Non-coding regions of nuclear-DNA-encoded mitochondrial genes and intergenic sequences are targeted by autoantibodies in breast cancer.

Autoantibodies against mitochondrial-derived antigens play a key role in chronic tissue inflammation in autoimmune disorders and cancers. Here, we identify autoreactive nuclear genomic DNA (nDNA)-encoded mitochondrial gene products (GAPDH, PKM2, GSTP1, SPATA5, MFF, TSPOAP1, PHB2, COA4, and HAGH) recognized by breast cancer (BC) patients' sera as nonself, supporting a direct relationship of mitochondrial autoimmunity to breast carcinogenesis. Autoreactivity of multiple nDNA-encoded mitochondrial gene products was mapped to protein-coding regions, 3' untranslated regions (UTRs), as well as introns. In addition, autoantibodies in BC sera targeted intergenic sequences that may be parts of long non-coding RNA (lncRNA) genes, including LINC02381 and other putative lncRNA neighbors of the protein-coding genes ERCC4, CXCL13, SOX3, PCDH1, EDDM3B, and GRB2. Increasing evidence indicates that lncRNAs play a key role in carcinogenesis. Consistent with this, our findings suggest that lncRNAs, as well as mRNAs of nDNA-encoded mitochondrial genes, mechanistically contribute to BC progression. This work supports a new paradigm of breast carcinogenesis based on a globally dysfunctional genome with altered function of multiple mitochondrial and non-mitochondrial oncogenic pathways caused by the effects of autoreactivity-induced dysregulation of multiple genes and their products. This autoimmunity-based model of carcinogenesis will open novel avenues for BC treatment.

Mitochondria Autoimmunity and MNRR1 in Breast Carcinogenesis: A Review.

We review here the evidence for participation of mitochondrial autoimmunity in BC inception and progression and propose a new paradigm that may challenge the prevailing thinking in oncogenesis by suggesting that mitochondrial autoimmunity is a major contributor to breast carcinogenesis and probably to the inception and progression of other solid tumors. It has been shown that MNRR1 mediated mitochondrial-nuclear function promotes BC cell growth and migration and the development of metastasis and constitutes a proof of concept supporting the participation of mitochondrial autoimmunity in breast carcinogenesis. The resemblance of the autoantibody profile in BC detected by IFA with that in the rheumatic autoimmune diseases suggested that studies on the autoantibody response to tumor associated antigens and the characterization of the mtDNA- and nDNA-encoded antigens may provide functional data on breast carcinogenesis. We also review the studies supporting the view that a panel of autoreactive nDNA-encoded mitochondrial antigens in addition to MNRR1 may be involved in breast carcinogenesis. These include GAPDH, PKM2, GSTP1, SPATA5, MFF, ncRNA PINK1-AS/DDOST as probably contributing to BC progression and metastases and the evidence suggesting that DDX21 orchestrates a complex signaling network with participation of JUND and ATF3 driving chronic inflammation and breast tumorigenesis. We suggest that the widespread autoreactivity of mtDNA- and nDNA-encoded mitochondrial proteins found in BC sera may be the reflection of autoimmunity triggered by mitochondrial and non-mitochondrial tumor associated antigens involved in multiple tumorigenic pathways. Furthermore, we suggest that mitochondrial proteins may contribute to mitochondrial dysfunction in BC even if mitochondrial respiration is found to be within normal limits. However, although the studies show that mitochondrial autoimmunity is a major factor in breast cancer inception and progression, it is not the only factor since there is a multiplex autoantibody profile targeting centrosome and stem cell antigens as well as anti-idiotypic antibodies, revealing the complex signaling network involved in breast carcinogenesis. In summary, the studies reviewed here open new, unexpected therapeutic avenues for cancer prevention and treatment of patients with cancer derived from an entirely new perspective of breast carcinogenesis.

Mitochondrial autoimmunity and MNRR1 in breast carcinogenesis.

