Nursing care study. Von Recklinhausen's disease: a family team copes with tragedy.
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Biomedical subjects
Publications and source records attributed to P Gold.
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This study is to examine the potential usefulness of immunohistochemical staining for carcinoembryonic antigen (CEA)-like material in the differential diagnosis of mesotheliomas (12 cases) from other lung cancers (14 cases) that had been previously diagnosed by transmission and scanning electron microscopy and conventional light microscopy. Indirect immunofluorescent staining for CEA was carried out on formalin-fixed paraffin-embedded sections, and the slides were examined under code. All 9 cases of diffuse mesothelioma were negative, and all 12 cases of adenocarcinoma and bronchioloalveolar carcinoma were positive for CEA-like material. Three localized mesotheliomas and a carcinoid tumor were also negative. A squamous cell carcinoma was positive. A positive immunohistochemical result for CEA-like material in lung cancers will raise the possibility of its being of bronchial epithelial origin.
Immunofluorescent staining for carcinoembryonic antigen (CEA)-like material and immunoglobulin A (IgA) was performed on 54 gastric specimens showing normal mucosa and various lesions including malignancy. Both CEA-like material and IgA were demonstrated in normal mucosa and benign and malignant epithelial lesions. Abnormal findings in respect to CEA-like material included staining of cell membranes with disordered pattern and increased cytoplasmic staining. Several staining characteristics for CEA-like material were shown by various types of malignant epithelial tumors. This staining provides a means of distinguishing anaplastic carcinoma from histiocytic lymphoma, as the latter does not demonstrate CEA-like material. IgA was consistently absent in anaplastic carcinomas, but was noted on the inner surface of tubular components in the differentiated adenocarcinomas, indicating functional preservation in the differentiated tumors. Immunohistochemical staining for CEA-like material and IgA is considered to be useful in the structural and functional study of gastric malignancies.
Explored a multivariate approach to the prediction of 8-year academic achievement. Ss were black, of low socioeconomic status, and had been diagnosed as suspect neurologically impaired at age 7. A serial array of early predictors that included maternal education, sex, birth weight, 8-month and 4-year intelligence, and 3-year speech, hearing, and language were entered into multiple regression analyses to determine their value in predicting 8-year academic achievement in word recognition, arithmetic, spelling, and oral reading. The 4-year intelligence measure was the best overall predictor, although maternal education, sex, and birth weight contributed slightly to the predictions. The resulting equations, however, could not be used to predict accurately 8-year academic achievement.
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beta 2-Microglobulin is a low molecular weight protein that is found in most biological fluids. It was originally isolated from urine of cadmium-poisoned patients. Its amino acid sequence was established and shown to be structurally related to immunoglobulin constant domains. With the aid of antibodies specific against beta 2-microglobulin, the protein was detected on the membranes of all nucleated cells, normal and neoplastic. Measuring the quantity of beta 2-microglobulin showed that high levels are present in patients with renal tubular deficiencies and several other pathological conditions including neoplastic diseases. Extremely high levels were detected in seminal fluid and colostrum. Despite the structural relationship to immunoglobulins, no immunological relationship was demonstrated with these proteins using antibodies specific for beta 2-microglobulin. However, such antibodies are cytotoxic to all cells carrying beta 2-microglobulin on their surfaces. The discovery that beta 2-microglobulin is an integral part of the histocompatibility antigens of human and murine origin stimulated further research and interest in this molecule. Several groups of investigators have shown that beta 2-microglobulin is the low molecular weight chain and is noncovalently bound to a high molecular weight chain which carries the histocompatibility antigens. The structure of the histocompatibility antigens of lymphocytes (HLA) was shown by immunochemical as well as biological methods, and it is now well accepted. The antibodies against beta 2-microglobulin are extremely useful in the isolation of the histocompatibility antigens for sequence studies. Furthermore, the antibody to beta 2-microglobulin revealed that other structures may be bound to beta 2-microglobulin such as phytohemoagglutimin (PHA) receptors, mixed lymphocyte culture (MLC) antigens, etc. Murine thymus leukemia (TL) antigen also contains beta 2-microglobulin as an integral part of its structure; other tumor antigens may have a similar structure. Through all these studies, beta 2-microglobulin emerged as the best known membrane protein that can serve as a model for study of the arrangement and the function of the cell membrane.
