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Biomedical subjects

A Crawford

Publications and source records attributed to A Crawford.

At least 19 recordsLinked to original sources
PubMed1999

Evolutionary applications of MIRs and SINEs.

It is believed that short interspersed elements (SINEs) are irreversibly inserted into genomes. We use this concept to try to deduce the evolution of whales using sequence and hybridization studies. The observation that microsatellites are associated with SINEs lead us to screen sequences surrounding cetacean microsatellites for artiodactyl-derived SINEs. Two sequences that were thought to be cetacean SINEs and the bovine SINE were aligned for comparison to sequences flanking microsatellites from ungulates. The bovine SINE was observed only in ruminants while CetSINE1 and 2 were found in mammals. Hybridization studies using these three SINEs revealed that CetSINE1 was found in all ungulates and cetaceans with the strongest hybridization signal observed in the hippopotamus and beluga; CetSINE2 hybridized to all ungulate suborders, while the bovine SINE was only observed in Ruminantia. It is proposed that these putative SINEs are not 'generic' SINEs but mammalian-wide interspersed repeats (MIRs). Caution is urged: what initially appears to be a SINE may instead be a MIR and have reduced evolutionary resolving power.

Animals↗
PubMed1998

Secondhand smoke, hypofibrinolysis, and Legg-Perthes disease.

In 39 children with Legg-Perthes disease who were nonsmokers, the specific aim was to assess relationships among parental cigarette smoking during pregnancy, household smoking before diagnosis of Legg-Perthes disease, hypofibrinolysis, and thrombophilia. Fifteen (38%) children had no secondhand smoke exposure; 24 (62%) had secondhand smoke exposure before their diagnosis. Seventeen (71%) of these 24 children were exposed while in utero to smoking by a parent or live in relative and also had exposure to household smoke during childhood; seven (29%) had only household smoke exposure in childhood. In the full cohort of 39 children, secondhand smoke exposure correlated inversely with the major stimulator of fibrinolysis, stimulated tissue plasminogen activator activity. Of the children exposed to smoking, 48% had low stimulated tissue plasminogen activator activity (< 2.19 IU/ml) compared with 7% of the children without secondhand smoke exposure and 14% of 22 healthy control children. Secondhand smoke exposure had no significant effects on other measures of coagulation. Secondhand smoke exposure while in utero and during childhood appears to lower stimulated tissue plasminogen activator activity and additionally may depress heritable low stimulated tissue plasminogen activator activity, leading to hypofibrinolysis. Hypofibrinolysis may facilitate thrombotic venous occlusion in the head of the femur, leading to venous hypertension and hypoxic bone death, Legg-Perthes disease.

Adult↗
PubMed1997

A novel approach to providing children's dentistry in general dental practice.

Although more dentists are deciding to specialize in one specific area, these specialist subjects tend to deal with adult treatments. Few choose to specialize in children's dentistry. In this article, Dr A Crawford and Mr P Shaw, put forward a system whereby high quality and cost effective dentistry can be provided for children in the practice using the principles of purchaser/provider.

Child↗
PubMed1997

Modulation of cytokine production by human mononuclear cells following impairment of Na, K-ATPase activity.

Cytokines, including TNF alpha and IL-l beta, are central to the chronic inflammatory process and tissue damage that characterises diseases such as rheumatoid arthritis. The mechanisms responsible for long-term generation of these molecules are poorly understood. We have previously demonstrated impaired activity of Na, K-ATPase, a key enzyme regulating intracellular cation levels, on rheumatoid mononuclear cells. Mimicking this 'defect' on normal mononuclear cells with ouabain has been shown to induce TNF alpha and, in particular, IL-l beta production, whereas IL-6 synthesis was suppressed. A similar pattern of cytokine generation was noted when mononuclear cells were treated with the sodium ionophore, monensin. Induction of cytokine production was related to up-regulation of the appropriate mRNA, although enhanced secretion of processed IL-l beta was also observed. The mechanism underlying these cellular responses appears to involve sodium/calcium exchange across the cell membrane. Impaired Na,K-ATPase activity might promote pro-inflammatory cytokine secretion in patients with rheumatoid arthritis.