BACKGROUND: Autoantibodies function as markers of tumorigenesis and have been proposed to enhance early detection of malignancies. We recently reported, using immunoscreening of a T7 complementary DNA (cDNA) library of breast cancer (BC) proteins with sera from patients with BC, the presence of autoantibodies targeting several mitochondrial DNA (mtDNA)-encoded subunits of the electron transport chain (ETC) in complexes I, IV, and V. METHODS: In this study, we have characterized the role of Mitochondrial-Nuclear Retrograde Regulator 1 (MNRR1, also known as CHCHD2), identified on immunoscreening, in breast carcinogenesis. We assessed the protein as well as transcript levels of MNRR1 in BC tissues and in derived cell lines representing tumors of graded aggressiveness. Mitochondrial function was also assayed and correlated with the levels of MNRR1. We studied the invasiveness of BC derived cells and the effect of MNRR1 levels on expression of genes associated with cell proliferation and migration such as Rictor and PGC-1α. Finally, we manipulated levels of MNRR1 to assess its effect on mitochondria and on some properties linked to a metastatic phenotype. RESULTS: We identified a nuclear DNA (nDNA)-encoded mitochondrial protein, MNRR1, that was significantly associated with the diagnosis of invasive ductal carcinoma (IDC) of the breast by autoantigen microarray analysis. In focusing on the mechanism of action of MNRR1 we found that its level was nearly twice as high in malignant versus benign breast tissue and up to 18 times as high in BC cell lines compared to MCF10A control cells, suggesting a relationship to aggressive potential. Furthermore, MNRR1 affected levels of multiple genes previously associated with cancer metastasis. CONCLUSIONS: MNRR1 regulates multiple genes that function in cell migration and cancer metastasis and is higher in cell lines derived from aggressive tumors. Since MNRR1 was identified as an autoantigen in breast carcinogenesis, the present data support our proposal that both mitochondrial autoimmunity and MNRR1 activity in particular are involved in breast carcinogenesis. Virtually all other nuclear encoded genes identified on immunoscreening of invasive BC harbor an MNRR1 binding site in their promoters, thereby placing MNRR1 upstream and potentially making it a novel marker for BC metastasis.

Development of a T7 Phage Display Library to Detect Sarcoidosis and Tuberculosis by a Panel of Novel Antigens.

Sarcoidosis is a granulomatous inflammatory disease, diagnosed through tissue biopsy of involved organs in the absence of other causes such as tuberculosis (TB). No specific serologic test is available to diagnose and differentiate sarcoidosis from TB. Using a high throughput method, we developed a T7 phage display cDNA library derived from mRNA isolated from bronchoalveolar lavage (BAL) cells and leukocytes of sarcoidosis patients. This complex cDNA library was biopanned to obtain 1152 potential sarcoidosis antigens and a microarray was constructed to immunoscreen two different sets of sera from healthy controls and sarcoidosis. Meta-analysis identified 259 discriminating sarcoidosis antigens, and multivariate analysis identified 32 antigens with a sensitivity of 89% and a specificity of 83% to classify sarcoidosis from healthy controls. Additionally, interrogating the same microarray platform with sera from subjects with TB, we identified 50 clones that distinguish between TB, sarcoidosis and healthy controls. The top 10 sarcoidosis and TB specific clones were sequenced and homologies were searched in the public database revealing unique epitopes and mimotopes in each group. Here, we show for the first time that immunoscreenings of a library derived from sarcoidosis tissue differentiates between sarcoidosis and tuberculosis antigens. These novel biomarkers can improve diagnosis of sarcoidosis and TB, and may aid to develop or evaluate a TB vaccine.

Autoantibodies in breast cancer sera are not epiphenomena and may participate in carcinogenesis.

