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Biomedical subjects

C R Taylor

Publications and source records attributed to C R Taylor.

At least 199 records · Page 11Linked to original sources

Audibility of the fourth heart sound. Relationship to presence of disease and examiner experience.

To determine the meaning of an audible fourth heart sound (S4), 51 subjects (21 normal and 30 abnormal persons), aged between 38 and 74 years (mean, 55.4 years), were examined by nine "blinded" physicians (four cardiologists, five house staff officers). Audibility scores were compared with phonocardiographic, echocardiographic, and hemodynamic measurements. An S4 was recorded graphically in 35 (68.6%) of all 51 subjects and splitting of the first sound (S1), in 37 subjects (72.5%). The abnormal group did not differ significantly from the normal subjects in incidence of recordable S4 or splitting of S1. Audibility of S4, however, correlated with its recorded amplitude, size, and palpability of the presystolic apical impulse, left ventricular systolic and diastolic diameters, and history of myocardial infarction. Despite variation among examiners, house staff officers were likelier than cardiologists to believe an S4 present even in cases lacking a recordable S4 and in normal subjects and were more apt to believe an S4 present when splitting of S1 was identified graphically. We conclude that an audible S4 continues to provide evidence for cardiac disease, and that increasing examiner experience renders this finding fairly specific. Less experienced examiners are likelier to confuse splitting of S1 with the S4, suggesting that training should be focused on means to improve this differentiation.

Adult↗

Immunohistologic identification of phenotypic antigens associated with Hodgkin and Reed-Sternberg cells. A paraffin section study.

A combination of two monoclonal antibodies, designated LN-1 and LN-2, were used in an attempt to identify the corresponding antigens in Hodgkin and Reed-Sternberg cells. The LN-1 antibody has been shown in previous studies in our laboratories to identify follicular center cells, whereas LN-2 marks certain B-cell subpopulations as well as interfollicular histiocytes. Utilizing the peroxidase-antiperoxidase (PAP) technique, paraffin-embedded sections were examined representing 39 cases of various histologic subgroups of Hodgkin's lymphoma following immunostaining with LN-1, LN-2, and the antibody to S-100. Of these 39 cases, the LN-2 antibody was found to consistently mark the majority of Hodgkin and Reed-Sternberg cells. LN-1 was found to identify Hodgkin and Reed-Sternberg cells in a smaller number of cases. In no instance were Hodgkin or Reed-Sternberg cells found to mark for the S-100 protein. The use of LN-1 and LN-2 antibodies facilitated the identification of Hodgkin and Reed-Sternberg cells and produced additional information regarding the phenotypic nature of these cells.

Antibodies, Monoclonal↗

Serum beta-2 microglobulin levels in homosexual men with AIDS and with persistent, generalized lymphadenopathy.

In order to investigate the nature of the immune disorders associated with the acquired immune deficiency syndrome (AIDS) and the AIDS-related condition of persistent, generalized lymphadenopathy (PGL), serum beta-2 microglobulin (beta 2-M) levels were determined in patients with AIDS and PGL and in asymptomatic homosexual and heterosexual controls. Sixteen of 20 (80%) patients with AIDS exhibited elevated beta 2-M levels. In contrast, 20 of 44 (45%) patients with PGL, 4 of 20 (20%) asymptomatic homosexuals, and only 3 of 46 (7%) heterosexuals had increased serum beta 2-M levels (P less than 0.001). When considering mean levels of beta 2-M, only the asymptomatic control individuals had normal values. AIDS patients had significantly higher mean beta 2-M levels when compared to all other groups (P less than 0.05). The mean level for PGL patients was greater than that in the homosexual and heterosexual controls (P less than 0.05). No relationship was found between presence of antibody to human T-lymphotropic retrovirus (HTLV-III) and beta 2-M levels in the patients with AIDS or PGL. The authors conclude that beta 2-M is elevated in patients with AIDS and PGL, suggesting an increased turnover of a certain subpopulation of lymphocytes in these patients. Beta 2-M levels also appear to parallel disease activity, as well as immune dysfunction, with the greatest elevation occurring in patients with AIDS, followed by those with PGL, and asymptomatic homosexuals. Beta 2-M levels may be a useful confirmatory marker in AIDS and its related disorders.

Acquired Immunodeficiency Syndrome↗

A novel immunoperoxidase procedure of using human monoclonal antibodies for the detection of cellular antigens in tissue sections.

