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P C Phelps

Publications and source records attributed to P C Phelps.

At least 37 records · Page 2Linked to original sources
PubMed1988

Aberrant expression of monoclonal antibody-defined colonic mucosal antigens in inflammatory bowel disease.

Human proximal colon from patients with inflammatory bowel disease and from controls was studied by two techniques to detect tumor-associated antigen expression. A panel of four murine monoclonal antibodies that recognize tumor-associated antigens was used to test purified colonic mucins for epitope expression by radioimmunoassay and to test formalin-fixed, deparaffinized sections of colon by the immunoperoxidase technique. The panel included monoclonal antibodies 19-9, B72.3, DU-PAN-2, and CSLEX1. Colonic mucins were purified from uninvolved surgical specimens by gel filtration with Sepharose 4B and cesium chloride-guanidine hydrochloride density gradient ultracentrifugation. Purified mucins from uninvolved colonic mucosal specimens from 4 of 7 patients with ulcerative colitis expressed one or more of these epitopes by radioimmunoassay, whereas mucins from 6 disease controls did not. Reactivity patterns were heterogeneous. Immunoperoxidase testing demonstrated staining with two or more antibodies in 14 of 18 involved inflammatory bowel disease segments, whereas control sections rarely stained with these antibodies, with the exception of 19-9. Sections of uninvolved mucosa from 4 of 9 patients with ulcerative colitis stained with two or more antibodies. Staining patterns were heterogeneous. The results demonstrate that colonic expression of tumor-associated epitopes occurs frequently in involved segments from both patients with ulcerative colitis and with Crohn's disease, whereas only patients with ulcerative colitis frequently expressed these epitopes in uninvolved segments.

Antibodies, Monoclonal↗
PubMed1988

Long-term culture of hamster duodenal explants and cells.

Explants from adult Syrian hamster duodenum have been maintained in organ culture on gelatin sponges using CMRL 1066 serum supplemented media for 30 days. There was necrosis of the tall villi architecture during the 1st week in culture while columnar and mucous cells survived, migrated, and replicated along portions of the explant basement membrane and in the gelatin sponge matrix. Cells in the sponge multiplied and formed epithelial sheets which showed villus projections and cyst configurations. The cells in these epithelial structures were attached to one another by junctional complexes. Epithelial cells were isolated from the sponge matrix by collagenase digestion and were successfully grown in culture. These duodenal explants and cells show potential for use as in vitro models for experimental studies, involving acute and chronic response of cells to injury or carcinogen-induced transformation.

Animals↗
PubMed1988

Extracellular Ca2+-dependent elevation in cytosolic Ca2+ potentiates HgCl2-induced renal proximal tubular cell damage.

While normal fluctuations of cytosolic Ca2+ ([Ca2+]i) occur physiologically, the deregulation of cellular Ca2+ homeostasis leads to cellular injury. The contribution of [Ca2+]i to the process of cellular damage was assessed in a model system where HgCl2 was used to induce plasma membrane damage in renal tubular cells. In the presence of 1.37 mM extracellular Ca2+, HgCl2 (10-50 microM) induced a slow, dose-dependent, 4-6 fold increase in [Ca2+]i (as measured by Quin 2) by 10 min of exposure, which could be abolished by prior incubation of the cells with dithiothreitol. Correlates of cellular injury, i.e., decrease in cell viability, change in cellular morphology, such as bleb formation, membrane distortion and mitochondrial swelling, were induced after HgCl2 addition. The rate and dose-responses of these changes were similar to that of [Ca]i elevation. When cells were exposed to HgCl2 in the absence of added extracellular Ca2+, there was no increase in [Ca2+]i and both the rate and extent of cell damage were reduced. When Ca2+ was readded to the extracellular medium after HgCl2, there was a rapid elevation of [Ca2+]i, increased cell killing and bleb formation. The observed correlation between [Ca2+]i elevation, decreased cell viability and morphological aberrations in terms of (i) dose-dependency for HgCl2, (ii) requirement for high extracellular Ca2+, and (iii) rate of change, suggests that HgCl2-induced renal cell damage involves the entry of Ca2+ from the extracellular milieu which potentiates the progression of cellular injury.

Animals↗
PubMed1987

HgCl2-induced changes in cytosolic Ca2+ of cultured rabbit renal tubular cells.

