Endoscopic follow-up and management of Barrett's esophagus in relation to its preneoplastic potential.

Barrett's esophagus is an acquired clinical condition in which the squamous epithelium of the distal esophagus is replaced by a columnar epithelium. The diagnosis requires histological confirmation of specialized intestinal metaplasia, in which goblet cells must be present. Barrett's esophagus is a risk factor for the development of esophageal adenocarcinoma, a tumor with an incidence and mortality have increased alarmingly in recent years in the western world. It has been estimated that the annual incidence of cancer in patients with Barrett's esophagus has increased from 0.2-2%. Once diagnosed, Barrett's esophagus is estimated to have an annual neoplastic transformation rate of 0.5% per patient. The highlights of the endoscopic diagnosis and treatment are reviewed here, as well as the screening and monitoring of this process.

Anti-idiotype antibodies in cancer treatment.

As a cancer immunotherapy tool, idiotypes (Ids) have been used in different ways over the last three decades, depending on the actual human tumor cell target. It all started with passive, monoclonal, anti-Id antibody treatment of B-cell lymphoma, a setting in which results were tantalizing, but logistics unsustainable. It then moved toward the development of anti-Id vaccines for the treatment of the same tumors, a setting in which we have recently provided the first formal proof of principle of clinical benefit associated with the use of a human cancer vaccine. Meanwhile, it also expanded in the direction of exploiting the antigenic mimicry of some Ids with Id-unrelated, tumor-associated antigens for the immunotherapy of a number of solid tumors, a setting in which clinical results are still far from being consolidated. All in all, over the years Id-based immunotherapy has paved the way for a number of seminal therapeutic improvements for cancer patients, including the development of most if not all Id-unrelated monoclonal antibodies that have recently revolutionized the field.

The polymorphisms -318C>T in the promoter and 49A>G in exon 1 of CTLA4 and the risk of aplastic anemia in a Caucasian population.

Aplastic anemia (AA) is a rare disease with a major autoimmune pathogenetic component. CTLA4 is a T-lymphocyte surface molecule involved in the maintenance of immune tolerance. Some polymorphisms associated with a reduced expression of CTLA4, and thus presumably with increased tendency to autoimmunity, have been associated with various autoimmune diseases. In this study, we evaluated the distribution of the low expression polymorphisms -318C > T and 49A > G of CTLA4 in a population of 67 patients with acquired AA and in 100 normal controls. There was no difference in the distribution of the tested polymorphism between patients and controls and, within the patient group, between those who responded to immunosuppression vs those who did not respond. This study indicates that the polymorphisms -318C > T and 49A > G of CTLA4 do not affect the risk of developing AA and do not influence the response to immunosuppression.

Thrombopenic purpura induced by a monoclonal antibody directed to a 35-kilodalton surface protein (p35) expressed on murine platelets and endothelial cells.

OBJECTIVE: With the aim of obtaining monoclonal antibodies (mAbs) against mouse endothelial surface antigens, immunization of rats with a mouse-derived endothelial cell line (PY4.1) and subsequent hybridoma production were performed. MATERIALS AND METHODS: One of the mAbs produced by hybridoma EOL5F5 was selected for its surface binding to endothelial cell lines, and identification of the mAb-recognized antigen was performed by immunoprecipitation. Experiments were performed to analyze the effects of EOL5F5 on systemic administration to mice. RESULTS: EOL5F5-recognized antigen was a single band of 35 kDa under reducing and nonreducing conditions, features that do not match other known differentiation antigens with comparable tissue distribution. In vivo administration of purified EOL5F5 mAb to mice (n = 20) induced intense cutaneous purpura as well as severe but transient thrombocytopenia. Expression of EOL5F5-recognized antigen was detected on platelets from which it immunoprecipitated a moiety of identical electrophoretic pattern in SDS-PAGE, as the one recognized on endothelial cells. Immunohistochemically, EOL5F5-recognized antigen (p35) also was expressed on dermal capillaries, suggesting that, in addition to thrombocytopenia, damaging effects of the antibody on endothelial cells also might cause the observed purpura. CONCLUSIONS: Our results show induction of thrombocytopenic purpura in mice with an mAb against a single antigenic determinant expressed on both platelets and endothelium. EOL5F5 mAb injection sets the stage for useful experimental models that resemble immune thrombocytopenic purpura.