A sensitive immunoperoxidase method was utilized to detect binding of human monoclonal antibodies to cellular antigens in formalin-fixed and paraffin-embedded tissue sections. The method was a 2-layer system utilizing biotin-labeled human monoclonal antibody and an avidin-biotin-horseradish peroxidase complex (ABC). A comparative study of this and a 4-layer peroxidase-antiperoxidase (PAP) staining method was made. In the PAP system, the monoclonal was followed by rabbit anti-human IgG, swine anti-rabbit IgG as the bridge-antibody and rabbit PAP complex. In both cases, the reaction was visualized by the use of aminoethylcarbazole (AEC) as chromogens. The former procedure was almost as sensitive and, most importantly eliminated an inherent problem associated with the latter namely the difficulty in distinguishing binding of the primary human monoclonal antibody from endogenous human Igs in tissue section. In addition, the 2-stage ABC procedure by comparison requires almost half the time.

Antibodies, Monoclonal↗

The distribution of lysozyme, alpha-1-antitrypsin, and alpha-1-antichymotrypsin in normal hematopoietic cells and in myeloid leukemias: an immunoperoxidase study on cytocentrifuge preparations, smears, and paraffin sections.

Blood and bone marrow samples from 20 individuals with reactive conditions and 26 cases of acute and chronic myeloid leukemias were tested for the presence of lysozyme, alpha-1-antitrypsin (alpha-1-AT), and alpha-1-antichymotrypsin (alpha-1-ACT). We compared the reactivity of samples in smears, cytocentrifuge preparations, and paraffin sections. Lysozyme, alpha-1-antitrypsin, and alpha-1-antichymotrypsin were found only in polymorphonuclear leukocytes and monocytes and their precursors. Lymphocytes, E-rosetting cells, Con A-activated lymphocytes, natural killer (NK) cells, red blood cells, erythroblasts, and megakaryocytes were consistently negative. Leukemic myeloblasts showed definite reactivity for both alpha-1-antitrypsin and alpha-1-ACT, but not for lysozyme. By contrast, lysozyme was present in poorly differentiated leukemic monoblasts, while alpha-1-antitrypsin and alpha-1-antichymotrypsin showed only weak reactivity. More mature myeloid and moncytic cells showed positive staining for all three antigens tested with differences in staining distribution and intensity. In four cases of chronic myeloid leukemia (CML), circulating mature polymorphonuclear leukocytes were deficient in both lysozymne and alpha-1-antitrypsin. The use of lysozyme, alpha-1-antitrypsin, and alpha-1-antichymotrypsin identifies normal and leukemic cells of the myeloid-monocytic series at all stages of maturation and is applicable to a variety of sample preparations.

Bone Marrow↗

Periostitis and osteomyelitis in chronic drug addicts.

Periostitis and osteomyelitis can occur in drug addicts not only by hematogenous dissemination of the infecting organisms, but as a result of introduction of bacteria by direct injection into periosteum or injection through infected skin and subcutaneous tissues. A spectrum of examples of osteomyelitis of the bones of the forearm in drug addicts is presented to illustrate this phenomenon. Neglect of these infections and the trauma of continued injections can lead to extensive tissue and bone loss.

Adult↗

The differentiation antigens of macrophages in human fetal liver.

Macrophage populations from human fetal liver were examined for the sequential appearance of different antigenic determinant during maturation. Frozen sections of liver, from 12 to 21 weeks gestation were analyzed using a series of four monoclonal antibodies with known specificity. The macrophage monoclonal antibodies used were OKM-1, which defines monocytes, macrophages, and granulocytes; Leu M-3 and MO-2, which identify monocytes and macrophages; and 6B8, a new macrophage monoclonal antibody which binds to tissue macrophages. The staining pattern described by each of these monoclonal reagents was compared with the distribution of morphologically distinguishable tissue macrophages in fetal liver, based on the expression of surface and/or cytoplasmic antigens. The data indicate that the antigens defined by OKM-1 and 6B8 are present on large numbers of cells as early as 12 weeks gestation. In contrast, the antigenic determinants identified by Leu M-3 and MO-2 are present only on cells in 15 to 21 weeks of gestation; thus these antigens are mature differentiation antigens. Furthermore, double-staining studies confirmed that with the increase in fetal age unique macrophage populations can be identified based on the matrix of antigenic determinants. Thus, macrophage heterogeneity in the fetal liver may be a function of maturation.

