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Biomedical subjects

A Davies

Publications and source records attributed to A Davies.

At least 73 records · Page 4Linked to original sources
PubMed1999

The human and mouse GATA-6 genes utilize two promoters and two initiation codons.

GATA-6 has been implicated in the regulation of myocardial differentiation during cardiogenesis. To determine how its expression is controlled, we have characterized the human and mouse genes. We have mapped their transcriptional start sites and demonstrate that two alternative promoters and 5' noncoding exons are utilized. Both transcript isoforms are expressed in the same tissue-specific and developmental stage-specific pattern, and their ratio appears similar wherever examined. The more upstream noncoding exon showed a substantial degree of homology between the two mammalian species, suggesting a conserved regulatory function. Moreover, in transfection assays we show that elements within this exon act to promote its transcription. Positive regulatory elements that effect transcription from the more downstream exon were not apparent in this assay, revealing a regulatory distinction between the two promoters. We also demonstrate alternative initiator codon usage in both the human and mouse GATA-6 genes. Both isoforms of the protein are synthesized in vitro regardless of which 5' noncoding exon is present in the RNA, although the larger protein has greater transcriptional activation potential in transfection assays. Thus, GATA-6 function in the cell is controlled by a complex interplay of transcriptional and translational regulation.

Alternative Splicing↗
PubMed1999

Interactions between the thiol-group reagent N-ethylmaleimide and neutral and basic amino acid transporter-related amino acid transport.

The neutral and basic amino acid transport protein (NBAT) expressed in renal and jejunal brush-border membranes is involved in amino acid and cystine absorption. NBAT mutations result in Type 1 cystinuria. A C-terminal myc-tagged NBAT (NBATmyc) retains the amino acid transport and protein-protein interaction properties of NBAT when expressed in Xenopus oocytes. Neutral amino acid (Ala, Phe)-cationic amino acid (Arg) heteroexchanges related to NBATmyc expression in oocytes are inactivated by treatment with the thiol-group reagent N-ethylmaleimide (NEM), although significant Arg-Arg and Ala-Ala homoexchanges persist. Inactivation of heteroexchange activity by NEM is accompanied by loss of >85% of alanine and cystine uptake, with smaller (<50%) inhibition of arginine and phenylalanine uptake. NEM-sensitive cystine uptake and arginine-alanine heteroexchange (system b(0,+) activity) are not expressed by an NBAT truncation mutant (NBATmyc-Sph1) lacking the 13 C-terminal amino acid residues, but the mutant expresses NEM-resistant transport activity (system y(+)L-like) equivalent to that of full-length NBATmyc. The deleted region of NBATmyc-Sph1 contains two cysteine residues (671/683) which may be the targets of NEM action. The synthetic amino acid 2-trifluoromethylhistidine (TFMH) stimulated alanine efflux at pH 7.5 and arginine at pH 5.5, but not vice versa, establishing the existence of distinct pathways for cationic and neutral amino acid homoexchange (TFMH is zwitterionic at pH 7.5 and cationic at pH 5.5). We suggest that NBAT expresses a combination of system b(0,+) and y(+)L-like activities, possibly by interacting with different light-chain subunits endogenous to oocytes (as does the homologous 4F2hc protein). The C-terminus of NBAT may also have an additional, direct role in the mechanism of System b(0,+) transport (the major transport activity that is defective in Type 1 cystinuria).

Amino Acid Sequence↗
PubMed1999

The use of atropine for facilitation of direct current cardioversion from atrial fibrillation--results of a pilot study.

BACKGROUND: The importance of the role of the autonomic nervous system (ANS) in the initiation and propagation of atrial fibrillation has been demonstrated in the condition of paroxysmal atrial fibrillation. However, the role of the ANS in patients with chronic atrial fibrillation is less clear. Some patients with chronic atrial fibrillation are resistant to the standard techniques of direct current (DC) cardioversion. HYPOTHESIS: We sought to investigate whether excessive vagal tone might prevent the restoration of sinus rhythm and to establish that the abolition of vagal tone using intravenous atropine will facilitate DC cardioversion in patients with atrial fibrillation who are resistant to the standard cardioversion techniques. METHODS: Beginning in August 1994, a change in the protocol for elective DC cardioversion of atrial fibrillation was made to include the use of intravenous atropine for patients resistant to the standard techniques of DC cardioversion. RESULTS: Over a 2-year period, 140 elective cardioversions were performed for atrial fibrillation. Sinus rhythm could not be restored on 31 occasions. Intravenous atropine prior to a further 360 J shock with paddles in the anteroposterior position allowed sinus rhythm to be restored on nine occasions. Patients with successful cardioversion after atropine had significantly better left ventricular function than those who remained in atrial fibrillation (p = 0.001) as well as a tendency toward a smaller left atrium. CONCLUSION: This study suggests that high vagal tone, which is dominant in patients with structurally normal hearts, may prevent the termination of atrial fibrillation by standard techniques of DC cardioversion, and that the abolition of high vagal tone by atropine facilitates the restoration of sinus rhythm.

