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A J Cochran

Publications and source records attributed to A J Cochran.

At least 73 records · Page 4Linked to original sources
PubMed1990

Periappendicitis is a significant clinical finding.

Periappendicitis has heretofore been regarded as a pathologic curiosity with little clinical significance. In this report, we have reviewed the UCLA experience with periappendicitis. Between 1955 and 1985, resected appendices of 353 patients showed periappendicitis on pathologic examination. Sixty-one of these patients, in whom exploratory surgery was performed for reasons other than acute appendicitis, underwent incidental appendectomy. In 251 of the remaining 292 patients, appendectomy was performed either for pathologically confirmed acute appendicitis or concomitant with treatment of other unsuspected abnormalities discovered intraoperatively. Although the remaining 41 patients were also believed to have acute appendicitis, their resected specimens revealed only periappendicitis. The latter group was composed of 9 males and 32 females, with a mean age of 29 years (range: 6 to 76 years). Twenty-four complications occurred in 18 of these patients (44%). Seven additional operative procedures were required in 5 of the 41 patients (12%). One patient died (2%). We conclude that identification of periappendicitis in the patient presumed to have acute appendicitis is of definite clinical significance and may merit further clinical investigation.

Acute Disease↗
PubMed1989

S-100 protein stimulates cellular proliferation.

S-100 protein (S-100p) is a small, acidic, calcium-binding protein that is present (predominantly) in the cytoplasm of many types of cells including those of neuroectodermal origin, such as glial cells, schwann cells and melanocytes. In human melanoma cells S-100p is abundant relative to the small quantities expressed by normal melanocytes. We investigated the possibility that this protein may be a growth factor. Purified S-100p from bovine brain or human melanoma cells was added exogenously to human melanoma cells and peripheral blood lymphocytes (PBL) and their growth in the presence of different concentrations of S-100p was determined using a [3H]dT-uptake proliferation assay. The growth of melanoma cells was stimulated by S-100p at concentrations of 1.95-31.25 micrograms/ml. Slight inhibition of cell proliferation occurred at high concentrations (125 micrograms/ml). Maximum stimulation of PBL was at 31.25 micrograms/ml. PBL were not inhibited even at high concentrations of S-100p (125 micrograms/ml). PBL stimulation by S-100p did not require the presence of monocytes/macrophages. Though stimulation by S-100p is not restricted to a specific cell type, when released by melanoma cells it may function as an "autocrine" tumor growth factor. Other cells, such as PBL, coming in contact with S-100p are also stimulated to proliferate.

Cell Cycle↗
PubMed1989

Variations in lymphokine generation by individual lymph nodes draining human malignant tumors.

Individual lymph nodes draining tumors vary in their degree of immunological activity. Cell suspensions from tumor-free nodes located relatively near to tumors are spontaneously less reactive and respond poorly to exogenous stimulation by mitogens and lymphokines. Diminished spontaneous uptake of tritiated thymidine by lymph node cells not exposed to exogenous stimulation suggests that tumor-proximate immune suppression exists in vivo and is not purely a laboratory artefact. The present study was undertaken to explore that possibility further. Fluid in which cell suspensions from tumor-free nodes were prepared, and supernatants from short-term cultures of nodes located at different distances from tumors were compared for their capacity to inhibit the in vitro migration of the human lymphoblastoid cell line QIMR-WIL. Inhibitory activity of fluids from individual nodes was related to their position relative to the tumor and their immune competence, assessed by the responses to mitogens of cell suspensions prepared from them. Cell suspension fluids from 92/111 nodes (83%) significantly inhibited the migration of QIMR-WIL, at a level similar (44 +/- 14%) to that induced by the supernatants of mixed lymphocyte cultures (43 +/- 17%). Fluids from the nodes of melanoma patients were more inhibitory than those from breast cancer patients (49 +/- 12% and 37 +/- 13%, respectively, P = 0.003). The inhibitory activity of the different nodes of individual node groups varied significantly in 25 of 33 patients (76%), the node nearest the tumor generating least inhibitory activity (indexing the greatest immune suppression) in 20 of these 25 patients (80%). The strength of migration-inhibitory activity was concordant with the responsiveness to mitogen stimulation in up to 14 of 18 patients (78%). Studies of molecular size and heat stability indicated that the inhibitory factors had characteristics consistent with common migration-inhibitory lymphokines such as leukocyte-migration-inhibitory factor, macrophage-inhibitory factor and interleukin-2. Our findings further support the hypothesis that lymph nodes nearest to tumors are relatively immune-suppressed in vivo.

