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Biomedical subjects

J C Byrd

Publications and source records attributed to J C Byrd.

At least 19 recordsLinked to original sources
PubMed1995

Successful treatment of invasive aspergillosis complicating prolonged treatment-related neutropenia in acute myelogenous leukemia with amphotericin B lipid complex.

Herein we report the successful treatment of invasive aspergillosis with the liposomal amphotericin B (AMB) formulation, Amphotericin B Lipid Complex (ABLC). This investigational compound was employed in a 50-year-old patient with acute myelomonocytic leukemia complicated by prolonged, treatment-induced granulocytopenia and documented Aspergillus flavus sinusitis with signs of disseminated aspergillosis. The patient demonstrated radiographic signs of pulmonary aspergillosis and biochemical signs of hepatic involvement that were resistant to a 23 day course of conventional AMB (Fungizone) therapy. Following therapy with ABLC her fever abated, her chest X-ray findings improved, and her hepatic function tests improved with eventual resolution.

Adult↗
PubMed1995

Inhibition of mucin synthesis by benzyl-alpha-GalNAc in KATO III gastric cancer and Caco-2 colon cancer cells.

Previous studies from our laboratory have shown that benzyl-alpha-GalNAc inhibits the glycosylation of mucin in colon cancer cells. In this study, we determined whether benzyl-alpha-GalNAc inhibits mucin glycosylation in KATO III gastric cancer cells. We also examined its effects on expression of mucin antigens, and compared the mucins made by KATO III with those of a colonic cancer cell line, Caco-2. Results of these experiments suggest that benzyl-alpha-GalNAc (2 mM) inhibited [3H]glucosamine labelling of mucins by 82% in KATO III and by 70% in Caco-2. For both cell lines, the mucin secreted in the presence of benzyl-alpha-GalNAc was less acidic. Both cell lines secreted benzyl-oligosaccharides, but those from KATO III (8-9 sugars) were larger than those from Caco-2 (6-7 sugars). In mucins purified from the medium of treated cells, peripheral carbohydrate antigens (sialyl Lex in KATO III and terminal fucose in Caco-2) were decreased (compared with control), while core carbohydrate antigens (T antigen in both cell lines and sialyl Tn in Caco-2) were increased. Western blots of cell homogenates showed differences between KATO III and Caco-2 in MUC 1 apomucin protein antigens, in sialyl Lex and in sialyl Tn antigens. We conclude that benzyl-alpha-GalNAc does inhibit the glycosylation of mucin in KATO III gastric cancer cells as in human colon cancer cells, but that alterations in mucin antigens occur in a cell line-specific manner.

Acetylgalactosamine↗
PubMed1995

Extramedullary myeloid cell tumors in acute nonlymphocytic leukemia: a clinical review.

PURPOSE: To discuss the predisposing risk factor for all forms of extramedullary leukemia (EML) and to review the clinical features, prognostic significance, and treatment strategies for primary EML and leukemia cutis (LC)/granulocytic sarcomas (GS) in the setting of acute nonlymphocytic leukemia (ANLL). METHODS: A review of all reports published since 1965 related to all forms of extramedullary leukemia (LC, GS, gingival hypertrophy, and meningeal leukemia [ML]). RESULTS: Several factors, including chromosomal abnormalities [t(8;21), inv(16)], cell-surface markers (CD56, CD2, CD4, CD7), French-American-British (FAB) subtype (M2, M4, M5), blast differentiation and maturation, patient nutritional status, age, cellular immune dysfunction, high presenting leukocyte count, and decreased blast Auer rods, have been associated with a higher incidence of EML. Of 154 published cases of primary EML identified, 71 (46%) were initially misdiagnosed. The addition of immunohistochemical stains can assist in preventing such misdiagnoses and should be included in all atypical lymphoma/carcinoma cases. Only one of the patients (3%) with primary EML did not progress to ANLL in the absence of chemotherapy. In contrast, 66% of patients who received chemotherapy for the primary EML never developed ANLL. The prognostic significance of EML at presentation and medullary relapse of ANLL is uncertain. Isolated extramedullary recurrence of ANLL always heralds bone marrow relapse and should be treated with reinduction chemotherapy. Close clinical follow-up observation is necessary to insure resolution of EML. Radiation therapy is an effective local treatment for resistant or symptomatic EML. CONCLUSION: Many advances in diagnoses and treatment of EML have been made. Future investigations are needed to define the clinical significance of EML in patients with ANLL treated with modern chemotherapy or bone marrow transplantation.

