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Biomedical subjects

M Callow

Publications and source records attributed to M Callow.

7 recordsLinked to original sources
PubMed2003

Finger and toe ratios in humans and mice: implications for the aetiology of diseases influenced by HOX genes.

The differentiation of gonads, fingers, and toes is influenced by HOXA and HOXD genes. Therefore variation in the development of the gonads, and their fetal products such as testosterone, may be reflected in the morphology of the fingers and toes. One trait, the relative length of the second and fourth digits (2D:4D), shows sex differences (lower values in males) which are determined early, and 2D:4D has been found to correlate with fetal growth, sperm counts, family size, autism, myocardial infarction, and breast cancer. HOX genes are highly conserved in mammals and they influence the differentiation of all the fingers and toes. We suggest that (a) 2D:4D and other ratios of finger and toe length show sex differences throughout the mammals including humans and mice, (b) finger and toe ratios correlate with sex determination, the fetal production of sex steroids, and fetal programming of disease, and (c) HOX gene influences on sex determination, the morphogenesis of the urinogenital system, fertility, haematopoiesis, and breast cancer suggests that finger and toe ratios in humans and mice may correlate with many sex dependent diseases.

Animals↗
PubMed2001

Private specificities can dominate the humoral response to self-antigens in patients with cryptogenic fibrosing alveolitis.

BACKGROUND: The pathogenetic mechanisms that underlie the interstitial lung disease cryptogenic fibrosing alveolitis (CFA) may involve an immunological reaction to unidentified antigens in the lung, resulting in tissue damage. METHOD: In order to identify the range of target autoantigens, we used expression cloning, employing serum from an index patient as the probe against an expressed cDNA library that was derived from a tumour cell line. We screened over 5 x 105 recombinants and obtained sequence information on three antigens that had provoked strong responses with immunoglobulin heavy chain class switching, presumably as a consequence of T-cell recognition. RESULTS: All of the antigens were identifiable by comparison with sequence data from the US National Center for Biotechnology Information. Alanyl tRNA synthetase (ATS) was picked on six occasions; five of these incidences reflected independent recombination events, indicating that the library was not biased. Antibodies to ATS (anti-PL-12) represent the most common reactivity that defines the antisynthetase syndrome, which is typically expressed as polymyositis, dermatomyositis and interstitial lung disease (ILD). The index patient never showed symptoms other than those associated with alveolitis, even though sera obtained from him over a period of 2 years contained antibodies with the same specificity. Autoantibodies to ATS were never detected in serial bleeds from 11 other patients with CFA, and neither did we detect antibodies to the other two antigens identified from the serum of the index patient. CONCLUSION: The humoral response in patients with CFA can be dominated by autoantibodies with private specificities. This suggests that the antibodies are epiphenomenal and are a secondary feature of tissue damage induced by some other mechanism.

Antibody Diversity↗
PubMed2000

Serologic responses in patients with malignant mesothelioma: evidence for both public and private specificities.

Malignant mesothelioma (MM) is a pulmonary malignancy that appears to be immunogenic based on a large number of studies in both animals and humans. This notion is supported by our recent demonstration using Western blot analysis of immunoglobulin G antibodies reactive with a variety of autoantigens in many patients with MM. In view of the enormous potential of such antigens in early diagnosis, immunotherapy, and vaccination of at-risk individuals, it was essential to identify these antigens. We therefore applied the SEREX technique (serologic identification by recombinant expression cloning), using a serum pool from six patients as the probe against an expressed complementary DNA library derived from a cloned MM cell line. We screened over one million recombinants and obtained sequence information on eight antigens that had provoked immunoglobulin heavy chain class switching, presumably as a consequence of T-cell recognition. Six of these antigens were identifiable (U2AF[65], Siah binding protein, topoisomerase IIbeta, ZFM1, mIre1, and pendulin), and of the others, one was found as a single EST from a myotube library (Jemm-1); the other (Jemm-2) was not represented in any EST database even as a weak homolog. Consistent with our previous findings, each of the characterizable antigens would be expected to be associated with the cell nucleus. Each of the autoantibody specificities was uniquely associated with a single patient with the exception of antibodies to TOPIIbeta and U2AF(65). We found 13 of 14 (93%) patients with MM had antibodies to TOPIIbeta and two of 14 (14%) patients had antibodies to U2AF(65). The number of serum reactivities, taken as a measure of the complexity of the immune response, correlates with patient survival and with an index of systemic inflammation. These data suggest that a broader range of serologic reactivities reflects a more active host response to the presence of tumor.

Animals↗
PubMed1994

Raf-1 interferes with Ras and Rap1A effector functions in yeast.

Raf-1 is a serine/threonine kinase that acts downstream of Ras in mitogenic signal transduction pathways, but the mechanism by which Ras transmits signals to Raf-1 is not known. We have examined the interaction between Raf-1 and human H-ras in three different systems that utilize H-ras-induced phenotypes in Saccharomyces cerevisiae. In each system, the effects of H-ras depend on guanosine triphosphate and appear to be mediated through the H-ras effector binding region. H-ras effector function was blocked in each case by expression of the N-terminal regulatory domain of Raf-1. These inhibitory effects did not require the Raf-1 kinase domain. Raf-1 also blocked Rap1A effector function in S. cerevisiae. Raf-1, therefore, appears to interact with H-Ras and Rap1A in these in vivo systems with properties that suggest it is an immediate downstream effector.

Cell Cycle Proteins↗
PubMed1986

Marathon fatigue: the role of plasma fatty acids, muscle glycogen and blood glucose.

The role of carbohydrate depletion in marathon fatigue was examined in 6 marathon runs. Four of the runs were potentially 'fast-time' marathons and culminated in fatigue. The utilization of carbohydrate, lipid and protein, and plasma concentrations of free fatty acids (FFA), glucose and lactate were measured at intervals throughout the runs. The contribution from protein to energy output was low (1-2%). The utilization of lipid was dependent upon plasma concentrations of FFA, which rose throughout the run. The utilization of carbohydrate mirrored that of FFA and thus fell throughout the run. Fatigue was characterized by a drop in running speed, a drop in carbohydrate utilization, an unchanging FFA utilization and a fall in blood glucose. The fall in blood glucose was not seen in the non-fatigued runners. These results are consistent with carbohydrate depletion being the cause of fatigue. The implications of these data are that lipid is the preferred fuel, but is rate-limiting, and that carbohydrate depletion, even though it causes fatigue, ensures an optimal-time marathon.

Adult↗