Fura 2 was used to measure changes in cytosolic [Ca2+] ([Ca2+]i) in cultured rabbit kidney proximal tubule cells exposed to HgCl2. Treatment with 2.5-10 microM HgCl2 resulted in an extracellular [Ca2+] ([Ca2+]e)-independent 2- to 12-fold increase in [Ca2+]i above resting levels of about 100 nM. Treatment with 25-100 microM HgCl2 caused a rapid [Ca2+]e-independent 10- to 12-fold increase in [Ca2+]i within 1 min followed by a recovery to about 2-fold steady state by 3 min. With 25-100 microM HgCl2, both magnitude and rate of Ca2+ increase were similar, but recovery was greater with increasing doses. A slower, secondary increase in [Ca2+]i followed which varied with HgCl2 concentration and required [Ca2+]e. The first increase in [Ca2+]i represents release from intracellular pools. Calcium channel blockers, calmodulin inhibitors, and mitochondrial inhibitors do not alter the patterns of [Ca2+]i changes due to HgCl2. The recovery response with higher HgCl2 concentrations appears to be triggered by Hg2+ and not by the increased [Ca2+]i. Sulfhydryl modifiers N-ethylmaleimide, PCMB and PCMBS produced [Ca2+]e-independent [Ca2+]i increases similar to those induced by low HgCl2 concentrations. Cell killing with HgCl2 was about 50% greater with normal [Ca2+]e than with low [Ca2+]e, suggesting that [Ca2+]e influx is important in accelerating injury leading to cell death.

Animals↗
PubMed1986

Lewisx- and sialylated Lewisx-related antigen expression in human malignant and nonmalignant colonic tissues.

Biochemical studies have revealed that some normal cells express the LeX trisaccharide Gal beta 1----4(Fuc alpha 1----3)GlcNAc either on short-chain fucolipids or as a single immunodeterminant on glycolipid oligosaccharide side chains. Cancer cells, including those from colonic adenocarcinomas, express this antigen on longer type 2 blood group side chains as difucosylated or trifucosylated fucolipids. Moreover, sialylated forms of difucosylated LeX also accumulate in colon cancer but not in normal colonic mucosa. In the present study, six monoclonal antibodies which selectively recognize the various LeX-related antigens were used for immunohistochemical examination of these antigens in serial sections of human colonic tissue. All of these antigens were oncodevelopmental in human colon. Monoclonal antibodies anti-SSEA-1 and AH8-183, directed against short-chain, monofucosylated LeX, were unable to discriminate well between normal and malignant colonic tissue. However, the other four antibodies were much better at distinguishing cancer from normal tissue. FH6 was the most specific in that no normal tissues bound this antibody. However, FH6 failed to stain poorly differentiated cancers and some colloid-type carcinomas. FH4, which was also highly specific, stained almost all cancers, regardless of the degree of differentiation. FH4 primarily stained cancer cell cytoplasm, whereas the sialylated antigen defined by FH6 predominantly stained cell membranes. Differences were noted between the expression of LeX-related antigens in autopsied normal mucosa compared to mucosa of benign colonic diseases. Monoclonal antibodies recognizing long-chain polyfucosylated and sialylated LeX-related antigens appear to be useful tools for detection of colon cancer.

Antibodies, Monoclonal↗
PubMed1985

Distribution of blood group antigens A, B, H, Lewisa, and Lewisb in human normal, fetal, and malignant colonic tissue.

In humans, most blood group substances (BGS) are expressed throughout the fetal colon but are absent from the distal portion of adult colon. Cancers of the distal colon frequently reexpress BGS thereby suggesting that these antigens behave as oncofetal antigens at this organ site. We used a sensitive immunoperoxidase method with monoclonal antibodies directed against blood groups A, B, O (H), Lewisa and Lewisb to systematically evaluate BGS expression in fetal colon, normal adult colon from immediate autopsies of kidney donors, mucosa adjacent to cancer (transitional mucosa) and colorectal cancer tissues. In normal colon, BG-A, B, H, and Lewisb were expressed in proximal but not distal colon, whereas Lewisa was distributed uniformly throughout the colon. In colon cancer, and fetal colon, the proximal-distal gradient of BG-A, B, H, and Lewisb expression was abolished because of enhanced distal expression of these antigens. In cancer tissues, three patterns of altered BGS expression emerged: (a) incompatible expression of BG-A or BG-B (over 50% of patients); (b) deletion of BGS; and (c) precursor BG-H accumulation (80% of 25 tumors). BGS staining of transitional mucosa closely resembled that of the adjacent tumor except that no examples of BGS deletion were encountered in transitional mucosa. The goblet cell secretory vacuole accounted for most of the BGS expression in normal colon, but cancer cells demonstrated differentiation-dependent antigenic expression such that well-differentiated tumors expressed BGS on cell apical membranes and glandular contents, but poorly differentiated cancers exhibited diffuse cytoplasmic staining. These findings confirm the oncofetal nature of BGS in distal colon cancer, and provide immunohistochemical evidence for a diverse repertoire of altered antigen expression in colon cancer. Further investigation is needed to elucidate the possible genetic and biochemical mechanisms involved.

