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Biomedical subjects

A Davies

Publications and source records attributed to A Davies.

At least 91 records · Page 5Linked to original sources
PubMed1998

Designer deletion strains derived from Saccharomyces cerevisiae S288C: a useful set of strains and plasmids for PCR-mediated gene disruption and other applications.

A set of yeast strains based on Saccharomyces cerevisiae S288C in which commonly used selectable marker genes are deleted by design based on the yeast genome sequence has been constructed and analysed. These strains minimize or eliminate the homology to the corresponding marker genes in commonly used vectors without significantly affecting adjacent gene expression. Because the homology between commonly used auxotrophic marker gene segments and genomic sequences has been largely or completely abolished, these strains will also reduce plasmid integration events which can interfere with a wide variety of molecular genetic applications. We also report the construction of new members of the pRS400 series of vectors, containing the kanMX, ADE2 and MET15 genes.

Alleles↗
PubMed1998

A comparison of the genetic pathways involved in the pathogenesis of three types of colorectal cancer.

Patterns of allele loss (loss of heterozygosity, LOH) have been studied in order to investigate the genetic pathways involved in the pathogenesis of three types of colorectal cancer (CRC): sporadic CRC without replication errors (RER-) (32 cases); sporadic RER+ CRC (23 cases); and ulcerative colitis-associated CRC (UCACRC) (16 cases). Each tumour was assessed for allele loss at ten microsatellite markers which map close to known or putative tumour-suppressor genes: APC (5q21-q22); DCC (18q21.1); 1p35-p36; p16 (9p21); 22q; 8p; E-cadherin (16q22.1); beta-catenin (3p22-p21.3); RB1 (13q14.1-q14.2); and HLA. Overall, high frequencies of allele loss (> 30 per cent) were found near DCC (42 per cent), p16 (38 per cent), 22q (37 per cent), 1p35-p36 (34 per cent) and APC (31 per cent), and low frequencies (< 20 per cent) near RB1 (16 per cent) and E-cadherin (13 per cent). LOH near beta-catenin, HLA, and on 8p occurred at frequencies between 20 and 30 per cent. The overall frequency of allele loss did not differ among the three tumour groups, but some variation was seen at individual loci. There was a significantly higher frequency of LOH at 1p35-36 in RER+ tumours compared to RER- tumours. Allele loss at this site was also associated with a more advanced Dukes' stage at presentation. In addition, RER- tumours showed a higher frequency of allele loss at p16 than RER+ tumours. No significant difference existed at any locus between the frequency of LOH in sporadic CRC and in UCACRC. Pairwise analysis showed a negative association between LOH at APC and DCC, and between LOH at chromosome 22p and p53 overexpression. Thus, there may be specific differences between the mutation spectra of RER+ and RER- CRCs, but there are large degrees of overlap among the underlying genetic pathways of these cancers and UCACRCs.

Adult↗
PubMed1998

How to increase the proportion of hysterectomies performed vaginally.

OBJECTIVES: The main purpose of our study was to identify the patient characteristics of women undergoing hysterectomy and to estimate the proportion of hysterectomies that could be done vaginally by recognized surgical techniques. STUDY DESIGN: The records of 500 women who underwent hysterectomy were reviewed. The characteristics of patients without an absolute contraindication to vaginal hysterectomy were analyzed. RESULTS: Overall, 96 (19.2%) of our study group underwent vaginal hysterectomy. A total of 382 (76.4%) women were judged not to have an absolute contraindication to this route. The most frequent characteristics of this group were lack of uterine prolapse (76.4%), a myomatous uterus (44.5%), and a need for oophorectomy (43.2%). We did not exclude women who did not have significant uterine prolapse or a history of pelvic surgery or pelvic tenderness and we included those requiring oophorectomy or with a uterine size up to that of 14 weeks' gestation; with these criteria more than two thirds of the entire study population could undergo vaginal surgery. CONCLUSIONS: To maximize the proportion of hysterectomies performed vaginally, gynecologists need to be familiar with surgical techniques for dealing with nonprolapsed uteri, uterine leiomyomas, and vaginal oophorectomy.

Adult↗
PubMed1998

GFRalpha1 is an essential receptor component for GDNF in the developing nervous system and kidney.

Glial cell line-derived neurotrophic factor (GDNF) is a distant member of the TGFbeta protein family that is essential for neuronal survival and renal morphogenesis. We show that mice who are deficient in the glycosyl-phosphatidyl inositol (GPI) -linked protein GFRalpha1 (GDNFRalpha) display deficits in the kidneys, the enteric nervous system, and spinal motor and sensory neurons that are strikingly similar to those of the GDNF- and Ret-deficient mice. GFRalpha1-deficient dopaminergic and nodose sensory ganglia neurons no longer respond to GDNF or to the structurally related protein neurturin (NTN) but can be rescued when exposed to GDNF or neurturin in the presence of soluble GFRalpha1. In contrast, GFRalpha1-deficient submandibular parasympathetic neurons retain normal response to these two factors. Taken together with the available genetic and biochemical data, these findings support the idea that GFRalpha1 and the transmembrane tyrosine kinase Ret are both necessary receptor components for GDNF in the developing kidney and nervous system, and that GDNF and neurturin can mediate some of their activities through a second receptor.

Aging↗
PubMed1998

p53 mutation is a poor prognostic indicator for survival in patients with hepatocellular carcinoma undergoing surgical tumour ablation.

