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Biomedical subjects

S Daly

Publications and source records attributed to S Daly.

At least 37 records · Page 2Linked to original sources
PubMed1998

A maternal complex partial seizure in labor can affect fetal heart rate.

We describe a 33-year-old woman who had a complex partial seizure during labor. Intrauterine pressure catheter and fetal heart monitoring during the seizure revealed a strong, prolonged uterine contraction and simultaneous significant fetal heart rate deceleration for 3.5 minutes. This patient demonstrates that complex partial seizures may result in uterine hyperactivity during labor, which may result in fetal hypoxia.

Adult↗
PubMed1997

Minimum effective dose of folic acid for food fortification to prevent neural-tube defects.

BACKGROUND: Although a daily supplement of 400 micrograms folic acid has been shown to prevent neural-tube defects (NTD), most women do not take the recommended supplement. Thus, food fortification is to be introduced in the USA and is being considered in the UK. Because of safety concerns, the USA has chosen a level of fortification that will increase the average woman's intake by only 100 micrograms. Such an increase, although safe, may be ineffective; but a trial to assess its efficacy would be unethical. Because women with red-cell folate concentrations above 400 micrograms/L have a very low risk of NTD, we undertook a randomised trial of several folic acid doses to find out how much is needed to reach this protective concentration. METHODS: We screened 323 women. 172 with red-cell folate between 150 micrograms/L and 400 micrograms/L were invited to take part in the trial. 121 women were randomly assigned placebo or 100 micrograms, 200 micrograms, or 400 micrograms daily of additional folic acid. Compliance was monitored by having the women sign a dated sheet when taking the tablet. 95 women completed the 6-month study. FINDINGS: There were significant increases in red-cell folate in all folic acid groups. The placebo group showed no significant change. The median incremental changes and median post-treatment concentrations were 67 micrograms/L (95% CI 43-120) and 375 micrograms/L (354-444) in the 100 micrograms/day group, 130 micrograms/L (108-184) and 475 micrograms/L (432-503) in the 200 micrograms/day group, and 200 micrograms/L (125-312) and 571 micrograms/L (481-654) in the 400 micrograms/day group. INTERPRETATION: A fortification programme that delivered 400 micrograms folic acid daily to women would protect against NTD, but at the expense of unnecessarily high exposure for many people. Delivery of 200 micrograms daily is also effective against NTD and safer for the general population. Based on projections from the positive folate balance in the group that received 100 micrograms daily, this dose taken continually, as it will be in fortified food, will also produce an important decrease in NTD.

Adult↗
PubMed1997

Thermolabile variant of 5,10-methylenetetrahydrofolate reductase associated with low red-cell folates: implications for folate intake recommendations.

BACKGROUND: The dietary reference values for folate, as for other nutrients, are targeted to the general and supposedly normal population, not people with special needs, such as those with genetic or metabolic abnormalities or diseases. However, 5-15% of general populations are homozygous for a thermolabile variant of 5,10-methylenetetrahydrofolate reductase (C677T) which causes mild hyperhomocysteinaemia and is positively associated with the development of vascular disease and the risk of neural-tube defects. If tissue-folate status is compromised in large sectors of the population by this or other genetic variants, the present dietary reference values may need to be changed. METHODS: We identified the C677T genotype and measured red-cell folate concentrations in two groups of healthy women (pregnant, 242, not pregnant, 318). We then analysed the effect of genotype on red-cell folates, which are a reliable marker for tissue folate stores. FINDINGS: In the pregnant group there were 20 TT homozygotes, 114 wild-type CC homozygotes, and 108 CT heterozygotes. In the non-pregnant group, the numbers were 41, 148, and 129. In both pregnant and non-pregnant groups, red-cell folate was significantly lower among TT homozygous than CC homozygous women (mean 252 [95% CI 202-317] vs 347 [321-372] micrograms/L, p = 0.002 for pregnant women; 284 [250-327] vs 347 [342-372] micrograms/L, p = 0.01 for non-pregnant women). Plasma folate was also significantly lower in TT homozygous than in CC homozygous women in the pregnant group (p = 0.009) but not in the non-pregnant group. INTERPRETATION: These results suggest that a substantial minority of people in general populations may have increased folate needs. Future studies may show the presence of other common genetic variants that interact with particular nutrients and place doubts on the validity of assuming "normality" for nutrient requirements in any general population.

Diet↗
PubMed1997

Isolation and characterization of a gene encoding alpha-tubulin from Candida albicans.

A gene encoding the alpha-tubulin of Candida albicans has been cloned and characterized. Nucleotide sequence analysis reveals the presence of an intron within the structural gene and predicts the synthesis of a polypeptide of 448 amino acid residues. Comparison of nucleotide and amino acid sequences with the Saccharomyces cerevisiae alpha-tubulin encoding genes shows a 75% homology and about 92% similarity respectively. In contrast to S. cerevisiae, C. albicans appears to possess only one gene for alpha-tubulin which is able to functionally complement a S. cerevisiae cold-sensitive tub1 mutant.