BACKGROUND: The objective of this work was to demonstrate that autoantibodies in breast cancer sera are not epiphenomena, and exhibit unique immunologic features resembling the rheumatic autoimmune diseases. METHODS: We performed a comprehensive study of autoantibodies on a collection of sera from women with breast cancer or benign breast disease, undergoing annual screening mammography. All women in this study had suspicious mammography assessment and underwent a breast biopsy. We used indirect immunofluorescence, the crithidia assay for anti-dsDNA antibodies, and multiple ELISAs for extractable nuclear antigens. RESULTS: Autoantibodies were detected in virtually all patients with breast cancer, predominantly of the IgG1 and IgG3 isotypes. The profile detected in breast cancer sera showed distinctive features, such as antibodies targeting mitochondria, centrosomes, centromeres, nucleoli, cytoskeleton, and multiple nuclear dots. The majority of sera showing anti-mitochondrial antibodies did not react with the M2 component of pyruvate dehydrogenase, characteristic of primary biliary cirrhosis. Anti-centromere antibodies were mainly anti-CENP-B. ELISAs for extractable nuclear antigens and the assays for dsDNA were negative. CONCLUSIONS: The distinctive autoantibody profile detected in BC sera is the expression of tumor immunogenicity. Although some of these features resemble those in the rheumatic autoimmune diseases and primary biliary cirrhosis, the data suggest the involvement of an entirely different set of epithelial antigens in breast cancer. High titer autoantibodies targeting centrosomes, centromeres, and mitochondria were detected in a small group of healthy women with suspicious mammography assessment and no cancer by biopsy; this suggests that the process triggering autoantibody formation starts in the pre-malignant phase and that future studies using validated autoantibody panels may allow detection of breast cancer risk in asymptomatic women. Autoantibodies developing in breast cancer are not epiphenomena, but likely reflect an antigen-driven autoimmune response triggered by epitopes developing in the mammary gland during breast carcinogenesis. Our results support the validity of the multiple studies reporting association of autoantibodies with breast cancer. Results further suggest significant promise for the development of panels of breast cancer-specific, premalignant-phase autoantibodies, as well as studies on the autoantibody response to tumor associated antigens in the pathogenesis of cancer.

Anti-centrosome antibodies in breast cancer are the expression of autoimmunity.

Centrosome abnormalities have been observed in nearly all human solid tumors, but their role in tumorigenesis is unclear. We have demonstrated that autoantibodies reacting with antigens in centrosomes are frequently found in BC sera. In this work, we attempted to characterize the centrosome antigens associated with BC. We immunoscreened a T7 cDNA library of BC proteins with BC sera, and the autoantigens identified were printed as a microarray and hybridized with BC and control sera. We used immunohistochemistry (IHC) to investigate the expression of the cloned autoantigens in BC tissue. Immunoscreening with BC sera led to the cloning of autoantibodies recognizing epitopes developing in a family of proteins located on centrosomes such as peri-centriolar material-1, isomorph CRA, stathmin1, HS actin gamma1, SUMO/sentrin peptidase 2, and ubiquitin-conjugating enzyme E2 variant 1. Antibody reactivity to these proteins that are associated with centrosome assembly and/or microtubule function was highly associated with the diagnosis of BC. IHC staining of formalin-fixed paraffin-embedded sections with specific antibodies showed that aurora and stathmin are expressed in BC. The discovery of autoantibodies to important centrosome antigens associated with BC suggests that this immune reactivity could be related to autoimmunity developing in BC. Our finding that some of these antibodies are also present in a group of healthy women suggests that breakdown of tolerance to centrosome proteins may occur early in breast carcinogenesis and that autoantibodies to centrosome antigens might be biomarkers of early BC.

Autoantibodies in breast cancer.

In addition to their historical role, autoantibodies appear promising as biomarkers to facilitate diagnosis, improve patient outcome and decrease mortality in cancer. Autoantibodies may also be useful in the identification of subjects at risk for cancer, that is, those bearing premalignant changes. Numerous studies have demonstrated that cancer serum contains a variety of autoantibodies that react with autologous cellular antigens, that is, tumor-associated antigens. Interestingly, some of these antigens are involved in signal transduction, cell cycle regulation, cell proliferation, and apoptosis. As such, identification of these molecules has additional importance for development of novel anticancer drugs and vaccines. This review focuses on the use of autoantibodies in breast cancer, a major public health problem. We also address the need for additional research to validate this approach in cancer diagnostics and therapeutics in general.

Serologic laboratory findings in malignancy.

