Biomedical subjects

J Li

Publications and source records attributed to J Li.

At least 19 recordsLinked to original sources

PubMed1992

The removal of the type-2 copper from Rhus vernicifera laccase.

We have studied the removal of the type-2 copper from tree laccase (Rhus vernicifera) by treatment with EDTA at pH 5.2 in the presence of a redox buffer containing ferri- and ferrocyanide. The efficiency with which the copper is removed depends on the Fe(CN) 6(4-)/Fe(CN) 6(3-) ratio. We have varied this ratio from approx. 2:1 to about 50:1 and the best results were obtained with the highest ratio, i.e., the most cathodic solution potential. Nevertheless, the presence of Fe(CN) 6(3-) is required for the procedure to be effective. Although we cannot exclude the possibility that a mixed-valence form of laccase is the reactive species, we believe the results are better explained by a model which assumes that the removal of the type-2 copper depends upon an ordered sequence of oxidation-reduction reactions. Specifically, we propose that the copper is released as the monovalent ion from previously reduced laccase and then reoxidized in solution and sequestered with EDTA. The reoxidation step drives the reaction because recombination with the protein is inhibited when copper is in the divalent form. In testing this model, we have also shown that the type-2 copper can be removed under strictly reducing conditions when 4,4'-dicarboxy-2,2'-biquinoline (BCA) is present to complex the copper(I) ion. Although the BCA method is effective, the reaction takes longer, perhaps because of the limited solubility of BCA at the pH values of interest. Finally, we have found that the best results are obtained with either method when a cyanometalate ion such as Fe(CN) 6(3-) or Co(CN) 6(3-) is present in the medium. The exact role of this factor has yet to be established, but there is no indication that free cyanide has a role in the process. The most likely interpretation is that some type of binding interaction with the protein facilitates copper release.

Buffers↗

PubMed1992

Efficient transfer and sustained high expression of the human glucocerebrosidase gene in mice and their functional macrophages following transplantation of bone marrow transduced by a retroviral vector.

A recombinant retroviral vector (MFG-GC) was used to study the efficiency of transduction of the human gene encoding glucocerebrosidase (GC; D-glucosyl-N-acylsphingosine glucohydrolase, EC 3.2.1.45), in mouse hematopoietic stem cells and expression in their progeny. Transfer of the GC gene to CFU-S (spleen cell colony-forming units) in primary and secondary recipients was virtually 100%. In mice 4-7 months after transplantation, highly efficient transfer of the human gene to bone marrow cells capable of long-term reconstitution was confirmed by detection of one or two copies per mouse genome in hematopoietic tissues and in cultures of pure macrophages. Expression of the human gene exceeded endogenous activity by several fold in primary and secondary CFU-S, tissues from long-term reconstituted mice, and explanted macrophages cultures. These studies are evidence of the feasibility of efficient transfer of the GC gene to hematopoietic stem cells and expression in their progeny for many months after reconstitution. The results of this study strengthen the rationale for gene therapy as a treatment for Gaucher disease.

Animals↗

PubMed1992

Retinal and retinol promote membrane fusion.

Disk membranes from the bovine retinal rod outer segments (ROS) were found to fuse with vesicles made of lipids extracted from unbleached ROS disk membranes, using a lipid mixing assay for membrane fusion (relief of self-quenching of R18, octadecylrhodamine B chloride). If the retinal chromophore of rhodopsin was reductively linked to opsin before lipid extraction, the vesicles made of the extracted lipids were not suitable targets for fusion of the disk membranes. The addition of retinal and retinol to these vesicles restored their ability to fuse. Therefore, the presence of all-trans retinal was implicated in promoting membrane fusion in this system. To test this possibility, the ability of retinal and retinol to influence the phase behavior and the fusion capability of large unilamellar vesicles (LUV) of N-methyl dioleoylphosphatidylethanolamine (N-methyl-DOPE) was examined. Both retinal and retinol stimulated the fusion of vesicles of N-methyl-DOPE (contents mixing with ANTS, 1-aminonaphthalene-3,6,8-trisulfonic acid; DPX, p-xylylene bis(pyridinium bromide)). Both compounds reduced the onset temperature for isotropic resonances in the 31P-NMR spectra of N-methyl-DOPE dispersions and the onset temperature, TH, for formation of hexagonal II phase. These results were consistent with previous studies in which the onset temperature for the 31P-NMR isotropic resonances were correlated with stimulation of membrane fusion. These data suggested that both retinal and retinol may stimulate membrane fusion by destabilizing the bilayers of membranes.