Body Fluids↗
PubMed1989

Paragangliomas: assessment of prognosis by histologic, immunohistochemical, and ultrastructural techniques.

To predict clinical outcome, we studied 42 paragangliomas from 37 patients by routine histology, immunohistochemistry, and electron microscopy. A panel of antisera to neuron-specific enolase (NSE), chromogranin, and met-enkephalin was used to identify chief (type I) cells, and S-100 protein and glial fibrillary acid protein (GFAP) sustentacular (type II) cells. The intensity of staining of type I cells and the density of type II cells were assessed semiquantitatively (0 to 4+) in a total of 38 tumors. A total of 23 of 24 low-grade tumors (solitary, multiple, or associated with other neoplasms; 95.8%) contained type II cells immunoreactive with either S-100 protein or GFAP, and all were positive when S-100 protein and GFAP were used in combination. Five of the nine intermediate-grade (recurrent and/or locally aggressive) tumors were identified as glomus jugulare tumors (GJT). Three intermediate-grade GJTs were devoid of GFAP-reactive type II cells and four GJTs were negative for S-100 protein. Type II cells were identified in only one of five high-grade (malignant) paragangliomas and that tumor contained vanishingly rare cells that were weakly S-100 protein positive but GFAP negative. Sustentacular cell density and chief cell staining intensity were both inversely related to tumor grade. The most sensitive chief cell marker was NSE (92.1%), followed by chromogranin (84.2%). The least sensitive (73.0%) and specific marker was met-enkephalin. Combinations of NSE or chromogranin with met-enkephalin identified chief cells in all cases. Electron microscopy identified neurosecretory granule-containing chief cells, but was of less value in delineating sustentacular cells because of their scarcity and the absence of specific features. By comparison, immunohistochemistry was superior in identifying sustentacular cells. The use of an immunohistochemical panel, in addition to routine histology, can confirm the diagnosis of a paraganglioma and can give an indication of the likely prognosis for a patient.

Adolescent↗
PubMed1989

Modulation of human macrophage functions by gangliosides.

In human tumors of neuroectodermal origin cell surface expression of individual gangliosides is either increased or decreased relative to comparable normal cells. We have previously shown that gangliosides shed from melanoma cells can immunomodulate T cell activity. Monocytes/macrophages (m/m) are known to play an important role as accessory and effector cells in immune responses. We therefore investigated the effect of exogenous gangliosides derived from melanoma on m/m functions in vitro. Gangliosides commonly expressed on human melanoma such as GM3, GD3, GM2, and GD2 were investigated, as well as GM1, a major component of human neural tissue. Monocytes were isolated from human peripheral blood mononuclear cell populations, treated with gangliosides in vitro, and evaluated in several functional assays. Treatment of m/m with GM2 and GM3 gave the greatest inhibition of Fc receptor expression. GM1 and GD3 on the other hand most inhibited the production of interleukin-1 (IL-1) by m/m. Production of tumor necrosis factor (TNF) like monocytoxin was not affected by incubation with individual gangliosides. These studies suggest that individual melanoma gangliosides have different regulatory effects on m/m functions.

Gangliosides↗
PubMed1989

Histomorphometry in the assessment of prognosis in stage II malignant melanoma.