Calcimycin↗
PubMed1997

Two unbalanced translocations, t(12;22)(p13;q11) and t(12;?)(p13;?), in an aggressive chronic B-cell leukemia: TEL gene analysis using FISH.

The translocation t(12;22)(p13;q11) has been consistently described in myeloid malignancies and shown to result from a fusion between the TEL and MN1 genes. Previously described deletions of 12p in acute lymphoblastic leukemias have been recently shown to harbor undetected translocations involving the TEL gene at 12p13. We document a case of an aggressive chronic B-cell leukemia whose cells had trisomy 12 and two unbalanced translocations involving 12p13, including a t(12;22)(p13;q11) as shown by conventional cytogenetics and fluorescence in situ hybridization (FISH). The 12p13 breakpoint of the t(12;22)(p13;q11) was telomeric to the TEL gene, and the second unbalanced translocation with breakpoint 12p13 resulted in the deletion of TEL. This case demonstrates that TEL gene deletions may be relevant in cases of mature B-lymphoproliferative diseases.

Chromosomes, Human, Pair 12↗
PubMed1997

Resistance to activated protein C and Legg-Perthes disease.

Thrombophilia may cause thrombotic venous occlusion in the femoral head, with venous hypertension and hypoxic bone death, leading to Legg-Perthes disease. Resistance to activated protein C, the most common thrombophilic trait, was measured in 64 children with Legg-Perthes disease. Genomic deoxyribonucleic acid was studied to delineate the CGA-->CAA substitution at position 1691 of the Factor V Leiden gene responsible for resistance to activated protein C. The activated protein C ratio was calculated by dividing clotting time obtained with activated protein C-calcium chloride by clotting time obtained with calcium chloride alone. Resistance to activated protein C, with a low activated protein C ratio (less than 2.19, the 5th percentile for 160 normal pediatric controls) was the most common coagulation defect, found in 23 of 64 children with Legg-Perthes disease versus 7 of 160 pediatric controls. Eight of 64 children with Legg-Perthes disease had a low activated protein C ratio and the mutant Factor V gene (7 heterozygotes, 1 homozygote) versus 1 of 101 normal pediatric controls. Two or 3 generation vertical and horizontal transmission of heterozygosity for the mutant Factor V gene was found in 4 of the 8 kindreds. Of 64 children with Legg-Perthes disease, only 14 (22%) had entirely normal coagulation measures. Resistance to activated protein C appears to be a pathogenetic cause of Legg-Perthes disease.

Blood Coagulation Disorders↗
PubMed1996

Expression of TIA-1 and TIA-2 in T cell malignancies and T cell lymphocytosis.

OBJECTIVE: To investigate the reactivity with TIA-1 and TIA-2, two monoclonal antibodies that recognise, respectively, granular structures in T lymphocytes and the T cell receptor chain in cells from a variety of T cell disorders. METHODS: Cytoplasmic staining with TIA-1 and TIA-2 was carried out by the immunoalkaline phosphatase anti-alkaline phosphatase technique in 67 cases with a T cell disorder: 31 large granular lymphocyte (LGL) leukaemia, nine T-prolymphocytic leukaemia (T-PLL), five Sezary syndrome, four peripheral T cell lymphoma (PTCL), 13 T cell lymphocytosis, and five T-acute lymphoblastic leukaemia (T-ALL). All had over 75% abnormal T cells which were CD2+, CD3+, CD5+, CD7+, and negative with B cell markers. RESULTS: TIA-1 was positive in 77% cases of LGL leukaemia and half of the PTCL and T-ALL, whereas it was negative in all Sezary syndrome and most T-PLL (8/9) and reactive T-lymphocytosis (10/13). In LGL leukaemia, TIA-1 was positive irrespective of the membrane phenotype, whether CD8+, CD4- or CD4+, CD8-, and was more often positive in cases where cells were CD16+, CD56+, or CD57+. TIA-2 was positive in 60% of cases encompassing all diagnostic types of T cell disorder. There was no correlation between TIA-2 expression and that of other T cell markers, activation antigens, and natural killer markers. CONCLUSIONS: The pattern of TIA-1 expression in T cell malignancies may help in the differential diagnosis among LGL leukaemia (high expression), T cell lymphocytosis and other T cell diseases (low expression). As TIA-2 is expressed in over 95% mature T lymphocytes and thymic cells, its assessment may be useful to demonstrate aberrant phenotypes which can be exploited for detecting minimal residual disease.