Animals↗

PubMed1992

A reactive nucleophile proximal to vicinal thiols is an evolutionarily conserved feature in the mechanism of Arg aminoacyl-tRNA protein transferase.

Aminoacyl-tRNA protein transferases post-translationally aminoacylate protein N-termini. At least in part, these enzymes function to allow a subset of cellular proteins to be targeted for protein degradation. A eukaryotic enzyme of this class, Arg aminoacyl-tRNA protein transferase, arginylates N-terminal Glu or Asp residues of proteins, allowing such proteins to be recognized by a specific ubiquitin-protein ligase. We showed previously that inorganic arsenite, a reagent expected to bind specifically to protein vicinal thiol groups, inhibited Arg aminoacyl-tRNA transferase activity in rabbit reticulocyte lysate (N. S. Klemperer and C. M. Pickart, 1989, J. Biol. Chem. 264, 19245-19252). We now report that a bifunctional arsenoxide reagent, p-[(bromoacetyl)-amino]phenylarsenoxide, is a potent and irreversible inactivator of the same enzyme (K0.5 = 11.5 microM). Bromoacetyl aniline, which lacks the arsenoxide moiety, has no effect. These results show that the transferase has a reactive nucleophile proximal to the site which binds arsenoxides. The related monofunctional arsenoxide reagent, p-aminophenylarsenoxide, is a reversible inhibitor whose potency (K0.5 = 7.7 microM) is 20-fold greater than that of inorganic arsenite. As expected for a mechanism in which p-aminophenylarsenoxide binds to vicinal thiol groups: (i) pretreatment of reticulocyte lysate with a thiol-blocking reagent prevents binding of the transferase to a phenylarsenoxide-Sepharose column; and (ii) inhibition by p-aminophenylarsenoxide is reversed by a competing chemical dithiol, but not by a monothiol reagent. Like the rabbit enzyme, Arg aminoacyl-tRNA protein transferase from the yeast Saccharomyces cerevisiae (expressed in Escherichia coli) is reversibly inhibited by the monofunctional phenylarsenoxide and irreversibly inactivated by the bifunctional phenylarsenoxide (but not by bromoacetylaniline). Thus, a reactive nucleophile proximal to vicinal thiol groups is a conserved feature of the activity of the transferase. We speculate that these groups are catalytic elements in the transferase active site.

Acyltransferases↗

PubMed1992

Identification of immunogenic human melanoma antigens in a polyvalent melanoma vaccine.

An essential element in the development of effective vaccines against human malignant melanoma is the identification of antigens which are relevant for vaccine construction as evidenced by their ability to stimulate antimelanoma immune responses in humans. In this study, we identified immunogenic melanoma antigens using as probes antibodies induced in patients immunized with a vaccine which contains a broad range of potential immunogens. By immunoprecipitation/sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of detergent lysates of radioiodinated melanoma cells, we found that 17 (65%) of 26 patients sequentially immunized with a polyvalent melanoma antigen vaccine developed antibodies to one or more melanoma cell surface antigens with approximate molecular weights of 38,000-43,000, 75,000, 110,000, 150,000, and 210,000. The immunodominant antigens which most frequently stimulated antibody responses were the M(r) 110,000 antigen followed by the M(r) 210,000 and 38,000-43,000 antigens, which induced antibody responses in 62%, 27%, and 19% of patients, respectively. These three antigens were commonly expressed on different melanomas but rarely on nonmelanoma cells and are unrelated to class I or II human leukocyte antigens or to the previously described p97 or M(r) 240,000 proteoglycan melanoma-associated antigens. Thus, these three antigens are attractive candidates for the construction of melanoma vaccines, because they are immunogenic in humans and are preferentially expressed on melanomas.

Antibodies, Neoplasm↗

PubMed1992

Host factor requirements for processive antitermination of transcription and suppression of pausing by the N protein of bacteriophage lambda.