The prognosis for patients with node-spread melanoma is often based on the number of nodes that contain tumor. This predicts survivors with 85% accuracy but melanoma deaths with only 40% accuracy. This overall predictive accuracy of 61% may be due, in part, to node-counting that takes no account of the volume of tumors in the nodes. We examined the capacity of morphometric techniques (planimetry, image analysis, and measurement of tumor diameter by ocular micrometer) to improve predictive accuracy. A combination of the number of tumor positive lymph nodes (less than or equal to 3 nodes positive = favorable; greater than or equal to 4 nodes positive = unfavorable) and the aggregate micrometer measured tumor diameter as a percentage of aggregate node diameter (less than or equal to 15% = favorable; greater than or equal to 15% = unfavorable) significantly increased predictive accuracy. Favorable outcome was accurately predicted for 12 of 13 patients (92%), and death from melanoma was accurately predicted in 12 of 15 patients (80%), an overall predictive accuracy of 86%.

Humans↗
PubMed1989

Monoclonal antibodies in the diagnosis and treatment of carcinoma of the breast.

In relative terms, biologic research with Mab has reached early middle age. Information on the behavior of Mab in disease of the breast is interesting--indeed, tantalizing--in many areas, but practical applications for diagnosis and treatment are not yet available. The evidence implies that it will be forthcoming.

Antibodies, Monoclonal↗
PubMed1989

A review of the histology, ultrastructure, immunohistology, and molecular biology of extra-adrenal paragangliomas.

This review summarizes our understanding of extra-adrenal paragangliomas, a subject that has evolved considerably during the past several years. Our object was to review the anatomical, histologic, and biological features of normal and neoplastic glands, with emphasis on immunohistologic studies, and briefly discuss the potential application of nucleic acid hybridization. Since it is difficult to predict clinical outcome for patients with paragangliomas, we have emphasized the differences between benign and malignant paragangliomas, concentrating on recent results obtained using immunohistologic techniques. These studies have emphasized the critical importance of the identification, by immunohistologic means, of two distinct cell populations, chief cells (type I) and sustentacular cells (type II). The relationship between these two cell populations, stable in normal glands and benign tumors, is progressively lost in tumors of increasing degrees of malignancy, sustentacular cells being absent from the most progressively metastasizing paragangliomas.

Adrenal Gland Neoplasms↗
PubMed1988

Gangliosides from human melanoma immunomodulate response of T cells to interleukin-2.

The gangliosides expressed by normal melanocytes are predominantly GM3 (greater than 90%) and GD3 (less than 5%). Malignant melanoma can express several other types of gangliosides in significant quantities, including GM2 and GD2. Melanoma patients can develop an immune response against some of these ganglioside antigens on autologous melanoma cells. The four major gangliosides expressed by human melanoma cells (GM3, GD3, GM2, and GD2) were examined for their immunomodulatory effect on lymph node lymphocytes from melanoma patients. Gangliosides were added exogenously to lymphocytes grown in the presence of IL-2. Preferential interactions of specific melanoma gangliosides on IL-2 stimulation were found. While GM2 and GD2 enhanced the lymphocyte response to IL-2, GM3 and GD3 significantly inhibited this response. GM2 and GD2 differ from GM3 and GD3 by the presence of a terminal N-acetylgalactosamine. Since different gangliosides can up-regulate and down-regulate lymphocyte responses to IL-2, the ganglioside phenotype of melanoma cells may play a major role in determining whether an individual tumor causes immune stimulation or suppression.

Cell Survival↗
PubMed1988

Occult tumor cells in the lymph nodes of patients with pathological stage I malignant melanoma. An immunohistological study.

We examined 2,227 lymph nodes from 100 patients with clinical Stage I cutaneous melanoma for the presence of microscopic deposits of tumor. On examination of hematoxylin-and-eosin-stained sections, none had melanoma. Sixteen nodes from 14 patients had melanoma detectable by an antiserum to S-100 protein in a peroxidase-antiperoxidase (PAP) assay. The melanomatous nature of these cells was confirmed by their reaction with the melanoma-directed monoclonal antibody NKl/C3. The incidence of occult nodal metastases was highest in patients with deeply invasive and micrometrically thick primary tumors. The incidence of occult melanoma was not increased where additional serial sections were cut and semiserial sections examined. Pitfalls in the identification of occult melanoma cells (OMC) include S-100 protein-positive interdigitating dendritic cells, capsular nevus cells, a minority of sinus "macrophages," and the Schwann cells of node-associated nerves. Thus, we conclude that the incidence of early melanoma metastases in the regional lymph nodes of patients with clinical Stage I melanoma is greater than has previously been appreciated on the basis of assessment of routine hematoxylin-and-eosin-stained sections. Six of the 14 patients with OMC died of melanoma (41%), as compared to only 18 of 86 patients without OMC (21%; 0.10 greater than P greater than 0.05).