ABO Blood-Group System↗
PubMed1984

Cell calcium, cell injury and cell death.

The role of calcium in cell injury has been the subject of much recent investigation. The movement and redistribution of this cation from extra to intracellular compartments and the calcium shifts between intracellular compartments may well play a determinate role in the cell's reaction to injury. Therefore, data of such shifts and their correlation with morphological, biochemical and cytoskeletal studies will provide a better understanding of these processes. To study the effects of calcium regulation on acute lethal anoxic injury and the effects of inhibition of respiration with cyanide, three experimental systems were utilized: Ehrlich ascites tumor cells, isolated rabbit proximal tubule segments and suspended or cultured rat proximal tubule cells. Although our data showed no correlation between total cell calcium and cell death except in highly selected cell systems, they did indicate that calcium can be an important control variable. Therefore, massive increases in total cell calcium, as seen in Ca3(PO4)2 precipitation in mitochondria, must be a secondary event and represent the modern day equivalent of the classical dystrophic calcification seen by pathologists in the past. Although the involvement of extracellular calcium in cell death may well be significant in some cell types, redistribution of calcium within the intracellular compartments may play an even more important role.

Adenosine Triphosphate↗
PubMed1983

Resting human female breast tissue produces iodinated proteins.

Normal resting human breast tissue was obtained from immediate autopsies performed on six women who had died from head injuries sustained in accidents. Tissue samples containing epithelium were dissected asceptically and either fixed immediately or placed into culture. Samples in culture for 2 or 3 days were exposed to radioiodide for 4 hr in order to establish whether or not the isotope became incorporated into proteins. Light and electron microscope autoradiographs were prepared and evaluated. Radiolabeled secretory material was observed in both the terminal ductules and intralobular terminal ducts, but not within the larger ducts. Therefore the products in these separate compartments of the mammary epithelial tree differ in composition. Extensive gap junctions were discovered between adjacent myoepithelial cells in the terminal ductules and intralobular terminal ducts. These junctions probably serve to coordinate contractions which facilitate the movement of material from the most distal parts of the gland into larger ducts.

Adolescent↗
PubMed1982

Human large intestinal epithelium: light microscopy, histochemistry, and ultrastructure.

Despite numerous reports of morphologic characteristics of premalignant and malignant large intestinal epithelium, the literature lacks comprehensive reports of the morphologic features of the epithelium of the normal large intestine, except of the rectum. Large intestinal epithelium from 41 persons was obtained, and samples from the ascending, transverse, descending, and rectosigmoid areas were studied by light microscopy, histochemical techniques, and transmission and scanning electron microscopy. The morphologic features and histochemical reactions of the various segments of the large intestine are different. Neutral mucopolysaccharide is predominant in the ascending colon, whereas the rectum has predominantly or exclusively acidic mucin. Only three basic epithelial cell phenotypes have been identified: undifferentiated cells, mucous cells, and endocrine cells. The columnar cells at the surface between the crypts appear to be a variant of mucous cells. Compared with other segments, the rectum shows an unusually high concentration of endocrine cells, positively correlating with the high incidence of carcinoid tumors in that segment of the large intestine. The mucous cells in all segments contain large mucous vacuoles and small apical vesicles. The apical vesicles show variable electron density, being most dense in the ascending colon and becoming progressively less dense at the transverse and descending colon and most electron-lucent in the sigmoid colon and rectum. Ultrastructurally, the mucin shows a variable degree of heterogeneity in the proximal segments. This study suggests that some of the previously described ultrastructural features of abnormal large-intestinal epithelium may be only the result of failure to compare the so-called abnormal cells with normal cells from the same region. Well-controlled studies of the abnormal epithelium of a particular segment of large intestine must include the normal epithelium from the identical segment as control in order to make interpretations accurate.

