Search PubMed⌕ Search

Biomedical subjects

M Daly

Publications and source records attributed to M Daly.

At least 127 records · Page 7Linked to original sources
PubMed1991

The complex genetic locus polyhomeotic in Drosophila melanogaster potentially encodes two homologous zinc-finger proteins.

Differential expression of the homeotic gene complexes, ANT-C and BX-C, of Drosophila melanogaster is partly controlled by trans-regulating factors located outside the two complexes. The complex genetic locus, polyhomeotic (ph), is one of these trans regulators required during development for correct expression of the homeotic selector genes. The ph locus comprises two genetically independent units whose functions are largely redundant. There are two duplicated sequences arranged as a tandem repeat in the ph region, defining two molecular ph units. Sequence analysis of the 28.6 kb of DNA comprising the locus shows varying degrees of sequence conservation between these two molecular units. Long open reading frames with a high degree of conservation have been localized in each tandem repeat. Putative protein products encoded by both the proximal and the distal unit contain several identical or practically identical protein domains: a zinc-finger-forming motif, an alpha-helix motif, a domain rich in serine and threonine residues and stretches of glutamine residues. The presence of these protein domains supports the hypothesis that ph encodes a transcription factor that may function as part of a protein complex. Possible molecular mechanisms leading to the particular structure of the locus are discussed.

Amino Acid Sequence↗
PubMed1991

Antithrombin Cambridge II, 384 Ala to Ser. Further evidence of the role of the reactive centre loop in the inhibitory function of the serpins.

Four unrelated individuals have been identified with an identical antithrombin variant, associated in one of them with episodes of recurrent venous thromboses. In each case, the plasma antithrombin concentration was normal and the only function abnormality was a minor but consistent decrease in the heparin-induced thrombin inhibition suggesting a mutation at or near the reactive centre of the molecule. Amplification and direct sequencing of exon 6 showed a G----T mutation at nucleotide 1246, which corresponds to a substitution of a serine for an alanine at residue 384. This is one of a series of conserved alanines that form the stalk to the reactive centre loop. The observed changes in this variant are compatible with recent structural studies that infer that mobility of this stalk with partial re-entry into the A-sheet of the molecule is necessary for optimal inhibitory activity.

Aged↗
PubMed1991

Identification of bile duct stones in patients undergoing laparoscopic cholecystectomy.

To identify patients with common bile duct stones, all patients considered for laparoscopic cholecystectomy in this unit undergo intravenous cholangiography (IVC) with tomography and, more recently, operative cholangiography. To date 100 consecutive patients with symptomatic gallstones have undergone laparoscopic cholecystectomy with no specific exclusion criteria. Eight patients of 100 were found to have duct stones on IVC with one false-positive. These IVC data were compared with data from 52 patients who also had operative cholangiograms performed. One stone was detected on operative cholangiography that was not identified on IVC. No additional information was gained from operative cholangiography. These data suggest that preoperative IVC is adequate for the detection of duct stones in patients considered for laparoscopic cholecystectomy.

Adolescent↗
PubMed1991

Asymptomatic primary hyperparathyroidism.

Of 118 consecutive white patients referred for asymptomatic primary hyperparathyroidism, the diagnosis was clinically confirmed in 100, of whom 85 adults had a serum calcium less than 3.0 mM (12 mg/dl) and no skeletal, rheumatic, or significant neuropsychiatric symptoms, azotemia, or other significant illnesses. Among these 85, 68 had both asymptomatic and medically uncomplicated hyperparathyroidism, whereas 17 had historical, radiographic, or ultrasonic evidence of renal stone disease. The 20% with past or present renal calculi concentrated their urine significantly better than the 68 others (p = 0.05), but these two groups were otherwise not distinguished by the tests we performed, so all 85 patients were analyzed together. Systolic and diastolic blood pressures were normal, but premature osteopenia and/or impaired renal function were present in 29-36% of the patients. Micrometer measurements of metacarpal radiographs and 125I photon absorptiometry at the shaft of the radius revealed cortical osteopenia. Osteopenia was equally significant in the distal radius (cortical plus trabecular bone). These quantitative measurements were superior to routine bone radiography, and ROC analysis showed that 125I absorptiometry at either site was superior (p less than 0.01) to metacarpal cortex measurements for detecting premature osteopenia, which was present in more than a third of these patients. Creatinine clearances (24 h) and maximum urine concentrating capacity (overnight dehydration plus the synthetic vasopressin analog DDAVP) were each significantly reduced, despite all patients' normal BUN and serum creatinine levels. Sequential performance of a 24 h creatinine clearance and a urine concentration test revealed abnormalities in the renal function of 27 of 74 patients (36%), with a specificity of 95% and a higher sensitivity than either test alone (27-29%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

The incidence of dysfunctional antithrombin variants: four cases in 210 patients with thromboembolic disease.

