naevi.

Calcium-Binding Proteins↗

PubMed1987

Antibody to S-100 protein aids the separation of pagetoid melanoma from mammary and extramammary Paget's disease.

We evaluated the usefulness of immunohistological staining for S-100 protein in differentiating mammary and extramammary Paget's disease from primary malignant melanoma of superficial spreading (pagetoid) type. This technique was compared to both the mucicarmine and periodic acid-Schiff (PAS) methods. The tumor cells of 10 melanomas contained abundant cytoplasmic S-100 protein. In tissues from mammary and extramammary Paget's disease, S-100 protein was detected in myoepithelial cells, Langerhans cells, and Schwann cells of cutaneous nerves, but was not present in tumor cells. The mucicarmine stain was most useful for vulvar Paget's disease, mucicarminophilic material being present in 9/10 cases. In mammary Paget's disease, only 2/8 cases stained by the mucicarmine technique. Cytoplasmic PAS-positive material was present in the tumor cells of 9/10 cases of vulvar Paget's disease, but was noted in only 1/9 cases of mammary Paget's disease. Melanoma cells from two cases stained weakly with both mucicarmine and PAS indicating that these stains are not specific for Paget's disease in this comparison. The PAS and mucicarmine stains are helpful in differentiating anogenital Paget's disease from pagetoid melanoma, but are less useful in mammary Paget's disease. Immunohistological demonstration of S-100 protein provides an additional diagnostic tool to aid the separation of Paget's disease from pagetoid melanoma.

Antibodies↗

PubMed1987

Identification and quantification of subsets of mononuclear inflammatory cells in melanocytic and other human tumors.

We used monoclonal antibodies and an indirect immunoperoxidase technique to identify mononuclear inflammatory cells associated with human tumors. The absolute number of the different types of inflammatory cells was assessed by using a point-counting technique. We studied tissues from six primary cutaneous melanomas, six metastatic melanomas, eight melanocytic nevi, 14 breast cancers, seven examples of fibrocystic disease of the breast, 11 lung cancers, and six colon cancers. Virtually all tumors were associated with substantial numbers of T lymphocytes (Leu3a-positive T helper-inducer cells predominating) and macrophages. Primary melanomas contained significantly more T lymphocytes (P less than .002), macrophages (P less than .005), and Langerhans/dendritic cells (P less than .002) than nevi or normal skin and had a higher proportion of T cells than metastatic melanomas (P less than .01). Breast cancers contained more T lymphocytes and macrophages than occur with fibrocystic disease (P less than .0001 and P less than .002, respectively) and more B lymphocytes. Cancers of the lung and colon contained moderate numbers of T lymphocytes and macrophages; however, colon cancers contained a higher proportion of B cells. Leu7-positive NK/K cells were noted in small numbers in all tumors examined.

Female↗

PubMed1987

Zoned immune suppression of lymph nodes draining malignant melanoma: histologic and immunohistologic studies.

Node-to-node heterogeneity of reaction and recognizable patterns of reaction in node groups draining melanoma were sought. Nodes from 72 patients undergoing lymphadenectomy for high-risk, primary melanoma (57) or node-spread melanoma (15) were accurately oriented to the nearest melanoma. Reactivity of paracortex, follicular areas, and sinuses was assessed on a 0-3+ scale. Reactivity was prominent in paracortex and sinuses but varied from node to node within node groups. Nodes nearest to tumor showed least reaction; nodes at intermediate distances from tumor were most reactive, while those farthest away showed mostly little reaction. Variation of nodal reaction that correlated with the node position relative to the nearest melanoma (zoned reaction) was seen in 92% of patients with nodal metastases of melanoma and in 64% of patients with primary malignant melanoma. Follicular and sinusoidal reactions showed no significant zoning. S-100 protein-positive paracortical dendritic cells (PDCs) in tumor-oriented nodes were quantified. PDCs were infrequent in nodes partly replaced by melanoma or located near to melanoma but were numerous in nodes located farther from tumor. Changes of nodal activity (relative stimulation or suppression) correlate with the distance of the node from the nearest deposit of primary or metastatic melanoma.