Autoantibodies are extremely promising diagnostic and prognostic biomarkers of cancer, and have the potential to promote early diagnosis and to make a large impact by improving patient outcome and decreasing mortality. Moreover, autoantibodies may be useful reagents in the identification of subjects at risk for cancer, bearing premalignant tissue changes. Great efforts are being made in many laboratories to validate diagnostic panels of autoantibodies with high sensitivity and specificity that could be useful in a clinical setting. It is likely that prospective studies of sufficiently large cohorts of patients and controls using high-throughput technology may allow the identification of biomarkers with diagnostic significance, and perhaps of discrete antigen phenotypes with clinical significance. The identification of TAAs may also be essential for the development of anticancer vaccines, because autoantibodies found in cancer sera target molecules involved in signal transduction, cell-cycle regulation, cell proliferation, and apoptosis, playing important roles in carcinogenesis. On this basis, molecular studies of antigenantibody systems in cancer promise to yield valuable information on the carcinogenic process. TAAs identified by serum antibodies in cancer sera can be natural immunogenic molecules, useful as targets for cancer immunotherapy. An important problem encountered in the practice of medicine is the identification of healthy individuals in the general population who unknowingly are at high risk of developing cancer. For the rheumatologist, a related problem is the identification of those patients with rheumatic diseases who are at high risk for developing a malignant process. These problems encountered in the fields of cancer and the rheumatic diseases can in the future be helped by new diagnostic instruments based on antibodies. The need for promoting the early diagnosis of cancer is a recognized major public health problem in need of significant research support for the validation of multiple promising but inconclusive studies, with the intention of producing diagnostic panels of autoantibodies in various types of cancers. Cancer developing in patients with rheumatic diseases is also an important problem requiring prospective longterm follow-up studies of patients with rheumatic diseases, particularly because some of the new biologic therapies seem to increase the cancer risk. It is possible that a panel of autoantibodies common to patients with cancer and the rheumatic diseases may prove to be of value in the identification of those patients with ADs at high risk for neoplasms.

New insight into the molecular mechanisms of the biological effects of DNA minor groove binders.

BACKGROUND: Bisbenzimides, or Hoechst 33258 (H258), and its derivative Hoechst 33342 (H342) are archetypal molecules for designing minor groove binders, and widely used as tools for staining DNA and analyzing side population cells. They are supravital DNA minor groove binders with AT selectivity. H342 and H258 share similar biological effects based on the similarity of their chemical structures, but also have their unique biological effects. For example, H342, but not H258, is a potent apoptotic inducer and both H342 and H258 can induce transgene overexpression in in vitro studies. However, the molecular mechanisms by which Hoechst dyes induce apoptosis and enhance transgene overexpression are unclear. METHODOLOGY/PRINCIPAL FINDINGS: To determine the molecular mechanisms underlying different biological effects between H342 and H258, microarray technique coupled with bioinformatics analyses and multiple other techniques has been utilized to detect differential global gene expression profiles, Hoechst dye-specific gene expression signatures, and changes in cell morphology and levels of apoptosis-associated proteins in malignant mesothelioma cells. H342-induced apoptosis occurs in a dose-dependent fashion and is associated with morphological changes, caspase-3 activation, cytochrome c mitochondrial translocation, and cleavage of apoptosis-associated proteins. The antagonistic effect of H258 on H342-induced apoptosis indicates a pharmacokinetic basis for the two dyes' different biological effects. Differential global gene expression profiles induced by H258 and H342 are accompanied by unique gene expression signatures determined by DNA microarray and bioinformatics software, indicating a genetic basis for their different biological effects. CONCLUSIONS/SIGNIFICANCE: A unique gene expression signature associated with H342-induced apoptosis provides a new avenue to predict and classify the therapeutic class of minor groove binders in the drug development process. Further analysis of H258-upregulated genes of transcription regulation may identify the genes that enhance transgene overexpression in gene therapy and promote recombinant protein products in biopharmaceutical companies. DATA DEPOSITION: The microarray data reported in this article have been deposited in the Gene Expression Omnibus (GEO) database, www.ncbi.nlm.nih.gov/geo (accession no.GSE28616).

Rare cause of thoracic myelopathy: ossified ligamentum flavum.

