Biomedical subjects
Publications and source records attributed to D Rowe.
Type I collagen synthesis in osteoblasts is regulated by a variety of systemic hormones, growth factors and locally produced factors. With the use of cDNA probes and hybridization analysis, it appears that many of these agents alter collagen synthesis by a pretranslational mechanism.
The distribution of T lymphocytes expressing the different polypeptides of the leucocyte common antigen (LCA) family detected by CD45R and UCHL1 antibodies has been studied in normal lymphoid tissues. In the thymus most cortical thymocytes express UCHL1 and co-express CD4 and CD8. The more mature membrane CD3+ (mainly medullary) T cells are heterogenous and may express both UCHL1 and CD45R weakly or be restricted to display CD45R or UCHL1 alone. In the medulla both the CD45R+ and UCHL1+ subpopulations contain single positive CD4 and CD8 cells. In tonsils, germinal centre T cells are almost exclusively UCHL1+, CD4+ and a proportion also express HNK-1 (Leu 7) antigen. In the paracortical areas approximately equal numbers of CD45R+ and UCHL1+ cells are found but these separately occupy nests of cells containing one or the other type. Again, both CD45R+ and UCHL1+ cells include single CD4+ and CD8+ lymphocytes. A small proportion (less than 5%) of strongly CD45R+, UCHL1+ double-stained cells are also seen, and these probably represent recently activated lymphocytes. In the gut, small clusters of such strongly double-labelled cells are in the submuscular mucosae while cells of the lamina propria are almost exclusively UCHL1+. Many intra-epithelial lymphocytes are only weakly positive or negative for UCHL1 and appear to be CD45R-. These results are consistent with the view that expression of different CD45 polypeptides identifies successive stages of thymocyte-T-cell maturation and that following their thymic education, unprimed T lymphocytes are CD45R+, while primed memory T cells are UCHL1+. These populations occupy different microenvironments.
In an open prospective study performed in 2 neonatal units, infants with suspected neonatal sepsis (SNS) of unknown microbial cause were randomly allocated to receive treatment with either cefotaxime (CTX) or netilmicin plus penicillin (N + P). 236 patients were entered into the trial, of whom 222 were evaluable. The number of 'definitely' and 'probably' infected babies was similar in both groups. There was no difference in clinical outcome between patients in the 2 treatment groups and no side effects were recorded for either of the antibiotic regimens. Antibiotic sensitivity testing of bacterial isolates from peripheral sites showed almost universal sensitivity of potential pathogens to both antibiotic regimens at the start of treatment in all infants. Thereafter, organisms resistant to CTX were isolated from patients in both treatment groups, possibly reflecting the antibiotic sensitivity profile of the colonising bacteria in both neonatal units. The results of this study indicate that either CTX or N + P are suitable, in our units, for the 'blind' treatment of early SNS. In units where listerial infections are prevalent, specific cover should be added to CTX. For SNS developing after admission, the choice of antibiotics will depend upon the background antibiotic sensitivity profile of the colonising bacteria.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Epstein-Barr (EB) virus isolates can be classified as type A or type B depending upon the identity of the virus-encoded nuclear antigen EBNA 2; the EBNA 2A and 2B proteins show limited amino-acid homology and induce largely non-cross-reactive antibody responses in humans. To examine whether EBNA 2 might also be a target for virus-specific cytotoxic T-cell responses (like "intracellular" antigens in other viral systems), normal B cells from non-immune donors of known HLA type were transformed in vitro with virus isolates either of type A (from the B95-8 and IARC-BL74 cell lines) or of type B (from the AG876 and IARC-BL16 cell lines) to provide a suitable panel of target cells. DNA hybridization with type-specific probes and immunoblotting with type-specific antisera confirmed the EBNA 2 type of the resident virus in the various in vitro transformants. These cells were then tested as targets for virus-specific cytotoxic T cells, the latter being prepared from type-A virus-infected donors by in vitro reactivation of memory cells from peripheral blood using autologous type-A virus-transformed cells as stimulators. Such effector cells lysed type-A virus-transformed and type-B virus-transformed target cells equally well, indicating that EBNA 2 (in particular that part of the protein which varies between virus types) seems not to be a dominant antigen for the induction of EB virus-specific cytotoxic responses.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
The sera of 12 patients with presumed chronic active Epstein-Barr virus (EBV) infection lacked antibody to a component of the Epstein-Barr nuclear antigen (EBNA) complex encoded by the BamHI K fragment of viral DNA. This anomaly, detected in approximately 18% of sera obtained from patients with a diagnosis of "chronic mononucleosis," was more often found in patients with severe disease (approximately 32%) who had objective clinical findings and markedly elevated antibody titers to EBV replicative antigens than in those patients with the "fatigue syndrome" (10%). The lack of antibody to the K nuclear antigen is specific because most of those who did not have antibody to the K antigen made antibody to other latent nuclear (EBNA 2) antigens or nuclear early antigens. Such patients are thus able to lyse immortalized cells, release nuclear products, and present them to the immune system. Three hypotheses are suggested to explain the lack of antibody to the K antigen: a viral mutation, a failure of immune recognition, or lack of in vivo expression of the antigen due to extensive viral replication. Lack of antibody to one component of EBNA may serve as an objective serological marker for certain patients with chronic EBV infection.