210 patients, with a history of venous thrombosis, have undergone prothrombotic investigations. In nine cases a consistent deficiency of antithrombin was identified. In five there was a reduction in the plasma antigenic concentration of antithrombin and in a further four cases deficiency was due to the presence of a dysfunctional antithrombin variant. The variants have all been characterized by DNA analysis and in three the mutations have been confirmed by peptide sequencing (antithrombin Basel (41 Pro to Leu). Hamilton (382 Ala to Thr). Cambridge I (384 Ala to Pro) and Cambridge II (384 Ala to Ser). The incidence of antithrombin deficiency in patients with a history of venous thrombosis has previously been quoted at between 2% and 3%: there is no published data available on the incidence of antithrombin variants. In our series 5% of patients who presented before the age of 40 years had antithrombin deficiency, and 2% of the total number of patients investigated had a dysfunctional variant. Our figures indicate that a significant number of cases of antithrombin deficiency are due to dysfunctional variants and that the true incidence of antithrombin deficiency in patients with a history of venous thrombosis is in the order of 5%.

Adult↗
PubMed1991

Screening for heparin binding variants of antithrombin.

A chromogenic assay for use as a screening test for the identification of antithrombin deficiency is described. The heparin concentration and the incubation time in the assay were optimised specifically to permit the detection of heparin binding defects of antithrombin. The sensitivity of antithrombin assays for the detection of this type of variant was significantly impaired when an incubation time of more than 30 seconds was used. Several commercially available assays recommend a longer incubation time than 30 seconds and therefore some patients with heparin binding defects of antithrombin may not be identified. The assay described here allows heparin binding variants of antithrombin to be identified and distinguished from other types of antithrombin deficiency in a simple two stage procedure.

Antithrombins↗
PubMed1990

Antithrombin Dublin (-3 Val----Glu): an N-terminal variant which has an aberrant signal peptidase cleavage site.

Antithrombin Dublin is an electrophoretically fast variant of antithrombin which has normal heparin affinity. Direct sequencing of amplified exon 2 revealed a Val----Glu substitution at position -3. N-terminal sequencing of antithrombin from two individuals, heterozygous for the Dublin mutation, showed the presence of a truncated antithrombin in which the N-terminal dipeptide is absent. We propose that the prepeptide mutation redirects signal peptidase cleavage to a site two amino acids downstream into the mature protein.

Adult↗
PubMed1990

Are primary alloresponses truly primary?

Proliferative T cell responses against major histocompatibility complex (MHC) incompatible stimulator cells in the mixed lymphocyte reaction are conventionally regarded as primary. However, it is generally accepted that the recognition of allogeneic MHC products results from a cross-reaction by self-MHC-restricted cells. These two assumptions were tested by examining the contribution of previously primed and naive T cells to 'primary' alloresponses. Peripheral blood T cells were separated into LFA-3+, memory, and LFA-3-, naive, populations by fluorescence-activated cell sorting. In contrast, to recall antigen responses to Candida albicans which were almost entirely confined to the LFA-3+, memory, population, the proliferative response to MHC incompatible stimulator cells, including HLA-DR-expressing mouse L cell transfectants, was equally distributed between the two T cell subsets in 5 day assays. Furthermore, limiting dilution analysis showed that the frequency of alloreactive T cells did not differ significantly between the two populations. The kinetics of proliferation in the two populations differed but were consistent with their naive and memory phenotype, in that after 3 days of culture the LFA-3+ cells proliferated more strongly to MHC alloantigens. These results show that a substantial proportion of 'primary' alloresponses are contributed by previously primed cells. In addition, the evidence for the cross-reactive hypothesis is supported and extended from the clonal to the population level.

Animals↗
PubMed1990

Is parent-offspring conflict sex-linked? Freudian and Darwinian models.