Adult↗
PubMed1999

The excision of uterine fibroids by vaginal myomectomy: a prospective study.

OBJECTIVE: To evaluate the clinical effectiveness and safety of the excision of uterine fibroids by vaginal myomectomy. DESIGN: Prospective study. SETTING: A gynecology department of a university teaching hospital. PATIENT(S): Women with menorrhagia, pelvic pain, symptoms of pressure, or subfertility attributable to moderate-sized uterine fibroids who otherwise would have required abdominal or laparoscopic myomectomy. INTERVENTION(S): Vaginal myomectomy. MAIN OUTCOME MEASURE(S): The feasibility of vaginal surgery, operative complications, postoperative recovery, and relief of symptoms. RESULT(S): Myomectomy was completed vaginally in 32 (91.4%) of 35 patients and none required hysterectomy. The overall operating time was 78 minutes, the estimated operative blood loss was 313 mL, and the mean postoperative hospital stay was 4 days. Pelvic hematomas developed in 4 patients, and one colpotomy required resuture. Seventy-four percent of the women reported relief of their symptoms at 3 months' follow-up. Three patients have had full-term pregnancies since the operation. CONCLUSION(S): Myomectomy can be performed by the vaginal route in selected cases with low morbidity and a good short-term success rate. Unlike open myomectomy, it requires no skin incision, and unlike laparoscopic myomectomy, it can be used in patients who have numerous, relatively large, and intramural fibroids.

Adult↗
PubMed1999

Ocular abnormalities in Alagille syndrome.

OBJECTIVE: To assess the type and frequency of ocular abnormalities occurring in Alagille syndrome (AS) in a large group of affected patients and their parents and the potential pathogenetic role of fat-soluble vitamin deficiency. DESIGN: Observational case series. PARTICIPANTS: Twenty-two children with AS and 23 of their parents participated. MAIN OUTCOME MEASURES: Participants underwent full ophthalmic examination, including refraction, orthoptic examination, keratometry, slit-lamp examination, and funduscopy. Corneal diameter measurement was performed in a subset of nine and fluorescein angiography in a subset of six. Serum levels of vitamins A and E and cholesterol were measured. RESULTS: The most common ocular abnormalities in patients with AS were posterior embryotoxon (95%), iris abnormalities (45%), diffuse fundus hypopigmentation (57%, a previously unreported finding), speckling of the retinal pigment epithelium (33%), and optic disc anomalies (76%). Microcornea was not associated with large refractive errors, and visual acuity was not significantly affected by these ocular changes. Vitamin levels were normal. Ocular abnormalities including posterior embryotoxon, iris abnormalities, and optic disc or fundus pigmentary changes were detected in one parent in 36% of cases. CONCLUSIONS: Alagille syndrome is associated with a characteristic group of ocular findings without apparent serious functional significance and probably unrelated to fat-soluble vitamin deficiency. Simple ophthalmic examination of children with neonatal cholestatic jaundice and their parents should allow early diagnosis of AS, eliminating the need for extensive and invasive investigations.

Abnormalities, Drug-Induced↗
PubMed1999

Skin complications in the intensive care unit.

Critically ill patients usually have multiple risk factors for the development of pressure ulcers. Pressure ulcers involve all levels of tissue from bone to skin, and result from excessive pressure and shearing. Control of incontinence, maintenance of adequate oxygen delivery and nutritional support is the key to minimizing the effects of skin breakdown in the intensive care unit. Consistent assessment and surveillance of skin for early signs of pressure ulcer development are essential, as is an interdisciplinary approach with nursing specialists and surgical consultants for pressure ulcers that have developed.