Myelopathy due to ossification of ligamentum flavum was first described in 1938 by Anzai (J Jpn Orthop Assosc. 1938;13:305-316). This is a rare condition that has been described mostly in the far east, most commonly in Japan (Miyasaka et al, Am J Neuroradiol. 1983;4:629-632). Cases reported from the western hemisphere are rare, particularly in the African-American population (Wiseman et al, J Spinal Disord Tech. 2002;15:542-545). We report an African-American patient who presented with progressive back and chest pain of recent onset, numbness, tingling, and gait disturbance due to T3 paraplegia secondary to ossified ligamentum flavum resulting in thoracic spinal stenosis. On cross-sectional imaging, there was cord effacement at multiple levels, most pronounced at T10. The patient required emergency laminectomies, which allowed him to recover significant function. This case presentation should heighten physician awareness to this unusual clinical entity, since early diagnosis and timely surgical intervention can prevent permanent neurologic deficits.

Autoantibodies in breast cancer sera: candidate biomarkers and reporters of tumorigenesis.

A plethora of promising breast cancer-associated autoantigens have been cloned by immunoscreening cDNA expression libraries with breast cancer sera or identified using proteomics, yet no biomarkers, whether individual autoantigens or panels of antigens developed using antibody-based methods have been validated and incorporated to routine oncologic practice for the early diagnosis of breast cancer. Recently, the addition of genomics, proteomics and high throughput technology to traditional immunological techniques has revived the interest in this field, and some of the most promising breast cancer autoantigens are in the process of being validated prospectively in large cohorts of patients with breast cancer. In addition, some of the identified breast cancer-associated autoantigens are recognized by T-cells and may prove to have a role in the treatment of breast cancer in the future. Autoantibodies found in breast cancer patient sera provide important clues about their significance. The discovery of breast cancer-associated antigens has provocative implications beyond the quest for novel diagnostic biomarkers, because autoantibodies target molecules involved in signal transduction, cell cycle regulation, cell proliferation and apoptosis, all of them key processes in carcinogenesis. Molecular components of the DNA double-strand break repair machinery as well as several members of the rapamycin-sensitive pathway elicit an autoantibody response in breast cancer. Data obtained by screening cDNA expression libraries of breast cancer antigens with autoantibodies present in breast cancer sera suggest that autoantibodies in cancer sera may be linked to the process of apoptosis. The studies reviewed here, clearly demonstrate the participation of autoimmunity in breast cancer to an extent previously unsuspected, which may have broad implications for the discovery of molecular targets for drug therapy and cancer biomarkers in general.

Improved approach to identify cancer-associated autoantigens.

The failure to identify biomarkers of clinical significance for cancer diagnosis and prognosis generated a great deal of skepticism in regard to the usefulness of autoantibody-based methods. SEREX was a major advancement in immunoscreening that resulted in the identification of a large group of autoantigens recognized by cancer sera. However, few SEREX-defined autoantigens have proven to have definitive diagnostic value in clinical practice. Often, the identified antigens are patient-specific rather than tumor-specific and many tumor-associated antigens are rare in expression libraries made from non-autologous cells. Since autoantibodies are part of the normal immune response, it can be difficult to single out tumor-associated antibodies from the scores of irrelevant patient-specific responses. In our view, any practical approach for identifying cancer-related autoantigens must include an integral strategy for demonstrating tumor relevance early in the screening process. Care must also be taken not to exclude potentially important autoantibodies by pre-screening manipulations to patient sera. We have introduced substantial modifications in SEREX, designed to minimize confounding effects of unrelated autoantibodies and to eliminate steps that preclude the identification of cancer-related autoantigens commonly recognized by cancer sera. In addition, we incorporate methodology to identify candidate antigens that have potential diagnostic or prognostic value prior to their molecular cloning and characterization.

Spectra of antinuclear antibodies in patients with squamous cell carcinoma of the lung and of the head and neck.

