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Biomedical subjects

H H Fudenberg

Publications and source records attributed to H H Fudenberg.

At least 271 records · Page 15Linked to original sources

Improved method for detection of cystic fibrosis protein in serum using the LKB multiphor electrofocusing apparatus.

We have developed an improved method for the detection of cystic fibrosis protein (CFP). The method employs the LKB Multiphor to electrofocus whole serum, instead of the apparatus used in previous studies. Two basic modifications were necessary: (1) a pH 2.5--10.0 gradient instead of a pH 5--10 gradient, and (2) constant power for focusing the serum proteins instead of constant voltage. The first modification ensured adequate dissolution of the CFP-IgG complexes (or other precursor complexes which may liberate CFP). The second modification ensured a linear gradient (between pH 3.8 and pH 9.2), excellent resolution in the pH 8--9 region, and the separation of CFP within 2 hr without overheating of the gel. Electrofocusing with the LKB Multiphor permits the detection of CFP in as many as 24 serum samples per gel. Results obtained from the analysis of 31 cystic fibrosis, 28 obligate heterozygote carrier, and 28 normal control sera indicate that CFP can be reproducibly and accurately detected in sera using the LKB Multiphor.

Asthma↗

alpha-1-antitrypsin (Pi) phenotypes in a Finnish population.

alpha-1-antitrypsin (Pi) phenotypes of 548 normal Finnish blood donors were determined by isoelectric focusing in polyacrylamide gel. The frequencies obtained (M, 93.3%; FM, 0.4%, GM, 0.2%; MS, 3.5%; MZ, 2.7%) differed from those reported earlier for a more restricted Finnish population but agreed better with the frequencies reported for other Scandinavian populations. The disagreement with the earlier report was attributed to differences in sampling and laboratory techniques. The present study confirms an earlier finding of a sarcity of fast Pi variants in the Finnish population. One M variant was found. The isoelectric focusing technique used in this study has several advantages over the methods previously described for Pi typing.

Female↗

Sex steroid hormones and circulating IgE levels.

The possible influence of sex steroid hormones on circulating IgE levels in general and IgE anti-Candida antibodies in particular was studied by quantification of plasma levels of progesterone, estradiol and IgE (total and anti-Candida-specific) in females during the follicular and luteal phases of the menstrual cycle, and during pregnancy. IgE levels during the follicular and luteal phases were not significantly different, although the mean values for the luteal phase were slightly lower. This trend was apparent in daily samples from two normal females during one menstrual cycle. During pregnancy, when the levels of circulating sex steroids were high, IgE levels were only slightly higher than in the follicular and luteal phases. In men and in gonadal dysgenetics, circulating progesterone levels were similar to those of women during the follicular phase (i.e., lower than in the luteal phase or in pregnancy), but the IgE levels were not different. The apparently low levels of IgE during the luteal phase may therefore be due to physiological factors other than fluctuations in the sex steroid hormones. From the present studies, it is apparent that sex steroid hormones have little or no effect on humoral IgE levels, in marked contrast to previously described correlations for other immunoglobulins, especially anti-Candida antibodies.

Antibodies, Fungal↗

Evidence for common and distinct determinants of colon carcinoembryonic antigen, colon carcinoma antigen-III, and molecules with carcinoembryonic antigen activity isolated from breast and ovarian cancer.

This study was designed to answer the question, do molecules with carcinoembryonic antigen (CEA) activity from colon, breast, and ovarian cancer differ? Extracts of two breast and three ovarian cancers with CEA activity were compared to three colon cancer CEA preparations and to the related antigen, colon carcinoma antigen-III, in terms of lectin- and antiserum-binding properties. With the use of Farr-type radioimmunoassays with the lectins, concanavalin A and wheat germ agglutinin, the iodinated colon CEA and CEA-like preparations from breast and ovarian cancer all showed distinctly different patterns of binding. Specificity of binding was confirmed by inhibition studies with the relevant monosaccharides. Similarly, with antisera prepared against colon CEA, colon carcinoma antigen-III, or breast CEA, it was shown that, although all preparations shared some antigens, unique antigenic determinants were also present on all preparations. These data are consistent with the concept of a series of closely related CEA and CEA-like molecules with distinct characteristics for each tissue source of CEA.

