Restoration of squamous mucosa after ablation of Barrett's esophageal epithelium

BACKGROUND: Antireflux therapy has generally failed to induce regression of Barrett's epithelium. It was hypothesized that squamous epithelium could be restored if the columnar tissue was ablated while gastric acid secretion was suppressed. METHODS: Ten white men with Barrett's esophagus received 40 mg of omeprazole daily. Thereafter, every 2-5 weeks they underwent videotaped endoscopies to argon laser photoablate columnar tissue, obtain biopsy specimens, and assess results. Squamous re-epithelialization was assessed by correlation of videotapes and directed biopsies. RESULTS: Patients had one to eight areas ablated, totaling 0.5-12.0 cm2. Videotape assessments were corroborated by biopsy in all but one instance. Thirty-eight of 40 treatment locations partially or completely re-epithelialized with squamous tissue. Squamous regrowth appeared to occur by spread from contiguous squamous borders and de novo from glandular tissue. Regrowth was influenced by the extent of squamous borders and completeness of ablations. Nonablated glandular tissue persisted beneath squamous epithelium. CONCLUSIONS: Ablation of Barrett's epithelium and suppression of acid secretion facilitated squamous re-epithelialization. A progenitor cell within the metaplastic tissue has the potential to differentiate normally.     

Penicilloyl peptides are recognized as T cell antigenic determinants in penicillin allergy

Although hapten immune responses have been intensively studied in the mouse, very little is known about hapten determinants involved in human allergic reactions. Penicillins, as chemically reactive compounds of low molecular weight, constitute typical examples of hapten allergens for humans. Penicillins become immunogenic only after covalent binding to carrier proteins and in this form frequently induced IgE-mediated allergic reactions in patients subjected to antibiotic treatment. However, our previous data strongly indicated that penicillins also form part of the epitopes contacting the antigen receptors of beta lactam-specific T cells in allergic individuals. We have therefore investigated the molecular constraints involved in the T cell immune response to penicillin G (Pen G). Designer peptides containing a DRB1*0401-binding motif and covalently modified with Pen G via a lysine epsilon-amino group were found to induce proliferation of Pen G-specific T cell clones. A precise positioning of the hapten molecule on the peptide backbone was required for optimal T cell recognition. Furthermore, we extended these observations from our designer peptides to show that a peptide sequence derived from a natural DRB1*1101-binding peptide modified in vitro with Pen G, also acquired antigenic properties. Our data for the first time provide insight into the manner in which allergenic haptens are recognized by human T cells involved in allergic reactions to drugs and suggest possible mechanisms leading to the onset of these adverse immune responses.     

Insulin-like growth factor I activates the invasion suppressor function of E-cadherin in MCF-7 human mammary carcinoma cells in vitro

The calcium-dependent cell-cell adhesion molecule E-cadherin has been shown to counteract invasion of epithelial neoplastic cells. Using three monoclonal antibodies, we have demonstrated the presence of E-cadherin at the surface of human MCF-7/6 mammary carcinoma cells by indirect immunofluorescence coupled to flow cytometry and by immunocytochemistry. Nevertheless, MCF-7/6 cells failed to aggregate in a medium containing 1.25 mM CaCl2, and they were invasive after confrontation with embryonic chick heart fragments in organ culture. Treatment of MCF-7/6 cells with 0.5 microgram ml-1 insulin-like growth factor I (IGF-I) led to homotypic aggregation within 5 to 10 min and inhibited invasion in vitro during at least 8 days. The effect of IGF-I on cellular aggregation was insensitive to cycloheximide. However, monoclonal antibodies that interfered with the function of either the IGF-I receptor (alpha IR3) or E-cadherin (HECD-1, MB2) blocked the effect of IGF-I on aggregation. The effects of IGF-I on aggregation and on invasion could be mimicked by 1 microgram ml-1 insulin, but not by 0.5 microgram ml-1 IGF-II. The insulin effects were presumably not mediated by the IGF-I receptor, since they could not be blocked by an antibody against this receptor (alpha IR3). Our results indicate that IGF-I activates the invasion suppressor role of E-cadherin in MCF-7/6 cells.     

CMV infection and cytomegalovirus disease in immunodepressed patients

An active entomologic survey was conducted by a team of trained health workers in a rural area endemic for Chagas' disease in central Brazil. They used pyrethrum as a flushing agent and 4,232 houses were inspected for triatomine bugs both inside and in the immediate environs. Houses with Triatoma infestans or evidence of an established colony were identified and defined as infested houses (cases). The building and environmental characteristics of 161 randomly selected infested houses were compared with 161 matched, noninfested houses (controls) that were the shortest distance from the infested house. Domestic and peridomestic potential risk factors associated with house infestation by Triatoma infestans were assessed by logistic regression analysis. Incomplete house construction (odds ratio [OR] = 2.5, 95% confidence interval [CI] = 1.5-4.1) was confirmed as a risk factor related to the presence or evidence of Triatoma infestans in the dwellings. The study also disclosed a statistically significant association between the presence of rats (OR = 1.6, 95% CI = 1.1-2.6) and indoor crop storage (OR = 2.3, 95% CI = 1.1-5.2) and house infestation. Further experimental field studies using tagged rodents should be conducted to assess their epidemiologic role in the domestic chain of Trypanosoma cruzi transmission.     

Poly-(L-lactic) acid membranes in palatal surgery in beagle dogs: clinical and histologic evaluation

This article reports on the histologic findings from a larger study that was designed to investigate whether the attachment of scar tissue to underlying bone, which is normally found after palatal surgery, can be prevented by using biodegradable poly-(L-lactic) acid membranes. Von Langenbeck's procedure was simulated in 12-week-old beagle dogs without clefts. In one group normal wound healing was allowed. In two groups, membranes were inserted immediately after surgery or 3 weeks thereafter. Sham and control groups were also included. Histologic evaluation was carried out at regular intervals. Reports have been published on other aspects, such as clinical wound healing, contraction and maxillary arch development in beagle dogs following this treatment. After direct implantation of membranes, wound healing was retarded. Disintegration of the membranes started soon after implantation and remaining particles were surrounded by a fibroblastic sheath and a fibrous capsule. At sites where membrane particles persisted, attachment of the scar tissue to the underlying bone by Sharpey's fibers was prevented.