Adult↗
PubMed1988

Quantitative alterations in cutaneous Langerhans cells during the evolution of malignant melanoma of the skin.

Melanomas are associated with a T-cell predominant infiltrate that may cause their regression. Langerhans cells (LC) are essential for initiation and maintenance of specific T-cell-mediate responses in the skin. Therefore, a change in this antigen-presenting LC population may alter the host response. To determine whether the LC population varies during the evolution of primary cutaneous melanoma 32 melanocytic lesions, nevi, and cutaneous melanomas were studied by quantitative immunohistology. The monoclonal antibody, Leu-6, and the avidin biotin complex immunoperoxidase method were used to identify LC. Compared with histologically normal melanoma-adjacent skin, epidermal LC were depleted above "deeply invasive" melanomas but were relatively unchanged above nevi, "early invasive" melanomas, and cutaneous metastatic melanoma nodules. Dermal LC were significantly increased around in situ and "early invasive" melanomas but not around "deeply invasive" melanomas or cutaneous metastatic nodules. Dermal LC are thus associated with early transformed melanocytes and may present neoantigens to T lymphocytes in situ or after LC maturation in the draining lymph node. Melanoma-associated LC decline in number as melanoma progresses.

Cell Count↗
PubMed1988

Immunohistochemical demonstration of S-100 protein and melanoma-associated antigens in melanocytic nevi.

Thirty-nine melanocytic nevi of varying histologic structure and stages of development were examined for the presence of S-100 protein and melanoma-associated antigens (MAA) by the indirect immunoperoxidase technique, using a polyclonal anti-serum to S-100 protein and monoclonal antibodies to MAA. S-100 protein and MAA were found in the cells of all types of nevi, including dysplastic and congenital nevi. While S-100 protein was present in nevus cells at the epidermodermal junction and at all levels of the dermis, the melanoma-directed monoclonal antibodies BM 24-2, NKI/C-3, Mel-1, and Mel-2 reacted most prominently with the superficial (A-type) nevus cells; the B- and C-type cells being negative in these cells. An exception to this rule was melanoma-monoclonal antibody 34.1 which reacted with nevus cells at all levels; deep C-cells often being more intensely stained than the subepidermal A-cells. The cells of the different nevus cell layers, known to differ morphologically and enzymatically, are, thus, also different in their expression of MAA. Our data suggest that for most antibodies these variations may be due to differences in the metabolic activities of nevus cells at various distances from the epidermis.

Antibodies, Monoclonal↗
PubMed1988

Detection and quantification of S-100 protein in ocular tissues and fluids from patients with intraocular melanoma.

S-100 protein is a 21,000 dalton acidic calcium-binding protein present in ocular melanomas and some normal ocular tissues. Ocular fluids and extracts of ocular tumours were examined by a sensitive radioimmunoassay that could detect less than 5 ng of S-100 protein in minute volumes of fluid. Three ocular melanoma biopsy specimens had S-100 protein at levels between 25 and 1300 ng/ml, comparable to that found in a cutaneous melanoma biopsy specimen (1000 ng/ml). (SI conversion: ng/ml = microgram/l.) Six melanoma culture lines had 1000 to 125,000 ng/ml. Four lymphoblastoid cultures had less than 2 ng/ml, and three colon carcinoma cultures had 180 ng/ml. Subretinal fluid from 23 melanoma-containing eyes had 10 to 76,800 ng/ml. Lesser amounts were found in eyes with small, anteriorly located, lightly pigmented tumours. Vitreous from 3 melanoma-containing eyes had 10,000 to 11,000 ng/ml. Vitreous obtained from three eyes during tractional retinal detachment repair had 500 to 1600 ng/ml, and vitreous obtained at necropsy from six normal eyes had 2 to 120 ng/ml. Aqueous from six melanoma-containing eyes had 10 to 30 ng/ml, levels not significantly different from those observed in three normal eyes (80-120 ng/ml). This approach provides new insight into the interaction of ocular tumours and adjacent ocular fluids and may, with more specific tumour markers, have diagnostic applications.

