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Biomedical subjects

R Mesa-Tejada

Publications and source records attributed to R Mesa-Tejada.

At least 19 recordsLinked to original sources

Evidence of increased endothelial cell turnover in brain arteriovenous malformations.

OBJECTIVE: We hypothesized that human brain arteriovenous malformations (BAVMs) are nonstatic vascular lesions with active angiogenesis or vascular remodeling. To test this hypothesis, we assessed endothelial cell turnover in BAVMs. METHODS: We identified nonresting endothelial cells by use of immunohistochemistry for the Ki-67 antigen. From archived paraffin blocks, we selected BAVM vessels without intravascular thrombosis or embolic material in areas nonadjacent to the nidus edge. For controls, we used 50- to 100-microm diameter cortical vessels from temporal lobe cortex removed for epilepsy treatment. The Ki-67 index was calculated as a percentage of Ki-67-positive endothelial cells. The data were analyzed by the nonparametric Mann-Whitney test and reported as mean +/- standard deviation. RESULTS: Thirty-seven specimens that met the above criteria were selected. There were 26 +/- 15 vessels counted in each BAVM specimen versus 18 +/- 5 in each control cortex (n = 5). The mean Ki-67 index was higher for BAVM vessels than control cortical vessels (0.7 +/- 0.6 versus 0.1 +/- 0.2%; P = 0.005), which represented an approximately seven-fold increase in the number of nonresting endothelial cells. In the BAVM group, there was a trend for younger patients to have a wider variation and higher Ki-67 index than older patients; no trend was evident in the control group. CONCLUSION: Compared with control vessels, BAVM vessels have higher endothelial cell turnover, which suggests the presence of active angiogenesis or vascular remodeling in BAVMs.

Adult↗

Abnormal pattern of Tie-2 and vascular endothelial growth factor receptor expression in human cerebral arteriovenous malformations.

OBJECTIVE: Human cerebral arteriovenous malformations (AVMs) are speculated to result from abnormal angiogenesis. Vascular endothelial growth factor receptors (VEGF-Rs) and Tie-2 play critical roles in vasculogenesis and angiogenesis. We hypothesized that the abnormal vascular phenotype of AVMs may be associated with abnormal expression of VEGF-Rs and Tie-2. METHODS: We measured the expression of Tie-2, VEGF-R1, and VEGF-R2 in AVMs and normal brain tissue, using immunoblotting. To assess active vascular remodeling, we also measured endothelial nitric oxide synthase expression. CD31 expression was used to control for endothelial cell mass for Tie-2, VEGF-Rs, and endothelial nitric oxide synthase. Immunoblotting data were presented as relative expression, using normal brain tissue values as 100%. RESULTS: CD31 was expressed to similar degrees in AVMs and normal brain tissue (99+/-29% versus 100+/-20%, mean +/- standard error, P = 0.98). Tie-2 expression was markedly decreased in all AVMs, compared with normal brain tissue (16+/-9% versus 100+/-37%, P = 0.04). VEGF-R1 expression was decreased in four of five AVMs, but the difference between the mean values was not significant (35+/-8% versus 100+/-42%, P = 0.14). VEGF-R2 expression was decreased in all AVMs, compared with normal brain tissue (28+/-6% versus 100+/-29%, P = 0.03). There was no difference in endothelial nitric oxide synthase expression between AVMs and normal brain tissue (106+/-42% versus 100+/-25%, P = 0.91). CONCLUSION: AVM vessels exhibited abnormal expression of Tie-2 and VEGF-Rs, both of which may contribute to the pathogenesis of AVMs.

Adult↗

Metastatic endometrial adenocarcinoma to the skin of a toe.

A 55-year-old woman had a history of prolonged vaginal bleeding. Dilatation and curettage confirmed poorly differentiated endometrial adenocarcinoma. After hysterectomy, salpingo-oophorectomy, and 5,040 cGy of postoperative irradiation, lung metastases developed, which temporarily responded to chemotherapy that included adriamycin and cisplatin. Metastatic lesions developed later in the left acetabulum and the hallux. The latter, clinically reminiscent of pyogenic granuloma, affected only skin. The poorly differentiated toe metastasis duplicated areas of the primary endometrial adenocarcinoma and was immunohistochemically similar to it. While appearing quite rarely, and generally late in the disease, pedal skin lesions may represent metastases from known or occult visceral cancers.

Adenocarcinoma↗

Patterns of immunocytochemically detected Z-DNA in the recrudescing testicular epithelium of the Turkish hamster (Mesocricetus brandti).