Normal subjects were admitted to a psychiatric unit devoted to the study and treatment of affective illness. Initially the authors were concerned about the difficulties volunteers might have living with psychiatric patients. However, the volunteers adjusted with relative ease, while the patients' depressive symptoms were exacerbated. Their confrontation with the volunteers "normality" triggered an acute awareness of their underlying sense of failure. This response is analogous to depressed patients' reactions before discharge, when they struggle not only with their special vulnerability to separation and loss but with inevitable challenges to their fragile self-esteem during reintegration into the outside world. The presence of normal volunteers highlighted these issues and led to increased therapeutic work and considerable resolution.
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A patient with disseminated coccidioidomycosis initially had pulmonary and skin manifestations and survived for 14 years before dying of meningitis due to Coccidioides immitis. In addition to several courses of amphotericin B therapy the patient received injections of transfer factor derived from appropriate donors and miconazole nitrate therapy. The immunologic defence mechanisms of the patient during the course of his disease were studied and the possibility of a cell-mediated immunologic defect, potentially reversible by transfer factor, was demonstrated.
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A method for the isolation of HLA antigen molecules from normal and cancerous solid human tissue is described. The method employs anti-beta2-microglobulin (beta2m) antiserum coupled to Sepharose beads as an immunosorbent affinity medium. The anti-beta2m affinity chromatography procedure greatly purifies and selectively enriches HLA and any material that copurifies by affinity, with beta2m and/or HLA molecules. The HLA isolated by this purification procedure was used to immunize rabbits. The antisera obtained were absorbed on beta2m to remove all anti-beta2m antibody activity. The use of such anti-HLA antisera in radioimmunoassays, immunoprecipitation studies, and F(ab')2 blocking experiments demonstrated that these antisera are directed against a common HLA determinant present on the heavy (alloantigen-bearing) chain of all HLA molecules. The use of an identical procedure employing human tumor tissues has resulted in the isolation of HLA-like or HLA-associated tumor-specific antigens as demonstrated by the leukocyte adherence inhibition (LAI) assay.
In the present study the tube LAI assay was used to monitor the isolation of the TSA of 4 different types of human cancers. Each tumour antigen was found to be specific for tumours arising in the organ from which the TSA was initially derived and which were histopathologically similar. Immunochemical studies revealed that these molecules co-isolate with normal human HLA antigens and are associated with beta2m. On Sephadex G-150, the majority of the papain-solubilized tumour antigen eluted in the mol. wt range 70,000-150,000. Analysis of this material by SDS-PAGE and 6M guanidine-HC1 column chromatography indicated that the material is composed of smaller subunits with prominent peaks at approximately 40,000, 25,000 and 12,000 mol. wt. Immunoadsorbent affinity chromatography of the solubilized tumour-membrane constituents on AH-Sepharose-linked horse anti-human-beta2m indicated that the tumour antigens, like HLA molecules, contain a beta2m subunit. The specificity of binding of TSA to the immunoadsorbent columns and the immunologically specific abrogation of LAI reactivity were clearly shown. The present study, therefore, indicates that by the isolation of beta2m, human tumour antigens can also be isolated, since human tumour antigens are associated with beta2m. Whether human TSAs may perhaps be modified histocompatibility antigens remains to be answered. Although the change upon malignant transformation in the pattern of the cell-surface proteins expressing the TSA determinant remains obscure, it would appear that for tumours arising within a given organ, a consistent alteration of cell-surface proteins occurs.