Cytokine gene transfer into dendritic cells for cancer treatment.

Bone marrow-derived dendritic cells have been used to treat established experimental tumors by unleashing a cellular immune response against tumor antigens. Such antigens are artificially loaded onto dendritic cells' antigen-presenting molecules by different techniques including incubation with synthetic antigenic determinants, tumor lysates or nucleic acids encoding for those relevant antigens. Ex vivo gene transfer with viral and non-viral vectors is frequently used to obtain expression of the tumor antigens and thereby to formulate the therapeutic vaccines. Efficacy of the approaches is greatly enhanced if dendritic cells are transfected with a number of genes which encode immunostimulating factors. In some cases, such as with IL-12, IL-7 and CD40L genes, injection inside experimental malignancies of thus transfected dendritic cells induces complete tumor regression in several models. In this case tumor antigens are captured by dendritic cells by still unclear mechanisms and transported to lymphoid organs where productive antigen presentation to T-cells takes place. Many clinical trials testing dendritic cell-based vaccines against cancer are in progress and partial clinical efficacy has been already proved. Transfection of genes further strengthening the immunogenicity of such strategies will join the clinical club soon.

Molecular detection of respiratory syncytial virus in postmortem lung tissue samples from Mexican children deceased with pneumonia.

BACKGROUND: Respiratory syncytial virus (RSV) is the major viral cause of severe respiratory infections in children younger than 2 years of age. Nevertheless there are not enough epidemiologic data about the role of RSV as a cause of infantile mortality from pneumonia, mainly in young children from developing countries Aim. To determine the frequency of RSV infection in lung tissue samples from Mexican children deceased with pneumonia, by reverse transcription (RT) and PCR. METHODS: Postmortem lung tissue samples from 98 children younger than 2 years of age who died of pneumonia during the period of 1989 to 1997 were studied. Paraffin was removed with xylene from 10-microm lung sections, the total RNA was extracted and complementary DNA was obtained by RT reaction. A nested PCR with the use of oligonucleotides specific for the F glycoprotein gene was developed. Samples negatives for RSV were tested for the absence of polymerase inhibitors and for complementary DNA integrity. RESULTS: Twenty-nine of the 98 (30%) children deceased with pneumonia were positive for RSV by RT-PCR; 8 were detected from 13 (62%) children with histopathologic diagnosis of viral pneumonia and 21 from 85 (25%) children with histopathologic diagnosis of bacterial pneumonia (P = 0.018). There was no significant difference in RSV infection according to age groups or seasonal pattern. CONCLUSIONS: RSV infection is frequent in Mexican children younger than 2 years of age who died of pneumonia. Although RSV was more common in viral pneumonia, mixed infections with RSV and bacterial pneumonia were also common.

Changes in the threshold of pentylenetetrazol-induced seizures in cats with a chronic granuloma in brain amygdala.

A parenchymal brain granuloma is the final consequence of a localized inflammatory reaction against an infectious agent, particularly parasites. In humans, these lesions are frequent causes of epilepsy. We studied the pattern of seizures induced by pentylenetetrazol (PTZ) in cats with a chronic granuloma induced 1 year earlier by injection of silicates into the brain amygdala. Compared with controls, the seizure threshold to myoclonic seizures was significantly decreased in cats with granuloma, while the threshold for tonic-clonic seizures was not altered. Thus, the difference in PTZ doses between the initial and final components of the seizure became significantly enlarged (P < 0.001). Our results indicate that a granulomatous lesion in amygdala facilitates the generation and propagation of myoclonic seizures, whereas other components of PTZ-induced seizures are not affected.

Infection of pregnant women with hepatitis B and C viruses and risks for vertical transmission.