Amino Acid Sequence↗
PubMed1997

Monocyte chemoattractant protein-2 is a potent agonist of CCR2B.

The binding and functional activity of the CC chemokines monocyte chemoattractant protein-1 (MCP-1), MCP-2, and MCP-3 have been characterized using Chinese hamster ovary DXB-11 cells transfected with the chemokine receptor CCR2B. Receptor binding studies demonstrated that 125I-labeled MCP-1 bound to a single class of high-affinity receptors with a Kd of 0.14 (0.07-0.32) nM. In competition studies MCP-1, MCP-2, and MCP-3 completely inhibited 125I-labeled MCP-1 binding with Ki values of 0.3 (0.16-0.46), 8.8 (3.4-26), and 12.2 (0.6-22) nM, respectively. In calcium mobilization studies, MCP-1 and MCP-3 induced robust elevations in intracellular calcium concentrations, whereas MCP-2 was only weakly active. In contrast, using changes in extracellular acidification rate as a functional readout, all three chemokines were identified as potent agonists of CCR2B. These data demonstrate that MCP-2, in addition to MCP-1 and MCP-3, is a potent agonist of CCR2B and furthermore that MCP-2 activates either different or a subset of the signaling pathways activated by MCP-1 and MCP-3.

Animals↗
PubMed1996

Aplastic anemia: evidence for dysfunctional bone marrow progenitor cells and the corrective effect of granulocyte colony-stimulating factor in vitro.

We investigated the effects of granulocyte-macrophage colony-stimulating factor, interleukin-3, stem cell factor, interleukin-6, and granulocyte colony-stimulating factor (G-CSF) alone, and in combination, on the clonogenic potential of normal and aplastic anemia (AA) bone marrow mononuclear cells (BMMC and CD34+ cells. AA BMMC consistently produced a significantly lower absolute number of colonies than normal, but, when account was taken of the reduced proportion of CD34+ cells in AA BM, there was no significant difference in terms of cloning efficiency (CE). However, when removed from the influence of accessory cells, the CE of AA CD34+ cells decreased significantly more than normal, indicating a defect in their function, either in terms of dependence on accessory cell-derived factors or susceptibility to cell damage when sorted. Of the factors studied, G-CSF had the most significant effect on the response of CD34+ cells from both groups when removed from their accessory cells. This was particularly true for AA CD34+ cells, whose response to cytokine stimuli containing G-CSF enabled them to match the response of normal CD34+ cells.

Adult↗
PubMed1995

The effect of human flt-3 ligand on committed progenitor cell production from normal, aplastic anaemia and Diamond-Blackfan anaemia bone marrow.

We investigated the effect of the human ligand for flt-3 (FL) on the committed progenitor colony formation of normal bone marrow (BM) (n = 9) and BM from four aplastic anaemia (AA) and three Diamond-Blackfan anaemia (DBA) patients. Methylcellulose committed progenitor cell assays were carried out using FL alone and in combinations with granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3) and c-kit ligand (KL). FL alone had a limited, though significant, effect on the production of granulocyte-macrophage colony-forming unit (CFU-GM) colonies from normal BM and showed an additive effect with IL-3 and GM-CSF separately, but not in combination. FL did not increase the stimulation of KL and did not have an effect on the production of erythroid progenitor colonies. FL had no effect on the AA and DBA BMs studied.

Adult↗
PubMed1995

Haemopoietic growth factor production by normal and aplastic anaemia stroma in long-term bone marrow culture.

Defective marrow stroma, or microenvironment, have been proposed as one of several mechanisms to account for bone marrow failure in aplastic anaemia (AA). This could involve defects in positive- or negative-acting haemopoietic regulator expression by AA stroma, or alteration of normal stroma-stem cell interactions. We have used a sensitive bioassay to investigate production of granulocyte-colony stimulating factor (G-CSF), granulocyte-macrophage-colony stimulating factor (GM-CSF), interleukin (IL)-3, IL-6 and stem cell growth factor (SCF), by normal and AA stroma in long-term bone marrow culture (LTBMC). LTBMC were grown to confluence, irradiated and harvested to yield a single cell suspension. These cells were cocultured with normal target bone marrow mononuclear cells (BMMC), or CD34+ cells, in clonogenic assays, in the absence of exogenous cytokines. Cytokines responsible for the colony-stimulating activity (CSA) and burst-promoting activity (BPA) produced by stromal cells were identified by neutralizing antibodies to specific cytokines. All normal stroma populations produced G-CSF and GM-CSF, 93% produced IL-3, 80% produced IL-6, and 70% produced SCF. Similarly, all AA stroma produced G-CSF and GM-CSF, and 71% produced SCF. In contrast, only 71% of AA stroma produced IL-3 and 36% produced IL-6. Target cell stimulation was not dependent on direct stroma-target cell contact, suggesting production of soluble cytokines. However, although both IL-6 and G-CSF were detected in LTBMC supernatants by enzyme-linked immunoassay (ELISA), IL-3 and GM-CSF were undetectable, perhaps indicating low-level local production of these factors.