Age Factors↗
PubMed1994

Recurrent granulocytic sarcoma. An unusual variation of acute myelogenous leukemia associated with 8;21 chromosomal translocation and blast expression of the neural cell adhesion molecule.

This study reports on a patient with acute myelogenous leukemia (AML) in remission who had a series of 11 granulocytic sarcomas (chloromas or myeloblastomas) appearing periodically over a 29-month interval in a variety of anatomic sites without evidence of bone marrow recurrence. This isolated extramedullary recurrence of AML is distinctly unusual with only 24 cases described previously. This patient had the greatest number and longest reported interval of recurrent granulocytic sarcomas (GS) before bone marrow relapse. Furthermore, he represents the first case of a patient with GS presenting with both an 8;21 chromosomal translocation and neural cell adhesion molecule (CD56) expression. The authors hypothesize that these two abnormalities identified previously as predisposing factors to GS may, in fact, be synergistic for this phenomenon. His case and the review of the literature demonstrate some of the important clinical and management features of a patient who develops GS while in complete marrow remission from previous AML. Although highly sensitive to radiation therapy, the onset of granulocytic sarcomas is almost always followed by bone marrow relapse and should be treated with aggressive reinduction chemotherapy and local irradiation. Such therapy is associated with the longest interval of disease-free survival.

Adult↗
PubMed1992

Mucin oligosaccharide biosynthesis in human colonic cancerous tissues and cell lines.

BACKGROUND: The Tn, sialosyl-Tn, and T antigens are carbohydrate-associated antigens that represent initial steps in mucin O-linked glycosylation. Previous immunohistochemical studies have shown that these three antigens are rarely, if ever, expressed in normal colonic mucosa; however, most colonic cancerous tissues express these structures. Little is known about the factors that control the expression of these antigens in colonic tissues or cell lines. One hypothesis is that cancers have increased levels of the glycosyltransferase activities responsible for synthesizing these antigens. METHODS: The current study analyzed antigen expression by immunohistochemistry and glycosyltransferase enzyme activities for Tn, sialosyl-Tn, and T antigens in colonic tissues and cell lines to (1) compare values between normal and cancerous tissues and (2) correlate these results with tumor stage, histologic findings, and location. RESULTS: All nine colonic cancer cell lines expressed Tn antigen; sialosyl-Tn and T antigens were expressed by the more mucin-producing cell lines. Sialosyl-Tn transferase activity was higher in the more mucinous cell lines; T transferase activity was higher in those with less mucin. In paired specimens of normal and cancerous tissues, levels of each of the three glycosyltransferases were similar. In cancerous tissues, enzyme activity did not correlate with tumor location, stage, or histologic type. There also was no correlation between glycosyltransferase activity and expression of the relevant antigen. CONCLUSIONS: Thus, because normal and malignant colonic tissues have comparable levels of Tn, sialosyl-Tn, and T glycosyltransferases, the absence of these antigens in normal mucosa apparently is related to other factors such as antigen masking.

Aged↗
PubMed1992

Expression and characterization of mucins associated with the resistance to methotrexate of human colonic adenocarcinoma cell line HT29.

A series of experiments were conducted to study synthesis and secretion of mucin in mucus-secreting subpopulations of HT29 human colonic adenocarcinoma cells selected by resistance to methotrexate (MTX). Mucin was quantitated by [3H]glucosamine labeling and chromatography on Sepharose CL-4B. The mucinous nature of the labeled high molecular weight glycoprotein was verified by alkaline borohydride treatment, cesium chloride density gradient ultracentrifugation, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The results of these experiments demonstrated that MTX-treated cells have increased amounts of mucin in medium, cytosol, and membrane fractions. This was associated with the increase in the activities of polypeptidyl-N-acetylgalactosaminyltransferase and beta-1,3-galactosyltransferase compared to control cells. DEAE-Sephacel chromatography of [3H]glucosamine-labeled high molecular weight glycoproteins suggest that MTX-treated cells are less acidic compared to controls. Using complementary DNA probes for two distinct human intestinal mucins (MUC2 and MUC3) and one mammary mucin (MUC1), it was found that MTX-treated cells expressed more mucin messages compared to untreated cells. These results were consistent with immunoblots using anti-MRP (MUC2 repeat peptide), anti-M3P (MUC3 repeat peptide), 139H2 (MUC1 peptide), anti-T (peanut lectin), anti-Tn (91S8), and anti-sialosyl Tn (JT10e) antibodies. These data indicate that MTX-resistant HT29 cells show enhanced secretion and synthesis of mucin as well as expression of MUC1-, MUC2-, and MUC3-related mucin polypeptide epitopes.

