Gastroesophageal reflux in asthmatic patients: an incidence study and clinical correlation

The prevalence of gastroesophageal reflux (GER) in asthmatic patients is elevated, but the exact frequency remains unknown. The relationship between GER and asthma has not been investigated in Mexico. The objective of this study is to know the frequency of GER in Mexican asthmatic patients and the possible relationship with the severity of asthma. Fifty patients with adult-onset asthma were studied. AII of them fulfill the diagnostic criteria of the National Institutes of Health, U.S. The evaluation included a symptoms questionnaire, spirometry, esophageal manometry, 24-h esophageal pH-recording, and an upper gastrointestinal endoscopy. Twenty-three patients had mild asthma (46%), 16 moderate (32%) and 11 had severe asthma (22%). Twenty-seven (54%) reported heartburn and regurgitation at least twice a week. The esophageal pH-recording showed pathologic GER in 37 subjects (74%) and endoscopic esophagitis was found in 7 cases (14%). The pH-recording showed pathologic GER in 13 patients with mild asthma (57%), in 13 with moderate asthma (81%) and in all patients with severe asthma (100%). The frequency of GER in Mexican asthmatic patients is high and increases proportionately with the severity of asthma. This factor must be considered in the integral evaluation of these patients.     

Identification of two homologous antigenic peptides derived from L1 HPV-16 and 18 proteins specific for the HLA-B*3901 allele

Summary.  In this work we present evidence that the homologous peptides IHSMNSTIL and IHSMNSSIL derived from L1 HPV-16 and 18 proteins respectively, and with high specificity for the allele HLA-B^*3901, according with an algorithm prediction program, induced T cell stimulation in patients with advanced cervical cancer positive for HPV-16 or 18 infection and for the HLA-B^*3901 allele. Interestingly, T lymphocytes derived from a patient with HPV-18 infection and stimulated with the peptide IHSMNSTIL were capable to kill a cervical cancer cell line named Rova, derived from the tumor of the same patient. In addition, the cytotoxic activity was strongly increased when this cell line was previously treated with hrIFN-γ. These results suggest that the CTL immune response to L1 HPV-16 and 18 protein derived epitopes is maintained in patients with advanced cervical cancer within specific alleles, and opens the possibility that homologous epitopes may be used in the generation of prophylactic vaccines for cervical tumors bearing different HPV-types. Received March 4, 2002; accepted May 20, 2002     

Phase I clinical evaluation of a neutralizing monoclonal antibody against epidermal growth factor receptor in advanced brain tumor patients: preliminary study

High levels of growth factors and their receptors have been demonstrated in human tumors. Gliomas and meningiomas are characterized by overexpression of epidermal growth factor receptor (EGF-R). Ior egf/r3, is a neutralizing murine monoclonal antibody (MAb) against EGF-R, and was generated at the Cuban Institute of Oncology. The antibody recognizes EGF-R with high affinity, inhibiting tyrosine kinase activation. A clinical trial was conducted in brain tumor patients to evaluate toxicity, immunogenicity, and clinical benefit of escalating doses of the antibody. Nine patients with histologically confirmed gliomas or meningiomas, who had active or recurrent disease after receiving conventional treatment, received four intravenous doses of ior egf/r3. Total dosages ranged from 160 to 480 mg. As inclusion criteria, radioimmunoscintigraphy with the same MAb labeled with 99mTechnetium (99mTc) was performed. Immune response against the murine antibody was also evaluated. After four doses of ior egf/r3 MAb, no significant toxicity was found, except in one patient who developed a grade 4 allergic adverse event. This reaction was probably related with previous sensitization to the same MAb and the development of human anti-mouse antibodies (HAMA) response. Despite no major objective antitumor responses, eight patients had stable disease on the 6-month evaluation, and two patients remain alive after four years of MAb therapy.     

Two new mutations and three novel polymorphisms in the<Emphasis Type="Italic"> RB1</Emphasis> gene in Ecuadorian patients

RB1 is the gene responsible for retinoblastoma, the most common malignant intraocular tumor of infancy and early childhood. There are no reports about this gene in Ecuadorian populations, and only a few studies have been published in Latin America about this subject. There is a spectrum of more than 370 mutations described in the RB1 gene mutation database (http://www.d-lohmann.de/Rb/mutations.html), and alterations have been found in 25 of the 27 exons. During the exon-by-exon analysis of 31 tumor and blood samples from Ecuadorian patients, we found two new mutations and three novel polymorphisms. One of the polymorphisms is located in intron 26 where no alterations of the gene have been described previously. The polymorphisms were found in all of the patients tumor samples, but not in normal population, suggesting there might be a relationship between these polymorphisms and the development of retinoblastoma in the Ecuadorian population.The nucleotide sequence data reported are available in the GenBank database under the accession numbers: AY243567, AY260472, AY260473, AY273783     

Odor response properties of neighboring mitral/tufted cells in the rat olfactory bulb

