Takeaway nappies.
Explore the source record for details and available documents.
Environmental Health↗
Biomedical subjects
D Thomas
Publications and source records attributed to D Thomas.
Correlation between left ventricular hypertrophy and GAA trinucleotide repeat length in Friedreich's ataxia.
BACKGROUND: Friedreich's ataxia (FA), the most common inherited ataxia, is associated frequently with cardiac hypertrophy, and death is often cardiac related. Recently, the disease has been associated with a mutation that consists of an unstable expansion of GAA repeats in the first intron of the gene encoding frataxin on chromosome 9. METHODS AND RESULTS: We studied 44 consecutive patients with FA, determined the size of GAA expansions in the frataxin gene, and examined the relation between the genotype and cardiac phenotype assessed by M-mode and two-dimensional echocardiography. All the patients were homozygous for the mutation. The size of the GAA expansion on the smaller allele varied from 270 to 1200. We found a correlation between the size of GAA expansion and the left ventricular wall thickness (r = .51, P < .001) and the left ventricular mass index (r = .45, P = .002). Left ventricular hypertrophy was observed in 81% of patients with a number of GAA repeats above the median value of 770 compared with only 14% in the other group (P = .002). CONCLUSIONS: These data demonstrate that in FA, the severity of left ventricular hypertrophy is related to the number of GAA repeats. These results suggest that abnormalities of the gene encoding frataxin, a protein of unknown function highly expressed in the normal heart, may play an important role in the modulation of cardiac hypertrophy.
Adult↗
Assembly of a bZIP-bHLH transcription activation complex: formation of the yeast Cbf1-Met4-Met28 complex is regulated through Met28 stimulation of Cbf1 DNA binding.
Transcriptional activation of sulfur amino acid metabolism in yeast is dependent on a multi-functional factor, the centromere-binding factor 1 (Cbf1) and on two specific transcription factors, Met4 and Met28. Cbf1 belongs to the basic helix-loop-helix DNA-binding protein family while Met4 and Met28 are two basic leucine zipper (bZIP) factors. We have shown previously that in cell extracts, the three factors are found in a high molecular weight complex. By using mobility shift assays, we report here that the in vitro reconstitution of the Cbf1-Met4-Met28 complex on MET16UAS can be obtained with purified recombinant proteins. DNase I protection experiments confirm that the Cbf1-Met4-Met28 complex is formed over the TCACGTG sequence. The experiments also show that both Met4 and Met28 bind to DNA only in the presence of Cbf1. Moreover, Met28 is shown to enhance the DNA-binding activity of Cbf1. Analysis of MET28 gene regulation reveals that its expression requires Met4. Thus the biochemical activity of Met28 allows the establishment of a positive regulatory loop. The results thus provide evidence of a new functional relationship between bHLH and bZIP proteins and demonstrate that the association of such factors may serve to discriminate between the different TCACGTG sequences found in the chromosomes.
Base Sequence↗
Should paediatric intensive care be centralised? Trent versus Victoria.