Z-DNA has been considered a labile but essential structural form of DNA in recombination and gene expression, two significant activities in mammalian seminiferous epithelium. The present study has utilized the recrudescing testes of Mesocricetus brandti to study in detail the potential Z-DNA sites in specific testicular cell types as detected by an immunoprobe. Testicular regression was physiologically induced by modifying environmental photoperiods and/or temperature. Partial atrophy of seminiferous epithelium occurred in all experimental groups but Sertoli cells persisted throughout regression. Recrudescence of testicular activity was marked in all experimental groups by characteristic sequences of reappearance of potential Z-DNA sites to a final positive or negative mature state of the cell type. It is suggested that Z-DNA is a functionally important from of DNA in many cell types of the active seminiferous epithelium of the Turkish hamster, and perhaps other mammals.

Animals↗

Tumor localization in nude mice bearing human breast carcinoma xenografts using 111In-DTPA conjugates of monoclonal antibodies.

Biodistribution of monoclonal antibody T43 and its F(ab')2 111In-DTPA conjugates were determined in nu/nu mice bearing human breast tumor and rat pituitary tumor xenografts. T43 localized in the target tumor with tumor/blood ratios of 3.9 (P less than 0.01) and 4.5 (P less than 0.05) at 48 and 72 h, respectively. T43 F(ab')2 fragments localized with tumor/blood ratio of 14.2 (P less than 0.1) at 72 h. Tumors as small as 4 mm were detected without computer subtraction technique. These studies suggest that T43 and T43 F(ab')2 might be useful reagents in radioimaging.

Animals↗

Prediction of prognosis in primary breast cancer by detection of a high molecular weight mucin-like antigen using monoclonal antibodies DF3, F36/22, and CU18: a Cancer and Leukemia Group B study.

Three monoclonal antibodies (MAbs) (DF3, F36/22, CU18) were used to monitor expression of distinct epitopes present within a family of mucin-like, breast carcinoma-associated molecules. Primary tumor specimens from more than 190 stage II breast cancer patients were evaluated for expression of the high molecular weight antigens. With a median follow-up of 6 years, patients whose tumors exhibited high immunoperoxidase staining scores (greater than 50% positive cells) with MAb DF3 had a superior disease-free survival ([DFS] 56% +/- 6% v 37% +/- 5% at 6 years; P = .0088) and overall survival ([OS] 72% +/- 5% v 59% +/- 5% at 6 years; P = .025). Staining scores with the other two antibodies did not correlate with improved prognosis. For MAbs DF3 and CU18, patients whose tumors exhibited predominantly apical cellular reactivity patterns had improved DFS, although differences reached conventional levels of statistical significance only with MAb CU18. In multivariate analyses, the prognostic value of MAb DF3 staining was independent of other identified prognostic factors. Furthermore, the concordance between primary and axillary lymph node metastases staining with each MAb was 73%, 80%, and 85% for MAbs DF3, F36/22, and CU18, respectively. These results suggest that staining with MAb DF3 identifies a group of node-positive women with a relatively favorable prognosis. Expression of the DF3 mucin-like glycoprotein is related to better differentiation, and staining with MAb DF3 provides an accurate and objective estimate of clinical outcome independent of histopathologic evaluation.

Adult↗

Monoclonal antibodies: their importance to surgeons.

A tremendous technological advance occurred in 1975 when a method was developed to fuse two cells producing a "hybridoma" which secretes a single clone of antibody, having one immunoglobulin (Ig) class, one structure, one affinity, and one specificity for an antigenic determinant. Because monoclonal antibodies are more precise reagents than conventional antisera they open new doors to diagnosis and therapy of disease, and they are useful tools in research. The pathologist uses monoclonals in immunocytochemistry to determine tumor type; the surgeon uses monoclonals for immunosuppression in renal transplantation; the immunologist uses monoclonals to decipher cellular and humoral interactions that could not be appreciated with polyclonal reagents. This review outlines the background of monoclonal antibodies and some of their clinically important uses, both in vitro and in vivo. We also project into the future and describe chimeric antibodies and their possible uses.

Animals↗

Immunohistochemical characterization of fibrin(ogen)-related antigens in human tissues using monoclonal antibodies.

