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J J Ho

Publications and source records attributed to J J Ho.

At least 55 records · Page 3Linked to original sources
PubMed1993

Multiple forms of intracellular and secreted mucins in a pancreatic cancer cell line.

Mucins have been implicated in circumventing the defenses of the body against tumorigenesis. A better understanding of the structures of mucins may assist in the development of new therapeutic approaches. Monoclonal antibody Ea6, developed against mucins purified from xenografts of the pancreatic cancer cell line SW1990, was used to identify a new type of pancreatic cancer mucin. The following characteristics suggest that Ea6 antibody reacts with the core structure of O-linked oligosaccharides, the Tn antigen (N-acetylgalactosamine-serine/threonine): (a) increased reactivity with ovine and bovine submaxillary mucins after desialylation; (b) reactivity was inhibitable by N-acetylgalactosamine; and (c) no reactivity with blood group A oligosaccharides. Ea6 mucins from cultured SW1990 cells had lower buoyant densities (1.36 versus 1.44 g/ml) than mucins identified by another monoclonal antibody directed against SW1990 mucins, SPan-1, and were less acidic. High density and molecular mass (> or = 400 kD) secreted antigens were unaffected by sulfhydryl bond reduction. After partial deglycosylation secreted SPan-1 antigens reacted with MUC1 peptide specific antibodies, SM-3 and HMFG-2, as well as polyclonal antisera directed against deglycosylated xenograft mucins. However, Ea6 antigens did not. SW1990 cytosol also contained SPan-1 antigens with apparent molecular weights of 160,000 and 210,000 and low buoyant densities (< or = 1.22 g/ml). These reacted with monoclonal antibodies specific for the MUC1 apomucin with no prior treatment. No Ea6 reactivity was detected with this fraction. These results suggest that Ea6 antibody identifies a new population of mucins that is distinct from SPan-1 mucins.

Animals↗
PubMed1993

Expression of CA19-9, DU-PAN-2, and SPan-1 antigens on two types of normal salivary mucins.

Mucins are important in cancer diagnosis and therapy. A better understanding of the characteristics of mucins in normal and malignant tissues could make them more effective clinical targets. Levels of the sialylated carbohydrate mucin antigens CA19-9, DU-PAN-2, SPan-1, and TAG-72 are elevated in sera from patients with pancreatic cancer. In this study we examined normal saliva for the presence of these antigens. TAG-72 reactivity was not detected in the samples examined. SPan-1 expression correlated with the expression of CA19-9 except in Le(a)- individuals. In these individuals CA19-9 was absent; SPan-1 was expressed to varying degrees. Little, if any, reactivity was detected with four monoclonal antibodies directed against the MUC1 mucin peptide. A high-buoyant-density-fraction (1.35 to 1.55 g/mL) of normal saliva, containing most of the sialic acids and O-linked oligosaccharides, was separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Western blots showed that CA19-9, DU-PAN-2, and SPan-1 antigens were found on two forms of mucins. DU-PAN-2 reactivity was detected only in the absence of the sulfhydryl reducing agent beta-mercaptoethanol. The two main forms of antigens differed in molecular size (150 kDa and greater than 400 kDa) and buoyant density (1.38 and 1.49 g/mL) and have been reported to differ in amino-acid composition. In colon or pancreas, the CA19-9, DU-PAN-2, and SPan-1 carbohydrate structures have been reported to be present on the MUC1 mucin peptide. Our present results suggest that in saliva, these carbohydrate antigens may be found on mucin peptides other than MUC1.

Antigens, Neoplasm↗
PubMed1992

Differences in expression of SPan-1 and CA15-3 antigens in blood and tissues.