BACKGROUND: The mortality rate is lower among children admitted to specialist paediatric intensive care units (ICUs) than among those admitted to mixed adult and paediatric units in non-tertiary hospitals. In the UK, however, few children receive intensive care in specialist paediatric units. We compared the ICU mortality rate in children from the area the Trent Health Authority, UK, with the rate in children from Victoria, Australia, where paediatric intensive care is highly centralised. METHODS: We studied all children under 16 years of age from Trent and Victoria who received intensive care between April 1, 1994, and March 31, 1995. Children younger than 1 month were excluded unless they had cardiac disorders. We developed a logistic regression model that used information gathered at the time of admission to ICU to adjust for risk of mortality. FINDINGS: The rates of admission of children to intensive care were similar for Trent and Victoria (1.22 and 1.18 per 1000 children per year), but the mean duration of an ICU stay was 3.93 days for Trent children compared with 2.14 days for children from Victoria. 74 (7.3%) of the 1014 children from Trent died, compared with 60 (5.0%) of the 1194 children from Victoria. With adjustment for severity of illness at the time of admission to ICU, the odds ratio for the risk of death for Trent versus Victoria was 2.09 (95% CI 1.37-3.19, p < 0.0005). There were 31.7 (14.0-50.4) excess deaths in Trent children, which is equivalent to 42.8% of the deaths in ICU, and 11.1% of all deaths in children between the ages of 1 month and 16 years in Trent. INTERPRETATION: If Trent is representative of the whole country, there are 453 (200-720) excess deaths a year in the UK that are probably due to suboptimal results from paediatric intensive care. If the ratio of paediatric ICUs to children were the same in the UK as in Victoria, there would be only 12 paediatric ICUs in the country. Our findings suggest that substantial reductions in mortality could be achieved if every UK child who needed endotracheal intubation for more than 12-24 h were admitted to one of 12 large specialist paediatric ICUs.
Adolescent↗
Association between tubal ligation and endometrial cancer.
Explore the source record for details and available documents.
Age Factors↗
Inactivation of OGG1 increases the incidence of G . C-->T . A transversions in Saccharomyces cerevisiae: evidence for endogenous oxidative damage to DNA in eukaryotic cells.
The OGG1 gene of Saccharomyces cerevisiae encodes a DNA glycosylase that excises 7,8-dihydro-8-oxoguanine (8-OxoG) and 2,6-diamino-4-hydroxy-5-N-methylformamidopyrimidine. To investigate the biological role of the OGG1 gene, mutants were constructed by partial deletion of the coding sequence and insertion of marker genes, yielding ogg1::TRP1 and ogg1::URA3 mutant strains. The disruption of the OGG1 gene does not compromise the viability of haploid cells, therefore it is not an essential gene. The capacity to repair 8-OxoG has been measured in cell-free extracts of wild-type and ogg1 strains using a 34mer DNA fragment containing a single 8-OxoG residue paired with a cytosine (8-OxoG/C) as a substrate. Cell-free extracts of the wild-type strain efficiently cleave the 8-OxoG-containing strand of the 8-OxoG/C duplex. In contrast, cell-free extracts of the Ogg1-deficient strain have no detectable activity that can cleave the 8-OxoG/C duplex. The biological properties of the ogg1 mutant have also been investigated. The results show that the ogg1 disruptant is not hypersensitive to DNA-damaging agents such as ultraviolet light at 254 nm, hydrogen peroxide or methyl methanesulfonate. However, the ogg1 mutant exhibits a mutator phenotype. When compared to those of a wild-type strain, the frequencies of mutation to canavanine resistance (CanR) and reversion to Lys+ are sevenfold and tenfold higher for the ogg1 mutant strain, respectively. Moreover, using a specific tester system, we show that the Ogg1-deficient strain displays a 50-fold increase in spontaneously occurring G x C-->T x A transversions compared to the wild-type strain. The five other base substitution events are not affected by the disruption of the OGG1 gene. These results strongly suggest that endogeneous reactive oxygen species cause DNA damage and that the excision of 8-OxoG catalyzed by the Ogg1 protein contributes to the maintenance of genetic stability in S. cerevisiae.
Base Sequence↗
Malignant cerebral glioma. Modern radiotherapy can give good quality survival for six months.
Explore the source record for details and available documents.
Brain Neoplasms↗
Heteromultimeric complexes of CD40 ligand are present on the cell surface of human T lymphocytes.