Antibodies, Neoplasm↗

[Adenosine deaminase deficiency in primary immunodeficiencies (author's transl)].

The occurrence of severe combined immunodeficiency (SCID) with adenosine deaminase (ADA) deficiency in erythrocytes has been reported in 14 patients. Enzyme deficiency may result in early depression of the lymphatic system. ADA is detectable in different tissues by photometric and electrophoretic methods. The gene locus for ADA has been localised on chromosome 20. Studies on the enzyme defect in different forms of primary immunodeficiencies led to the description of a well defined nosological entity. New aspects can be expected in the fields of pathogenesis, prenatal diagnosis, genetic councelling, and possibly therapeutic trials.

Adenosine Deaminase↗

Partial amino acid sequences of kappa-chains of rat immunoglobulins: genetic and evolutionary implications.

Partial amino acid sequences have been determined for several kappa-type light chains prepared from sera or urine of inbred LOU/C/Wsl rats bearing plasma cell tumors. Comparison of these sequences with those of human, rabbit, and mouse kappa-chains available in the literature indicates that the constant region of rat kappa-chains shows more amino acid sequence homology to that of the mouse kappa-chain than to human and rabbit kappa-chains, a result expected from the phylogenetic relationship of the species compared. Examination of the N-terminal amino acid sequences indicated that the variable regions of rat kappa-chains can also be classified into subgroups according to degree of sequence homology in a manner similar to that done for kappa-chains of other species (e.g., human, rabbit, and mouse). However, the prototype amino acid sequences of kappa-chain variable region subgroups of the rat were not homologous to those of other species including the closely related mouse. The implications of this observation with respect to the genetics and evolution of immunoglobulins are discussed.

Amino Acid Sequence↗

Circadian rhythm of stimulated lymphocyte blastogenesis. A 24 hour cycle in the mixed leukocyte culture reaction and with SKSD stimulation.

The in vitro measurement of stimulated T lymphocyte blastogenesis by the incorporation of 14C-thymidine can be shown to be an acceptable and precise measurement with highly significant variations in blastogenesis over a 24 hr period. This circadian rhythm for human T lymphocyte blastogenesis has been demonstrated with specific antigen (SKSD) and in mixed leukocyte culture (MLC). The hours of peak reactivity were different for the SKSD stimulation and the MLC reaction. This biologic cycle in T cell reactivity has significant implications for the immunologic response.

Adult↗

Primary care.

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Education, Medical, Continuing↗

Chemical and genetic characterization of a monoclonal IgA(lambda) protein with both cryo- and pyro-precipitability.

Studies of a monoclonal IgA (lambda) protein with both cryo- and pyro-precipitability show that it belongs to the IgA2 subclass and is positive for the A2m(2) allotypic marker. Like other cryoglobulins, this protein also has an unblocked light chain, and its heavy chain belongs to the VHI subgroup. The first 22 N-terminal amino acids of the lambda chain of this protein showed less than 65% homology with those of other human lambda chains but showed 86% identity with that of an amyloid fibril protein reported by others. The alpha chain of this protein appears to have more glutamic acid or glutamine, or both, and less isoleucine residues than other human alpha chains.

Amino Acid Sequence↗

Carcinoembryonic antigen and cystic fibrosis protein in blood from cystic fibrosis homozygotes and heterozygote carriers.