Cell Differentiation↗
PubMed1992

Mucin synthesis and secretion in relation to spontaneous differentiation of colon cancer cells in vitro.

The synthesis and secretion of mucin-like high-molecular glycoprotein was studied in 2 human colon cancer cell lines that spontaneously differentiate in culture (Caco-2 and T84) and in 2 cell lines that do not spontaneously differentiate (LS174T and HT29). Mucin, quantitated by 3H-glucosamine labelling and chromatography on Sepharose CL-4B was found to be produced by all 4 cell lines. The mucinous nature of the labelled high-molecular glycoprotein was verified by enzymatic degradation treatments (heparinase, hyaluronidase, chondroitinase ABC, and N-glycanase), alkaline-borohydride treatment, inhibition of labelling by the glycosylation inhibitor benzyl-alpha-GalNAc, and by CsCl-density-gradient centrifugation. In all 4 cell lines, an inverse correlation of mucin synthesis with cell density was demonstrated. In Caco-2 cells, the spontaneous post-confluent enterocytic differentiation with increased brush-border enzyme expression was associated with a decrease in mucin synthesis and in the activities of polypeptidyl GalNAc transferase and beta 1,3-galactosyltransferase activity. Using cDNA probes for 2 distinct human intestinal mucins (MUC2 and MUC3), we found that all 4 colon cancer cell lines expressed mucin message, but the types of mucin mRNA expressed differed. These data indicate that mucin-like glycoproteins can be synthesized by cell lines derived from non-mucinous colon cancer, whether or not they undergo spontaneous differentiation in culture. These cell lines may serve as in vitro models for studying apomucin heterogeneity and control of mucin gene expression.

Cell Differentiation↗
PubMed1992

Efficacy of prophylactic sclerotherapy for prevention of a first variceal hemorrhage.

The efficacy of prophylactic sclerotherapy is unclear because published studies of prophylactic sclerotherapy have reached conflicting conclusions. Meta-analysis was used to determine the efficacy of prophylactic sclerotherapy of esophageal varices. The meta-analysis included all English-language articles reporting results of randomized controlled trials of prophylactic sclerotherapy in adults. Prophylactic sclerotherapy reduced the 13-month mortality rate by 11% (95% confidence interval, 4%-19%), which represents a 41% relative reduction in mortality rate. Across studies, the mortality rate reductions were positively correlated with the bleeding rate reductions and negatively correlated with complication rates. The pooled mortality reduction remained significant when sensitivity analyses included the interim results from the abstracts and foreign-language articles. Nonetheless, prophylactic sclerotherapy should not be widely applied at present because complication rates are high and less costly treatments are available. Furthermore, all published studies offered more intensive follow-up to treated patients, which may have confounded the results and consistently inflated the benefits of sclerotherapy.

Esophageal and Gastric Varices↗
PubMed1992

Environmental tobacco smoke. Medical and legal issues.

Adequate information is available linking ETS to several medical problems, including respiratory illnesses in children and lung cancer in adults; nonetheless, continuing investigation is necessary to clarify several issues. Reliable information needs to be gathered on the quantity and fate of ETS chemicals in ordinary indoor environments; improved surveys quantifying passive smoke exposure should be tested along with the use of biologic markers to quantify exposure-dose relationships in nonsmokers. To date, legislation and private initiatives have been the most promising of the various measures to protect nonsmokers from ETS. While nonsmokers' judicial action has had variable success, it places the burden of challenging smoking on the nonsmoker, and it entails piecemeal, case-by-case resolution. On the other hand, legislation and private policies relieve the nonsmokers' burden to initiate the challenge, and they protect greater numbers of nonsmokers. Furthermore, legislation and policies may have a great number of direct and indirect effects. In the short term, legislation and policies that are adequately implemented and enforced alter the behavior of smokers in areas where smoking is prohibited and should result in a reduced concentration of tobacco smoke in those areas. In the long term, policies and legislation that restrict smoking in public places and the workplace help to reinforce nonsmoking as the normative behavior in society. Smoking restrictions increase public awareness and acceptance of health risks of tobacco smoke. The combination of altered social norms and reduced opportunities to smoke may encourage smokers to quit and nonsmokers, especially adolescents, not to start.