Squamous cell carcinoma of the head and neck (HNSCC) and of the lung (LSCC) share some important risk factors, but differ substantially in terms of prognosis and treatment. A pulmonary nodule developing in patients with surgically cured HNSCC may pose a diagnostic dilemma. Markers able to distinguish these two common malignancies would be of major clinical importance. In this work we compared the spectrum of antinuclear antibodies (ANA) from 22 patients with SCCL to that of 40 patients with HNSCC. Patient sera were used to probe immunoblots of nuclear extracts from all four major lung cancer cell types, normal lung fibroblasts, cells cultured from a HNSCC, and keratinocytes cultured from the field cancerization. The ability to classify retrospectively LSCC from HNSCC based on serum ANA reactivities was determined by recursive partitioning analyses. We found that while both malignancies share reactivities to a small group of nuclear antigens, other reactivities are directed against proteins uniquely or preferentially expressed in either SCCL or in SCCHN cells. Our work shows that autoimmunity is a prominent feature of squamous cell carcinoma and suggests that molecular characterization of nuclear antigens recognized by ANAs may lead to the discovery of markers valuable to distinguish LSCC from HNSCC.

Paraneoplastic polyarthritis in an ovarian teratoma.

A 34-year-old woman presented to the rheumatology clinic with severe low back pain and arthralgia; later she developed bilateral knee pain and swelling, with limitation in ambulation and minimal improvement with nonsteroidal antiinflammatory drugs. Two weeks later she developed pain on the volar aspect of the right wrist and on the hypothenar region of the right hand. Examination showed swelling and tenderness of the right hypothenar region, tenderness and decreased flexion and extension of the right wrist, and bilateral knee effusions. The combination of arthritis and tenosynovitis raised the possibility of an ovarian tumor. A pelvic ultrasound revealed a complex, hyperechoic ovarian mass consistent with a cystic teratoma. Four weeks after removal of the teratoma, the polyarthritis and related symptoms resolved without therapy.

Autoantibodies to Annexin XI-A and Other Autoantigens in the Diagnosis of Breast Cancer.

We report on the identification of autoantigens commonly recognized by sera from patients with breast cancer. We selected ten sera from patients with invasive ductal carcinoma (IDC) of the breast with high titer IgG autoantibodies for biopanning of a T7 phage breast cancer cDNA display library. A high throughput method involved the assembly of 938 T7 phages encoding potential breast cancer autoantigens. Microarrays of positive phages were probed with sera from 90 patients with breast cancer [15 patients with ductal carcinoma in situ (DCIS) and 75 patients with IDC of the breast], with 51 non-cancer control sera and with sera from 21 patients with systemic autoimmune diseases. A 12-phage breast cancer predictor group was constructed with phage inserts recognized by sera from patients with breast cancer and not by non-cancer or autoimmune control sera (P < 0.0001). Several autoantigens including annexin XI-A, the p80 subunit of the Ku antigen, ribosomal protein S6, and other unknown autoantigens could significantly discriminate between breast cancer and non-cancer control sera. Biopanning with three different sera led to the cloning of partial cDNA sequences identical to annexin XI-A. IgG autoantibodies reacting with the amino acid 41-74 sequence of annexin XI-A were found in 19% of all women with breast cancer but in 60% of sera from women with DCIS of the breast. In addition, partial sequences identical to annexin XI-A, nucleolar protein interacting with the forkhead-associated (FHA) domain of pKi-67, the KIAA1671 gene product, ribosomal protein S6, cyclin K, elongation factor-2, Grb2-associated protein 2, and other unknown proteins could distinguish DCIS from IDC of the breast and appear to be potential biomarkers for the diagnosis of breast cancer.

Estudio histoquímico de los cambios en la expresión de glicanos durante una gingivitis experimental en humanos / A histochemical study of glycan expression changes in a human experimental gingivitis

