Search PubMed⌕ Search

Biomedical subjects

H A Azar

Publications and source records attributed to H A Azar.

At least 19 recordsLinked to original sources

Arthur Purdy Stout (1885-1967), a pioneer of surgical pathology: a survey of his Notes on the Education of an "Oncological" Surgical Pathologist.

Arthur Purdy Stout (1885-1967) started his medical career as a surgical intern and house surgeon at institutions that were to join the Columbia-Presbyterian Medical Center. With virtualy no formal training in pathology and little supervision, he was given the opportunity to work in a laboratory of surgical pathology. He focused his attention on neoplasms and tumor-like conditions, and authored Human Cancer in 1932. This book was organized according to topography of lesions and set a model for the Atlas of Tumor Pathology project. In addition to his many articles and slide seminars, Stout embarked during his "postretirement" years, with the help of residents and fellows, on a systematic study of soft tissue tumors in children. In 1950, he also began his Notes on the Education of an "Oncological" Surgical Pathologist. This manuscript of 427 typewritten pages offers candid details on his development as a surgical pathologist from rather primitive and chaotic beginnings, and on the post-World War II rise of surgical pathology. Notes provides interesting glimpses of his rapidly changing world, particularly of New York, the College of Physicians and Surgeons of Columbia University, and other pathologists. It also portrays an individual absorbed by his work and intent on leaving behind the legacy of a pioneer in the field of surgical pathology.

Academic Medical Centers↗

Rudolf Virchow, not just a pathologist: a re-examination of the report on the typhus epidemic in Upper Silesia.

Rudolf Virchow (1821-1902) is mainly remembered as the "father" of cellular pathology; however, he was not just a pathologist. His contributions to anthropology, archeology, ethnography, and history, as well as his involvement in epidemiology, public health, and politics, portray a man with multiple interests, deeply engaged in the controversies of his time. In his Report on the Typhus Epidemics of Upper Silesia of 1848, the young Virchow reveals himself to be a self-assured pathologist, although his postmortem examinations failed to shed much light on typhus. Despite of his shortcomings and biases, Virchow's genius is revealed in his deep appreciation of the importance of the total physical, socio-cultural, economic, and political background of epidemic diseases. One can discern in the Report the making of Virchow, the politician and statesman who will contribute to the modernization of Germany's public health, and of the physician-scholar and physician-citizen who, despite of his shortcomings and militancy, continues to inspire and challenge us today.

Disease Outbreaks↗

Percutaneous needle autopsy sampling.

Despite the recognized advantages of a complete postmortem examination, autopsy rates continued to decline in recent decades. This study compares postmortem needle sampling to the complete, conventional autopsy to determine whether needle sampling is a viable alternative when consent for a complete autopsy is denied. A prospective study where postmortem percutaneous biopsies were obtained from the heart, the lungs, the liver, the kidney, and any other clinically relevant tissue or body fluid before the complete autopsy in 20 consecutive patients is presented. Cultures of the lungs, the spleen, and any other suspicious body fluid were also obtained. Liver and heart were recovered from all 20 of the patients, lung from 18 (90%), and kidney from 16 cases (80%). The cause of death was confirmed in 67% of the patients. Needle sampling correlated with the complete autopsy in 87% of the additional major diagnoses and with equally pertinent negative results. Postmortem needle lung cultures correlated with the complete autopsy in 17 (85%) of 20 patients and 16 (80%) of 20 spleen cultures. Cultures of the brain (one patient), cerebrospinal fluid (two patients), peritoneum (two patients), and serum (one patient) correlated 100% when compared to the complete autopsy. A complete autopsy is the goal of every postmortem examination. Postmortem "biopsies" can be an alternative option in certain situations and may be more acceptable to relatives of the deceased when consent for a complete autopsy is declined.

Adolescent↗

Plasma levels of a squamous cell carcinoma-associated antigen in athymic nude mice bearing human squamous cell carcinoma xenografts of oral origin. With preliminary clinical data.

A human squamous cell carcinoma (SCC) of oral origin was transplanted into athymic mice that were then divided into six groups. The mice were killed at 1 to 6 weeks after tumor transplantation; the sixth group was killed 1 week after excision of SCC grafts. Plasma samples were obtained from each mouse at the time of death for the determination of SCC-associated antigen (SCCAA), a cytoskeletal protein fraction of about 48,000 daltons originally derived from SCC of the uterine cervix. The plasma SCCAA level rose gradually and proportionately to the growth of SCC xenografts from a baseline of 0.66 ng/ml [standard error (SE) + 0.12] to the preoperative peak of 8.44 ng/ml (SE + 1.86) at 5 weeks, to fall precipitously to the postoperative level of 1.05 ng/ml (SE + 0.27) at 6 weeks. No rise in plasma SCCAA level was observed in mice bearing a human malignant melanoma, and only modest rises were observed in mice bearing human adenocarcinomas and oat cell carcinoma. In this experimental model rising plasma SCCAA levels were found to be dependable indicators of SCC tumor growth. These observations and preliminary data on SCCAA levels in patients with or without SCC of the head and neck lend support to the clinical usefulness of serial plasma SCCAA determinations in monitoring patients with SCC of the oral cavity.

