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Biomedical subjects

J Shuster

Publications and source records attributed to J Shuster.

At least 19 recordsLinked to original sources
PubMed1979

beta 2-Microglobulin: methods and clinical applications.

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.

Amino Acid Sequence↗
PubMed1978

Isolation of HLA and tumor antigens by means of affinity chromatography employing anti-beta2-microglobulin (beta2m) antiserum.

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.

Antigens, Neoplasm↗
PubMed1978

Isolation of human tumour-specific antigens associated with beta2 microglobulin.

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.

Antigens, Neoplasm↗
PubMed1978

Physicochemical approach to the purification of human alpha1-fetoprotein from the ascites fluid of a hepatoma-bearing patient.

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.

Ascitic Fluid↗
PubMed1977

Neuropsychologic effects of continuous oxygen therapy in the aged.

This study investigated the effects of continuous therapy with oxygen on the neuropsychologic functioning of aged subjects professing problems with their memory. Nineteen men (mean age, 71 years) were evaluated on eight neuropsychologic measures during three different periods of time. Subjects were tested before any treatment, after a month of continuous therapy with oxygen, and after a period of sham treatment. The results indicated statistically significant improvement in the Wechsler Memory Quotient and, with one exception, improvement in all other measurements in favor of the treatment with oxygen. Differences between the results of this investigation and those of other studies are discussed, along with the factors possibly accounting for these differences.

Aged↗
PubMed1977

Alpha1-fetorprotein concentrations in maternal serum during normal pregnancy.

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.

Adolescent↗
PubMed1977

Oncofetal antigens. Increasing the specificity of the CEA radioimmunoassay.

The biologic and clinical significance of the oncofetal antigens carcinoembryonic antigen (CEA) and alpha1-fetoprotein (AFP) are discussed. Although the current assays for these molecules are not tumor-specific, measurement of these molecules in the circulation of cancer patients is useful either for tumor diagnosis or for management of the cancer patient in the postoperative or post-chemotherapy state. An approach to increasing the specificity of the CEA radioimmunoassay is described.

Amniotic Fluid↗
PubMed1976

beta 2-microglogulin levels in cancerous and other disease states.

Serum beta2-microglobulin levels were measured, by radioimmunoassay, in patients suffering from a variety of benign and malignant clinical disorders. Elevated beta 2-microglobulin values were found in neoplastic and non-neoplastic disorders affecting a variety of organs. The most striking increases in beta 2-microglobulin are found in the plasma cell dyscrazias and several solid tumors, particularly those affecting the lung. Lymphoid neoplasms demonstrate a spectrum of changes of serum beta 2-microglobulin. At the one end of this spectrum were the plasma cell tumors, which show a high incidence of raised beta 2-microglobulin levels, while patients with Hodgkin's disease rarely show such increases in circulating beta 2-microglobulin.

Beta-Globulins↗
PubMed1976

Chromosomal assignment of the HL-A common antigenic determinants in man-mouse somatic cell hybrids.

In the study presented here, man-mouse somatic cell hybrid clones were examined by means of radioimmunoassays for the presence of both beta2-microglobulin (beta2m) and the HL-A xenoantigenic determinant. In addition, the clones were examined for their karyotype and the expression of enzymes with known chromosomal assignments. The results obtained indicate that the gene coding for the HL-A xenoantigenic determinant is carred on chromosome 6. The data obtained provides a direct demonstration that the gene coding for beta2m segregates independently of that coding for the alloantigenic polypeptide chain of the HL-A molecule, and that the gene coding for beta2m is carried on chromosome 15.

Animals↗
PubMed1976

The isolation and characterization of tumor-specific antigens of rodent and human tumors.

Putative tumor-specific transplantation antigens (TSTA) from both a carcinogen-induced rodent tumor (MC-1) and 2 human tumors were purified. The antigens were solubilized from the tumor cell membranes by limited papain digestion in a manner similar to that described for the isolation of normal histocompatibility antigens. The antitumor immune response of the tumor-bearing host was used to monitor the purification of the putative TSTA in both the rodent and human tumor systems. In the case of the rodent tumor, a major step in the purification of the TSTA involved affinity chromatography on Sepharose beads coupled to autologous antitumor antiserum. A comparable procedure was utilized in the purification of the TSTA from human tumors by using affinity chromatography on anti-human beta2-microglobulin antiserum coupled to a solid phase. The data obtained indicate that the TSTA of human tumors contains a beta2-microglobulin chain that is immunochemically identical with, and very similar in size to, that found in normal human histocompatibility antigens. A subunit of similar size was also identified in the carcinogen-induced rodent tumor. These results suggest that the TSTA in both humans and rodents may well be altered histocompatibility antigens.

Animals↗
PubMed1975

Constipated plasma cells associated with monomeric macroglobulinemia.

Low molecular weight macroglobulinemia was observed in a patient with chronic pulmonary infection. An enlarged cervical lymph node contained many abnormal plasma cells, which were distended with immunoglobulin; this material appeared to be released into lymph spaces when the cells burst. The macroglobulin production is considered to be a non-neoplastic reactive immune response to the pulmonary infection. It is postulated that the association of constipated plasma cells and 7s-IgM can best be explained as an acquired defect in macroglobulin polymerization.

Chronic Disease↗
PubMed1975

Studies of the linkage relationship of beta-2-microglobulin in man-mouse somatic cell hybrids.

Beta-2-microglobulin (beta2mu) production has been studied in 33 primary man-mouse hybrid clones and in 26 secondary man-mouse hybrid clones. These clones have also been examined for the presence of 15 human enzyme phenotypes. Karyotypic analyses have been carried out on clones. From these studies the following conclusions can be drawn: (1) Gene(s) determining human beta2mu production in humans are apparently syntenic with the MPI gene on chromosome 15. (2) Long-term fibroblast lines may be of limited use in mapping studies as chromosomal rearrangements frequently occur in these lines. (3) The gene(s) determining beta2mu production in humans segregate independently of chromosome 6. If the assignment of the genes determining HL-A alloantigens to chromosome 6 is correct, our results imply that beta2mu and HL-A alloantigens are determined by genes carried on different chromosomes, despite the fact that beta2mu forms an integral part of the HL-A molecule.

Animals↗