Humans↗

PubMed1987

Bronchial anastomosis with a tissue adhesive.

Air leakage and necrotic degeneration may occur after bronchial anastomosis and can lead to death from secondary pneumothorax and pneumonia. We studied the ability of a new tissue adhesive (N-butyl-cyanoacrylate monomer) to enforce the bronchial suture line. The left main bronchus in each of five pigs in Group A was completely transected and closed by four stitches and tissue adhesive. The transected left main bronchus in each of the other five pigs in Group B was connected with 11 to 14 interrupted polyglycolic acid 3-0 sutures. The time required for reconstruction was 10 +/- 3.6 minutes in Group A and 25.0 +/- 6.5 minutes in Group B. No symptoms of a constricted airway were apparent in Group A. All pigs were examined at an interval of from 5 to 8 weeks after operation. Evidence of infection at the bronchus appeared in three animals: two in Group A and one in Group B. One instance of air leakage at the anastomosis occurred in Group B. We measured the maximum tensile strength of the bronchial suture line by means of an electromechanical testing machine comparing the tensile strength of the treated left bronchus with that of the control right bronchus. The maximum tension of the treated bronchus in Group A was 10.3 +/- 1.52 (pounds) and that of control was 8.0 +/- 1.56 (pounds) (p less than 0.05). The maximum tension of Group B was 7.93 +/- 0.29 (pounds) on the treated side and 6.78 +/- 0.32 (pounds) on the control side (p less than 0.05). The suture line with tissue adhesive was enforced sufficiently to act as a stable connective tissue. Histologic studies in Group A revealed that the suture line was completely healed without tissue damage and was strengthened by the tissue adhesive.

Animals↗

PubMed1986

Recurrence potential of thin primary melanomas.

Between April 1971 and January 1985, the University of California at Los Angeles (UCLA) Division of Surgical Oncology has seen 649 patients diagnosed with thin primary melanomas, as defined by a Clark level less than IV and Breslow depth less than 0.76 mm. Thirty-six patients, whose primary diagnosis was confirmed by UCLA pathologists, presented with or subsequently developed melanoma metastases. Twenty-four (67%) had Clark level II lesions, whereas the remaining 12 (33%) had Clark level III lesions. Metastases were noted more frequently in men than in women, with a man-to-woman ratio of 3 to 2. The site of the primary lesion in this group was most frequently on the trunk (16 of 36 cases, 44%), followed by the head and neck (9 of 36 cases, 25%) and arm and shoulder (7 of 36 cases, 19%). Metastasizing thin lesions were least likely to occur on the leg and hip (4 of 36 cases, 11%). Twenty of these lesions were recently reexamined, and 17 of 20 cases (85%) demonstrated evidence of regression. Twenty-eight patients (78%) had their first metastases to regional lymph nodes. Fifteen remained alive with no evidence of disease at a median follow-up of 99 months. Twenty patients died from systemic metastases, and one patient was alive with brain metastasis at the time of this article. Although infrequent, metastases from thin melanomas do occur, suggesting the need for careful long-term follow-up and immediate investigation of adenopathy even in low-risk patients.

Adult↗

PubMed1986

S-100 protein in amelanotic melanoma. A convenient immunocytochemical approach compared to electron microscopy.

16 amelanotic melanomas were investigated immunocytochemically using two different antibodies against S-100 protein. In six cases electron microscopy was carried out. All 16 tumors showed a positive reaction for both antisera in epithelioid as well as in spindle-shaped tumor cells. Ultrastructurally the six investigated tumors contained stage II to IV melanosomes. Immunocytochemical and electron microscopical results are compared and discussed with regard to their significance in routine surgical pathology.

Adult↗

PubMed1986

The classification of malignant melanoma, its histological reporting and registration: a revision of the 1972 Sydney classification.