Pregnant women infected with hepatitis B and C viruses pose a risk for infecting their newborn infants by vertical transmission. We studied 6,253 pregnant women aged 12-49 years for infection with hepatitis B (HBV) and C (HCV) viruses. Infection was diagnosed by measuring IgG antibodies against HBc, HBs, HBe, as well as IgM-HBc and HCV viral antigens with commercially available immunoassay kits. HBV infection was detected in 113 cases (1.8%), and prevalence was significantly higher (2.4%) in a group of women with a high-risk pregnancy who were attending a perinatology hospital than in healthy pregnant women (1.67%, p < 0.05). Infection with HBV was significantly higher in women older than 30 years old (p < 0.05). HBsAg was found in blood, colostrum and vaginal exudate of two pregnant women; HBsAg was detected in the gastric aspirate but not in the blood of the two newborn infants. HBeAg and IgM-HBc were not detected in any of the samples. DNA-HBV was detected in serum of seven women, and DNA-HBV was detected in the gastric aspirate of only one of the newborns. HCV infection was diagnosed in three out of 111 women with markers for HBV infection (2.7%), and in 6 out of 1,000 women without these markers (0.6%). Anti-HCV antibodies were found in the serum of six of their infants during up to six months of age. Infants were monitored for one year and none of them developed any sign of hepatic disease. These results suggest that special attention should be paid to women older than 30 years and with a high-risk pregnancy, as they are at a higher risk of HBV and HCV infections.

[Prevalence of rubella virus antibodies in pregnant women in two zones of Valle de Mexico]. / Prevalencia de anticuerpos para el virus de rubéola en mujeres gestantes de dos zonas del Valle de México.

The aim of this study was to determine the prevalence of specific antibodies against rubella virus in pregnant women from Iztapalapa and Nezahualcóyotl areas of the valley of Mexico, in order to evaluate susceptibility to this virus in these areas. Serum samples collected from 5535 women between 15 and 44 years old were studied by the hemaglutination inhibition test. 92.6% of positivity was obtained and no significant difference was observed between different age groups. The prevalence of rubella antibodies in pregnant women was 92.4% for Iztapalapa zone and 92.8% for Nezahualcóyotl. The titles of antibodies against rubella virus more frecuently presented were 1:16 (36.3%) and 1:32 (29.6%). The data obtained in this study suggest that women attending Medical Services of the Mexican Institute of Social Segurity in reproductive age from the Iztapalapa and Nezahualcóyotl areas, do not need massive vaccination against rubella virus.

[Active immunotherapy in the treatment of haematological neoplasias]. / Inmunoterapia activa en el tratamiento de neoplasias hematológicas.

The continuous search for therapeutic approaches that improve the conventional treatments of neoplasms, together with an improved understanding of the immune system, has led in recent years to the development of Immunotherapy. Basically, a distinction can be made between two forms of immunotherapy: passive immunotherapy, which consists in the transfer of antibodies or cells previously generated in vitro that are directed against the tumour, and active immunotherapy, which attempts to activate in vivo the immune system and induce it to elaborate a specific response against the tumor antibodies. Hematological neoplasms, specifically some B lymphomas, express in their membrane an immunoglobulin that is considered a specific antigen of the tumour, which is why these diseases have become the ideal target for immunotherapy treatments. There are many alternatives, ranging from protein vaccines, which have already shown clinical benefits, to those of the second generation, which make use of the new techniques of molecular biology to increase the efficacy of the vaccines and obtain their production in a quicker and less costly way, but with which there are not yet definitive clinical results.

[Hepatitis B and delta: the prevalence of seroepidemiological markers in volunteer blood donors and their families]. / Hepatitis B y delta: prevalencia de marcadores seroepidemiológicos en donadores de sangre voluntarios y su grupo familiar.