The N protein of phage lambda prevents termination of transcription by Escherichia coli RNA polymerase at Rho-dependent and -independent terminators in the lambda early operons. The modification of RNA polymerase by N requires an N-utilization (nut) site, present in each lambda early operon, and involves the E. coli factors NusA, NusB, NusG, and ribosomal protein S10. We show that, in the presence of NusA, N inhibits pausing by RNA polymerase and Rho-dependent termination in vitro at three sites in the lambda terminator tR1 which are located less than 100 base pairs downstream from nutR. NusA is also sufficient for partial antitermination at sites located farther downstream from nutL and nutR if there is a high concentration of N in the reaction. At low concentrations of N, the additional factors NusB, S10, and NusG are essential for antitermination at distal sites. In these conditions, the presence of NusA, NusB, S10, and NusG in the reaction enables N-modified RNA polymerase to elongate efficiently and processively through Rho-dependent and -independent terminators over distances as great as 7 kilobases downstream from the lambda nut sites. This substantial processivity of antitermination in vitro also occurs in vivo and probably reflects the stable association of N, NusA, NusB, S10, and NusG with RNA polymerase and nut site RNA in elongation complexes transcribing the lambda chromosome.

Bacterial Proteins↗

PubMed1992

Suppression of nociceptive responses in parafascicular neurons by stimulation of substantia nigra: an analysis of related inhibitory pathways.

A total of 166 neurons in parafascicular nucleus (PF) were studied, 85 from intact animals, 72 following dorsal spinal cord transection (D.Sp.C.X.), and 9 following complete transection of the spinal cord. Two patterns of nociceptive responses were identified following noxious stimulation and these responses were classified as 'nociceptive-on' and 'nociceptive-off' neurons, respectively. The effects of stimulating the substantia nigra (SNS) on the spontaneous and on the nociceptive evoked discharges were observed and compared in intact, D.Sp.C.X. and completely transected spinal cord rats. The results show that SNS significantly suppresses both the spontaneous and the nociceptive evoked discharges elicited by peroneal nerve stimulation. With an intact spinal cord, SNS suppressed both the spontaneous [-37 +/- 3.2% (P less than 0.05)] and the nociceptive evoked discharges [-52.8 +/- 2.8% (P less than 0.01)] of the 'nociceptive-on' cells respectively, while in the 'nociceptive-off' cells the same stimulation elicited an even more prominent suppression upon both discharges (-47.7 +/- 5.4%, P less than 0.01 and -64.9 +/- 5.0%, P less than 0.01), respectively. After D.Sp.C.X., the suppressive effects on the 'nociceptive-on' cells following SNS were diminished (-28.1 +/- 3.5% and -36.9 +/- 2.6%, respectively) but not abolished, while in the 'nociceptive-off' cells, the inhibitory effects on SNS were unchanged. In addition, the suppressive effects of SNS on the spontaneous activity of PF neurons in cases with completely cut spinal cords remains unchanged. These results suggest that SNS modulates the spontaneous and the noxious evoked responses of the PF neurons by way of supraspinal connections besides the previously described descending projecting pathways.

Action Potentials↗

PubMed1992

MacMARCKS, a novel member of the MARCKS family of protein kinase C substrates.

MARCKS is a specific protein kinase C (PKC) substrate that binds both calmodulin and actin and is phosphorylated during phagocyte activation, neurosecretion, and growth factor-dependent mitogenesis. We report here on MacMARCKS, a MARCKS homolog, whose synthesis is dramatically increased in macrophages when these cells are exposed to bacterial lipopolysaccharide. We have purified rabbit MacMARCKS and cloned its cDNA from rabbit and mouse. The effector domains of MacMARCKS and MARCKS are nearly identical, and both proteins bind calmodulin in a phosphorylation-regulated manner. MacMARCKS and MARCKS also share a second, highly conserved region also found in the internalization domain of the mannose-6-phosphate receptor. Our data suggest the existence of a family of PKC substrates that are targeted to different subcellular locations and that function to integrate PKC and calcium/calmodulin-dependent signals in the control of the plastic actin cytoskeleton.

Actins↗

PubMed1992

Long-term cardiac prognosis following noncardiac surgery. The Study of Perioperative Ischemia Research Group.

