Occupational paraffin-induced pulmonary fibrosis: a 25-year follow-up. (49/216)

Exogenous lipid pneumonia can exceptionally be caused by occupational exposure to paraffin. The authors report a case of severe interstitial pulmonary disease induced by occupational exposure to paraffin, leading to delayed fibrosis over a 25-year follow-up, despite cessation of exposure.  (+info)

Complementary reactivities of anti-carcinoembryonic antigen and antitumor-associated glycoprotein 72 monoclonal antibodies in lung carcinomas. (50/216)

Monoclonal antibodies (MAbs) COL-4 and COL-12, to the carcinoembryonic antigen (CEA), and B72.3, CC-49, CC-83, to the tumor-associated glycoprotein 72 (TAG-72), were used to study the expression of distinct epitopes of the two molecules in 71 cases of lung carcinoma of differing histotype. These MAbs reacted with the majority of adenocarcinomas by immunoperoxidase on tissue sections, but demonstrated a more restricted reactivity with squamous carcinomas. MAb CC-49 detected the highest percentages of adenocarcinoma cells while the B72.3 epitope was expressed more in squamous carcinoma cells. No significant reactivity with any of these MAbs was observed in small cell carcinomas. The expression of the CEA and TAG-72 epitopes in non-small cell lung cancers was highly heterogeneous: a distinct epitopes in non-small cell lung cancers was highly heterogeneous: a distinct epitope could be expressed by the majority of cells, whereas another of the same antigenic molecule was either poorly or not expressed. In adenocarcinomas, mixtures of anti-CEA, anti-TAG-72, and anti-(TAG-72 plus CEA) MAbs resulted in additive reactivity with an increase of the immunopositive tumors and of the percentages of immunostained cells. This was particularly evident for the anti-(TAG-72 plus CEA) mixture. In squamous cell carcinomas the increase was modest and was mainly related to anti-TAG-72 reactivity. These studies suggest variability in the antigenic structure of tumor-associated antigens expressed by carcinomas and indicate that anti-(TAG-72 plus CEA) mixtures may represent an immunological adjunct for clinical application in adenocarcinoma patients. On the other hand, TAG-72 should be considered a better target antigen, as compared to CEA, in the detection of squamous cell carcinomas.  (+info)

Accelerated arteriosclerosis in heart transplant recipients is associated with a T-lymphocyte-mediated endothelialitis. (51/216)

Accelerated arteriosclerosis has emerged as a major life-threatening complication in long-term survivors of heart transplantation. It has been proposed that accelerated arteriosclerosis is an immune-mediated complication of rejection. We observed a striking endothelialitis in the coronary arteries of two explanted hearts obtained from patients with severe transplant-related accelerated arteriosclerosis. This finding prompted us to review the pathologic changes in the coronary arteries of 23 autopsied patients who had received heart transplants. The infiltrate in these vessels was characterized using immunohistochemical stains for lymphocytes (CD45), macrophages (MAC-387), T lymphocytes (CD45RO), B lymphocytes (L-26), and smooth muscle cells (actin). In addition, a full panel of monoclonal antibodies was used on the fresh-frozen tissue available from one of the two explanted hearts. Ten of the eleven recipients with accelerated arteriosclerosis had a moderate to marked lymphocytic endothelialitis compared to 3 of 14 without transplant-related arteriosclerosis (P less than 0.005). Immunohistochemical staining of the paraffin-embedded material demonstrated that most of the lymphocytes in the subendothelial space of these vessels were T lymphocytes and that this infiltrate was associated with an accumulation of macrophages and a proliferation of smooth muscle cells in the intima. In the explanted heart from which fresh-frozen tissue was available for more detailed cell typing, the T cells marked predominantly as cytotoxic T lymphocytes (CD8+, CD2+). These results suggest that accelerated arteriosclerosis may be mediated, in part, by a cytotoxic T-lymphocyte-directed endothelialitis.  (+info)

Antiviral activity of HPMPC (cidofovir) against orf virus infected lambs. (52/216)

(S)-1-[3-hydroxy-2-(phosphonomethoxy)propyl]cytosine [corrected] (HPMPC, cidofovir, CDV, Vistide) is an acyclic nucleoside analogue with a potent and selective activity against a broad spectrum of DNA viruses including the poxviruses. In this study we present the results of different treatment regimens in lambs experimentally infected with orf virus with different cidofovir formulations prepared in Beeler basis and Unguentum M. Our results show that choice of excipient, concentration of codofovir [corrected] and treatment regimen were all important to the clinical outcome of the therapy. Whilst one particular regimen appeared to exacerbate the lesion, treatment with 1% (w/v) cidofovir cream, prepared in Beeler basis, for 4 consecutive days did result in milder lesions that resolved in milder lesions that resolved [corrected] more quickly than untreated lesions. Furthermore the scabs of the treated animals contained significantly lower amounts of viable virus meaning there should be less contamination of the environment with virus than would normally occur.  (+info)

