Biomedical subjects

K R Cleary

Publications and source records attributed to K R Cleary.

At least 91 records · Page 5Linked to original sources

PubMed1990

Carcinoembryonic antigen enhances metastatic potential of human colorectal carcinoma.

Patients with human colorectal carcinoma have a poor prognosis when serum carcinoembryonic antigen level exceeds 5 ng/mL. The hypothesis that carcinoembryonic antigen enhances metastasis by promoting the attachment of tumor cells to Kupffer cells and hepatocytes was tested in an experimental metastasis model in which colorectal carcinoma cells were injected into the spleens of BALB/c athymic nude mice and liver colonies counted 5 weeks later. Pretreatment with systemic injections of carcinoembryonic antigen significantly increased the metastatic potential of a poorly metastatic colorectal carcinoma cell line KM-12c, but did not induce the nonmetastatic colorectal carcinoma cell line HC 2998 to produce metastases, nor did carcinoembryonic antigen make the highly metastatic colorectal carcinoma cell line mHC 1410 more metastatic. Carcinoembryonic antigen did not stimulate proliferation of colorectal carcinoma but appeared to be a cofactor for metastasis possibly as an adhesion factor.

Animals↗

PubMed1990

The association of Shiga toxin and other cytotoxins with the neurologic manifestations of shigellosis.

The neurologic symptoms in human shigellosis have often been attributed to Shiga toxin, although its exact role has not been determined. By use of a [3H] thymidine-labeled HeLa cell assay, cytotoxic activity was demonstrated in stool but not cerebrospinal fluid or serum from five patients with shigellosis presenting with seizures or encephalopathy. Bacterial isolates produced 16.0-88.2 CD50 (50% cytotoxic dose) of cytotoxin/mg of protein. The toxin activity in stool and the cytotoxic activity of the isolates were not neutralized by antiserum to purified Shiga toxin. DNA hybridization studies showed that Shigella isolates from these patients lacked the structural genes for Shiga toxin. The cytotoxin produced was also distinct from Shiga-like toxins I and II. Sonicates of the Shigella strains injected intraperitoneally into mice caused lethargy and lethality. The toxin activity was heat-labile and sensitive to trypsin, indicating that its active component is protein. Ultrafiltration and gel filtration chromatography showed a molecular mass of 100-125 kDa. Thus Shiga toxin production is not essential for the development of neurologic manifestations of shigellosis; other toxic products may play a role.

Animals↗

PubMed1990

Lymphoepithelial cysts of the parotid region: a "new face" on an old lesion.

Lymphoepithelial cysts of the parotid gland and its lymph nodes have been known for nearly 100 years, but only in the past half-decade have they gained clinical prominence, if not significance. The lymphoepithelial cysts can now be added to the growing list of clinicopathologic manifestations of human immunodeficiency virus-associated diseases.

Adult↗

PubMed1990

Biopsy of the lip and Sjögren's syndrome.

The degree of focal chronic sialadenitis in a labial salivary gland biopsy specimen, expressed in terms of a semiquantitative focus score, is the best contemporary assessment of the salivary component in Sjögren's syndrome. A labial salivary gland focus score of greater than 1 focus per 4 mm2 serves as an acceptable threshold for the diagnosis.

Biopsy↗

PubMed1990

Sialadenoma papilliferum.

Sialadenoma papilliferum is a tumor of salivary tissues that has considerable histologic and biologic similarities to analogous tumors of the eccrine apparatus of the skin. Thus far found only at intraoral and parotid gland sites, sialadenoma papilliferum usually has the clinical course of a benign, locally significant lesion.

Humans↗

PubMed1990

Sialyl-dimeric Lewis-X antigen expressed on mucin-like glycoproteins in colorectal cancer metastases.