OBJECTIVE: To determine the long-term (2-year) cardiac prognosis of high-risk patients undergoing noncardiac surgery and to determine the predictors of long-term adverse cardiac outcome. DESIGN: Prospective cohort study. Historical, clinical, and laboratory data were collected during the in-hospital period, and at 6 months, 1 year, and 2 years following surgery. Data were analyzed using proportional hazards models. SETTING: University-affiliated Veterans Affairs medical center. POPULATION: A consecutive sample of 444 patients with or at high risk for coronary artery disease who had undergone elective noncardiac surgery and were discharged from the hospital in stable condition. MAIN OUTCOME MEASURES: Cardiac death, myocardial infarction, unstable angina, progressive angina requiring coronary artery bypass graft surgery or coronary angioplasty, and new unstable angina requiring hospitalization. RESULTS: Forty-seven patients (11%) had major cardiovascular complications during a 728-day (median) follow-up period: 24 had cardiac death; 11, nonfatal myocardial infarction; six, progressive angina requiring coronary artery bypass graft surgery or coronary angioplasty; and six, new unstable angina requiring hospitalization. Thirty percent of outcomes occurred within 6 months of surgery and 64% within 1 year. Five independent predictors of long-term outcome were identified. Three predictors reflected the preexisting chronic disease state: (1) the presence of known vascular disease (hazard ratio, 6.1; 95% confidence interval [CI], 2.5 to 15.0; P less than .0001); (2) a history of congestive heart failure (hazard ratio, 5.0; 95% CI, 2.0 to 12.0; P less than .0005); and (3) known coronary artery disease (hazard ratio, 3.7; 95% CI, 1.7 to 8.0; P less than .0007). Two predictors reflected acute postoperative ischemic events: (1) myocardial infarction/unstable angina (hazard ratio, 20; 95% CI, 7.5 to 53.0; P less than .0001) and (2) myocardial ischemia (hazard ratio, 2.2; 95% CI, 1.1 to 4.3; P less than .03). Patients surviving a postoperative in-hospital myocardial infarction had a 28-fold increase in the rate of subsequent cardiac complications within 6 months following surgery, a 15-fold increase within 1 year, and a 14-fold increase within 2 years (95% CI, 5.8 to 32; P less than .00001). Seventy percent of all long-term adverse outcomes were preceded by in-hospital postoperative ischemia that occurred at least 30 days (median, 282 days) before the long-term event. The development of congestive heart failure or ventricular tachycardia (without ischemia) during hospitalization was not associated with adverse long-term outcome. CONCLUSIONS: The incidence of long-term adverse cardiac outcomes following noncardiac surgery is substantial. At increased risk are patients with chronic cardiovascular disease; at highest risk are patients with acute perioperative ischemic events. We conclude that survivors of in-hospital perioperative ischemic events, specifically myocardial infarction, unstable angina, and postoperative ischemia, warrant more aggressive long-term follow-up and treatment than is currently practiced.

Acute Disease↗

PubMed1992

In-hospital and long-term mortality in male veterans following noncardiac surgery. The Study of Perioperative Ischemia Research Group.

OBJECTIVES: To determine the causes of and risk factors for mortality following noncardiac surgery. DESIGN: Prospective cohort study. SETTING: A university-affiliated Veterans Affairs medical center. PATIENTS: Consecutive series of 474 men between the ages of 38 and 89 years (mean age, 68 years) who were undergoing major noncardiac surgery involving general anesthesia. All subjects had known coronary artery disease or were at high risk for coronary artery disease. MEASUREMENTS AND RESULTS: During the initial hospitalization, 26 patients (5%) died, most commonly from sepsis (n = 6) or cardiac diseases (n = 6). Deaths occurred from postoperative days 2 to 69; half occurred more than 3 weeks after surgery. Multivariable analysis disclosed that a history of hypertension (odds ratio [OR] = 3.8; 95% confidence interval [CI], 1.1 to 13), a severely limited activity level (OR = 9.7; 95% CI, 2.5 to 37), and a creatinine clearance of less than 0.83 mL/s (OR = 6.8; 95% CI, 2.8 to 16) were all independently associated with an increased risk of postoperative mortality. The mortality rate in patients with two or more of these risk factors was 20%, nearly eight times higher (95% CI, 3.6 to 16) than those with one or no risk factors. An additional 82 patients died within the next 2 years; cancer, renal dysfunction, congestive heart failure, and obstructive pulmonary disease were independently associated with long-term mortality. CONCLUSIONS: Even in patients at high risk of cardiac complications following surgery, noncardiac causes of death are more common. Patients with a history of hypertension, severely limited activity, and reduced renal function appear to be at especially high risk of in-hospital mortality after noncardiac surgery.

Adult↗

PubMed1992

Adsorption behavior of milk proteins on polystyrene latex. A study based on sedimentation field-flow fractionation and dynamic light scattering.