Adult↗
PubMed1981

Colon epithelium. IV. Human colon carcinogenesis. Changes in human colon mucosa adjacent to and remote from carcinomas of the colon.

To verify the popular belief that the mucosa of the colon remote from a carcinoma is normal, in a retrospective study colon mucosae from 30 patients were studied; 15 patients had colon carcinoma and the other 15 patients without any obvious tumor in their colons served as controls. All the patients having colon carcinoma showed definite abnormalities in the mucosa remote from the tumor. None of the 15 control patients showed such morphologic changes in the mucosal sections sampled at random. The mucous changes observed were: dilatation and distortion of the crypts with flattening of the lining cells, overcrowding of crypts with mucous cells and basophilic cells, lining of the crypt with eosinophilic surface epithelial cells, and focal cellular stratification in the crypts. These abnormalities were also consistently observed in the transitional mucosa adjacent to the tumor in all of the 15 patients with colon cancer. Histochemical studies for the detection of epithelial acidic mucosubstances showed that sialomucin predominated in the colon mucosa harboring a carcinoma irrespective of the location of the tumor, whereas colon mucosa from otherwise normal individuals and patients with noncarcinomatous diseases showed a predominance of sulfomucin. Therefore, mucosa of the colon harboring a carcinoma was conclusively demonstrated to be morphologically and histochemically abnormal. The significance of these abnormalities and their possible role in the de novo histogenesis of colon carcinoma are discussed.

Adenocarcinoma↗
PubMed1981

Sodium and calcium regulation and the role of the cytoskeleton in the pathogenesis of disease: a review and hypothesis.

Recent years have seen a rapid development in knowledge concerning ion regulation and the cytoskeleton and their roles in many normal and abnormal cell processes. The structure and function of the cytoskeleton plays a key part in a number of cell properties including cell shape, potential mobility of intracellular proteins including receptors, cell to cell adhesion, and many other phenomena such as secretion, phagocytosis and autophagocytosis. Although earlier studies have emphasized the roles of sodium and calcium ion modification following acute and chronic cell injury, it has not been until recently that volume regulation and sodium modification have been found to be intimately linked through mechanisms such as sodium-calcium exchange and that the interaction of these regulations are associated with the cytoskeleton and the cell membrane. Therefore, it is the purpose of this review not only to summarize the vast amount of data which has rapidly accumulated in this field, and to put it into perspective, but also to advance a hypothesis which, we hope, will eventually establish that a wide variety of pathological phenomena ranging from acute cell death to chronic processes such as neoplasia, hypertension and aging are all a common series of cellular reactions.

Animals↗
PubMed1980

Cell surface changes in preneoplastic and neoplastic epithelium.

Reviewed are studies on alterations of the plasma membrane of neoplastic epithelial cells. Changes in the plasma membrane are probably of unique importance in the major clinical manifestations of cancer. Discussed are sequences in cell membrane changes in vivo and in vitro in both human tumors and chemical-induced animal models of carcinogenesis. Emphasis is placed on alterations in specializations of the plasma membrane, including cell junctions, antigenic and enzyme markers, intramembranous components, ion regulation, and the cytoskeleton. In general, the plasma membrane of neoplastic cells is less specialized than the cell of origin. In mammalian bladder, pleomorphis microvilli may occur concomitant with neoplastic transformation. Cell junctions in tumor cells may be reduced in number of functional characteristics compared to normal cells, which may affect cell-cell communication. Such alterations may be related to tumor cell invasion and metastasis. Normal membrane antigens may be lost or new ones gained in neoplasia. Thus, ABO blood group antigens may be lost in the case of human bronchus and bladder, while carcinoembryonic antigen occurs de novo in tumors of the colon and lung. Similarly, several marker enzymes may be reduced in activity, or appear de novo. Alterations in the number and pattern of distribution of intramembranous particles have been observed in bladder tumors, possibly related to changes in membrane function. Shifts in ion ratios (Na+/K+/Ca++) within neoplastic cells may result in abnormalities in cell shape, cell movement, and cell-cell communication. Many of these changes may reflect defects in function of the Golgi apparatus, which synthesizes components of the plasma membrane. Alterations in one or more components of the cytoskeleton may adversely affect cell shape, mobility of membrane proteins, cell-cell adhesion, etc., and play a major role in malignant cell behavior.

Animals↗