Colorectal primary carcinomas and metastases from 20 Dukes' stage C or D patients were examined for the immunohistochemical localization and contents of various fucosylated N-acetyl-lactosamine oligomers by specific monoclonal antibodies (MAbs). MAbs used were SH1, specific for Lewis X antigen; FH4, specific for dimeric Lewis X antigen; FH6, specific for sialyl-dimeric Lewis X antigen; and KH1, specific for Lewis Y-Lewis X antigen. The distribution of the carbohydrate antigens identified by these MAbs was heterogeneous within the primary tumor as well as within the metastatic lesion. Examinations of serial sections indicated that areas within an individual tumor which were stained with one MAb were not always reactive with the other MAbs, although these four MAbs identify closely related structures. The degree of MAb reactivity with carcinoma sections was classified by percentage positive carcinoma cells, and primary tumors and metastases from the same patients were compared. An equivalent or higher proportion of carcinoma cells in the metastatic lesions were reactive with MAb FH6 than in the primary colon carcinomas, but each correlation was not seen with the other MAbs. Electrophoretic separation of tumor tissue extracts followed by staining with these MAbs revealed that a component having an approximate molecular weight of 1,000,000 is the major site for the binding of MAbs, FH6, FH4, and KH1. The electrophoretic mobility of the antigenic molecule on polyacrylamide gels as shown by direct MAb bindings was slightly different from that of a major sialomucin revealed by wheat germ agglutinin in the same tissues. MAb FH6 binding to a high molecular weight component was eliminated by prior treatment of the glycoprotein with mild acid or sialidase to remove sialic acid. Simultaneously, binding of MAb SH2, specific for dimeric Lex antigen, to this component increased. An extract was prepared from a liver metastasis, and high molecular weight components were isolated by gel filtration and then fractionated by DEAE-cellulose ion exchange chromatography. A fraction eluted from DEAE-cellulose between 0.10-0.25 M sodium chloride contained most of the MAb FH6 reactivity, as shown by antibody affinity chromatography. These results support a hypothesis that high molecular weight glycoproteins produced by colorectal carcinoma tissues are heterogeneous with regard to their carbohydrate chains and their antigenic structures may change during tumor progression.

Adult↗

PubMed1990

Undifferentiated carcinoma with lymphoid stroma of the major salivary glands.

Undifferentiated carcinoma with lymphoid stroma or lymphoepithelial carcinoma of the major salivary glands is a demographically and histopathologically unique malignancy. Although whites may have the disease, it is preponderantly a carcinoma of North American Eskimos and native Greenlanders. The carcinoma shares many features with undifferentiated nasopharyngeal carcinomas, from which it must be distinguished: histologic appearance, putative relationship with Epstein-Barr virus, predilection for mongoloid races, and response to therapy. In some cases, the carcinoma appears to have evolved from a lymphoepithelial lesion.

Adult↗

PubMed1990

Histologic parameters and DNA ploidy as predictors of survival in stage B adenocarcinoma of colon and rectum.

Stage B adenocarcinomas of colon (61 carcinomas) and rectum (44 carcinomas) were retrospectively reviewed in order to define prognostic indicators and to determine if they are different for tumors arising at the two sites. Parameters evaluated included the substage of the tumor, histologic grade, presence of vascular/lymphatic invasion, residual adenoma or extracellular mucin, and tumor cell DNA content as determined by flow cytometry of paraffin-embedded tissues. Five-year survival was 81.0% for patients with colonic and 87.5% for those with rectal tumors. DNA ploidy was a significant predictor of overall and disease-free survival in patients with rectal adenocarcinomas (improved survival for those with diploid tumors) but not in those with colonic tumors and not in the two groups combined. The degree of differentiation of the tumor was prognostically significant in the colonic group and for the groups combined but not in the rectal group. There was a trend toward better survival in substage B1 tumors, as compared with substages B2 and B3, particularly in rectal neoplasms. Other histologic parameters did not predict survival. We conclude that the prognostic indicators in colonic adenocarcinoma seem to differ from those of adenocarcinoma arising in the rectum and that DNA ploidy has a significant impact upon outcome in stage B rectal adenocarcinomas.

Adenocarcinoma↗

PubMed1990

Transitional mucosa of colon. A morphological, histochemical, and immunohistochemical study.

We studied alterations in the transitional mucosa of the colon in 18 cases of primary colonic adenocarcinoma (4 from the cecum; 4, the ascending colon; 5, the descending colon; 2, the sigmoid colon; and 3, the rectum). One patient had 2 separate primary tumors. Formalin-fixed, paraffin-embedded sections were studied in all cases, and tissues fixed in methacarn fixative were available in 9. Sections of tumor and transitional mucosa were compared with those of normal mucosa distant from the tumor. Sections were stained with hematoxylin-eosin, Masson's trichrome, and alcian blue at a pH of 0.9 (sulfomucin) and at a pH of 2.5 (sialomucin and sulfomucin). Immunoperoxidase stains for collagen type IV (basal lamina) were also performed. Transitional mucosa showed morphological alterations, including increase in mucosal thickness and crypt distortion. An increase in lamina propria fibrosis was noted in transitional mucosa in 3 cases. Abnormal mucin content, consisting of a predominance of sialomucin, was noted in transitional mucosa in 12 cases. In one of these, sialomucin was predominant in both transitional and normal mucosa. No alterations in the thickness of the subepithelial collagen table were noted. Collagen type IV staining was effective in demonstrating an increase in lamina propria vascularity in transitional mucosa in 11 specimens.