Animals↗

Intraperitoneal administration of an I125 labelled monoclonal antibody for localization of human colorectal cancer in the nude mouse.

The monoclonal antibody (MoAb) HMGF-1 was evaluated in the radioimmunodetection of human colonic cancer transplanted intraperitoneally (i.p.) into athymic nude mice. This antibody reacts with a component of the human milkfat globule, as well as a wide range of epithelial cells and adenocarcinomas of various origins. Purified MoAb was iodinated with 125I and administered i.p. into nu/nu mice bearing (i.p.) xenografts of human colonic adenocarcinoma (X56). Differential tissue counts of radioactivity demonstrated preferential localization of the antibody in i.p. and subcutaneous (s.c.) tumor tissue as compared to normal tissues. Maximum per cent dose per g of tumor (25.17 +/- 1.37), maximum tumor: blood ratio (4.45 +/- 0.14) and maximum tumor: tissue ratios (34.2 +/- 0.12) were obtained at the optimal labelling time of 5 days after antibody injection. Selective localization to tumor was confirmed with a control anti-hepatitis virus MoAb of the same isotype and by localization studies in non-tumor bearing athymic mice. Half lives of the persistence of the iodine 125 in the tumor bearing and non tumor bearing mice were 5 and 7 days, respectively, indicating approximate antibody half lives. Whole body scans showed distinct tumor images without the use of subtraction techniques. This pilot experimental study demonstrates the feasibility of i.p. administration of labelled antitumor MoAb in the imaging of i.p. tumors in an athymic mouse system. Whether or not these observations are applicable to the human situation remains to be carefully established.

Adenocarcinoma, Mucinous↗

Filiform large-cell lymphomas. An ultrastructural and immunohistochemical study.

Ten cases of "undifferentiated" large-cell tumors were ultrastructurally characterized by cells with abundant filiform cytoplasmic projections without intercellular junctions. These cases were studied by means of the avidin-biotin-peroxidase complex (ABC) technique applied to formalin-fixed, paraffin-embedded sections using antibodies against high- and low-molecular weight keratins (Ker), vimentin (Vi), epithelial membrane antigen (EMA), S-100 protein, leucocyte common antigen (LCA), kappa (K) and lambda (L) light chains, Leu-M1, lysozyme (Ly), alpha-1 antitrypsin (A1AT) and alpha-1 antichymotrypsin (A1ACT). All 10 cases were negative for Ker and EMA but positive for Vi. S-100 was present only in scattered dendritic cells. LCA was identified in seven cases. In the three LCA-negative cases, two stained for Leu-M1, and one of these also showed intracytoplasmic L; one was negative for all markers but Vi. None of the tumors showed any significant staining for Ly, A1AT, or A1ACT. Our findings indicate that these tumors are nonepithelial and nonneuroectodermal, and that they are best classified as non-Hodgkin's lymphomas. The possibility that some of the filiform large-cell lymphomas may be derived from dendritic reticular cells cannot be excluded.

Adult↗

Application of immunochemistry to the diagnosis of human neoplasms in routine histologic sections.

The application of immunostaining techniques to the study of sections of formalin-fixed, paraffin-embedded tissues has deeply influenced the practice of surgical pathology of tumors. We have favored in our laboratory the avidin-biotin complex immunoperoxidase method and have gradually substituted monoclonal antibodies for polyclonal sera. Better results are sometimes obtained with trypsinization prior to the application of the primary antibody. The more common primary antibodies used are directed against the following categories of cellular antigens: intermediate filaments, oncofetal products, hormones or hormone-related peptides, enzymes or enzyme-related peptides, cell- or tissue-"specific" products, lymphocyte-leukocyte antigens, and immunoglobulin chains. Controls are essential to every immunohistochemical reaction. Because of the pitfalls of immunohistochemical techniques, immunohistochemistry as applied to the study of tumors should be used with utmost care and as an extension of routine surgical pathology.

Antibodies, Monoclonal↗

Carcinomas of the lung: an ultrastructural and immunocytochemical study.

Fifty-two primary carcinomas of the lung were studied by electron microscopy and by an immunoperoxidase method, using an anti-human keratin antiserum. The results were compared with light microscopic observations. One-third of the carcinomas of the lung showed ultrastructural evidence of both glandular and squamous differentiation. The group of small cell carcinomas was found to be particularly heterogenous ultrastructurally with only three out of eight tumors showing neurosecretory-type granules. Indirect immunoperoxidase staining revealed presence of a keratin-type protein in the vast majority of carcinomas, including foci of small cell carcinomas. Our studies emphasize the heterogeneity and frequent intermixing of the four major categories of lung carcinomas: squamous cell carcinomas, adenocarcinomas, small cell carcinomas, and large cell carcinomas. It is suggested that all these tumors might be derived from pluripotential "reserve" bronchial or bronchioalveolar cells. The segregation of small cell carcinomas from other groups continues to be justified on pragmatic grounds because these carcinomas constitute a group of predominantly small fast-replicating cells amenable to chemotherapy.