Pancreatic and mammary cancer cells are reported to have different oligosaccharides on the same apomucin, the MUCI gene product. A better understanding of the tissue specificity of these sugar structures may help in identifying the source of mucins when they are found in the sera. Serum levels of 3 pancreatic-cancer-associated carbohydrate epitopes identified by monoclonal antibodies (MAbs) SPan-1, 19-9 and DU-PAN-2, were compared to those of CA15-3 in a variety of malignant conditions. CA15-3 identifies both carbohydrate and peptide determinants associated with the MUC1 apomucin in breast tissues. SPan-1 antigen was elevated in a high percentage of patients with pancreatic, gastric and colorectal cancer but in only a few of the patients with malignancies of non-GI origin such as breast, ovary and lung. The 19-9 and DU-PAN-2 antigens had a similar pattern of much greater sensitivity for pancreatic cancer than for these non-gastrointestinal cancers. The levels of these 3 markers showed significant correlations in pancreatic cancer. In contrast, CA15-3 was elevated in a large number of patients with breast, lung, ovarian and pancreatic cancers. There was no correlation of CA15-3 with the 3 other markers in pancreatic cancer. SPan-1 and DF3/115D8 antigens in blood have different mobilities in SDS-PAGE and buoyant densities. Moreover, SPan-1 and DF3 antigenic determinants are localized in different regions of the same normal and malignant pancreas and breast tissues. Thus the SPan-1 determinant can be dissociated from the breast peptide and/or carbohydrate determinants.

Antigens, Neoplasm↗
PubMed1992

Tumor localization and biodistribution with radiolabeled monoclonal antibody against pancreatic cancer in tumor-bearing nude mice.

Nd2 is a murine monoclonal antibody produced against a mucin fraction purified from xenografts of a human pancreatic cancer cell line SW1990. Immunoperoxidase staining showed that the antigen recognized by Nd2 was present in 82.9% of pancreatic cancer tissues but not in tissues of normal pancreas and chronic pancreatitis. However Nd2 antigen was found not to be elevated in the sera of patients with pancreatic cancer. Four days after injection of 111In-Nd2 into athymic nude mice bearing SW1990 xenograft there was a higher accumulation in the tumor compared to 111In-normal mouse IgG1. When these mice were scanned with a gamma camera, labeled Nd2 was shown to accumulate in the tumor rapidly on the 1st day after injection and by the 4th day tumor accumulation was more distinctly visualized than non-specific accumulation in liver. These results indicate that Nd2 has high specificity and reactivity for pancreatic cancer and may have possible applicants in radioimmunodetection or targeting of therapeutic drugs in pancreatic cancer.

Animals↗
PubMed1992

Cryosurgical equipment: a critical review.

BACKGROUND: Cryosurgery is frequently used by family physicians to treat benign and premalignant epithelial disease. A professional medical team consisting of a practicing cryotherapist and a mechanical engineer independently critically evaluated the design, function, and performance of selected cryosurgical equipment. METHODS: Qualitative observations and quantitative measurements were performed on seven nitrous oxide cryosurgical units and one liquid nitrogen unit, representing seven manufacturers and distributors. Specific isotherm generation distributions, lateral spread of freeze and refreeze measurements, defrost intervals, recovery zone sizes, relative ease of use, and component characteristics were comparatively assessed. RESULTS: The in vitro mean lateral spread of freeze distance at 180 seconds varied between 5.8 mm for the Frigitronics CryoPlus and 4.6 mm for the Leisegang LM-900. The mean -20 degrees C isotherm generation time, measured by a thermocouple 3 mm lateral to the cryoprobe tip margin, ranged from 229 seconds for the Wallach WA-1000B to 361 seconds for the Spembly PCG 9R. Defrost times varied between 2 seconds for the Wallach WA-1000B and 320 seconds for the Brymill Mini-Cryogun. Refreeze time was quickest (36 seconds) using the GyneTech GT-1S. The mean in vitro recovery zones varied between 1.6 mm and 2.1 mm. CONCLUSIONS: This evaluation documented both differences and similarities among various cryosurgical units in terms of design, function, and performance. The Wallach, Frigitronics, and GyneTech nitrous oxide cryosurgical units demonstrated the best overall performance.

Cryosurgery↗
PubMed1991

Differential mucin gene expression in human pancreatic and colon cancer cells.

The purpose of this study was to determine the quantity and nature of the mucins synthesized and secreted by four different pancreatic cancer cell lines. Well- to moderately-differentiated SW1990 and CAPAN-2 human pancreatic cancer cells were found to produce more high-Mr glycoprotein (HMG) than less-differentiated MIA PaCa-2 and PANC-1 cells. Most of the labelled HMG was secreted within 24 h. The results of chemical and enzymic degradation, ion-exchange chromatography and density-gradient centrifugation indicated that the HMG in SW1990 and CAPAN-2 cells has the properties expected for mucins, whereas much of the HMG in MIA PaCa-2 and PANC-1 cells may not be mucin, but proteoglycan. These results are consistent with immunoblots and Northern blots showing the presence of apomucin and apomucin mRNA in SW1990 and CAPAN-2 cells, but not in MIA PaCa-2 and PANC-1 cells. The Western blots and Northern blots also show that SW1990 and CAPAN-2 cells, like breast cancer cells, have the mammary-type apomucin and mRNA coded by the MUC1 gene, but lack the intestinal type apomucin and mRNA coded by the MUC2 gene. In contrast, the colon cancer cell lines tested in culture express apomucin and mRNA coded by MUC2 but not by MUC1.