Antibodies, Monoclonal↗

Acute leukemias with both myeloid and lymphoid surface markers. Cytoplasmic alpha-1-anti-chymotrypsin and alpha-1-anti-trypsin as possible indicators of early granulocytic differentiation.

Blast cells from ten patients (seven adults, three children) with acute lymphoblastic leukemias (ALL) contained immunoreactive cytoplasmic alpha-1-anti-trypsin (alpha-1-AT) and alpha-1-antichymotrypsin (alpha-1-ACT). Cytochemically positive reactions for block-like periodic acid-Schiff and a localized acid phosphatase suggested that the cells were of lymphoid origin rather than myeloid origin: negative for sudan black-B, nonspecific esterase, chloroacetate esterase, and myeloperoxidase. By surface phenotype, the leukemia showed positive reactions for both lymphoid (common acute lymphoblastic leukemia antigen, Ia, OKT-10) and myeloid (OKM-1, Leu M-1) antigens. Three of three patients tested portrayed the Philadelphia chromosome. Nine patients were Mexican-American and one was Japanese: all were of Asian ethnic derivation. Both myeloid and lymphoid treatment regimens were employed, with survival less than expected. Early granulocytic differentiation detectable by cytoplasmic alpha-1-AT and alpha-1-ACT in lymphoid blasts is discussed.

Adult↗

Human monoclonal antibodies that distinguish cutaneous malignant melanomas from benign nevi in fixed tissue sections.

Human monoclonal antibodies were generated by fusing a nonsecretory variant of murine myeloma cells with lymphocytes obtained from the lymph nodes of patients with metastatic cutaneous malignant melanoma. Two human IgG monoclonal antibodies, designated 2-139-1 and 6-26-3, were extensively studied for their patterns of binding to cells in 64 specimens of formalin-fixed, paraffin-embedded tissue sections. These comprised: 23 cutaneous and 2 ocular melanomas; 4 specimens of lentigo maligna; 27 benign nevi; 2 basal and 2 squamous cell neoplasms of the skin; and 4 specimens of normal skin. A direct avidin-biotin-immunoperoxidase staining method was used. Under these conditions, the antibodies reacted with variable intensity to all 18 primary cutaneous malignant melanomas, 5 metastatic cutaneous melanomas, and both ocular melanomas. Antibody 2-139-1 reacted with 1 of 4 specimens and 6-26-3 with 3 of 4 specimens of lentigo maligna. Two of 5 dysplastic nevi reacted with both antibodies, each with a smaller proportion of cells than with melanomas. There was no reactivity with the 22 other nevi representing a spectrum of histologic types or with normal melanocytes. Basal cell and squamous cell carcinomas of the skin also were not stained. These human monoclonal antibodies appear to be useful in distinguishing malignant melanomas from benign nevi, with the exception of dysplastic nevi, and from basal and squamous cancers of the skin in routinely prepared tissue sections. They may also help to identify the cytoplasmic antigens that are immunogenic in humans.

Antibodies, Monoclonal↗

Bone strain: a determinant of gait and speed?

Principal strains were recorded in vivo from the radial and tibial midshafts of three goats as they increased speed and changed gait. These data were compared with strain data measured for the radius and tibia of the dog (Rubin & Lanyon, 1982) and the horse (Biewener, Thomason & Lanyon, 1983b) in order to test the hypothesis that similar peak bone strains (stresses) occur at functionally equivalent points in the gaits of different species. Multiple recordings of in vivo strain along the caudal diaphyses of the radius and tibia of one goat were made to test the validity of this technique for measuring peak locomotor stress. Measured strains were extremely consistent over the animal's full range of speed (coefficient of variation for the radius 0.05-0.08, and for the tibia 0.06-0.11). The data from the three gauges, which were spaced 15 mm apart, demonstrated that maximal strains act at the midshaft, substantiating the use of this technique to measure peak locomotor bone strains. Strain levels recorded at the trot-gallop transition and top galloping speeds of the goat were similar to the values reported for the dog and horse, despite large differences in absolute speed (goat, 4.3 ms-1; dog, 6.9 ms-1; horse, 7.5 ms-1 at maximum gallop). The second moments of area of the tibia and radius (+ ulna) of the dog are 29% and 113% greater than for goats of equal size, explaining how similar strains are achieved in the dog at higher speeds than the goat. Furthermore, peak bone strains recorded at the fastest trotting speed were similar to those recorded at the fastest galloping speed for each species. Peak strains recorded for the goat at a maximum gallop correspond to stresses of +37.9 MPa (cranial) and -47.7 MPa (caudal) in the radius and +36.3 MPa (cranial) and -50.3 MPa (caudal) in the tibia, representing a safety factor to yield failure of three.