A new approach to study the distribution of fibrin(ogen)-related antigens was investigated using three different monoclonal antibodies (MAbs) and the avidin-biotin complex immunoperoxidase technique. MAb I8C6 recognizes B beta 1-42 peptide and can react with either fibrinogen or fibrin I; MAb T2G1 recognizes B beta 15-42 peptide and detects fibrin II but does not cross-react with fibrinogen; MAb GC4 reacts with Fragments D/DD derived from plasmin degradation of fibrinogen or fibrin but not with intact fibrinogen. The method can be applied to frozen or Bouin's fixed paraffin-embedded tissues obtained at biopsy, surgery, and autopsy. The distribution of the three antigens observed with the three MAbs was compared with that obtained with a polyclonal antiserum to fibrinogen and with the more conventional histochemical stains used in pathology to demonstrate fibrin deposits in tissues (Lendrum and PTAH). The staining observed with the three monoclonals clearly detected three different populations of fibrin(ogen)-related antigen in the tissues examined. The staining with MAb T2G1 specifically detected fibrin II with greater sensitivity than did conventional stains. The results of this study suggest that this method allows the molecular form of fibrin(ogen)-related deposits in tissues to be determined and this information may help to elucidate the role of fibrin in various disease states, such as atherosclerosis and renal disease, and in tumor growth and metastasis.

Antibodies, Monoclonal↗

Multifocal cytomegalovirus encephalitis in AIDS.

A 43-year-old man with the acquired immunodeficiency syndrome had clinical evidence of multifocal disease of the brain, but computed tomography was negative. Magnetic resonance imaging revealed multifocal lesions, histologically proven to be caused by cytomegalovirus. Therapy with 9[2-hydroxy-1-(hydroxymethyl) ethoxymethyl] guanine (BW B759U) resulted in stabilization of the patient's clinical disease and radiographic improvement of the lesions.

Acquired Immunodeficiency Syndrome↗

The immunocytochemical localization of potential Z-DNA sites in human testicular tubule epithelium.

Z-DNA has been detected in several pro- and eukaryotic cells and possible roles in regulating transcriptional activity and meiotic recombination proposed. The present study examined the localization of reaction product to potential Z-DNA sites in human testicular tubule epithelium from three subjects using an avidin-biotin complex (ABC)-immunoperoxidase method with a specific rabbit antibody previously shown to react with rat spermatogonial nuclei. A total of 46,626 cells were scored, of which 5656 were Sertoli cells. Eighty-six percent of spermatogonia in mitotic metaphase were found to be negative. Interphase spermatogonia identified as A dark or pale were positive in 93 and 92%, respectively, of cells, and this positivity persisted through B spermatogonia into meiosis. Of 8083 leptotene/zygotene spermatocytes, 99% were positive. Pachytene spermatocytes were 98% positive in the autosomal bivalents. First meiotic metaphase nuclei were negative (92%), as were almost all cells scored of the spermiogenic series (16,195). Nuclei of Sertoli cells had reaction product over the chromatin in 81% of 5656 cells, with no reaction product on the prominent nucleolus. The presence of potential Z-DNA sites in the genome of human spermatogenesis and Sertoli cells during known active stages of transcription (pachytene) and recombination (zygotene/pachytene) suggests a role for this conformation during these stages.

Aged↗

Immunocytochemical distribution of a breast carcinoma associated glycoprotein identified by monoclonal antibodies.

A glycoprotein, BCA-225 (Mr 225,000-250,000), has been identified in cells and spent medium of clone 11 T47D breast carcinoma cells by three murine monoclonal antibodies, CU18, CU26, and CU46. The antigen was localized in paraffin sections of 167/178 (94%) Bouin's-fixed human breast carcinoma tissues and few other carcinomas (1/8 lung [squamous], 4/4 uterine cervix) in an intracellular pattern, whereas an apical or glycocalyx distribution was seen in several normal tissues, benign lesions, and malignant tumors. Although the immunocytochemical staining patterns observed with these antibodies have many similarities to those described with other previously reported monoclonal antibodies, notable differences include the lack of reactivity of CU18, CU26, and CU46 with lactating mammary gland and with gastrointestinal malignancies. BCA-225 binds to wheat germ lectin, not to concanavalin A, but monoclonal antibody binding does not appear to involve the carbohydrate component of the molecule. The frequency of the immunocytochemical detection of BCA-225 in breast carcinomas and its restricted distribution in other human tissues suggest considerable clinical potential for this antigen and its corresponding monoclonal antibodies.

Antibodies, Monoclonal↗

A new complication of AIDS: thoracic myelitis caused by herpes simplex virus.

Progressive thoracic myelopathy occurred in a patient with AIDS. Concurrent opportunistic infections included disseminated systemic cytomegalovirus, aspergillosis, and cutaneous herpes simplex virus (HSV). At autopsy, immune stains indicated that the myelopathy was caused by HSV type 2 infection of the spinal cord.