Labial biopsy specimens from eight patients with primary Sjögren's syndrome (SS), 10 patients with secondary SS, and three healthy controls were studied with monoclonal antibodies identifying HLA class I and class II antigens; interferon-alpha, beta, and gamma; interleukin 2 (IL2); and the IL2 receptor (Tac) among others. In the normal biopsy specimens there was evidence of HLA class I and, to a lesser extent, class II antigens in both ducts and acini, though this was much less marked than in the Sjögren's biopsy specimens. Interferon-gamma staining, but not interferon-alpha or beta, was also considerably enhanced in the biopsy specimens from the patients with Sjögren's syndrome. These data support the view that in Sjögren's syndrome the release of interferon-gamma may be involved in the induction of class II determinants. Our observations were broadly similar in both primary and secondary Sjögren's syndrome except that patients with primary Sjögren's syndrome tended to have more diffusely scattered T lymphocytes.
Patients with right or left hemisphere strokes were studied for the nature of emotion conveyed in speech, during the reading of three short passages chosen for the differing emotional tone of their content. Both groups of patients had prosodic qualities which led their speech to be rated as like that of depressed patients and different from that of non-depressed controls. None of the stroke patients had significant depression or anxiety at the time of testing, so this prosodic quality is presumed to relate directly to brain damage.
Explore the source record for details and available documents.
Seventy-one lung carcinomas from 66 different patients were stained with a panel of monoclonal antibodies. Twenty-nine were small cell lung carcinoma (SCLC), 15 adenocarcinomas, 17 squamous carcinomas and 10 large cell carcinomas. Three of the monoclonal antibodies recognize different cytokeratins, three recognize other epithelial antigens and one recognizes a neural antigen. Both formalin-fixed and cryopreserved tumours were studied using an indirect immunoperoxidase method. 23/29 SCLC reacted with all but one of the antibodies which recognize epithelial antigens. This staining was similar to that seen in non small cell lung carcinomas (NSCLC) and provides further evidence that SCLC are true epithelial tumours. All but one of the SCLC stained with the antibody recognizing a neural antigen. This antibody did not stain squamous or adenocarcinomas. However, four of the large cell carcinomas stained well with this antibody, suggesting that SCLC and some large cell carcinomas share a common pathway of differentiation. There were variations of staining seen both within and between tumours. This has obvious implications if immunotargetting with monoclonal antibodies is to be used diagnostically or therapeutically.
Collagen synthesis in rat osteosarcoma cell line 17/2 (ROS 17/2) was assessed by measuring the incorporation of [3H]proline into collagenase-digestible protein and the formation of [3H]hydroxyproline. PTH and 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] inhibited collagen synthesis in ROS 17/2 cells in a time- and dose-dependent manner. PTH reduced collagen synthesis after a 3-h incubation, whereas the effect of 1,25-(OH)2D3 was somewhat slower. Maximal and half-maximal inhibition of collagen synthesis occurred at approximately 1 and 0.1 nM of each hormone, respectively. At confluency, ROS 17/2 cells synthesized 96% type I and 4% type III collagen. PTH reduced the synthesis of type I, but not type III, collagen. PTH and 1,25-(OH)2D3 also reduced procollagen mRNA levels, as determined by a dot blot hybridization assay. Thus, ROS 17/2 cells are a convenient model system for studying the hormonal regulation of collagen metabolism and gene expression in a cloned cell line with the osteoblastic phenotype.
Muscle biopsies from nine patients with polymyositis, six with muscular dystrophy, six with other muscle diseases and three controls have been studied with a panel of 10 monoclonal antibodies (MoAb) identifying T lymphocytes, HLA-class I antigens, alpha, beta and gamma interferons and interleukin 2 (IL-2). The result confirm that the staining of the sarcolemma with anti-HLA class I antibody is weak or negative, except in areas adjacent to infiltrating leucocytes or where muscle fibre damage is evident. The very similar tissue distribution of alpha, beta and gamma interferons in the polymyositis biopsies supports the hypothesis that interferons are released by the inflammatory infiltrate and induce the class I antigen expression. In contrast, little interferon was demonstrated in the dystrophic muscle implying that class I expression in these disorders must occur by a different mechanism. Little IL-2 was demonstrated in any of the biopsies though some unexplained small dense accumulations were identified by one of the anti IL-2 MoAb.
The monoclonal antibody UCHL1 identified an antigen present on most thymocytes, a subpopulation of resting T cells within both the CD4 and CD8 subsets, and on mature activated T cells. The UCHL1 determinant is also present on cells of the myeloid lineage, but not normal B cells or NK cells. Functionally, UCHL1 identifies a subpopulation of T cells which proliferates maximally to soluble antigen and provides maximum help for PWM-stimulated immunoglobulin synthesis. In contrast, the UCHL1- cells do not induce immunoglobulin synthesis and do not proliferate in the presence of soluble antigen, although both the UCHL1- and the UCHL1+ fractions of T cells proliferate well in the presence of PHA. By standard immunoprecipitation techniques and SDS page, the antigen recognized by UCHL1 was found to have a molecular weight of 180,000-185,000. Preclearing experiments using antibodies identifying the leucocyte common antigen, LCA, and the lymphocyte function-associated antigen, LFA-1, which have similar molecular weights to UCHL1, showed that the UCHL1 determinant is not biochemically related to these antigens.
Explore the source record for details and available documents.
An Epstein-Barr virus (EBV) deletion mutant, HR-1, cannot immortalize lymphocytes. HR-1 was derived from a virus strain, Jijoye, that is immortalization competent. Using human antiserum from certain patients with chronic active EBV infection, we have identified in Jijoye cells a protein of apparent mass of 78-80 kDa that is missing in cells with the HR-1 genome. A protein of identical size and antigenicity has been stably expressed in mouse LTK- cells by gene transfer with cloned Jijoye EBV DNA that encompasses the deletion in the HR-1 genome. The expressed product is a nuclear neoantigen. The polypeptide we have identified is likely to be essential in the immortalization process.