Sedimentation field-flow fractionation (SdFFF) has been used to characterize the adsorption of the proteins beta-casein (BCN) or beta-lactoglobulin (BLG) on colloidal polystyrene latices; this system was used to model hydrophobic interactions between the proteins and the surfaces of fat droplets in protein-stabilized emulsions. It was found that the SdFFF technique could determine directly the surface concentrations of BCN and BLG irreversibly adsorbed to the latex surface, provided care was taken to maintain the ionic strength of the carrier at a level which suppressed particle-wall repulsion in the separation channel. The measured surface concentrations were similar for the two proteins (about 1 mg/m2), and this was verified by quantitative amino acid analysis. These concentrations were smaller than those found in depletion studies (3 and 4 mg/m2 respectively for BCN and BLG), in which loosely associated protein may have been included in the determinations. The thickness of the adsorbed layers was determined in situ by dynamic light scattering and was found to differ significantly for the two proteins (up to 15 nm for BCN vs. 2-3 nm for BLG). The implication of these findings in terms of different surface arrangements of the two proteins is discussed.

Calorimetry↗

PubMed1992

Recombinant human stem cell factor stimulates growth of a human glioblastoma cell line expressing c-kit protooncogene.

The growth of a panel of eight different human glioblastoma cell lines was examined in a human tumor cloning assay in agar, a tritiated thymidine uptake assay, and by counting cell numbers, in cultures performed in the absence or presence of increasing concentrations (1 to 100 ng/ml) of recombinant human stem cell factor (SCF). Growth of 7 of 8 cell lines was not significantly and reproducibly affected by recombinant human SCF. However, growth of the CRL 1620 cell line could be stimulated up to 5-fold by the cytokine. In contrast to the other cell lines investigated, CRL 1620 expressed the c-kit protooncogene assessed on the mRNA and protein level. Furthermore, SCF-induced proliferation of CRL 1620 cells was sensitive to the tyrosine kinase inhibitor erbstatin. Our data suggest that SCF can be operative in growth modulation of malignant cells outside the hematopoietic system, and this finding should be further studied for its possible clinical implications.

Cell Division↗

PubMed1992

NusG, a new Escherichia coli elongation factor involved in transcriptional antitermination by the N protein of phage lambda.

We have reconstituted biologically relevant transcriptional antitermination in vitro by the phage lambda N protein. This required the isolation of NusG, a newly identified Escherichia coli transcription elongation factor. NusG is encoded by an E. coli gene, formerly called U and now called nusG, in which a mutation affects antitermination by N in vivo. Efficient antitermination by N in our reconstituted system depends on the bacterial proteins NusG, NusA, NusB, and ribosomal protein S10 (which functions without ribosomes in transcriptional antitermination). In reactions containing E. coli S100 extract, NusG is stoichiometrically bound to lambda N-modified transcription elongation complexes. We used RNA polymerase affinity chromatography to show that NusG binds to the core component of E. coli RNA polymerase. This binding is weak, and the stable association of NusG with lambda elongation complexes additionally requires at least N, NusA, and the boxA component of an N utilization site. In reactions containing bacterial S100 extract, NusG and NusB are also present in elongation complexes transcribing E. coli boxA-containing rDNA.

Amino Acid Sequence↗

PubMed1992

A cDNA encoding RAP74, a general initiation factor for transcription by RNA polymerase II.

RAP30/74 (also known as TFIIF, beta gamma and FC is one of several general factors required for initiation by RNA polymerase II. The small RAP30 subunit of RAP30/74 binds directly to polymerase and appears structurally and functionally homologous to bacterial sigma factors in their RNA polymerase-binding region. RAP30/74 or recombinant RAP30 suppresses nonspecific binding of RNA polymerase II to DNA and is required for RNA polymerase II to assemble stably into a preinitiation complex containing promoter DNA and the general factors TFIID, TFIIA and TFIIB; both RAP30 and RAP74 are physical components of the preinitiation complex. A complementary DNA encoding human RAP30 has been isolated, and here we report the isolation of a cDNA encoding human RAP74. RAP30 and RAP74 produced in Escherichia coli can be used in place of natural human RAP30/74 to direct accurate transcription initiation by RNA polymerase II in vitro.

Amino Acid Sequence↗

PubMed1992

Direct interaction between two Escherichia coli transcription antitermination factors, NusB and ribosomal protein S10.

The Escherichia coli proteins NusB and ribosomal protein S10 are important for transcription antitermination by the bacteriophage lambda N protein. We have used sucrose gradient co-sedimentation and affinity chromatography with immobilized ribosomal protein S10, a glutathione S-transferase-S10 fusion protein, and NusB to show that NusB binds directly and very selectively to S10. The interaction is non-ionic and has an estimated Kd value of 10(-7) M. We hypothesize that NusB binds to N-modified transcription complexes primarily by interacting with S10.