Potassium hydride in paraffin: a useful base for organic synthesis. (53/216)

The preparation of potassium hydride as a 1:1 homogenate with paraffin, termed KH(P), is reported. KH(P), a solid at room temperature, is stable without special handling. On suspension in THF with a phosphonium salt, KH(P) rapidly generates the ylide. Wittig condensation with aromatic, aliphatic, and alpha,beta-unsaturated aldehydes proceeds with high Z selectivity. KH(P) should be a generally useful base for organic synthesis.  (+info)

Widespread p53 overexpression in human malignant tumors. An immunohistochemical study using methacarn-fixed, embedded tissue. (54/216)

p53 is a nuclear protein believed to play an important role, through mutation and overexpression, in the progression of human malignant tumors. The authors employed a monoclonal antibody, 1801, and investigated overexpression of p53 in a series of 255 malignant and benign tumors, using deparaffinized sections of methacarn-fixed tissue. Overall, immunohistochemically detected p53 overexpression was found in 39% of malignant tumors, with considerable variation within individual tumor types (34% of breast carcinomas, 92% of ovarian carcinomas, 33% of soft tissue sarcomas). Homogenous, heterogenous, and focal immunostaining patterns were noted. With rare exceptions, no immunostaining of any benign tumors was noted. No immunostaining was found in adjacent, benign tissues, or in a series of fetal tissues. This is the first demonstration of widespread p53 overexpression in alcohol-fixed, embedded tissue and confirms the major role played by p53 in human malignancies.  (+info)

Human papillomavirus 16 E5 oncogene contributes to two stages of skin carcinogenesis. (55/216)

High-risk human papillomaviruses (HPVs), which cause the vast majority of cervical cancer, other anogenital cancers, and a subset of head and neck squamous cell carcinomas, encode three oncogenes: E5, E6, and E7. To determine the oncogenic properties of HPV16 E5 in vivo, we previously generated K14E5 transgenic mice, in which expression of E5 was directed to the basal compartment of stratified squamous epithelia. In these mice, E5 induced epidermal hyperplasia and spontaneous skin tumors. In the current study, we determined how E5 contributes to tumor formation in the skin using a multistage model for skin carcinogenesis that specifies the role of genes in three stages: initiation, promotion, and malignant progression. Both initiation and promotion are required steps for papilloma formation. K14E5 mice treated with the initiating agent 7,12-dimethylbenz(a)anthracene (DMBA) developed more papillomas than like-treated nontransgenic mice, whereas neither K14E5 nor nontransgenic mice treated with the promoting agent 12-O-tetradecanoylphorbol-13-acetate (TPA) developed papillomas. K14E5 mice treated with both DMBA and TPA to induce large numbers of papillomas had a higher incidence and earlier onset of carcinoma progression compared with like-treated nontransgenic mice. Thus, HPV16 E5 contributes to two stages of skin carcinogenesis: promotion and progression. The progressive neoplastic disease in K14E5 mice differed from that in nontransgenic mice in that benign tumors converted from exophytic to endophytic papillomas before progressing to carcinomas. Initial genetic and immunohistopathologic analyses did not determine the underlying basis for this distinct morphology, which correlates with a highly penetrant neoplastic phenotype.  (+info)

Gene expression profiling from formalin-fixed paraffin-embedded tumors of pediatric glioblastoma. (56/216)

PURPOSE: Gene expression profiling has proved crucial for understanding the biology of cancer. In rare diseases, including pediatric glioblastoma (pGBM), the lack of readily available fresh frozen (FF) material limits the feasibility of this analysis, as well as its validation, on independent data sets, a step needed to ensure relevance, mandating the use of alternate RNA sources. To overcome the limitation of material number and to validate results we obtained on FF pGBM, we did microarray analysis on RNA extracted from formalin-fixed, paraffin-embedded archival samples from pGBM and control brains, wherein we had no control on the fixation process. EXPERIMENTAL DESIGN: RNA from 16 pGBM and 3 control brains was extracted and linearly amplified. Reverse transcription-PCR on housekeeping and formerly identified tumor-associated genes and microarray analysis were done on this RNA source. Results were validated by immunohistochemistry. RESULTS: Despite extensive RNA degradation, microarray analysis was possible on 16 of 19 samples and reproduced the pattern of results obtained on FF pGBM. Gene lists and ontology subgrouping were highly concordant in both sample types. Similar to the findings on FF samples, we were able to identify two subsets of pGBM based on their association/lack of association with evidence consistent with an active Ras pathway. CONCLUSIONS: Archival formalin-fixed, paraffin-embedded tissues are an invaluable resource as they are the most widely available materials often accessible in conjunction with clinical and follow-up data. Gene expression profiling on this material is feasible and may represent a significant advance for understanding the biology of rare human diseases.  (+info)