Acquired Immunodeficiency Syndrome↗

Increased incidence of mouse mammary tumor virus-related antigen in Tunisian patients with breast cancer.

Biopsies obtained from 74 Tunisian women with breast cancer (33 cases), benign breast disease (17 cases), and cervical cancer (24 cases) were assayed for the presence of an antigen cross-reacting with gp52 of the mouse mammary tumor virus (MMTV) in order to determine the frequency and possible prognostic significance of this antigen in a form of rapidly progressing breast cancer designated poussée évolutive or PEV. Antigen was detected in 23/33 breast carcinomas (70%) but in none of the 41 control specimens. An evaluation of reactivity according to tumor aggressiveness and survival could be performed in retrospect on 29 of the breast cancer patients with a follow-up of up to 11 years. The frequency of gp52-related antigen was similar in the patients with the most aggressive form of PEV with inflammatory signs (8/12 or 67% positive) and those breast cancer patients without PEV (12/17 or 71% positive). Within each of the two groups, PEV+ and PEV 0, no correlation was observed between the presence or absence of antigen and the disease-free interval or survival. We conclude that the identification of gp52-related antigens in the breast cancer biopsies from North African women has implications different from those observed in other populations. While thus far not indicative of disease aggressiveness and prognosis, the higher frequency of detectable antigen in comparison to biopsies obtained from patients born in the United States and Europe may have relevance to the etiology and pathogenesis of the disease.

Adenofibroma↗

Hepatitis B virus and myocarditis.

Myocarditis may be a serious extrahepatic complication of hepatitis. In this fatal case of serologically documented hepatitis B viral hepatitis, acute myocarditis was present, with histologic features consistent with a viral pathogenesis. Hepatitis B surface antigen was demonstrated by immunoperoxidase methods in small intramyocardial vessels, suggesting that hepatitis B virus infected the heart. The resulting inflammatory heart disease may have been caused either directly, by virus infecting the myocardium, or indirectly, by an immune-mediated mechanism.

Acute Disease↗

Properties of retrovirus-like particles produced by a human breast carcinoma cell line: immunological relationship with mouse mammary tumor virus proteins.

Clonal derivatives 8 and 11 of the T47D human breast carcinoma cell line release particles that have the biochemical characteristics of a retrovirus. Particles recovered from cultures of [3H]uridine-labeled clone 11 had a density of 1.18 g/ml and contained 60-70S and 35S RNAs associated with reverse transcriptase activity. The production of these particles was steroid-dependent. Clone 8 particles had a higher density, 1.195 g/ml, and their production was independent of steroid hormone. By RIA, antigens crossreactive with the 52,000-dalton envelope glycoprotein gp52, the major external protein of mouse mammary tumor virus, were found associated with these particles and in the media. Most of the gp52-related antigen was in soluble form, but it was enriched in the particle preparation. A lesser amount of antigen was distributed within the cultured cells. Absorption of rabbit antibody to gp52 with clone 11 particle preparations eliminated the ability of this antibody to detect immunocytochemically a crossreactive antigen previously localized in tissue sections of human breast carcinoma. These results indicate that the particle isolates from T47D contain the same gp52-related antigen found in human breast carcinomas and constitute an excellent source for the purification and characterization of this antigen.

Breast Neoplasms↗

Immunocytochemical localization of lysozyme and alpha-1-antichymotrypsin in the term human placenta: an attempt to characterize the Hofbauer cell.

The intracellular localization of lysozyme (LSZ) and alpha-1-antichymotrypsin (A1Ac), glycoproteins associated with macrophages, was used to confirm the monocytic lineage of the Hofbauer cell and to assess the maturity of its macrophage function. The peroxidase-labeled antigen method was used to localize these proteins, as well as immunoglobulins, light chains, and albumin, in Bouin-fixed, paraffin-embedded sections of 24 normal term placentas. The demonstration of the latter substances was used as an indication of passive diffusion or phagocytosis of serum proteins resulting in intracellular localization unrelated to synthesis. In all the placentas examined a strong cytoplasmic reaction for A1Ac was seen in the Hofbauer cells. The same cells on adjacent sections did not stain for LSZ, while the occasional maternal macrophage and numerous polymorphonuclear leukocytes in the intervillous spaces gave a positive reaction. The detection of A1Ac supports the contention that these cells are macrophages, previously suggested by their phagocytic capability and the demonstration of Fc receptors and nonspecific esterases. Since they do not appear to contain LSZ, a bactericidal enzyme, we propose that these cells are not fully differentiated macrophages, and the lack of this enzyme may have some relevance to the pathogenesis of certain placental infections.

Chymotrypsin↗