CD40 ligand (CD40L), a 33-kDa type II membrane glycoprotein expressed primarily on activated CD4+ T lymphocytes, is responsible for the helper function of T cells on resting B cells in a non-antigen-dependent, non-major histocompatability complex-restricted fashion. Interaction of CD40L with its receptor CD40 induces proliferation of and isotype switching in B lymphocytes. Recently we solved the x-ray structure of recombinant soluble CD40L and showed that, similar to other members of the tumor necrosis factor family, CD40L indeed exists as a trimer. We now report that, under normal physiological conditions, CD40L molecules exist as heteromultimeric complexes. These CD40L complexes, made of the full length and smaller fragments of CD40L, are present on the cell surface of T lymphocytes and are capable of interacting with CD40 molecule. A prominent fragment with a mass of 31 kDa accounts for as much as half of the CD40L on the surface of Jurkat cells. N-terminal sequence data revealed that this fragment lacks the cytoplasmic tail. A minor 18-kDa fragment of CD40L was also characterized which lacks the cytoplasmic tail, transmembrane region, and stalk region of the extracellular domain. The presence of CD40L heteromultimeric variants implies an additional regulation of the functional activity of this ligand complex.
Antigens, Differentiation, T-Lymphocyte↗
Aquaporin-related proteins in the filter chamber of homopteran insects.
In the Homopteran order of insects, the plant xylem feeders exhibit a highly differentiated part of their digestive tract known as the filter chamber. In this tissue, water crosses plasma membranes through a transepithelial osmotic gradient. In previous studies on the filter chamber of Cicadella viridis, we purified and characterized from the plasma membranes a 25 kDa protein that we demonstrated to be an aquaporin (or water channel, member of the major intrinsic protein family, a group of membrane channels for small solutes). We called this protein AQPcic for Cicadella aquaporin. In the present study, we used polyclonal antibody anti-AQPcic in Western blotting and immunocytochemical analysis of the intestinal tract of Cercopis sanguinolenta, Philaenus spumarius, Aphrophora alni (Cercopidae), Euscelidius variegatus, and Scaphoideus titanus (Jassidae). Western blotting experiments revealed that immunologically related AQPcic proteins are found in those species. The molecular weight of these proteins is 15-26 kDa. Immunocytochemical studies on ultrathin filter-chamber sections revealed that the anti-AQPcic antibody systematically labelled the membrane microvilli of epithelial cells. A good correlation thus exists between the physiology of these cells and the presence of aquaporin-related proteins in their membranes.
Animal Structures↗
Changes in protamine 1 distribution in human sperm nucleus during in vitro sperm-oocyte interaction: an immunoelectron microscopic study.
OBJECTIVE: To determine whether the process of sperm nuclear destabilization would begin before sperm-oocyte fusion in humans. DESIGN: Changes in the distribution of human protamine 1 were investigated in human spermatozoa from the ejaculate, in spermatozoa selected by swim-up or Percoll techniques, and in spermatozoa bound to zona pellucida (ZP) from oocytes that failed to fertilize in an IVF program. SETTING: Center for Infertility and Assisted Reproductive Technology, and university departments. PATIENT(S): Fifteen couples undergoing an IVF program. INTERVENTION(S): Women underwent a similar superovulation induction protocol that consisted of GnRH agonist associated with hMG. MAIN OUTCOME MEASURE(S): Comparative immunoelectron microscopic study of sperm nucleus labeling with an anti-human protamine 1 specific protamine monoclonal antibody. RESULT(S): After selection by swim-up or by Percoll, spermatozoa show a significantly lower nuclear labeling than in the ejaculate. After binding to the ZP, labeling increases, more in spermatozoa selected by swim-up than by Percoll, but, after Percoll selection, labeling in zona-bound spermatozoa is lower than in the ejaculate. CONCLUSION(S): In humans sperm binding to the ZP induces differences in the accessibility of the anti-human protamine 1 antibody, which are consistent with structural rearrangements of the DNA-nucleoproteins complex. These modifications must be a prelude to sperm decondensation, protamines replacement by histones, and subsequent reactivation of the sperm genome in the oocyte.
Cell Nucleus↗
Health and wages: evidence on men and women in urban Brazil.
Explore the source record for details and available documents.
Americas↗
Synaptophysin immunoreactivity in the aging rat pituitary gland.