Critical Illness↗
PubMed1999

Antigen S1, encoded by the MIC1 gene, is characterized as an epitope of human CD59, enabling measurement of mutagen-induced intragenic deletions in the AL cell system.

S1 cell membrane antigen is encoded by the MIC1 gene on human chromosome 11. This antigen has been widely used as a marker for studies in gene mapping or in analysis of mutagen-induced gene deletions/mutations, which utilized the human-hamster hybrid cell-line, AL-J1, carrying human chromosome 11. Evidence is presented here which identifies S1 as an epitope of CD59, a cell membrane complement inhibiting protein. E7.1 monoclonal antibody, specific for the S1 determinant, was found to react strongly with membrane CD59 in Western blotting, and to bind to purified, urinary form of CD59 in ELISAs. Cell membrane expression of S1 on various cell lines always correlated with that of CD59 when examined by immunofluorescent staining. In addition, E7.1 antibody inhibited the complement regulatory function of CD59. Identification of S1 protein as CD59 has increased the scope of the AL cell system by enabling analysis of intragenic mutations, and multiplex PCR analysis of mutated cells is described, showing variable loss of CD59 exons.

Animals↗
PubMed1999

Mixed leg ulcers.

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Angiography↗
PubMed1999

EMG responses to free fall in elderly subjects and akinetic rigid patients.

OBJECTIVES: The EMG startle response to free fall was studied in young and old normal subjects, patients with absent vestibular function, and patients with akinetic-rigid syndromes. The aim was to detect any derangement in this early phase of the "landing response" in patient groups with a tendency to fall. In normal subjects the characteristics of a voluntary muscle contraction (tibialis anterior) was also compared when evoked by a non-startling sound and by the free fall startle. METHODS: Subjects lay supine on a couch which was unexpectedly released into free fall. Latencies of multiple surface EMG recordings to the onset of free fall, detected by a head mounted linear accelerometer, were measured. RESULTS AND CONCLUSIONS: (1) EMG responses in younger normal subjects occurred at: sternomastoid 54 ms, abdominals 69 ms, quadriceps 78 ms, deltoid 80 ms, and tibialis anterior 85 ms. This pattern of muscle activation, which is not a simple rostrocaudal progression, may be temporally/spatially organised in the startle brainstem centres. (2) Voluntary tibialis EMG activation was earlier and stronger in response to a startling stimulus (fall) than in response to a non-startling stimulus (sound). This suggests that the startle response can be regarded as a reticular mechanism enhancing motor responsiveness. (3) Elderly subjects showed similar activation sequences but delayed by about 20 ms. This delay is more than can be accounted for by slowing of central and peripheral motor conduction, therefore suggesting age dependent delay in central processing. (4) Avestibular patients had normal latencies indicating that the free fall startle can be elicited by non-vestibular inputs. (5) Latencies in patients with idiopathic Parkinson's disease were normal whereas responses were earlier in patients with multiple system atrophy (MSA) and delayed or absent in patients with Steele-Richardson-Olszewski (SRO) syndrome. The findings in this patient group suggest: (1) lack of dopaminergic influence on the timing of the startle response, (2) concurrent cerebellar involvement in MSA may cause startle disinhibition, and (3) extensive reticular damage in SRO severely interferes with the response to free fall.

Accidental Falls↗
PubMed1999

Posterior sternoclavicular dislocations--a diagnosis easily missed.

Posterior dislocation of the sternoclavicular joint is a relatively rare injury and can be difficult to diagnose acutely. We report 3 cases of posterior dislocation of the sternoclavicular joint who presented to the Accident & Emergency Department within a 3 month period. All 3 patients had sustained a significant injury to the shoulder region and complained of pain around the medial clavicle. Two patients had also complained of dysphagia following the injury. Plain X-rays of the shoulder and chest were reported as normal by junior and senior medical staff. The diagnosis was delayed until CT scans were performed, and once this was established, open reduction and stabilisation was performed.

Accidental Falls↗
PubMed1999

The advantages of cardiac rehabilitation.

Cardiac rehabilitation is a significant element in recovery from myocardial infarction. An effective programme may reverse arterial damage without the aid of lipid-lowering medication. Benefits can occur for patients three to four years after undertaking a programme.

Follow-Up Studies↗