Adenocarcinoma↗
PubMed1991

Relationship of pancreatic cancer apomucin to mammary and intestinal apomucins.

Pancreatic cancer mucins have several carbohydrate antigens that are potentially useful in the detection of pancreatic cancers, but little is known about the core polypeptides of pancreatic cancer mucins. In this study, purified mucin from SW1990 pancreatic cancer xenografts was deglycosylated by treatment with hydrogen fluoride to give pancreatic cancer apomucin. Consistent with near-complete removal of carbohydrate, the apomucin had 10- to 70-fold decreased binding of lectins and, unlike the native mucin, served as an acceptor for polypeptidyl N-acetylgalactosaminyl transferase. Antibodies prepared against the apomucin did not bind to native mucin, and antibodies that bound to native mucin did not bind to apomucin. On the basis of cross-reaction with deglycosylated colon cancer mucin and intestinal mucin repeat peptide, apomucins from SW1990 pancreatic cancer xenografts contain the intestinal mucin repeat peptide. On the basis of binding of breast cancer-reactive monoclonal antibodies 139H2, DF3, and HMFG-2, apomucins from SW1990 pancreatic cancer xenografts also have the mammary mucin repeat peptide. Using complementary DNA probes specific for intestinal mucin and breast mucin sequences, both types of apomucin mRNA were detected in nude mouse xenografts of SW1990 cells. In immunohistochemical staining, antibody against deglycosylated SW1990 mucin stained normal breast and pancreas but not normal colon. Some pancreatic and mammary cancers and most colonic cancers, however, were stained by antibodies against both intestinal apomucin and mammary apomucin. We conclude that pancreatic cancers can produce mucins with the intestinal repeat peptide as well as those with mammary repeat peptide sequences.

Breast↗
PubMed1991

Characterization of new pancreatic cancer-reactive monoclonal antibodies directed against purified mucin.

Although mucins have been found to be useful in the diagnosis of pancreatic cancer, the carbohydrate and peptide structures of pancreatic mucins are still not well characterized. Monoclonal antibodies were produced using mucins purified from xenografts of a human pancreatic cancer cell line as the immunogen. One of these, Ia3, reacted with almost all pancreatic, gastric, and colorectal carcinomas examined by immunoperoxidase staining, but with few normal tissues. Ia3 antigen was elevated in sera of 50.4% of individuals with gastrointestinal tumors, but its levels did not correlate with those of CA15-3, CA19-9, or DU-PAN-2. Serum Ia3 antigens migrated more slowly in sodium dodecyl sulfate-polyacrylamide gel electrophoresis than the polymorphic epithelial mucins recognized by DF3 or 115D8. Ia3 reacted only with native, and not with partially deglycosylated, pancreatic cancer xenograft mucins. Periodate or neuraminidase treatment destroyed this reactivity, but protease had little effect. The antigen recognized by another antibody, Nd2, was not detected in normal pancreatic, colonic, or gastric tissues but was present in approximately 60% of the pancreatic and gastric carcinomas examined. Nd2 reactivity with native and partially deglycosylated mucin was lost after pretreatment with protease and beta-mercaptoethanol. We conclude that, while Ia3 reacts with carbohydrates, Nd2 reactivity appears to be dependent on the integrity of the mucin protein core. The antigenic determinants of Ia3 and Nd2 are different from those of B72.3, CA19-9, DU-PAN-2, SPan-1, and several breast cancer mucin-directed antibodies. These results suggest that the malignancy-associated structures identified by Ia3 and Nd2 may provide new information on the carbohydrate and peptide structure of pancreatic cancer mucins.

Antibodies, Monoclonal↗
PubMed1991

Colpophotography systems: a review.