Carcinoembryonic antigen (CEA) activity was measured by radioimmunoassay in blood from cystic fibrosis (CF) homozygotes, heterozygote carriers of CF, normal healthy controls, and other patient controls with carcinomas involving gastrointestinal organs. All samples were also screened by electrofocusing for cystic fibrosis protein (CFP), a metabolic marker previously shown to be associated with the CF gene. Significantly increased levels of CEA activity were found in all CFP-positive groups; however, with one exception all patient controls with marked increases in CEA activity were CFP-negative. Immunodiffusion of perchloric acid extracts of CEA-like material from heterozygote carrier blood indicated that the CEA-like material, which was elevated in homozygotes and heterozygotes for CF, showed only partial identity with two separate CEA preparations obtained from colon carcinomas and was not identical to either A, B, or O(H) blood group substances. This glycoprotein material did, however, react with three different anti-CEA antisera. Our finding of an abnormally increased glycoprotein in cystic fibrosis, taken together with previous reports demonstrating abnormalities in the carbohydrate portion of glycoproteins found in various exocrine secretions in CF, further suggests that the primary defect in this disease is manifested partly as a defect in glycoprotein metabolism. This defect may result from an abnormality in one or more of the glycosyltransferases, possibly caused by a more primary defect in polyamine metabolism.

Adolescent↗

Alpha-1-antitrypsin (Pi) types in Down's syndrome.

Alpha-1-antitrypsin (Pi) phenotypes have been determined in 40 patients suffering from Down's syndrome. Thirty-six of the patients were found to have a normal M phenotype, whereas two deficient phenotypes of the MS variety were observed. In addition, two M variants were noted. The significance of an M variant phenotype in some patients with Down's syndrome is not completely understood and is currently under investigation. Since the majority of the patients had a normal alpha-1-antitrypsin phenotype, the results of this study indicate that a deficiency in alpha-1-antitrypsin plays no role in the respiratory fragility of individuals with Down's syndrome.

Adolescent↗

Dialyzable transfer factor in the treatment of human osteosarcoma: an analytic review.

In conclusion, then, we would answer the seven questions raised earlier concerning transfer factor as follows: Certianly, as shown by clinical results, it does exist. It does have a definite immunologic effect in humans, boosting cell-mediated immunity, as shown by a rise in the level of active T cells. Its clinical effects have been demonstrated repeatedly, and it should become useful in still other clinical situations as further research provides more effective therapeutic modalities. Transfer factor from selected donors appears to provide prophylaxis against metastasis when administered to osteosarcoma patients with no clinically evident metastases at the time of surgical removal of the primary tumor; whether this treatment is superior to chemotherapeutic prophylaxis is conjectural and controversial. Its mechanism of action has not been demonstrated as yet, although many theories exist. The best evidence is that the effects are both specific and nonspecific. It appears to be produced by T lymphocytes. The exact nature of the substance we call "transfer factor" remains to be elucidated. Further research should provide more conclusive answers to these questions.

Animals↗

Studies on cystic fibrosis using isoelectric focusing. II. Demonstration of deficient proteolytic cleavage of alpha2-macroglobulin in cystic fibrosis plasma.

A protein with an isoelectric point (pI) of 5.48 was found to be deficient in plasma from most cystic fibrosis (CF) homozygotes and obligate heterozygote carriers of CF as compared with normal control plasma. Purification of the protein with a pI of 5.48 from normal plasma was performed using ammonium sulfate precipitation, DEAE-cellulose and CM-cellulose chromatography, Sephadex G-200- gel filtration, starch block electrophoresis, and Sepharose 4B gel filtration. The purified protein migrated as a single band on polyacrylamide gel electrophoresis, and displayed a single arc on immunoelectrophoresis against polyvalent antiserum to whole human serum. Results from various techniques used in its characterization indicate that this protein is a fragment of alpha2-macroglobulin (alpha2M) which is derived from alpha2M by proteolytic cleavage of intact alpha2M subunits. Quantitation of alpha2M levels in plasma indicated no significant differences between levels of alpha2M in CF homozygote, obligate heterozygote carrier, or normal control plasma samples. Quantitation of arginine esterase activity in plasma treated with cloroform and ellagic acid indicated that both the total arginine esterase activity and that fraction of arginine esterase activity inhibited by soybean trypsin inhibitor (SBTI) were decreased in most CF homozygote and obligate heterozygote plasma samples relative to normal control values. The results of this study indicate that plasma samples from CF homozygotes and obligate heterozygote carriers for CF show deficient proteolytic cleavage of alpha2M as compared with normal control plasma, and suggest that a structural abnormality in alpha2M or a deficiency in plasma proteolytic activity may be responsible for this deficiency in proteolysis.

Arginase↗