Adenocarcinoma↗

"Undifferentiated" large cell malignancies: an ultrastructural and immunocytochemical study.

One of the most difficult areas of surgical pathology is the classification of "undifferentiated" or "anaplastic" large cell malignant tumors. The differential diagnosis of these tumors includes poorly differentiated carcinomas, large cell malignant lymphomas, and amelanotic malignant melanomas. In this study of 56 such cases, the application of electron microscopy and, in selected instances, of indirect immunofluorescence and immunoperoxidase staining methods have helped us reach a precise histopathologic diagnosis in the majority of neoplasms that were considered to be "undifferentiated" by light microscopy.

Adolescent↗

Immunohistochemical localization of keratin-type proteins in epithelial neoplasms. Correlation with electron microscopic findings.

A rabbit antiserum prepared against human keratins isolated from calluses was applied to sections of 108 neoplasms using indirect immunofluorescence and immunoperoxidase technics. The vast majority of epithelial neoplasms were strongly positive for keratin-type proteins, even in the absence of obvious keratinization or squamous differentiation as revealed by light microscopy. This keratin-positivity was invariably correlated with the identification of intermediate-sized filaments arranged in loose or dense bundles in the cytoplasm of neoplastic epithelial cells. Keratin-negative neoplasms included nevi, malignant melanomas, carcinoid tumors, malignant lymphomas, and a variety of connective-tissue tumors. Immunologic identification of keratin-type proteins was particularly helpful in establishing the epithelial nature of "undifferentiated" malignant tumors, including oat cell carcinomas.

Adenocarcinoma↗

Synthesis of pro-collagen type II by a xenotransplanted human chondroblastic osteosarcoma.

The chondroblastic component of a human osteosarcoma was established as a transplantable tumor in nude athymic mice for the first time. The collagen biosynthetic production of the excised tumor was studied in organ culture. The majority of the collagen secreted in the culture media was pro-Type II as identified by diethylaminoethyl cellulose (DEAE cellulose) chromatography, gel electrophoresis, and cyanogen bromide cleavage. This system should be useful for producing large quantities of human pro-Type II collagen and for studying neoplastic cell switching of collagen synthesis.

Adult↗

Diffuse large cell lymphomas (reticulum cell sarcomas, histiocytic lymphomas). Correlation of morphologic features with functional markers.

Electron microscopic findings in 15 cases of diffuse large cell lymphoma were correlated with other morphologic features, surface immunotype and cytoplasmic immunoglobulin content. Immunologically, the cases were: B cell, 8; null, 4; T cell, 2; and H cell (true histiocytic), 1. Ultrastructurally, all B cell and three null lymphomas were characterized by an abundance of polyribosomes and segments of rough endoplasmic reticulum. Concentric rough endoplasmic reticulum was observed in 4 cases of B cell lymphoma containing cytoplasmic immunoglobulin and in a null lymphoma. In 1 case of B cell lymphoma, the diastase-sensitive, periodic-acid-Schiff-positive cytoplasm showed evidence of widely dispersed monoparticulate glycogen granules. The two T cell lymphomas contained hyperlobulated or single round nuclei, and abundant smooth to rough endoplasmic reticulum. One null lymphoma appeared to share the ultrastructural features of T cell convoluted nuclei and the cytoplasmic organelles of myeloid precursor cells. The H cell lymphoma had features of monocytic-macrophagic differentiation. The large cell lymphomas, a morphologically and functionally heterogeneous group, were represented predominantly in this series by neoplasms with follicular center cells or early plasma cells.

Antigens, Neoplasm↗

N:NIH(S)-nu/nu mice with combined immunodeficiency: a new model for human tumor heterotransplantation.

A new "nude" mouse model was developed by successive crossings and backcrossings between athymic nu/nu mice, on an N:NIH(S) background, and female CBA/N mice that have an X-linked immune defect in B-lymphocyte function. The resulting doubly congenic N:NIH(S(II-nu/nu mice maintained the marked thymic hypoplasia and poor development of hair of the nu/nu mice. In contrast to nu/nu and CBA/N mice, in this new mouse model both T-cell zones of lymph nodes and the spleen were depleted of lymphocytes. Lymphocytic follicles were rare and diminutive; not germinal centers were noted. The nodal cortical and paracortical areas were represented principally by connective tissue, endothelial cells, and macrophages, including giant multinucleated cells. No medullary cords were recognized. The mice with combined immunodeficiency supported the growth of human tumor xenografts and were susceptible to murine viral hepatitis.

Animals↗