Aqueous Humor↗
PubMed1988

The expression of S-100 protein and neuron-specific enolase in meningiomas.

The distribution of S-100 protein and neuron-specific enolase (NSE) was examined in 19 meningiomas using the peroxidase-antiperoxidase (PAP) immunohistochemical technique. Positive cytoplasmic staining for NSE was observed in 16 tumors, and comparable staining for S-100 protein was observed in eight tumors. The finding of S-100 protein and NSE immunoreactivity in fibroblastic, meningiotheliomatous, and transitional meningiomas raises the possibility that these morphologically distinct neoplasms derive from a common pluripotential cell capable of differentiation along diverse paths.

Biomarkers, Tumor↗
PubMed1988

Detection of malignant melanoma with monoclonal antibodies.

Eleven murine monoclonal antibodies (MoAbs) were isolated that defined unique membrane antigens expressed on human melanoma cells but not detectable on human lymphoid cells by radioimmunometric assays. Five of these MoAbs each identified a separate melanoma cell surface antigen as shown by distinctly different in vitro MoAb binding patterns to a diverse panel of tumor cell lines. One of these 5 monoclonals, MoAb 34.1, reacted specifically with 9/11 melanoma lines and 0/28 other human tumor or lymphoid cell lines. The other 4 MoAbs reacted strongly with melanomas, but also bound to 1 or more non-melanoma lines. The remaining 6 MoAbs defined three distinct regions of a single melanoma cell membrane protein with a molecular weight of 125 kiloDaltons (kD) as shown by antibody crossblocking and gel electrophoresis. A sensitive radioimmunoassay developed with MoAbs to 2 epitopes of this 125 kD protein detected up to 500-fold higher levels of this antigen in extracts of melanoma cells compared to autologous lymphoid cells. The 125 kD antigen also was detected by indirect immunoperoxidase assays with the MoAbs on biopsied tumors in histologic tissue sections of 5/11 metastatic melanomas and 1/11 carcinomas but was found on some normal endothelium and smooth muscle. Another monoclonal, MoAb 705, reacted more broadly with tumor cells in 10/14 biopsied melanomas and 10/11 carcinomas, but also was reactive with basal epidermis and normal fibroblasts. By contrast, MoAb 34.1 bound specifically to tumor cells of 7/11 biopsied metastatic melanomas, but bound 0/10 carcinomas and few normal tissues except for some macrophages. Thus, MoAb 34.1 was the most specific diagnostic reagent for immunohistologic detection of melanoma. The 250 kD antigen defined by MoAb 34.1 is similar to a high molecular weight proteoglycan reported to be an excellent tumor marker for human melanomas. The results of these studies show that murine monoclonal antibodies can be used as sensitive reagents for radioimmunoassays and immunohistology of malignant melanoma.

Animals↗
PubMed1987

Isolation of lymphocytes from clotted blood.

A problem often faced in clinical cell-mediated immunology research is to obtain peripheral blood lymphocytes (PBLs) in sufficient numbers to carry out cellular immune assays. Obtaining sufficient amounts of blood for serum is usually more practical than for PBLs. Blood is usually drawn easily for serum, but obtaining PBLs from clotted blood has not been very practical. In this report we describe a procedure whereby PBLs can be recovered from clotted blood and used in functional immune assays. Using the enzyme streptokinase (SK) blood clots were dissolved and viable PBLs recovered up to 24 h post clotting. Concentrations of SK from 250 to 500 SK U/ml gave maximum recovery of PBLs.

Blood Coagulation↗