The density of synaptophysin (SN)-immunoreactivity (IR) was examined in pituitary glands of aging male Sprague-Dawley rats. SN-IR was observed as dense dots among endocrine cells of the intermediate lobe, while the neural lobe contained numerous, highly dense immunopositive regions. Some anterior lobe secretory cells contained SN-IR within the cytoplasm, suggestive of the presence of the protein in secretory granules, but no dot-like staining was observed between endocrine cells of that region. A quantitative analysis of the dot-like SN-immunostaining within the intermediate lobe found that tissue from groups of rats aged 13 months, or 15-17 months, contained significantly fewer SN-immunopositive areas than did tissues from 8-month-old animals. Diminished SN immunostaining is suggestive of reduced numbers of synapses in the intermediate lobe, which may lead to alterations in regulation of pituitary hormone secretion from endocrine cells in the older animals.
Aging↗
Postthyroidectomy analgesia: morphine, buprenorphine, or bupivacaine?
STUDY OBJECTIVE: To compare three analgesic regimens for pain relief after thyroidectomy. DESIGN: Randomized, double-blind, placebo-controlled study. SETTING: Inpatient anesthesia in a university department of endocrine surgery. PATIENTS: 342 patients scheduled for elective thyroidectomy with nitrous oxide-oxygen-isoflurane anesthesia in addition to fentanyl. INTERVENTIONS: Group 1 received preoperative oral controlled release morphine 10 mg, and Group 2 received postoperative sublingual buprenorphine 0.2 mg. Group 3 received 0.25% bupivacaine (10 ml) wound infiltration before skin closure. Eight hours after tracheal extubation, patients received a second dose of the same drug in each group except in Group 3, where medication was changed to sublingual buprenorphine 0.2 mg. MEASUREMENTS AND MAIN RESULTS: Patients in Group 2 required fewer additional analgesics: 0.54 +/- 0.68 vs. 0.96 +/- 0.84 in Group 1 and 0.79 +/- 0.78 in Group 3. Patients in Group 2 demonstrated a better pain score and this group showed a higher percentage of satisfied patients: 96% vs. 85% in Group 1 and 91% in Group 3. Group 2 also included more patients requiring no analgesics: 56% vs. 32% in Group 1 and 42% in Group 3. The side effects in all three groups did not differ. CONCLUSION: The administration of sublingual buprenorphine after thyroidectomy provides better analgesia than small doses of oral controlled-release morphine or than 0.25% bupivacaine wound infiltration at the end of surgery.
Administration, Sublingual↗
[Diagnostic importance of middle latency auditory evoked potentials (MLAEP) in multiple sclerosis].
This study was aimed at assessing the interest of middle latency auditory evoked potentials (MLAEP) recordings in multiple sclerosis (MS). Brainstem auditory evoked potentials (BAEP) and MLAEP were recorded in 40 control subjects and 65 patients who had MS according to Poser's criteria. Na and Pa latencies were significantly delayed in the MS group. These abnormalities were detected in 60% of the patients. In 26% of the cases with normal BAEP, abnormalities of MLAEP were present. In 71% of the patients abnormalities of both BAEP and MLAEP were observed. These results suggest the ability of MLAEP recordings to detect lesions of the auditory pathways rostral to the pons and show the value of their combined recordings in MS patients.
Adult↗
The hyper-CVAD regimen improves outcome in relapsed acute lymphoblastic leukemia.