Animals↗

Preferential expression of a Mr 155,000 milk-fat-globule membrane glycoprotein on luminal epithelium of lobules in human breast.

An integral membrane glycoprotein with an apparent molecular weight of 155,000 and isoelectric points ranging from 7.2 to 7.6 has been found to be predominantly expressed on the apical plasma membrane of luminal epithelial cell lining the lobules and terminal ducts in breast. The glycoprotein was purified to homogeneity from human milk-fat-globule membrane and was termed MFGM-gp 155. Polyclonal antibodies were raised which specifically reacted to a single component that electrophoretically comigrated with this glycoprotein in immunoblotting experiments. These antibodies appear to recognize epitopes which are expressed on the protein segment of the glycoprotein. Using an indirect immunohistological method, the glycoprotein was localized predominantly on the apical plasma membrane of luminal epithelial cells lining the alveoli of normal breasts. The expression of the antigen was maintained in both morphologically well- and poorly differentiated lobular carcinoma cells. The antigen was weakly detectable on normal epithelial cells lining the terminal ducts and malignant cells of infiltrating ductal and medullary carcinomas. Expression of the glycoprotein is not organ specific as it is detectable in normal epithelial cells of kidney, pancreas, salivary gland, and stomach and in malignant cells of colon and stomach. The antibodies did not react with large ductal, myoepithelial, stromal, endothelial, epidermal squamous epithelial cells, melanocytes, eccrine sweat glands and ducts, sebaceous glands, erythrocytes, and lymphocytes in breast and skin tissues. Thus, antibodies to this glycoprotein appear to be useful phenotype markers to study differentiation of mammary epithelial cells and the pathogenesis of different histological types of mammary carcinomas, including Paget's disease and signet-ring cell carcinoma of mammary gland.

Antibodies↗

Proximal renal tubular surface membrane antigens identified in primary and metastatic renal cell carcinomas.

Polyclonal antibodies to the brush border membrane of the human renal proximal tubule were found to identify two proteins with apparent molecular weights of 35,000 and 46,000 daltons. The antigens are distinct in their molecular weights from other antigens that have been localized to the human proximal tubular brush border. The antibodies were extensively studied for their immunoreactivity to fixed, embedded tissue sections by indirect immunoperoxidase staining. These sections were from 36 primary and 37 metastatic renal cell carcinomas, three renal oncocytomas, 87 cases of 28 different types of neoplasms, and 33 different types of normal tissues. Ninety-four percent of primary and 78% of metastatic renal cell carcinomas demonstrated expression of the antigens. Eight cases in which both primary tumor and its metastases were available revealed a general quantitative decrease in expression of the antigens in the metastases. Specificity analysis revealed immunoreactivity to the luminal surfaces of cells lining the epididymis, breast lobule, and bile ductules; the cytoplasm of the submandibular gland ductules; and to some adenocarcinomas of lung, breast, and small intestine, astrocytomas of brain, and squamous carcinomas of skin. The antibodies may be of some utility in the surgical pathology laboratory to help determine the primary site of metastatic clear cell tumors and may also be of use in the in vitro differentiation of renal epithelial cells. Development of monoclonal antibodies to these antigens may improve specificity and clinical utility.

Animals↗

Human monoclonal antibodies directed against melanoma tumor-associated antigens.