En tres voluntarios sanos se les indujo un modelo de gingivitis en la hemiarcada superior derecha (14 días sin ninguna medida de higiene bucal); la hemiarcada superior izquierda sirvió como control. Se tuvo el propósito de demostrar los patrones de expresión de diferentes residuos glicosídicos usando un grupo de ocho lectinas biotiniladas en encía sana y enferma. Se tomaron biopsias por congelación en los días 0, 7 y 14 del experimento y se procesaron con la técnica histoquímica de la inmunoperoxidasa. Fue posible determinar la adhesión selectiva de las lectinas a las diferentes estructuras de los tejidos epitelial y conectivo de la encía y se observó un cambio en la expresión de residuos sacáridos a medida que avanzaba la inflamación experimental, posiblemente atribuible a la creación de criptoepítopes mediante el clivaje del azúcar terminal de los glicanos, a la posible acción de una transferasa y a la especificidad de las lectinas por el grupo sanguíneo del paciente al que pertenecía el tejido bajo examen

Estudio histoquímico de los cambios en la expresión de glicanos durante una gingivitis experimental en humanos / Hystochemical study in changes of the expression of glycans during experimental gingivitis in humans

En tres voluntarios sanos se indujo un modelo de gingivitis en la hemiarcada superior derecha (14 días sin ninguna medida de higiene oral); la hemiarcada superior izquierda sirvió como control. Se tuvo el propósito de demostrar los patrones de expresión de diferentes residuos glicosídicos usando un grupo de ocho lectinas biotiniladas en encía sana y enferma. Se tomaron biopsia por congelación en los días 0.7 y 14 del experimento y se procesaron con la técnica histoquímica de la inmunoperoxidasa.- Fue posible determinar la adhesión selectiva de las lectinas a las diferentes estructuras de los tejidos epitelial y conectivo de la encía y se observó un cambio en la expresión de residuos sacáridos a medida que avanzaba la inflamación experimental, posiblemente atribuible a la creación de criptoepítopes mediante el clivaje del azúcar terminal de los glicanos, a la posible acción de una transferasa y a la especificidad de las lectinas por el grupo sanguíneo del paciente al que pertenecía el tejido bajo examen.

Valor pronóstico de la glicemia al ingreso en pacientes críticos con patologías neurológicas / Prognostic value of the blood glucose levels at the moment of admission in critical patients discharged with neurological pathology

Evaluamos lo que sucedió en nuestros pacientes con patología neurológica, no diabéticos, en cuanto al nivel de sus cifras de glicemia durante las primeras 24 horas de su ingreso a UTI, y si éstas tienen relación con la gravedad, evolución y mortalidad en este grupo de 226 pacientes. Encontramos en los egresados vivos, una media de glicemia de 151,72 mgrs por ciento Vs. 244,06 mgrs por ciento, en los fallecidos, lo cual fue estadísticamente significativo. El análisis estadístico estableció un valor crítico de 198 mgrs por ciento, por encima del cual, la probabilidad de muerte aumenta significativamente, logrando clasificar correctamente el 82 por ciento de los casos, en virtud de lo cual pensamos que cualquier medida terapéutica que contribuya a mantener la glicemia dentro de los valores normales en este grupo de pacientes será necesaria y está plenamente justificada.

Taquicardia ventricular polimorfa asociada a intoxicación por organofosforados / Ventricular arrhythmias associated with organophosphorus insecticide poisoning

A continuación se presenta un caso de taquicardia ventricular polimorfa (Torsade de Pointes) y QT prolongado asociado a intoxicación aguda con Parathion, la cual revirtió a ritmo sinusal exitosamente con sulfato de magnesio, siendo hasta el momento el primero que se reporta

Aneurisma disecante de la aorta torácica / Dissecting aneurysm of the aorta thoracic

La disección aórtica es una emergencia cardiovascular que tiene una alta mortalidad hasta de un 80 por ciento en las primeras dos semanas. Basados en la clasificación de Debakey ampliamente usada y reconocida permite seleccionar los pacientes con disecciones proximales para el tratamiento quirúrgico, se necesita en estos pacientes el diagnóstico rápido, así como ubicar origen y extensión de la disección. En este trabajo se recolectaron los pacientes que ingresaron en el Departamento de Cardiología del Hospital Militar "Dr. Carlos Arvelo" entre los años 1990 y 1994, con el diagnóstico de aneurisma disecante de la aorta torácico, se compararon las siguientes variables: edad, sexo, motivo de consulta, antecedentes personales, tipo de disección, estudios paraclínicos y mortalidad.