Immunological deficiency diseases.
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Biomedical subjects
Publications and source records attributed to S Sell.
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Sheep antisera specific for the three major immunoglobulin groups of the rabbit, i.e. IgG (gamma-chain), IgA (alpha-chain), and IgM (micro-chain), are each able to induce blast transformation of the peripheral lymphocytes of the rabbit when added to in vitro cultures. The per cent of lymphocytes transformed with each antiserum indicate that one-fourth of the peripheral lymphocytes carry or have the capacity to synthesize molecules of all three of the major immunoglobulin groups, and that the remaining three-fourths carry or have the capacity to synthesize only two (IgG and IgM). The data do not permit direct conclusions concerning the ability of a single cell to produce molecules belonging to more than one immunoglobulin group at the same time, or the ability of a given cell to make a transition from the synthesis of molecules of one immunoglobulin group to those of another group.
The addition of sheep antisera to rabbit IgG or to rabbit IgG subunits (L chain, H chain, Fab piece, Fc piece) to in vitro cultures of rabbit peripheral lymphocytes may induce up to 80-90% of the small lymphocytes to transform into immature "blast" cells. As many as 1 x 10(7) molecules of antibody may be required to stimulate each cell. It is concluded that each peripheral lymphocyte carries the antigenic specificities of the entire IgG molecule and thus could carry, and may produce specific antibody molecules. Such a conclusion supports the theory that the small lymphocyte may be the site of specific recognition of antigens in the primary response.
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Rabbit antiserums, originally prepared to react specifically with rabbit immunoglobulin allotypes Ab5 and Ab6, also react with some normal rabbit serums that clearly do not contain Ab5 or Ab6 allotypes. This reaction is due to antigenic specificity present on rabbit immunoglobulin M(IgM) and not on rabbit immunoglobulin G. Serums that contain this IgM allotype do not react with an antiserum that reacts with the known rabbit IgM allotype, Ms1. This specificity may therefore be identified as a second rabbit IgM allotype, Ms2.
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Lymphocytes from the peripheral blood of newborn rabbits heterozygous for IgG allotypes As4 and As5, or As5 and As6, obtained at an age when only the maternal allotypic determinants are detectable in the serum, may be stimulated in vitro to transform into "blast" cells with antiallotype sera directed against the determinants contolled both by the maternal and by the paternal chromosomes. This result rules out the possibility that allotypic specificity is conferred upon lymphocytes by environmental IgG and suggests that the lymphocytes of newborn rabbits have the potential to synthesize IgG determinants either in the form of intact IgG molecules or constituent polypeptide chains.
Specific antisera directed against all six of the well characterised allotypic determinants of rabbit IgG (As1, 2, 3, 4, 5, and 6) are capable of inducing blast transformation and DNA synthesis when added to lymphocyte cultures obtained from donor rabbits having the appropriate IgG allotype. Mixtures of antisera directed against two different allotypic determinants induce a "summation" of transformation and DNA synthesis over and above the effect of mixtures of two antisera directed against the same allotypic determinant. This summation effect is observed regardless of whether the antisera which have been mixed are directed against allotypic determinants controlled by the same locus or by different loci. The finding that summation occurs with mixtures of two antisera directed against both the allotypic determinants of a double homozygote rabbit (As1, 6) suggests that lymphocytes from the peripheral blood may be primed to produce only one or the other of the two polypeptide chains of IgG, but not both.
In vitro cultures of the peripheral blood lymphocytes of rabbits may be stimulated with phytohaemagglutinin, staphylococcal filtrate, antiallotype serum, or sheep anti-rabbit whole serum to synthesize protein, RNA and DNA as indicated by the incorporation of radiolabelled precursor substances into these products. A sequence of events found in all stimulated cultures characteristically shows protein synthesis followed by RNA synthesis, histologic blast transformation, DNA synthesis, and mitosis, with the complete sequence requiring 48 hours. All four stimulants induce essentially identical metabolic changes. Characterization of the proteins synthesized by lymphocytes in vitro has failed to demonstrate immunoglobulin synthesis by stimulated or non-stimulated cultures. It is concluded that the majority of proteins produced by peripheral lymphocytes stimulated in vitro are most likely cellular proteins related to the metabolic alterations necessary for mitosis. Absorption of sheep antisera to whole rabbit serum with rabbit IgG does not always remove the transforming capacity of the sheep antisera. Thus, it is likely that antibodies to proteins other than IgG present in the small lymphocyte may also be able to stimulate transformation. A possible common mechanism for the induction of lymphoblast transformation may be the ability of both specific and non-specific stimulants to react with protein constituents of the lymphocyte which may also be present in serum.