Sixty-six adults with refractory acute lymphocytic leukemia received salvage therapy with the 'hyper-CVAD' regimen, consisting of eight courses of alternating intensive chemotherapy with growth factor support, followed by oral maintenance chemotherapy. Their outcome was compared with 63 prognostically similar historical control patients treated with high-dose Ara-C plus mitoxantrone with or without GM-CSF. Overall, the complete response rates were similar in the treatment and control groups (29 of 66 (44%) vs 24 of 63 (38%)). There were more patients in the current study with primary resistant disease (10 of 66 (15%) vs one of 63 (2%), P = 0.006), and conversely fewer patients with secondary resistance (19 of 66 (29%) vs 28 of 63 (44%), P = 0.06). Recovery of granulocyte counts above 500/microl was significantly faster in the current study when compared to high-dose Ara-C-treated patients who were given GM-CSF (20 vs 25 days, P = 0.04). Survival was prolonged in the hyper-CVAD-treated patients, with most of the benefit seen in first salvage patients (42 vs 20 weeks, P = 0.016). When only first salvage patients were considered, there was a significant difference in disease-free survival in favor of hyper-CVAD (52 vs 20 weeks, P = 0.008). The hyper-CVAD regimen is a more effective and less toxic salvage regimen for relapsed acute lymphocytic leukemia than high-dose Ara-C-based regimens.
Adult↗
Cell salvage auto transfusion in total knee replacement surgery.
We conducted a prospective, randomized study to assess the impact of cell salvage, auto transfusion on the requirements for allogeneic blood for patients undergoing a total knee replacement (TKR). One hundred consecutive TKR patients were randomly allocated to receive either autologous blood (using cell salvage) or an allogeneic blood transfusion as necessary. Patients allocated to the autologous group were rescued with allogeneic blood if the postoperative haemoglobin fell below 9 g dL-1. Forty-two (84%) of 50 patients in the autologous group required no supplementary blood transfusion. Forty (80%) of 50 patients allocated to receive allogeneic blood required transfusion. There were no detrimental effects of autologous blood transfusion. We conclude that autologous blood transfusion, using the cell saver system, is a safe and effective method of reducing the need for allogeneic blood transfusion and, in doing so, reduces the risk of transmission of infections associated with allogeneic blood transfusion, whilst decreasing demand on precious allogeneic blood reserves.
Aged↗
Born before arrival (BBA) in Trinidad-a seven year case-control study.
A retrospective case-control study was made of 326 babies born before arrival (BBA) at hospital, in a Caribbean developing country. Each baby born before arrival was matched with hospital-delivered controls within the same week of delivery. Control group 1 (n=302) was matched by maternal age and parity and control group 2 (n=262) by gestational age and fetal birth weight. BBA occurred significantly more often in Afro-Caribbean when compared with those of Indo-Caribbean origin and was more common in grand multiparous women, those who had poor antenatal care and those who had a similar previous event. Perinatal mortality was more common than in the control groups. Unlike other studies, young maternal age and marital status were not significant contributing factors. These findings suggest that clinical features exist for identification of women at high risk for BBA which can therefore assist in its prevention and attendant serious consequences.
Journal Article↗
Nutritional status of urban homebound older adults.
The purposes of this study were to assess comprehensively the nutritional status of frail older adults living in an urban area and to identify factors associated with nutritional insufficiency. Subjects were 49 adults aged > or = 65 y followed by the Jefferson County Home Health Department. Twenty-nine percent of the women and 63% of the men had a body mass index (BMI; in kg/m2) < 24. Nineteen percent had serum albumin concentrations < 35 g/L (3.5 g/dL). More than one-half of the subjects reported symptoms of oral health problems. The key dependent variables were serum albumin concentration and BMI. In univariate analyses, a lower BMI correlated with oral symptoms, male sex, increased age, and less education. Lower serum albumin concentrations were associated with advanced age, increased dependence in Activities of Daily Living (ADL), oral symptoms, and presence of a caregiver. A stepwise multiple-regression model for BMI and serum albumin showed that predictors of low BMI were increased age, less education, difficulty in chewing, and absence of dentures. Variables in the model for lower serum albumin concentrations were sex, increased age, increased dependence in ADLs, and wearing of dentures. In a secondary analysis that controlled for age, education level, functional status, and sex, oral symptoms remained associated with lower BMI but not with lower serum albumin concentrations. This study found a high prevalence of undernutrition in urban homebound older adults and suggests that oral health disability may affect nutritional status in this population.
Black or African American↗