Antibodies, Monoclonal↗
PubMed1996

Association of antithrombotic factor deficiencies and hypofibrinolysis with Legg-Perthes disease.

Thirty-three (75 per cent) of forty-four unselected children who had Legg-Perthes disease were found to have coagulation abnormalities. Twenty-three children had thrombophilia (a deficiency in antithrombotic factor C or S, with an increased tendency toward thrombosis); nineteen of the twenty-three children had protein-C deficiency and four had protein-S deficiency. Seven children had a high level (0.25 gram per liter or more) of lipoprotein(a), a thrombogenic, atherogenic lipoprotein associated with osteonecrosis in adults. Three children had hypofibrinolysis (a reduced ability to lyse clots). The mean age of the children when the Legg-Perthes disease was first diagnosed was 5.8 +/- 2.7 years, and the mean age at the time of the present study was 10.1 +/- 4.4 years. At least one of the first-degree relatives of eleven of the nineteen probands who had a low protein-C level had a low protein-C level as well; all of these low levels represented previously undiagnosed familial protein-C deficiency. The eleven probands who had familial protein-C deficiency were more likely to have early onset of Legg-Perthes disease (at or before the age of five years) than the eleven children who had normal levels of protein C, protein S, and lipoprotein(a) as well as normal fibrinolytic activity (chi-square = 6.6; p = 0.01). At least one first-degree relative of one of the four probands who had a low protein-S level had a low protein-S level and previously undiagnosed familial protein-S deficiency. At least one first-degree relative of six of the seven probands who had a high level of lipoprotein(a) had a familial high level of lipoprotein(a). Six of the seven children who had a high level of lipoprotein(a) also had a low level of stimulated tissue-plasminogen activator activity, the major initiator of fibrinolysis. At least one first-degree relative of one of the three probands who had normal levels of protein C, protein S, and lipoprotein(a) but low stimulated tissue-plasminogen activator activity also had low stimulated tissue-plasminogen activator activity (familial hypofibrinolysis). Legg-Perthes disease, thrombophlebitis, premature myocardial infarction, and stroke, which are ramifications of the familial thrombophilic-hypofibrinolytic disorders, were common in the first and second-degree relatives of the thirty-three children with Legg-Perthes disease who also had thrombophilic-hypofibrinolytic disorders.

Adolescent↗
PubMed1995

Improved methods for structural studies of proteins using nuclear magnetic resonance spectroscopy.

The past few years have seen the development of three- and four-dimensional heteronuclear nuclear magnetic resonance methods. Increased sophistication in labelling strategies, use of pulse-field gradients and the application of these methods at higher magnetic fields has, in combination with improved software, allowed studies of the structure, interactions and dynamics of significantly larger proteins (now up to approximately 270 amino acid residues).

Animals↗
PubMed1994

Overexpression of cadherins and underexpression of beta-catenin inhibit dorsal mesoderm induction in early Xenopus embryos.

The cadherin-catenin complex has an important role in cell-cell adhesion and may also function in signaling pathways. We report that overexpression of three cadherin types in Xenopus embryos causes them to develop with reduced dorsal axial structures. The same phenotype is produced in embryos that have been depleted of maternal beta-catenin protein by an antisense oligodeoxynucleotide complementary to beta-catenin mRNA. They show an inhibition in the expression of dorsal mesodermal markers MyoD and goosecoid, but not of ventral and general mesodermal markers. They lack notochords, somites, and neural tubes and are defective in dorsal mesodermal signaling in Nieuwkoop assays. The phenotype can be rescued by the injection of beta-catenin mRNA and not by the injection of Xwnt-8 mRNA. These results show that beta-catenin has an important role in dorsal mesoderm induction. They directly demonstrate the activity of a maternal mRNA in axis specification.

Animals↗
PubMed1994

Interdependent MHC-DRB exon-plus-intron evolution in artiodactyls.