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Analysis of liver from rats exposed to chemical hepatocarcinogens has led to a model that postulates sequential premalignant changes, culminating in hepatoma formation from neoplastic nodules. Several experimental protocols devised during the last quarter century have focused upon this lineage model. But proof that neoplastic nodules are the definitive premalignant lesions has not been achieved. Recent work, using alpha-fetoprotein as a marker for liver cell alterations induced by different carcinogen-feeding regimens, suggests that chemically induced hepatomas may also arise from nonnodular cell populations. Therefore, the extensive biochemical and biological studies of presumed "premalignant" cells may have utilized the wrong cells. Unequivocal identification of the cell population at risk for malignancy is needed to delineate mechanisms by which chemicals cause hepatocellular carcinoma.
There are three levels of cells in the hepatic lineage that respond to injury or carcinogenesis: the mature hepatocyte, the ductular "bipolar" progenitor cell, and a putative periductular stem cell. Hepatocytes are numerous, and respond rapidly to liver cell loss by one or two cell cycles but can only produce other hepatocytes. The ductular progenitor cells are less numerous, may proliferate for more cycles than hepatocytes, and are generally considered "bipolar," i.e., they can give rise to biliary cells or hepatocytes. Periductular stem cells are rare in the liver, have a very long proliferation potential, and may be multipotent. Extrahepatic (bone marrow) origin of the periductular stem cells is supported by recent data showing that hepatocytes may express genetic markers of donor hematopoietic cells after bone marrow transplantation. These different regenerative cells with variations in potential for proliferation and differentiation may provide different sources of cells for liver transplantation: hepatocytes for treatment of acute liver damage, liver progenitor cell lines for liver-directed gene therapy, and bone marrow-derived cells for chronic long-term liver replacement. A limiting factor in the success of liver cell transplantation is the condition of the hepatic microenvironment in which the cells must proliferate and set up housekeeping.
OBJECTIVE: To quantify the influence of patient positioning on the determination of collodiaphyseal (CCD) angle and femoral neck anteversion based on computed tomography. Description of a method for positional correction. METHODS: We evaluated the CT scans of 84 femora from 77 patients, who received individually adapted prostheses. Projected as well as real anteversion and CCD angles were determined and corrected for positioning errors using a newly proposed mathematical method, and compared to other evaluation methods. RESULTS AND CONCLUSIONS: We determined an average tilt of 4.2 degrees in the sagittal and of 9 degrees in the coronary plane, which correlated definitely with the deviations found in the graphical determination of the projected anteversion angle. This produced measurement errors of the projected anteversion angle of up to 10 degrees. Mathematically independent angles, such as projected anteversion and real CCD angle, showed only a weak correlation. This indicates also an anatomical independence of these angles.
AIM: The purpose of this study was to determine the important predisposing factors associated with heterotopic ossifications (HO) after total hip arthroplasty. METHOD: 589 patients were examined 6 months after primary total hip arthroplasty with regard to periarticular ossifications. Several predetermining factors were evaluated using the hospitalization records and preoperative X-ray examination. RESULTS: A significantly increased frequency of heterotopic ossifications was found for male gender, patients with very high body mass index (BMI), low preoperative range of motion (ROM), long duration of operation and large preexistent osteophytes (p < 0.05). Only one out of the one hundred patients with an BMI < 22.6 developed severe HO (Brooker III). Out of the one hundred patients with the best preoperative ROM (> or = 140 degrees ) only one case developed severe ossifications (Brooker III). There was no correlation with the use of acrylic bone cement or the patient's age. The frequency of HO was significantly reduced both as well by nonsteroidal antiinflammatory drugs as from postoperative radiation prophylaxis. CONCLUSION: In patients undergoing total hip arthroplasty with low preoperative ROM in the hip joint, large osteophytes and a very high BMI an efficient prophylaxis against HO is of great importance.
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AIM: The purpose of this study was to compare muscle torque during isokinetic knee movements of patients after total knee arthroplasty (TKA) with a similar healthy group. METHOD: 43 patients were examined 3 years after primary total knee arthroplasty with an isokinetic dynamometer (Cybex 340). Torque measurements were evaluated for extension and flexion with 4 different velocities. The results were compared with a group of 43 people without knee disease. Bouth groups consist of 29 women and 14 men. The mean age was also comparable (66.4 vs. 65.8 years). RESULTS: A mean peak torque of 65.9 Nm was measured during extension with low velocity (60 degrees /s) in the group of patients with TKA -- 84.3 % of the control group (p = 0.079). At the highest velocity the patients produced 30.2 Nm. This was 72.8 % of the control group (difference statistically significant, p = 0.006). No differences were found in the Extension/Flexion ratio between the two groups. CONCLUSION: The deficites of knee strength in patients after TKA are more distinct in high velocities of motion.