Colpophotography and video colposcopy systems are useful for pathology documentation purposes, patient education, and colposcopy training. A wide variety of colposcopic visual media components are available to enhance routine colposcopy. Colpophotographic systems supplied by eight colposcope manufacturers were critically evaluated by a colposcopist and a medical photographer. Components were independently and objectively analyzed. Photographic examination considered color, illumination uniformity, and coverage of illumination at all possible colposcopic magnifications. Photographs were developed by a standardized technique. The investigation results clearly demonstrated variability between different colpophotographic systems. Quality colpophotography is dependent on certain colposcope features and potential modifications. Colpophotography and video colposcopy systems complement the standard colposcopic procedure.

Colposcopes↗
PubMed1991

Colposcopes: a critical review.

A multidimensional professional team consisting of a practicing colposcopist, a mechanical engineer, and a medical photographer independently critically evaluated the features of selected colposcopes. Qualitative observations and quantitative measurements were performed on 13 colposcopes representing eight manufacturers and distributors. Optical characteristics, ocular system operation, mobility and stability, relative ease of use, component characteristics, space for instrumentation, and visual illumination, uniformity, and color were comparatively assessed. The specific colposcope information provided may benefit practicing physicians or novice colposcopists who are contemplating purchasing a colposcope. The presented framework of critical feature evaluation may also facilitate the informed selection of other colposcopes not included in this selective, critical, comprehensive review.

Colposcopes↗
PubMed1990

[Establishment of monoclonal antibodies against purified mucin from human pancreatic cell line].

Thirty four murine monoclonal antibodies were produced against mucin which was isolated from nude mouse xenografts of the SW1990 pancreatic adenocarcinoma cell line. Twelve of them reacted with formalin-fixed SW1990 cells. The antigenic determinants of these antibodies were composed of carbohydrates and their immunoreactivities were predominant at CsCl fraction #6. The remaining 22 antibodies did not react with formalin-fixed cells, 5 epitope specificities of which antibodies are present in the polypeptide part or the part of linkage between oligosaccharide and polypeptide and the immunoreactivities were predominant at CsCl fraction #5. Immunohistochemical study showed that the incidence of epitope expression of the latter 22 antibodies were higher in pancreatic cancer tissues and lower in normal pancreatic tissues than that of the former 12 antibodies. The incidence of Nd2 (one of the 22 antibodies) expression was highest in pancreatic cancer tissues and lowest in normal tissues. ELISA showed that Nd2 antigen was non-secreting type. In vivo tumor distribution studies showed that Nd2 antibody tended to accumulate in cancer tissues. These results seem to support the clinical availability of Nd2.

Adenocarcinoma↗
PubMed1989

Evaluation of factors affecting the performance of enzymatic SPan-1 immunoassays for pancreatic cancer.

An avidin-biotin complex (ABC) sandwich enzymatic immunoassay was developed utilizing SPan-1, a murine monoclonal antibody of the IgM isotype. Biotin was attached to the epsilon-amino group of lysines of SPan-1 using biotin-N-hydroxysuccinimide esters with or without a spacer (aminohexane). Addition of biotin to carbohydrates was with biotin hydrazide after periodate oxidation of the immunoglobulin. The resultant assays were compared to a sandwich radioimmunoassay and to another form of the SPan-1 enzymatic immunoassay in which oxidized horseradish peroxidase had been directly conjugated to SPan-1. Comparable antigen detection limits were obtained regardless of whether biotin was added to the peptide or carbohydrates or whether a spacer was used or not. The ABC assay had approximately the same SPan-1 antigen detection limit as the radioimmunoassay. 90.6% of the human pancreatic cancer sera tested positive in the ABC assay as compared to a previously reported 93% positive rate with a radioimmunoassay.

Antibodies, Monoclonal↗
PubMed1988

Mucin-like antigens in a human pancreatic cancer cell line identified by murine monoclonal antibodies SPan-1 and YPan-1.