Bacterial Proteins↗

PubMed1992

Percutaneous transluminal coronary angioplasty in a patient with paroxysmal nocturnal hemoglobinuria.

Paroxysmal nocturnal hemoglobinuria (PHN) is an acquired chronic hemolytic anemia associated with an unusual susceptibility to hemolytic crisis, infection, and venous thrombosis which would be aggravated by a number of factors including surgery. We report a case of PHN undergoing percutaneous transluminal coronary angioplasty and discuss the corresponding perioperative management.

Adult↗

PubMed1992

Polyunsaturated lecithin prevents acetaldehyde-mediated hepatic collagen accumulation by stimulating collagenase activity in cultured lipocytes.

We recently found that polyunsaturated lecithin prevents ethanol from causing cirrhosis in the baboon. Because transformation of lipocytes to transitional cells plays a key role in hepatic fibrogenesis in vivo, and because this process in alcohol-fed baboons was found to be attenuated by polyunsaturated lecithin, we focused on lipocytes to study the mechanism of the protective effect. Rat lipocytes cultured on plastic undergo spontaneous activation, accompanied by expression of alpha-smooth muscle actin isoform and production of substantial amounts of type I collagen. The latter was further increased on incubation with acetaldehyde. This in vitro model was used here to study how acetaldehyde-mediated collagen production and accumulation can be turned off. Addition of polyunsaturated lecithin (10 mumols/L) was found to prevent the acetaldehyde-induced increase in collagen accumulation by 83% (p less than 0.001). By contrast, a saturated phospholipid (10 mumols/L dilauroyl phosphatidylcholine), a monounsaturated one (10 mumols/L linoleoyl-palmitoyl phosphatidylcholine) or linoleic acid (20 mumols/L bound to albumin) had no such effect. Incorporation of [3H]proline into collagen and the expression of alpha-1 (I) procollagen mRNA were increased by acetaldehyde; the latter was not significantly affected by polyunsaturated lecithin. Polyunsaturated lecithin increased lipocyte collagenase activity by 100% (p less than 0.001), whereas dilauroyl phosphatidylcholine, linoleoyl-palmitoyl phosphatidylcholine and linoleic acid had no such action. We concluded that (a) polyunsaturated lecithin selectively prevents the acetaldehyde-induced increase in collagen accumulation in lipocyte cultures, whereas other phospholipids or linoleate have no such effect; and (b) polyunsaturated lecithin does not modify the acetaldehyde-mediated increase in alpha-1 (I) procollagen mRNA, but it increases collagenase activity, suggesting that the protective effect exerted by polyunsaturated lecithin against alcohol induced fibrosis in vivo is due at least in part to stimulation of collagenase activity, which may prevent excess collagen accumulation by offsetting increased collagen production.

Acetaldehyde↗

PubMed1992

Precancerous lesions of the human esophagus: multiparametric study of esophageal biopsies from a high-risk population in Linxian, China.

Histopathology, morphometry, tritiated thymidine incorporation and immunohistochemistry were studied in 221 esophageal biopsies from subjects with cytologica hyperplasia in Linxian, China. A spectrum of 7 morphologic entities were found: (1) normal/near normal (NN); (2) basal cell hyperplasia 0 (BHO); (3) simple hyperplasia (SH); (4) mixed basal and spinous cell hyperplasia (MBS); (5) basal cell hyperplasia 1 (BH1); (6) dysplasia (D); and (7) non-proliferative lesion (NP). Forty percent of the biopsies had combinations of histologic types. The thickness of the epithelium was increased in SH, MBS, and BH1, but not in BHO and NP. Elongation of papillae was frequently seen in SH, MBS, BH1, and D. Papillary bleeding was very prevalent in the esophageal specimens studied. A variety of cellular changes were found in peripapillary areas especially when bleeding occurred. [3H]-thymidine labeling index was dramatically increased in the entire epithelium in dysplasia, and also increased in cell layer 3 of MBS, BH1 and D. Blood group antigen LeY and lectin WGA showed consistent positivity in cellular membranes of the squamous cells, and these changes occurred before gross morphologic alterations. These findings provide a hypothesis for the sequence of pathogenetic events leading to esophageal carcinoma, and define each step with corresponding biomarkers for cancer prevention studies.

Biopsy↗