A group of pathologists with an interest in malignant melanoma met in Sydney in 1982 to update the classification of melanoma formulated in Sydney in 1972. The group recommended that malignant melanoma be classified as follows: malignant melanoma with an adjacent component of superficial spreading type, malignant melanoma with an adjacent component of lentigo maligna type, malignant melanoma with an adjacent component of acral lentiginous type, malignant melanoma with an adjacent component of mucosal lentiginous type, malignant melanoma with no adjacent component, malignant melanoma of unclassifiable histogenetic type. The data recorded in the surgical pathology report should include: diagnosis of primary malignant melanoma, histogenetic classification, presence/absence of ulceration, micrometer-measured thickness, microanatomical level, mitotic rate/mm2, presence/absence of vascular invasion, presence/absence of regression, completeness of resection. The recommendations for the examination of specimens and the recording of data for research purposes and for tumour registries are described.

Biopsy↗

PubMed1986

Inhibition of lymphocyte motility by interleukin 2.

These studies described were designed to determine whether interleukin 2 (IL-2) inhibits lymphocyte migration. The human lymphoblastoid cell line QIMR-WIL was used as an indicator of lymphocyte migration inhibition. Interleukin 2 inhibited QIMR-WIL migration in a dose-dependent manner, high doses of IL-2 (100 units) being strongly inhibitory, and low doses (12.5 units) less inhibitory. Purified natural IL-2 and recombinant IL-2 both inhibited QIMR-WIL migration. The effect of IL-2 on lymphocyte migration was specific. When the IL-2 receptors were blocked with anti-Tac (anti-IL-2 receptor) antibodies, the inhibitory effect of IL-2 was significantly reduced. Similarly antibody to IL-2 blocked the inhibitory effect of IL-2. Lymph node lymphocytes were also used as indicator cells in migration studies and IL-2 inhibited their motility. These data suggest a role for IL-2 in inhibiting lymphocyte migration similar to that of lymphocyte migration inhibition factor produced by antigen- or mitogen-stimulated T lymphocytes. While it is widely recognized that lymphocyte motility can be reduced by lymphocyte migration inhibition factor, these data indicate that IL-2 can also reduce lymphocyte motility.

Cell Line↗

PubMed1986

Diagnostic immunopathology.

The application of immunologic techniques to tissue sections has added a new dimension to the investigation and classification of various processes. Virtually every section of diagnostic pathology has been enhanced by using specific monoclonal antibodies or polyclonal antiserum. Neoplasms formerly diagnosed as poorly differentiated or anaplastic may be precisely identified as to their origin through the use of specific membrane or cytoplasmic markers. Other cellular products, including viruses, hormones, enzymes or highly specific proteins, are also available to study neoplastic and nonneoplastic processes. New and more specific reagents are regularly becoming available for the diagnostic repertoire of pathologists. We present some of the principles of diagnostic immunopathology to show the scope and importance of the techniques.

Adult↗

PubMed1986

Myxoid malignant melanoma. A previously undescribed histologic pattern noted in metastatic lesions and a report of four cases.

Four patients are presented with malignant melanoma in which the stroma showed a prominent myxoid change. Since this peculiar feature had not been previously reported, metastatic lesions with this change caused considerable diagnostic confusion with other more commonly encountered myxoid tumors. On the basis of light microscopy, special stains, and electron microscopy, we demonstrated the melanomatous nature of the metastases and that the myxoid matrix is derived from reactive stromal cells rather than from the melanoma cells themselves. Three of the four patients had a history of primary melanoma; the longest interval between the primary lesion and the metastasis was 24 years.

Adult↗

PubMed1985

Acquired immune deficiency syndrome. Pathogenic mechanisms of ocular disease.