To analyze the humoral immune response to melanoma, human-mouse hybridomas were generated by the fusions of regional lymph node lymphocytes of patients with the mouse myeloma cell line M5. Six stable hybridomas were cloned from six separate lymphocyte parents obtained from three patients. Ascites were obtained from nude mice after i.p. injection with cultured hybridoma cells. The monoclonal antibodies, four immunoglobulin Gs and two pentameric immunoglobulin Ms, were partially purified to remove mouse immunoglobulin and then conjugated to biotin for immunocytochemical and immunohistochemical studies. With the avidin:biotin:peroxidase complex method to detect and amplify binding by the biotin-conjugated human monoclonal antibodies, we found the six antibodies to be reactive against cytoplasmic determinants in five short-term melanoma cultures and formalin-fixed paraffin-embedded melanoma tumors from four patients. The antigenic target of the antibodies identified was not carcinoembryonic antigen. Two antibodies, 2-139-1 and 6-26-3, were studied in more detail. Each stained 25 of 25 specimens of melanomas. Little or no reactivity was detected against fixed sections of normal skin, which included tissues such as epidermis, dermis, monocytes, lymphocytes, and vascular endothelium. More striking was the absence of binding to melanocytes in the basal layer of the skin or to pigmented nevus cells. Both antibodies showed cross-reactivity against other tumors, in particular colonic and prostatic carcinomas. In the normal colon, reactivity was restricted to the surface of the columnar epithelium; no reactivity was detected against normal prostatic epithelium. Reactivity was also not observed against liver and lung. However, the epithelia of the renal tubules, pancreatic ducts, and salivary ducts were all reactive. These human monoclonal antibodies identify cytoplasmic melanoma-associated tumor antigens that appear different from the membrane antigens defined by serological approaches and by most mouse monoclonal antibodies.

Antibodies, Monoclonal↗

Monoclonal antibodies reactive with B-lymphocytes and histiocytes in paraffin sections.

Representative sections of normal lymph nodes, cases of reactive lymphadenopathy, and Hodgkin's disease were examined using two monoclonal antibodies reactive in paraffin sections using an immunoperoxidase technique. Antibody LN-1 recognizes B-lymphocytes in follicles; antibody LN-2 recognizes a broader spectrum of B-cells, and also shows positivity with some monocytes/histiocytes. The pattern of immunostaining with these antibodies is described with particular reference to Hodgkin The pattern of immunostaining with these antibodies is described with particular reference to Hodgkin and Reed-Sternberg cells. Some of the implications are discussed.

Antibodies, Monoclonal↗

B- and T-lymphocytes in Hodgkin's disease. An immunohistochemical study utilizing heterologous and monoclonal antibodies.

Immunohistologic techniques utilizing monoclonal antibodies have made possible the identification of leukocytes by their phenotypic characteristics rather than by morphologic features alone. A panel of antibodies for T-lymphocyte, B-lymphocyte, and monocyte/histiocyte markers has been applied to frozen sections of nodular sclerosing and mixed cellularity Hodgkin's disease to identify more precisely the various cell types present in tissues involved in Hodgkin's disease. The majority of lymphocytes expressed detectable T-cell phenotypic markers, with a predominance of the "helper" phenotype (Leu 3/OKT4) in most cases. Lymphocytes reacting with anti-B-cell antibodies were also demonstrated; their distribution is described here and has not previously been reported. The anti-B- and anti-T-cell antibodies used in this study failed to give positive reactivity with Reed-Sternberg cells. However, one of the anti-monocyte antibodies (Leu-M1) reacted with diagnostic Reed-Sternberg cells in some cases. The patterns of staining observed varied widely within the two histologic types of Hodgkin's disease, leading to a conclusion that this disease may be more heterogeneous than is currently suspected.

Antibodies, Monoclonal↗

Tn, a carcinoma-associated antigen, reacts with anti-Tn of normal human sera.

Tn antigen is the immediate precursor of the carcinoma (CA)-associated T antigen; both are masked in non-CA tissues. Tn antigen was detected by absorption of human anti-Tn antibody in 46 of 50 primary breast CAs and in all 6 metastases originating from Tn-positive primary CAs. Thirteen of 25 (52%) anaplastic CAs, but only 2 of 15 (13%) well differentiated CAs had more Tn than T; 1 anaplastic CA had neither antigen. Eighteen of 20 benign breast lesions had no Tn; the 2 positive lesions were premalignant. All 19 breast CAs, studied immunohistochemically, reacted strongly with human polyclonal anti-Tn; benign or normal glandular tissues had minimal or no reactivity. Among live cancer cell lines, the most malignant sublines had more Tn than T on their cell surfaces. Preliminary studies with rodent monoclonal anti-Tn and anti-T antibodies gave immunohistochemical reactivity patterns similar to those of the polyclonal antibodies, but the former were less sensitive in absorption tests. Tn is a CA marker that promises to be useful in tumor detection.

Animals↗