Adenocarcinoma of the human colon produce carcinoembryonic antigen (CEA), one of a family of glycoprotein molecules that may be produced by various human cancers and, occasionally, by other abnormal tissues. The physicochemical nature and tissue distribution of CEA have been well established and a variety of radioimmunoassays have been developed for the detection of this material in the circulation of patients with CEA-producing tumours. Although the assay should not be used as a screening test for cancer of the bowel, it may serve as a helpful adjunct in the diagnosis of digestive system tumours in conjunction with other routine investigations. More important is the utilization of the radioimmunoassay for CEA under the following circumstances: 1. Preoperatively as an indicator of tumour dissemination based upon the quantitative concentrations of CEA in the circulation. 2. As an indicator of potentially curative resection manifested by a decrease in circulating concentrations of CEA to below detectable limits. 3. As an early warning of recurrent tumour growth, by detecting the reappearance of CEA in the circulation of a patient rendered CEA-negative after tumour resection, 3 months to 2 years or more before any other presently available technology can detect clinical evidence of recurrence. This last observation is now under investigation for its potential value as an indicator for second-look surgery in patients who have undergone potentially curative surgery for colorectal cancers.
A method for the purification of human alpha1-fetoprotein from the ascites fluid of a hepatoma-bearing patient is described that is capable of yielding large quantities of pure alpha1-fetoprotein within a relatively short period of time. The technique is based entirely on the physicochemical properties of the alpha1-fetoprotein molecule and uses sequential purification steps: ion-exchange chromatography on DEAE-Sephadex A-50, molecular-sieve chromatography on Sephadex G-200, negative-affinity chromatography on Sepharose-Blue Dextran, positivepaffinity chromatography on concanavalin A-Sepharose and, finally, molecular-sieve chromatography on Sephadex G-100. The efficiency of the entire procedure in its present form is 15% of the alpha1-fetoprotein activity of the starting preparation from ascites fluid. The purity of the final product was shown by polyacrylamide gel electrophoresis, radioimmunoelectrophoresis, and determinations of the NH2-terminal and COOH-terminal amino acid residues of the alphs1-fetoprotein isolated. Amino acid analysis of the final product revealed a composition very similar to those reported for alpha-fetoprotein preparations that have been previously isolated by the use of immunochemical technology.
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Measurement of amniotic fluid concentrations of alpha1-fetoprotein has been proposed as a potentially important screening test of fetal well-being. Because maternal serum is more easily obtainable, the present study was performed to determine if there is a definable normal pattern of maternal serum alpha1-fetoprotein levels during gestation. Sequential alpha1-fetoprotein determinations were performed throughout gestation on the serums of 151 women having apparently normal pregnancies. Before 13 weeks, all samples contained less than 20 nanograms of alpha1-fetoprotein per milliliter of serum, and in 12.5 per cent of normal pregnancies, alpha1-fetoprotein was still undetectable as late as 21 weeks of gestation. One normal term delivery followed a negative alpha1-fetoprotein determination at the 24th week of pregnancy. Beyond the 21st week of pregnancy, there was a wide range of normal absolute values noted between women at the same stage of pregnancy. Moreover, wide fluctuations in maternal serum concentrations of alpha1-fetoprotein were observed from point to point in specimens from individual women studied longitudinally throughout gestation. The distribution of alpha1-fetoprotein concentrations at each stage of pregnancy was skewed. We conclude that studies of maternal serum alpha1-fetoprotein concentrations are likely to be more meaningful from a diagnostic point of view prior to 21 weeks of gestation, when the range of circulating maternal alpha1-fetroportein values is relatively small. Undetectable maternal serum alpha1-fetoprotein as late as the 24th week of pregnancy is compatible witha viable conceptus. Because unexplained and marked elevations of maternal alpha1-fetoprotein may occur, particularly in the third trimester, it would appear inappropriate to base clinical decision on maternal serum alpha1-fetoprotein measurements alone, and such decisions certainly should not be taken after only single maternal serum alpha1-fetoprotein measurements. Finally, no correlation was found between maternal alpha1-fetoprotein concentrations near term and the birth weight of the infant.