Adolescent↗
PubMed1995

IL-3 is produced by normal stroma in long-term bone marrow cultures.

Interleukin-3 (IL-3) has been shown to have significant effects on haemopoiesis in vitro, but early investigations of normal human long-term bone marrow cultures (LTBMC) have failed to demonstrate IL-3 production by stromal cells, either by Northern blotting for mRNA, or assaying for bioactivity in culture supernatants. One recent report, using reverse transcription-polymerase chain reaction (RT-PCR), demonstrated IL-3 expression in only one of eight cultures. We have developed a sensitive bioassay for the detection of IL-3 production from normal stroma in LTBMC. LTBMC were grown until confluent, irradiated, and stroma harvested by trypsinization to yield single-cell suspensions. These cells were then cocultured with target bone marrow mononuclear cells (BMMC), or CD34+ cells in clonogenic assays, either in the presence or absence of anti-IL-3 neutralizing antibodies. We have demonstrated IL-3 production in 32/34 cases. In addition, by separating stroma from target cells using cell culture inserts, we have shown that direct stroma:stem cell contact is not necessary for colony growth, suggesting that IL-3 diffuses into the supernatant. However, when supernatants from LTBMC were assayed by enzyme-linked immunoassay (ELISA), no IL-3 was detected. This suggests that IL-3 is probably produced at low levels and has a short-range interaction. Stroma production of IL-3 was confirmed by the detection by RT-PCR of IL-3 mRNA in 3/3 cases. The simultaneous detection of CD2 mRNA demonstrated that T cells are part of the bone marrow stroma. It is therefore possible and probably likely that these cells are the source of IL-3.

Base Sequence↗
PubMed1995

[Peripartum hysterectomy. Report of eleven cases].

A series of hysterectomies performed during labor or shortly after delivery, all as emergencies is reported. The study covered the ten years 1982-1991, during which 65,488 deliveries resulted in infants with a birth weight of 500 g or more. There were no hysterectomies among the 21,998 primipara, the incidence in multipara being 1 per 3,954 deliveries. Five operations were performed for rupture of the uterus and six for cataclysmic bleeding. Seven of the 11 patients had history of caesarean section. In multipara, the existence of a caesarean scar multiplied the risk of emergency hysterectomy by a factor of 18. There were no maternal deaths but all patients required transfusion with more than 6 units of packed cells. These results emphasize the fact that a history of caesarean is the principal etiologic factor in patients experiencing complications of pregnancy which require emergency peri-partum hysterectomy.

Blood Transfusion↗
PubMed1994

Sequence of a dihydrofolate reductase-encoding gene from Candida albicans.

The nucleotide (nt) sequence of the dihydrofolate reductase (DHFR)-encoding gene (DFR1) of Candida albicans was determined. The gene contains an open reading frame of 576 nt, coding for a protein of 192 amino acid (aa) residues (calculated M(r) 22,222), that is 38.5 and 31% similar to the Saccharomyces cerevisiae and human enzymes, respectively. The first 36 residues, at the N terminus, of the deduced aa sequence are identical to those determined by sequencing of the purified enzyme from C. albicans. Putative transcription start points were also determined. Restriction-fragment-length polymorphism analysis of the DFR1 chromosomal region suggests the presence of a single copy of the gene per haploid genome and shows a limited variability among the different C. albicans strains tested.

Amino Acid Sequence↗
PubMed1994

Cloning and characterization of a sulphite-resistance gene of Saccharomyces cerevisiae.

In this paper we describe the cloning and sequencing of the gene (SUL1) responsible for sulphite resistance in a Saccharomyces cerevisiae mutant (Casalone et al., 1992). The deduced amino acid sequence predicted that the gene codes for a zinc-finger protein with five fingers. Comparison of wild-type and mutant gene sequences demonstrated that the mutation event was a transversion from C to G; as a consequence of the mutation a histidine substituted an aspartic acid, affecting directly the fourth finger structure. The SUL1 gene sequence corresponds to that of FZF1 gene (Breitwieser et al., 1993) to which no function was attributed.

Amino Acid Sequence↗
PubMed1994

Biochemical studies on the lethal effects of solar and artificial ultraviolet radiation on Staphylococcus aureus.