Adenocarcinoma↗

PubMed1989

Increased expression of sialyl-dimeric LeX antigen in liver metastases of human colorectal carcinoma.

We collected a total of 78 tissue specimens, including primary colorectal carcinoma, normal colonic mucosa, and liver metastases of colon carcinoma, to examine whether the extracts of these tissues inhibited the binding of a monoclonal antibody FH6, specific for sialyl-dimeric LeX antigen. The results of inhibition assays demonstrated that: (a) contents of FH6-reactive molecules were greater in carcinoma tissues than in normal colonic mucosa; (b) metastatic foci in livers contained more FH6-reactive molecules than primary tumors; (c) primary tumors from Dukes' stage B1 patients contained less FH6-reactive molecules than primary tumors from Dukes' stage D patients. The inhibitory activity of these tumor tissue extracts against the binding of a monoclonal antibody FH6 to cultured colon carcinoma cells was eliminated by prior treatment of the extracts with sialidase, confirming that the FH6-reactive materials were sialyl-dimeric LeX antigen. Electrophoretic separation of tumor tissue extracts on 3% polyacrylamide gels followed by direct staining with monoclonal antibody FH6 revealed that very high molecular weight glycoproteins, presumably mucins, contained sialyl-dimeric LeX antigen.

Antibodies, Monoclonal↗

PubMed1989

Metastatic potential of human colorectal carcinomas implanted into nude mice: prediction of clinical outcome in patients operated upon for cure.

To determine whether the production of experimental hepatic metastases in athymic nude mice by human colorectal carcinomas (HCC) correlated with the clinical outcome in patients, we harvested colorectal carcinomas from 82 patients, dissociated the tumors with collagenase and DNase, and injected them into groups of nude mice, either in the flank to assess experimental tumorigenicity or into the spleen to produce experimental metastasis in the liver. Growth in mice was then associated with clinicopathological factors and clinical outcome. Growth of HCC in either the flanks or the livers of nude mice was associated with the time to recurrence in a Wilcoxon analysis. Analysis of the outcome data in a Cox proportional hazards model suggested that there was an interaction between tumorigenicity and metastatic potential of HCC in nude mice and serum CEA concentration in the patient and stage of disease. A univariate analysis indicated that both tumorigenicity and metastatic potential of HCC in nude mice were significantly associated with the serum CEA concentration of the patient but not with the other variables of stage of disease, mucin production, local tissue invasion, state of differentiation, or sex. A subset of 57 patients was operated upon for cure and followed prospectively for up to 61 months. Tumorigenicity and, to a lesser extent, experimental metastatic potential were associated with disease recurrence in 23 of these patients. Seventy-eight % of the subset of patients who were operated upon for cure developed liver metastasis as one site of their progressive disease. Thus, the ability of HCC cells isolated from surgical specimens to grow in athymic nude mice correlates with the development of advanced disease in patients.

Adult↗

PubMed1989

Monoclonal antibody against human colonic sulfomucin: immunochemical detection of its binding sites in colonic mucosa, colorectal primary carcinoma, and metastases.

Previous studies using metabolic labeling of fresh colonic mucosa and colorectal carcinoma with [35S]sulfate followed by biochemical analysis demonstrated that the amount of a sulfated high-molecular-weight glycoprotein expressed in primary colorectal carcinoma was lower than that in normal mucosa, and that the amount further decreased in liver metastases. This suggested that this sulfated molecule represented a sulfomucin previously defined by histochemical reactivity with a cationic dye. We have extracted and partially purified this high-molecular-weight sulfated glycoprotein from normal human colonic mucosa. We immunized mice with the partially purified sulfomucin and generated hybridomas. One cloned hybridoma, designated as 91.9H, produced a monoclonal antibody strongly reactive with a component which migrated at an identical position as the metabolically [35S]sulfate-labeled high-molecular-weight glycoprotein after polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. The reactive molecules appeared to have a polydisperse nature with a molecular weight ranging between 400,000 and 900,000. The [35S]sulfate-labeled high-molecular-weight glycoprotein was bound to Staphylococcus Protein A-agarose coated with this monoclonal antibody but did not bind to unconjugated Protein A-agarose. The immunoprecipitated substance also migrated at an apparent molecular weight range of 400,000 to 900,000. The reactivity of monoclonal antibody 91.9H with the extracts of normal mucosa, colorectal primary carcinoma, and metastasis was compared by dot blot assay on a nitrocellulose membrane. This antibody was more reactive with the extracts of mucosa adjacent to carcinoma tissues than with the carcinoma extracts. Primary tumors showed higher reactivity than metastases in most of the cases. These results strongly suggest that this antibody is specific to colonic sulfomucins or at least to mucins closely related to colonic mucins previously identified by metabolic labeling with [35S]sulfate.