A gross, light, and electron microscopic study of the eyes from 35 consecutive autopsy cases of the acquired immune deficiency syndrome revealed cotton-wool spots (71% of cases), retinal hemorrhage in areas without cytomegalovirus infection (40%), cytomegalovirus retinitis (34%) with associated retinal detachment, Roth's spots (23%), retinal microaneurysms (20%), papilledema (14%), conjunctival Kaposi's sarcoma (9%), cryptococcal chorioretinitis (6%), Mycobacterium avium-intracellulare in retina and in choroidal granulomas (6%), ischemic maculopathy (6%), bilateral keratitis (3%), and herpes simplex retinitis (3%). Ocular infection with candida or toxoplasmosis were not found in this autopsy series. Immunocytologic studies demonstrated deposition of immunoglobulins in arteriolar walls, consistent with immune complex mediated disease. Ultrastructural studies showed a vasculopathy in the areas near cotton-wool spots. A mechanism is proposed linking the deposition of immune complexes with subsequent small vessel lesions, ischemia, cotton-wool spots and later spread of cytomegalovirus to retina via damaged vascular endothelium.

Acquired Immunodeficiency Syndrome↗

PubMed1985

Assessment of immunological techniques in the diagnosis and prognosis of ocular malignant melanoma.

Tests of cell mediated immunity (one and two stage leucocyte migration inhibition assays) and humoural immunity (membrane immunofluorescence and serum effects on leucocyte migration) were done with leucocytes and sera from 36 patients with uveal melanoma, five with conjunctival melanoma, 21 with non-malignant ocular disease, and 189 with cutaneous melanoma. Cell mediated reactivity with melanoma extracts and serum reactivity with cultured melanoma cells were significantly more frequent in the melanoma patients, but control donor reactivity was also relatively high. Maximum reactivity was found with cells or serum from those patients in whom, on pathological examination, the intraocular melanoma had penetrated the sclera and in patients with conjunctival melanoma. Maximum separation of melanoma patients from control donors was achieved by consideration of the results of several tests done simultaneously. These immunopathological studies were made during the period from 1972 to 1978. At follow-up in 1983 four of the five patients suffering from conjunctival melanoma had died from metastases, and 10 of the 36 with uveal melanoma had died from metastatic disease. The immunological reactions, while of some value in separating melanoma patients from those without melanoma, did not predict whether a particular patient with uveal melanoma would die of metastatic disease or would survive.

Antibody Formation↗

PubMed1985

S-100 protein as a marker for melanocytic and other tumours.

The majority of melanocytic tumours are easily diagnosed but they become a problem when they are amelanotic and the tumour cells resemble those of other tumours. This applies particularly to secondary melanoma. Detection of S100 protein is a useful identifying marker. S100 protein, so named for its solubility in saturated ammonium sulphate, is derived from brain tissue. It is a dimer and belongs to a calcium binding group of proteins. The protein was first thought to be in neural or neural crest derived tissues but has been found in chondrocytes, adipocytes, myoepithelial cells, dendritic cells of lymphoid tissue, Langerhans cells and T lymphocytes. The protein is present in a high proportion of malignant melanomas and nevocytic nevi of skin, but is less positive in eye melanomas. It is present in gliomas, Schwannomas and neurofibromas but not in neurone derived tumours such as neuroblastomas. Chondromas, chondrosarcomas, liposarcomas, some osteogenic sarcomas and some histiocytic tumours are positive. The tumours that do not contain S100 protein are listed. Pending development of melanoma-directed monoclonal antibodies, the use of anti-serum to S100 protein plus anti-keratin and anti-leukocyte reagents is useful in the identification of tumours of doubtful histogenesis.

Body Fluids↗

PubMed1984

Occult melanoma in lymph nodes detected by antiserum to S-100 protein.

Sections of 1,273 nodes from 58 patients with melanoma were stained in an immunoperoxidase assay using an antiserum to S-100 protein and aminoethyl carbazole as indicator. By the hematoxylin and eosin (H. and E.) technique, 128 nodes were seen to contain melanoma (10%); by the anti-S-100 protein technique, 363 (29%) were found to be tumor-positive. The additional tumor-positive nodes contained single tumor cells or small groups of tumor cells and were adjacent to nodes that were partly or wholly replaced by melanoma. Penetration of nodes by single tumor cells was seldom seen in node groups containing no tumor that was visible on H. and E. staining. The anti-S-100 protein approach more accurately identified those patients who would die of their recurrent disease less than 5 years after lymphadectomy.

Hematoxylin↗