The effects of UV-B radiation generated in the laboratory and as a component of sunlight on the viability and particular biochemical activities of the bacterium Staphylococcus aureus have been examined. UV-B radiation progressively inhibits protein synthesis (assayed as 3H-alanine incorporation) and kills cells. Cell respiration, and RNA and DNA synthesis (3H-uridine and 3H-thymidine incorporation) were not greatly affected by UV-B irradiation. The OH. and 1O2-free radical scavengers protected cells against killing and inhibition of protein synthesis by UV-B, suggesting that such radicals mediate the effects of UV-B on this organism. A similar protective effect using a ferric ion chelator suggests an important role for metallic ions in UV-B lethality.

Chelating Agents↗
PubMed1994

Uterine rupture in pregnancy reviewed.

Uterine rupture is associated with maternal and fetal mortality and morbidity. In developed countries there have been many recent advances in the management of labour. This study, therefore, reviewed this Hospital's experience of uterine rupture in the decade 1982 to 1991. Excluding cases of asymptomatic scar dehiscence, there were 15 cases of uterine rupture in 65,488 deliveries, giving an overall incidence of 1 in 4,366. There was no case of rupture in 21,998 primigravidas. Of the 15 cases, only two occurred in 39,529 multigravidas without a previous uterine scar (1 in 19,765), and 13 cases occurred in the 3,961 multigravidas with a previous caesarean section scar (1 in 304). Twelve of the 13 ruptures after caesarean section occurred in the delivery immediately after the section. There were no maternal deaths but five (33%) patients required a hysterectomy. Three of the five perinatal deaths were attributable to the rupture. Ten of the 15 patients had labour induced, and a total of 13 patients received an oxytocic agent. Of the 15 cases, 8 were diagnosed during labour and 7 postpartum. Compared with earlier reports from Dublin, the incidence of uterine rupture was low due to a decrease in the number of ruptures associated with trauma or obstetric manipulation. The main associated feature was previous caesarean section. This review highlights the risk of uterine rupture when an oxytocic agent is administered to a multigravid patient with a previous caesarean section scar.

Female↗
PubMed1994

Plasma granulocyte-colony stimulating factor concentrations ([G-CSF]) in the early neonatal period.

We studied G-CSF concentrations ([G-CSF]) at birth and their relationship with neutrophil count, incidence of infection, gestational age, labour, and the presence of maternal pregnancy-induced hypertension. Plasma [G-CSF] were significantly elevated in babies with suspected infection and in those of hypertensive mothers, compared to healthy babies delivered by elective caesarian section (median [range] = 3101 [75- > 5000] pg/ml and 153 [45-857] pg/ml versus 32 [11-266] pg/ml; P < 0.0001); and were unrelated to neutrophil count and gestational age. Initial high concentrations (> 100 pg/ml) declined by 7 d (P < 0.0001).

Aging↗
PubMed1994

Aplastic anaemia following exposure to 3,4-methylenedioxymethamphetamine ('Ecstasy').

We report two cases of aplastic anaemia following exposure to 'Ecstasy' (MDMA, 3,4-methylenedioxymethamphetamine). In both cases the aplastic anaemia resolved spontaneously 7-9 weeks after presentation. Long-term bone marrow culture study of one patient demonstrated complete normalization of haemopoiesis at time of haematological recovery, suggesting either that damage to the haemopoietic stem cell had been only transient, or that a more mature, committed progenitor cell was the target. Because MDMA may have been a factor in the aetiology of the bone marrow suppression in these two cases, we recommend close haematological monitoring of young adults presenting with toxicity from MDMA, and a detailed history of exposure to recreational drugs in all new patients presenting with aplastic anaemia.

Adolescent↗
PubMed1994

Validation of a single point flow cytometric assay for determining P-glycoprotein activity in multidrug resistant cell lines.

P-glycoprotein, a transmembrane protein which acts as an energy dependent efflux pump, has been implicated as one mechanism of multidrug resistance (MDR) in human tumours. Commonly employed assays measure P-glycoprotein immunohistochemically or mdr1 messenger RNA. In this study we compared a single point flow cytometric assay for determining activity of P-glycoprotein with cellular expression of P-glycoprotein determined by Western blot. Five cell lines, with varying levels of multiple drug resistance, were incubated with daunorubicin (DNR) in the presence (treated) and absence (control) of cyclosporine or verapamil, agents known to inhibit the activity of P-glycoprotein. The treated cell lines, along with non-treated controls were examined for intracellular concentrations of DNR measured by fluorescence intensity using a flow cytometer. The ratio of fluorescence intensity expressed in the treated/control was used as an index of functional activity of P-glycoprotein. Functional activity of the P-glycoprotein as determined by flow cytometry correlates highly with cellular content of P-glycoprotein measured by western blot (correlation coefficients of r = 0.90-0.98 for the various cell line combinations). This method represents a rapid single point flow cytometric assay which may be suitable for screening clinical samples for P-glycoprotein activity.

ATP Binding Cassette Transporter, Subfamily B, Mem↗