Antibodies, Monoclonal↗

PubMed1989

Anaplastic and sarcomatoid carcinoma of the small intestine: a clinicopathologic study.

Carcinomas involving the jejunum and ileum are rare tumors. During a review of small intestinal neoplasms, six primary carcinomas of jejunum or ileum with an anaplastic and sarcomatoid histology were identified. At presentation, three of the patients had symptoms related to metastatic disease and three had symptoms referable to the local tumor. The tumors were large (greater than 4.5 cm in diameter), usually endophytic masses composed of large cells with eosinophilic cytoplasm, anaplastic nuclei, and prominent nucleoli. In many areas, the cells had a spindled configuration. Mucin positivity was identified in all six cases. Electron microscopic findings in two cases were indicative of epithelial differentiation. The tumors behaved aggressively; all five patients for whom there was clinical follow-up died of metastases within 40 months. The six anaplastic and sarcomatoid carcinomas were compared with 29 typical adenocarcinomas arising in the jejunum or ileum. Only two of the latter group had symptoms referable to distant metastases at presentation. These tumors also tended to be smaller at presentation (11 tumors were less than 4 cm in greatest dimension). Of 25 patients with typical adenocarcinomas who had acceptable follow-up, 18 (72%) died of disease and five (20%) were alive with no evidence of disease after 5 years. We conclude that anaplastic and sarcomatoid carcinoma is a rare variant of small intestinal carcinoma with an aggressive clinical course.

Adenocarcinoma↗

PubMed1989

Immunocytochemical identification of HIV (p24) antigen in parotid lymphoid lesions.

Antibodies to specific human immunodeficiency virus (HIV) polypeptides are important laboratory markers of HIV infection. We have used an antibody to the major structural gag protein p24 of HIV-1 virus to immunochemically localize this capsid antigen in lymphoid cells from seven of eight patients at risk for HIV infection and who presented with parotid lymphadenopathy and lymphoepithelial cysts of the parotid gland. A clinicopathological assessment of these two manifestations as they relate to HIV infection is also presented.

Acquired Immunodeficiency Syndrome↗

PubMed1989

The prevalence of Campylobacter pylori in gastric biopsies from cancer patients.

The prevalence of Campylobacter pylori (CP) in gastric biopsies from cancer patients has not been previously studied. We reviewed 112 gastric biopsies from 78 adult patients at a cancer hospital. The patients had a previous history or current diagnosis of gastric or esophageal carcinoma (26 patients), gastric lymphoma (15 patients), gastric stromal tumor (three patients), carcinoid tumor (two patients), nongastroesophageal malignancy (29 patients), or atrophic gastritis with nonhealing ulcer (three patients). The biopsies were stained with hematoxylin-eosin (H&E), Warthin-Starry, Giemsa, and Brown-Hopps. CP was identified in 30 biopsies from 26 patients. Eighteen of the biopsies showed active gastritis, nine showed chronic inflammation/intestinal metaplasia, and one contained an ulcer. CP was also identified in two stomachs bearing tumors (one adenocarcinoma, one carcinoid tumor). Active gastritis was present without CP in nine biopsies, including three from patients on chemotherapy and one from a patient with bile reflux. The organism was detected by the Warthin-Starry stain in 30 biopsies. The Giemsa stain was positive in 27, Brown-Hopps in 27, and H&E in 24. Non-CP bacteria were identified in the Brown-Hopps in seven cases and were mistaken for CP in H&E stains in two. We conclude that CP is frequently found in the cancer patient with active gastritis and is an occasional finding in tumor-bearing stomachs. Special stains are useful in identifying CP, and the Brown-Hopps is helpful in distinguishing CP from other bacteria.

Adolescent↗

PubMed1989

Spectrum of pathologic manifestations of Pneumocystis carinii pneumonia in patients with neoplastic diseases.