The antigenic determinant recognized by monoclonal antibody SPan-1 is greatly elevated in sera of patients with pancreatic cancer but not in sera of normal individuals. Here we describe the mucin-like characteristics of the SPan-1 antigen isolated from culture medium and xenografts of the human pancreatic cancer cell line SW-1990. YPan-1, another pancreatic cancer associated monoclonal antibody, also reacts with the SPan-1 antigen. The SPan-1/YPan-1 antigens have densities of 1.4-1.5 g/ml and elute in the void volume of Sepharose CL-2B columns. They are resistant to degradation by chondroitinase ABC, nitrous acid, and hyaluronidase but susceptible to protease digestion and reductive beta-elimination. All these characteristics suggest that the SPan-1 and YPan-1 determinants are carried on mucinous antigens. Both SPan-1 and YPan-1 immunoreactivities are unaffected by boiling or by alkylation and reduction of the mucins while they are abolished by mild periodate oxidation or neuraminidase and are markedly decreased by wheat germ agglutinin. Thus, their antigenic determinants are composed principally of carbohydrates with sialic acid, an absolute requirement for reactivity. However, the epitope specificities of SPan-1 and YPan-1 are different since YPan-1 does not compete with SPan-1 for binding to antigen. Moreover, YPan-1 and SPan-1 can be distinguished from several other sialic acid requiring, cancer associated antibodies such as B72.3, CSLEX-1, DU-PAN-2, OC-125, and 19-9 by either their epitope characteristics or their tissue reactivity patterns.

Animals↗
PubMed1987

The detection of human pancreatic cancer-associated antigen in the serum of cancer patients.

A radioimmunoassay (RIA) test for human pancreatic cancer-associated antigen (Span-1) was developed to evaluate the diagnosis of various gastrointestinal disorders. Serum Span-1 in normal subjects ranged from 5 to 275 U/ml, with a mean of 58.8 U/ml (+/- 58.7, standard deviation). All control subjects had levels of less than 400 U/ml. Study subjects, 93% with pancreatic cancer, 59% with hepatobiliary cancers, 23% with gastric cancers, and 13% with colonic cancers had serum Span-1 levels greater than 400 U/ml. Sensitivities of Span-1, CA 19-9, and Dupan-2 for pancreatic cancer were 94%, 85%, and 38% respectively. Span-1 in patients with Stage I pancreatic cancer showed a 50% positive rating but CA 19-9 and Dupan-2 showed only 0% and 25%. Although a positive rating of these three antibodies increased in advanced cases, Span-1 showed the highest positive rating. Span-1 reacted with colonic cancer tissues with Lewisa-b- phenotype. However, none of these tissues did not react against CA 19-9. From these results, Span-1 has a good predictive value for detecting pancreatic cancer compared with CA 19-9 and Dupan-2.

Antibodies, Monoclonal↗
PubMed1985

Human pancreatic cancer-associated antigens detected by murine monoclonal antibodies.

Two monoclonal antibodies, YPan1 and YPan2, were produced from spleen cells of mice immunized against a human pancreatic cancer cell line, Capan-2, which also reacted with eight other human pancreatic carcinoma cell lines and with sections of cancerous human pancreas tissue. Reactivity was also found with colonic and stomach carcinoma tissues. Whereas YPan1 reacted strongly with normal pancreatic tissue, it bound weakly, if at all, to a variety of other normal tissues. YPan1 reacted with both the membranes and cytoplasm of pancreatic adenocarcinoma cells and with constituents of normal pancreatic ductal cells and duct luminal contents. YPan2, on the other hand, reacts to a greater degree with intracytoplasmic constituents in pancreatic adenocarcinoma cells. Unlike YPan1, YPan2 reacted weakly with only one of 16 cases of normal pancreas. Pretreatment of the tissue with neuraminidase abolished YPan1's reactivity, which indicated that sialic acid may be involved in the antigenic activity of the molecule(s) recognized by YPan1. Neuraminidase pretreatment had no effect on YPan2 reactivity. Neither YPan1 nor YPan2 competed with 19-9 monoclonal antibody in binding to soluble CA 19-9 antigen. These results suggest that these monoclonal antibodies are of potential use in the diagnosis of pancreatic carcinoma.

Antibodies, Monoclonal↗
PubMed1983

Protein concentration in the pancreatic zymogen granule.

We have estimated the concentration of protein in the zymogen granule, a major storage depot for secretory protein in the pancreatic acinar cell, in four different ways. Each of these approaches yielded roughly similar values. The protein concentration in the granule is approx. 135-270 mg protein/ml granule volume in rat and rabbit, as compared to an average value for the protein concentration of tissue of 135 mg/g tissue for rabbits and 183 mg/g tissue for rats. This is equivalent to an average molarity for the contained proteins of between 4-9 mM based on an estimated average molecular weight for the mixture of 30 000-40 000. An upper limit for the concentration of protein in these granules can reasonably be set at about double the overall concentration of protein in the non-granule portion of the cell.

Amylases↗