Freud's Oedipal theory sees parent-offspring conflict as a within-gender rivalry, whereas most modern evolutionary models interpret it as a gender-blind disagreement about resource allocation. New analyses of family homicides and a critical review of prior evidence do not support the central Freudian claim of a same-sex contingency in parent-offspring antagonism during the Oedipal phase. Several errors of fact and interpretation in psychoanalytic theorizing about family relations are discussed. We argue that psychoanalysts mistake substantive conflicts between nonrelatives for symbolic manifestations of family conflicts.

Conflict, Psychological↗
PubMed1990

Suicide in Cork and Ireland.

The official suicide rate in Ireland increased markedly between 1970 and 1985. This is genuine increase in suicide and not an apparent one due to previous deficiencies in recording practices. Possible reasons for this change include an increase in 'anomie' shown by a rise in the rates of crime, illegitimacy and admissions to hospital for alcoholism, a decline in social cohesion revealed by a fall in the marriage rate and a rise in the number of separated couples, and an increase in unemployment.

Adolescent↗
PubMed1989

Identification and characterisation of an antithrombin III mutant (AT Dublin 2) with marginally decreased heparin reactivity.

The antithrombin III (ATIII) isoform patterns of plasma and serum samples from cancer patients and controls were analysed by isoelectric focusing and immunoblotting. A novel ATIII banding pattern was identified in two individuals: a patient with breast carcinoma who developed deep venous thrombosis and a blood donor. Family studies in the patient showed the abnormal pattern to be due to a mutant form of ATIII (AT Dublin 2). The coagulation properties of AT Dublin 2 heterozygotes were normal. Immunologic and activity levels of ATIII, measured by standard techniques, were normal. Mutant plasma ATIII showed reduced thrombin reactivity at low concentrations of thrombin and demonstrated decreased reactivity with heparin over a range of heparin concentrations. This was confirmed using a modified ATIII heparin cofactor activity assay with varying heparin concentrations. The abnormal ATIII was also found to elute from heparin agarose at a lower ionic strength than normal ATIII. Two dimensional gel electrophoresis showed the abnormal ATIII to have similar molecular size distribution to normal ATIII. Neuraminidase treatment of normal and mutant plasma reduced the ATIII isoforms to one in both samples. The possible role of AT Dublin 2 in predisposing to hypercoagulation is discussed.

Adult↗
PubMed1989

Antithrombin Cambridge, 384 Ala to Pro: a new variant identified using the polymerase chain reaction.

An antithrombin III variant was identified in the plasma of a female patient with a history of recurrent thromboses. The variant was shown to have normal antigenic levels but reduced heparin and progressive inhibitory activity consistent with an abnormality affecting function at the reactive centre. Polymerase chain reaction amplification of exon 6 of the gene with direct sequencing showed a point mutation resulting in the substitution of a proline for alanine at position 384. This substitution will predictably alter the conformation of the peptide loop containing the reactive centre of the molecule.

Adult↗
PubMed1989

Frequency and extent of allelic loss in the short arm of chromosome 3 in nonsmall-cell lung cancer.

DNA was prepared from tumour and normal tissue from 48 patients representing all common histological types of nonsmall-cell lung cancer. Using eight DNA probes, which detect nine restriction enzyme fragment length polymorphisms (RFLP) on chromosome 3, we established that among the 44 informative patients 32 had lost alleles on the short arm of one of their copies of chromosome 3. Of these 32, at least 13 had also lost alleles on the long arm of chromosome 3, suggesting that the whole chromosome might be lost. For one patient, cytogenetic analysis indicated that the mechanism of allelic loss was reciprocal translocation followed by chromosomal loss of one of the reciprocal products. Two patients with allelic loss distal to the D3S3 locus (which maps to 3p13-14) retained heterozygosity at that locus. These results indicate that loss of alleles on the short arm of chromosome 3 is a common event in lung tumours of the nonsmall-cell type, that this loss occurs by a variety of chromosomal mechanisms, and that the minimally deleted region is 3p13-14----3pter.

Alleles↗
PubMed1988

Evolutionary social psychology and family homicide.

Homicide is an extreme manifestation of interpersonal conflict with minimal reporting bias and can thus be used as a conflict "assay." Evolutionary models of social motives predict that genetic relationship will be associated with mitigation of conflict, and various analyses of homicide data support this prediction. Most "family" homicides are spousal homicides, fueled by male sexual proprietariness. In the case of parent-offspring conflict, an evolutionary model predicts variations in the risk of violence as a function of the ages, sexes, and other characteristics of protagonists, and these predictions are upheld in tests with data on infanticides, parricides, and filicides.

Age Factors↗