Cardiovascular Diseases↗
PubMed1992

Effect of benzyl-alpha-GalNAc, an inhibitor of mucin glycosylation, on cancer-associated antigens in human colon cancer cells.

Many cancer-associated antigens are present on mucin glycoproteins. These include peripheral antigens such as sialyl Lea and sialyl Lex and core region carbohydrate antigens such as T, Tn, and Sialyl Tn. We have recently described an inhibitor of mucin glycosylation, benzyl-alpha-GalNAc. The purpose of this study was to determine its effect on expression of mucin carbohydrate antigens. HM7 colon cancer cells were treated for 2 days in culture with 2 mM benzyl-alpha-GalNAc. This treatment did not affect viability or doubling time, but inhibited synthesis of [3H]glucosamine-labeled mucins. There was also secretion of benzyl-oligosaccharides and a decrease in the proportion of long oligosaccharides on 3H-labeled mucins. Mucins were purified from spent media by gel filtration and assayed for binding of monoclonal antibodies and lectins. Mucins from benzyl-alpha-GalNAc-treated cells had increased binding of peanut agglutinin (specific for T antigen, Gal beta 3GalNAc) and Vicia villosa agglutinin B4 (specific for Tn antigen, GalNAc alpha-Thr/Ser), but decreased binding of monoclonal antibodies 19-9, SNH3, and 91.9H (specific for sialyl Lea, sialyl Lex, and sulfomucin, respectively). Treatment of the cells with benzyl-alpha-GalNAc also decreased their binding to E-selectin (ELAM-1), which recognizes sialyl Lea and sialyl Lex. Thus, benzyl-alpha-GalNAc treatment, which decreases the level of peripheral carbohydrate carbohydrate antigens on mucins with accumulation of core region antigens, may be useful in modifying the immunological and biological properties of colon cancer cells.

Acetylgalactosamine↗
PubMed1991

Molecular cloning of rat intestinal mucin. Lack of conservation between mammalian species.

We have prepared antisera to deglycosylated rat intestinal mucin and used it to obtain immunoreactive clones from a rat jejunum cDNA library. Four of these clones were sequenced, and all were found to be partial cDNAs that contained 18-base pair tandem repeats characteristic of a mucin. These cDNAs encoded a repetitive peptide with a consensus sequence of TTTPDV. Thus, they bear little resemblance to either of the two human intestinal mucin cDNAs isolated previously (Gum, J. R., Byrd, J. C., Hicks, J. W., Toribara, N. W., Lamport, D. T. A., and Kim, Y. S. (1989) J. Biol. Chem. 264, 6480-6487 and Gum, J. R., Hicks, J. W., Swallow, D. M., Lagace, R. E., Byrd, J. C., Lamport, D. T. A., Siddiki, B., and Kim, Y. S. (1990) Biochem. Biophys. Res. Commun. 171, 407-415). One of these rat mucin clones, designated RMUC 176, was chosen for further analysis. This clone recognized a band of approximately 9 kilobases when used to probe RNA blots. A strong hybridization band was present using rat small intestine and colon RNA but was not detectable when RNA isolated from heart, liver, or kidney was tested. The RMUC 176 clone and the two previously isolated human intestinal mucin cDNA clones were used to probe blots prepared from BamHI-digested DNA of various species. Here, the human probes detected fragments present only in human and chimpanzee DNA, whereas the RMUC 176 clone recognized fragments only in rat and mouse DNA. Thus, the repetitive portions of intestinal mucin genes are apparently not well conserved between phylogenetically distant species.

Amino Acid Sequence↗
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

A sialoglycoprotein complex linked to the microvillus cytoskeleton acts as a receptor for pilus (AF/R1) mediated adhesion of enteropathogenic Escherichia coli (RDEC-1) in rabbit small intestine.