Pneumocystis carinii is the most common protozoan organism causing infection in immunosuppressed patients. This study, based on a review of 32 lung biopsies and 13 autopsies of patients with neoplastic diseases who developed P carinii pneumonia, emphasizes the morphologic variation of this disease. Excluded from this study are those patients with PCP secondary to bone marrow transplantation and AIDS. P carinii pneumonia occurred predominately in patients with malignant lymphoreticular neoplasms, 73% of those in our series, and the remaining 27% had solid tumors. There were 27 males and 18 females and their ages ranged from 1 to 73 years, with a median age of 30 years. Microscopically, the diagnostic intraalveolar foamy exudate of P carinii pneumonia was present in only 58% of the cases. Furthermore, diffuse alveolar damage alone was present in 26% of cases. This change was especially prominent when the characteristic foamy material was scanty. Other tissue reactions to P carinii included the presence of giant cells, epithelioid granulomas, desquamative interstitial-like pneumonitis, and interstitial lymphoid infiltrate. Extrapulmonary dissemination was not observed in this patient population. The pathologist should be aware of the marked variations that occur in the morphologic appearance of PCP, and the diagnosis of Pneumocystis infection should not be discarded until a careful search for the organisms using silver stains is rendered negative.

Adolescent↗

PubMed1989

Steroid-responsive chronic hepatic graft-versus-host disease without extrahepatic graft-versus-host disease.

A 29-yr-old woman developed severe, progressive cholestasis 5 months after allogeneic bone marrow transplantation. Extrahepatic graft-versus-host disease (GVHD) was absent. Skin biopsy was equivocal 2 months after transplant, rash was absent during the period of cholestasis, and cholangiographic abnormalities were absent. Liver biopsy 7.5 months posttransplant revealed chronic hepatic GVHD. Cholestasis dramatically resolved with high dose corticosteroid therapy. Chronic hepatic GVHD occurs in the absence of overt extraintestinal GVHD and respond promptly to therapy. This underscores the importance of aggressive diagnostic evaluation of posttransplant cholestasis.

Adult↗

PubMed1988

Differential expression of a sialoglycoprotein with an approximate molecular weight of 900,000 on metastatic human colon carcinoma cells growing in culture and in tumor tissues.

Wheat germ agglutinin (WGA)-binding cellular glycoproteins produced by HT-29 human colon carcinoma and its variant cells established from liver metastases in nude mice after intrasplenic injection were analyzed by polyacrylamide gel electrophoresis. On 5.5% polyacrylamide gels five major sialoglycoproteins (approximate Mr 115,000, 145,000, 190,000, 450,000, and 740,000) reactive with WGA were common to the parental and metastatic sublines. There was an additional component of Mr approximately 900,000 that was prominent in cells established from liver metastases. Specific removal of sialic acid from the glycoproteins eliminated WGA binding, indicating that all the WGA-binding glycoproteins including the Mr 900,000 component were sialoglycoproteins. Smith degradation following mild acid hydrolysis resulted in formation of WGA-binding carbohydrate chains on Mr 115,000, 145,000, 190,000, and 900,000 components, but not on Mr 450,000 and 740,000 components, which indicated that these two sialoglycoproteins bore different oligosaccharides from the other sialoglycoproteins. The Mr 900,000 component was more prominent with HT-29 cells growing in nude mice than those growing in vitro. WGA binding to the Mr 900,000 component of metastasis-derived HT-29 cells growing in a nude mouse was higher than that of parental cells growing in nude mice. The expression in liver metastases derived from parental as well as metastatic cells was higher than the primary tumor growing in the spleen of the same mouse, indicating that the levels of Mr 900,000 sialoglycoprotein (SGP = 900) were regulated by intrinsic and environmental factors. The influence of organ microenvironmental factors was confirmed by analyzing sialoglycoproteins of HT-29 cells growing in the liver of a nude mouse following intrahepatic injection. Analyses of human colorectal carcinoma tissues and liver metastases revealed a polydisperse WGA-reactive high-molecular-weight component similar to that seen in tumors growing in nude mice. The mean value of WGA binding to high-molecular-weight glycoproteins in the primary tumors of stage B1 patients was smaller than that of all other primary tumors. Comparison of primary tumors with liver metastases from the same patients indicated that the level of SGP-900-like high-molecular-weight glycoproteins in metastases was not always higher than those in primary tumors.

Adenocarcinoma↗