Olfactory perception initiates in the nasal epithelium wherefrom olfactory receptor neurons--expressing the same receptor protein--project and converge in two different glomeruli within each olfactory bulb. Recent evidence suggests that glomeruli are isolated functional units, arranged in a chemotopic manner in the olfactory bulb. Exposure to odorants leads to the activation of specific populations of glomeruli. In rodents, about 25-50 mitral/tufted cells project their primary dendrites to a single glomerulus receiving similar sensory input. Yet, little is known about the properties of neighboring mitral/tufted cells connected to one or a few neighboring glomeruli. We used tetrodes to simultaneously record multiple single-unit activity in the mitral cell layer of anesthetized, freely breathing rats while exposed to mixtures of chemically related compounds. First, we characterized the odorant-induced modifications in firing rate of neighboring mitral/tufted cells and found that they do not share odorant response profiles. Individual units showed a long silent (11.01 ms) period with no oscillatory activity. Cross-correlation analysis between neighboring mitral/tufted cells revealed negligible synchronous activity among them. Finally, we show that respiratory-related temporal patterns are dissimilar among neighboring mitral/tufted cells and also that odorant stimulation results in an individual modification that is not necessarily shared by neighboring mitral/tufted cells. These results show that neighboring mitral/tufted cells frequently exhibit dissimilar response properties, which are not consistent with a precise chemotopic map at the mitral/tufted cell layer in the olfactory bulb.     

Effects of hormonal replacement with androgens and estrogens on male sexual behavior and plasma levels of these steroids in gonadectomized golden hamsters (Mesocricetus auratus)

Because the endocrine control of sexual behavior in male hamsters remains controversial, this study analyzed the influence of different androgens and estrogens in the regulation of masculine, sexual behavior (MBS). Aromatizable androgens: androstenedione (A) and testosterone (T), a non-aromatizable androgen: 5α-dihydrotestosterone (DHT), as well as estrogens (E₂ and E₁) alone or in combination with DHT, were administered in gonadectomized, sexually experienced males, for 3 weeks. In addition, plasma levels of these steroids were determined. Gonadectomy completely suppressed masculine sexual behavior (MSB) after 4 weeks. Both A and T replacements restored all the sexual behavior parameters in castrated hamsters by the 3rd week of treatment, with A being more potent in restoring all copulatory series and maintaining all MSB parameters, including long intromissions. Castrated males treated with DHT showed little interest in the female and did not display any copulatory behavior. Gonadectomized males treated with estrogens alone showed active anogenital investigation and displayed some mounts, but did not ejaculate. Males treated with estrogens combined with DHT had longer latencies and less number of ejaculations than males treated with aromatizable androgens. Long intromissions were observed only in males treated with T or A. Plasma levels of A were significantly higher than T levels in intact males. In males treated with A both androgens and estrogens were present in plasma. These results support the notion that aromatizable androgens, mainly A, but not non-aromatizable androgens or even estrogens in combination with DHT, play a relevant role in the endocrine regulation of MSB in the golden hamster.     

Phage-displayed mimotopes recognizing a biologically active anti-HIV-1 gp120 murine monoclonal antibody

Antibody-dependent cellular cytotoxicity (ADCC) is a host defense mechanism in which Fc receptor-bearing effector cells in combination with antigen-specific antibodies recognize and kill antigen-expressing target cells. The authors previously described a murine monoclonal antibody (MAb-ID6) that mediated ADCC activity against HIV-infected cells. It was demonstrated that the specificity of MAb-ID6 maps to the first 204 amino acids of gp120; however, the exact epitope was not identified. In the present work, by screening phage display libraries with MAb-ID6, the authors have mapped the corresponding epitope to amino acids 86-100 (HIV-1 gp120 sequence). This epitope lies within the C1 region of gp120 and is highly conserved among all subtypes and circulating recombinant forms of HIV-1. Thus, these phage mimotopes of C1 may serve as components of a vaccine for the induction of gp120-specific antibodies mimicking MAb-ID6.     

A TaqI polymorphism in the 3'UTR of the IL-12 p40 gene correlates with increased IL-12 secretion

Interleukin-12 (IL-12) is a key cytokine for the induction of Th1 immune responses. We evaluated whether a TaqI polymorphism in the 3'UTR of the IL-12 p40 gene affects secretion of IL-12 in vitro, and whether this polymorphism is associated with susceptibility to Crohn's disease (CD). IL-12 p40 and p70 secretion by monocytes in relation to genotype was determined in 63 healthy donors. Genotype and allele frequencies of the TaqI polymorphism in 150 CD patients were compared with 145 ethnically matched healthy controls (HC). No significant association was found between genotype and IL-12 p40 secretion after stimulation of monocytes with SAC+IFNgamma. In contrast, increasing IL-12 p70 secretion was found across the categories of non-carriers, heterozygotes and homozygotes for the variant allele (median values+/-SEM: 147+/-27, 282+/-51 and 482+/-34 pg/ml, respectively; P<0.005). The allele and genotype frequencies of this polymorphism in patients with CD did not differ statistically significantly from HC. The presence of a TaqI polymorphism in the IL12 p40 3'UTR correlates with increased in vitro IL-12 p70, but not p40 secretion. While this polymorphism does not appear to be correlated with susceptibility to CD in the limited population of patients tested here, it could influence the occurrence of the disease in certain subsets of patients.