Escherichia coli strain RDEC-1 is an enteroadherent, diarrheagenic pathogen in rabbits that utilizes AF/R1 pili for initial (stage 1) adherence, but the host receptors for this adhesion are unknown. Here we demonstrate that RDEC-1 binds, via AF/R1 pili, to a specific rabbit ileal microvillus membrane glycoprotein receptor complex of subunits 130 and 140 kD. The binding involves sialic acid present on oligosaccharide moieties of the glycoprotein receptor. Furthermore, the microvillus membrane glycoprotein receptor complex appears to be associated with cytoskeletal components via brush border myosin 1. This newly described link between AF/R1 receptor and cytoskeletal components suggests that, in addition to this function in mucosal adherence, the pili may facilitate subsequent (second stage) close effacing attachment of RDEC-1 to the host epithelium by influencing cytoskeletal function.

Animals↗
PubMed1991

Ascorbic acid requirements for smokers: analysis of a population survey.

The recommended dietary allowance (RDA) of ascorbic acid for smokers was recently increased from 60 to 100 mg. To determine whether this new RDA for smokers is sufficient to reduce the risk of low serum ascorbic acid (AA) concentrations (LoC) to the same concentration as nonsmokers, we analyzed the dietary intakes and serum concentrations of AA in 11,582 adult respondents in the National Health and Nutrition Examination Survey (1976-1980). Serum AA concentrations and the risk of LoC (serum ascorbic acid levels less than 23 mumol/L) for smokers consuming different amounts of AA were compared with those for nonsmokers whose AA intake exceeded the RDA (60 mg). Serum AA concentrations were reduced, and risk of LoC increased, in smokers maintaining AA intakes greater than 60, 100, and 150 mg. Only smokers consuming greater than 200 mg AA/d had serum ascorbate concentrations and risk of LoC equivalent to nonsmokers meeting the RDA.

Adult↗
PubMed1991

Nursing home patients transferred by ambulance to a VA emergency department.

Nursing home residents are frequently transferred to hospital emergency departments. Delayed transfer may lead to poor outcomes. However, inappropriate transfer of the frail elderly may cause social and financial problems. We prospectively evaluated 221 consecutive ambulance transfers from community nursing homes to a VA emergency department. The objectives of the study were to describe the process and outcomes of transferred patients and to determine if alternative interventions were feasible. The results indicate that the problems of nearly half the study group could have been treated at the nursing home by a visiting physician with minimal medical equipment. Those admitted to the hospital (52%) were seriously ill, had prolonged lengths of stay (23.6 days), and had a high mortality rate (11%). Complex issues of physician reimbursement, proprietary nursing home budgeting, and day-to-day expediency appear to be involved in decisions to transport patients by ambulance to VA emergency departments.

Adult↗
PubMed1991

The structure of human intestinal apomucins.

Human intestinal mucins are large glycoconjugates (greater than 1,000,000 D) that coat the epithelium, serving to lubricate and protect. Apart from this physiologic function, mucins are important in that they are frequently altered in cancer; thus, they have potential usefulness as tumor markers. We have isolated mucins from human LS174T colon cancer cells and small intestine, deglycosylated these highly purified glycoconjugates, produced polyclonal antibodies to the apomucins, and used these antibodies to isolate two different types of cDNA clones that encode different apomucins. The first class of cDNA clones was isolated using antibodies to deglycosylated LS174T mucin. These cDNA, designated SMUC or MUC2, contain 69 nucleotide tandem repeats that encode a repetitive peptide that is extremely rich in threonine and proline. Northern blots using MUC2 cDNA as probes exhibit large (7,600 bases) and polydisperse hybridization bands. This gene is polymorphic within the human population and is located on chromosome 11. The second class of cDNA was isolated using antibodies to deglycosylated small intestinal mucin. These cDNA, designated SIB or MUC3, have 51 nucleotide tandem repeats that encode a threonine- and serine-rich repetitive peptide. This mucin also is encoded by a large, polydisperse message, but it is clearly distinct from MUC2 as it is located on chromosome 7. Both the MUC2 and MUC3 mucins are expressed in colonic tumors; however, the level of their expression is quite variable. Thus, at least two mucins are expressed by the human gastrointestinal tract. Elucidation of the regulation of these two genes will be important in understanding the physiology and pathophysiology of the human intestine.

Amino Acid Sequence↗