41 volunteer blood donors and his relatives were studied in order to know about the prevalence of hepatitis B and D virus infections in selected groups. Frequency of HBsAg+ carriers was 0.34 per cent in the Centro Nacional de la Transfusión Sanguínea and 0.15 per cent in the Banco Central de Sangre, IMSS. Most of the HBsAg+ blood donors were 21 to 40 years old (87.8%); 21.9 per cent had IgM antibodies against HBc and just 2.4 per cent were HBeAg positive. Forty one (26.9%) of 152 relatives had one or more of the HBV markers, 3.9 per cent were HBsAg carriers and 1.3 per cent were HBeAg positive. In the infected relatives group 36.6 per cent were ancestory or brothers and just 14.6 per cent of wives were infected. None of the HBsAg+ blood donors or his relatives had antibodies against delta agent. These results support the fact that the frequency of asymptomatic carriers of HBsAg in the volunteer blood donors group is similar to he frequency in the general population and identifies the group of relatives as those with the highest risk to acquire HBV infection.

[Past, present and future of anti-idiotype vaccination]. / Pasado, presente y futuro de la vacunación anti-idiotipo.

Cancer vaccines are conceived as therapeutic tools, in contrast to the prophylactic vaccines used to fight against infectious diseases. Among the most potent therapeutic vaccines, anti-idiotype vaccination is directed against the tumor idiotype, the only well-characterized tumor antigen displayed in neoplastic B-cells. Anti-idiotype vaccines have demonstrated clinical benefit against follicular lymphoma and are currently being evaluated in two different phase III clinical trials. Additional emerging strategies, which include the use of dendritic cells and the production of vaccines via molecular means will surely allow us to draw important conclusions concerning the treatment of cancer patients.

New targets in pediatric Acute Myeloid Leukemia.

In the last few years the improvements of chemotherapy regimens and supportive care has progressively ameliorated the prognosis of children suffering from Acute Myeloid Leukemia (AML). However, a still high percentage of children do not respond to first line treatments or relapse and need to undergo further treatments. The need to explore new agents other than chemotherapy has been highlighted in the last years in order to overcome drug related resistance and toxicity. Recently, novel therapies have been studied within early phases pediatric trials and seem to show encouraging results. In fact, the knowledge of molecular abnormalities related to AML pathogenesis has permitted to identify selective drugs that may represent an important tool for the development of patient-tailored treatments. Nowadays, FLT3, Aurora Kinases, mTORS's and proteasome inhibitors represents the most promising drugs that are being used in pediatric AML studies.

Chronic malnutrition caused by a corn-based diet lowers the threshold for pentylenetetrazol-induced seizures in rats.

The incidence of epilepsy is high in developing countries where malnutrition is prevalent. Although malnutrition is not a direct cause of seizures, chronic malnutrition may predispose the brain to seizures. In large undernourished human groups from Latin America, the most common sources of food are corn and corn derivatives. We used a rat model of chronic malnutrition, in which corn tortillas were the only solid food intake, to study the possible influence of malnutrition at late stages of brain development on the dynamics of experimental seizures induced by pentylenetetrazole (PTZ). The threshold and does of PTZ required to produce seizures were greatly reduced in malnourished rats. The model of malnutrition used in the study imitates a form of malnutrition common among large numbers of humans. Our results suggest that chronic malnutrition early in life induces changes that lower the seizure threshold and leave the brain more susceptible to seizures. Whether this observation relates to the high incidence of epilepsy in underdeveloped countries remains to be determined.

Colchicine, like methylprednisolone, decreases the perilesional fibrosis secondary to a chronic brain granuloma in cats.

We studied the effects of long-term administration of colchicine on the fibrosis surrounding a granulomatous lesion previously induced by stereotactic injection of aluminum silicate into the brain parenchyma of cats. Every week the animals received a single i.m. injection of colchicine (0.25 mg), or methylprednisolone (4 mg), or saline solution (controls) for 6 months. The mean area of fibrosis in animals treated with colchicine or with methylprednisolone was smaller than that of control animals (P < 0.05). In controls, a dense capsule of procollagen and collagen fibers was found around the granuloma, and myelinated neurites were scarce, whereas in animals treated with colchicine or with methylprednisolone the capsule and fibers were thinner and more myelinated neurites remained. These changes were more evident in animals treated with colchicine. Our results suggest that chronic administration of colchicine or methylprednisolone limit the fibrosis and histological damage around a granulomatous lesion of the brain.