Exon 2 sequences of an expressed MHC-DRB locus from sheep were examined for polymorphisms in both the antigen-binding regions and the adjacent intronic mixed simple tandem repeat. Twenty-one novel exon 2 Ovar-DRB alleles were identified. Short nucleotide motifs are extensively shared between certain exon 2 regions of Ovar-DRB alleles. The simple repeat variations, the number of different amino acids at usually polymorphic sites, and the number of silent substitutions were reduced in the intraspecies analyses of sheep DRB sequences, compared with those of cattle and goats. It was paradoxical that the abundance of different sheep alleles was similar to that of cattle and goats. This paradox may be explained by postulating a relatively small number of "ancient" alleles, with the present-day Ovar-DRB alleles being generated by reciprocal exchange of nucleotide motifs. At the antigen-binding sites, new combinations of amino acids were maintained in Ovar-DRB alleles by strong positive selection. In sheep--and less pronounced in goats and cattle--the DRB alleles can be divided into two groups. In one group, silent substitutions are increased when compared with the other. This suggests separate evolutionary pathways for certain groups of DRB alleles within a species. The simple repetitive sequences are also discussed with respect to the evolution of DRB alleles.

Amino Acid Sequence↗
PubMed1993

The paradox of MHC-DRB exon/intron evolution: alpha-helix and beta-sheet encoding regions diverge while hypervariable intronic simple repeats coevolve with beta-sheet codons.

Twenty-one different caprine and 13 ovine MHC-DRB exon 2 sequences were determined including part of the adjacent introns containing simple repetitive (gt)n(ga)m elements. The positions for highly polymorphic DRB amino acids vary slightly among ungulates and other mammals. From man and mouse to ungulates the basic (gt)n(ga)m structure is fixed in evolution for 7 x 10(7) years whereas ample variations exist in the tandem (gt)n and (ga)m dinucleotides and especially their "degenerated" derivatives. Phylogenetic trees for the alpha-helices and beta-pleated sheets of the ungulate DRB sequences suggest different evolutionary histories. In hoofed animals as well as in humans DRB beta-sheet encoding sequences and adjacent intronic repeats can be assembled into virtually identical groups suggesting coevolution of noncoding as well as coding DNA. In contrast alpha-helices and C-terminal parts of the first DRB domain evolve distinctly. In the absence of a defined mechanism causing specific, site-directed mutations, double-recombination or gene-conversion-like events would readily explain this fact. The role of the intronic simple (gt)n(ga)m repeat is discussed with respect to these genetic exchange mechanisms during evolution.

Alleles↗
PubMed1993

Ultrasound diagnosis of plantar fasciitis.

There is currently no objective reliable diagnostic test for plantar fasciitis inasmuch as diagnosis cannot be made on the basis of finding a heel spur on radiography (x-ray). In this single-blind observational study, ultrasonography was used to measure plantar fascia thickness in subjects with clinically suspected plantar fasciitis and in control subjects. It was concluded that the population mean plantar fascia thickness is greater for people with plantar fasciitis than for people without heel pain (P < .0005) and that the difference is clinically significant. The ultrasonic appearance of the plantar fascia in plantar fasciitis indicated inflammatory changes.

Adult↗
PubMed1991

Disability in persons hospitalized with AIDS.

This study documents the types and degree of disability seen in persons with AIDS at discharge from acute hospitalization. Based on 37 discharge evaluations using the Functional Independence Measure (FIM), 60% required human assistance in at least one of 18 FIM areas. Thirty-two percent required human assistance in five or more areas. Fifty-one and 38% required human assistance in stair climbing and ambulation, respectively. Feeding and bathing required assistance in about 33% and transferring to tub or shower in 25% of the sample. Increasing disability was associated with longer duration of AIDS diagnosis and increasing lengths of hospital stay (P less than 0.01 and P less than 0.05, respectively). There were individuals who remained nearly functionally independent up to 30 months after an AIDS defining event. The overall variability in function, however, was not significantly different between those with diagnoses less than and greater than 12 months. We conclude that significant physical disability exists in persons with AIDS at discharge from acute hospitalization. Consultation with and intervention by rehabilitation professionals may be helpful in the management of physical disability in this population and setting.

Acquired Immunodeficiency Syndrome↗