Forty-two patients with hepatocellular carcinoma (HCC) were resected and their tumours were analysed for p53 mutations by GC-clamped denaturing gradient gel electrophoresis (DGGE), single-strand conformation polymorphism (SSCP) and gene sequencing. All the exons have been analysed in this study. Eight of 12 HCCs with cirrhosis due to viral hepatitis and the two patients with sarcomatoid changes displayed p53 mutations. In contrast, no mutation was observed in the fibrolamellar variant (n = 9), non-cirrhotics (n = 13) and alcoholic cirrhosis (n = 6). The mutations observed were in exons 5-8. Two mutations were observed in codons 136 and 213 as well as a T insertion between residues 156 and 157 (exon 5) and these are reported for the first time in HCC. Likewise, the silent mutation polymorphism in codon 213 was noticed in 3 of the 42 patients. Survival analysis of these patients after surgery showed the mean and median survival in patients with wild-type p53 to be 60 and 43 months respectively. In the group with p53 mutations, the mean and median survival was 15 and 12 months. The difference was statistically significant (P= 0.003).

Adolescent↗
PubMed1998

Serology of collagen types I and III in normal healing of tibial shaft fractures.

OBJECTIVES: To establish that serological indicators of synthesis of collagens I and III in humans with normally healing tibial shaft fractures will display a temporal pattern consistent with the sequence of expression of these collagens observed histologically in animal models of fracture healing. DESIGN: Prospective. SETTING: Four district general hospitals in the United Kingdom supported by an academic unit. PARTICIPANTS: Twenty consecutive patients with isolated tibial shaft fractures were studied. On clinical and radiological grounds, seventeen of the cases united within twenty weeks; these seventeen cases formed the material for this review. INTERVENTIONS: Nineteen patients were treated conservatively, and a functional brace was applied at five weeks. One patient treated with an external fixator had a functional brace applied at twelve weeks. MAIN OUTCOME MEASURES: Assays of collagen I carboxy-terminal propeptide (PICP), collagen III amino-terminal propeptide (PIIINP), and collagen I carboxy-terminal telopeptide (ICTP) were made in serum samples taken at standard intervals from twenty-four hours to twenty weeks after fracture. RESULTS: PICP showed a significant, transient early drop, whereas ICTP rose, indicating early breakdown with uncoupling of collagen I formation and degradation. PIIINP levels rose significantly from day eight to week five, in keeping with early expression of collagen III in experimental fracture callus. PICP levels showed a gradual rise, consistent with later expression of collagen I. CONCLUSIONS: The changes observed are in keeping with previous histological work on animal fracture models, suggesting that serological measures may reflect events occurring at the fracture site and thus offer a means for noninvasive and dynamic observation of collagen synthesis after fracture. Final proof that such measurements reflect bony healing per se, as opposed to events in other tissues, would require comparison with similar data from a soft tissue injury model.

Adolescent↗
PubMed1998

The effect of acupuncture on nonallergic rhinitis: a controlled pilot study.

The purpose of this pilot project was to evaluate the immediate effects of real acupuncture compared with two placebo controls (sham acupuncture and mock transcutaneous electrical nerve stimulation) in the treatment of nonallergic rhinitis patients. These three treatments were given in a nonrandomized order to the same patients at weekly intervals. Real acupuncture showed an improvement in nasal airways resistance after treatment in 9 of 13 patients, sham acupuncture in 2 of 9, and mock transcutaneous electrical nerve stimulation in 3 of 10 patients. With the exception of improvement in a minimal cross-sectional area (measured by acoustic rhinometry) in the real acupuncture group following treatment, the outcome was not statistically significant. This pilot study raised a number of issues related to the effects of acupuncture in nonallergic rhinitis that must be addressed by a study involving more patients in which the order of treatment is randomized and the two placebo control treatments are evaluated in relation to their credibility.

Acupuncture Therapy↗
PubMed1997

Molecular cloning of human GATA-6 DNA binding protein: high levels of expression in heart and gut.

Human GATA-6 has been cloned from foetal heart by a combination of PCR-based methods and cDNA library screening. The 3.8 kbp cDNA has a coding sequence of 1347 bp the 449 aa protein is virtually identical in the two zinc-finger binding domains to other human GATA sequences, but varies considerably in the amino and carboxy terminal regions. The sequence shows greatest similarity to GATA-6-like sequences from rat, mouse, chicken and Xenopus. Northern analysis and in situ hybridisation show that GATA-6 is expressed at high levels in human adult and foetal heart as well as in gut derivatives. It is postulated that GATA-6, in concert with GATA-4, plays a crucial role in the regulation of cardiac differentiation.

Amino Acid Sequence↗
PubMed1997

Safety of ProHance in special populations.

The safety profile of ProHance in special populations was evaluated by analyzing data extracted from the database of phase I-III studies which included data on 2,656 ProHance injections of which 119 in pediatric patients, 814 in elderly patients and 30 in patients with varying degrees of renal impairment (moderate, severe or end stage requiring hemodialysis). ProHance was administered at doses ranging from 0.1 mmol/kg to 0.3 mmol/kg and was found to be safe in all patient populations irrespective of age and of pre-existing renal impairment. There appeared to be no correlation between incidence of adverse events and dose level in these special populations and the higher dose level of 0.3 mmol/kg could be safely administered also to patients with end stage renal disease requiring hemodialysis, from whom the contrast medium was rapidly and efficiently dialysed.

Adult↗
PubMed1997

Lignocaine aerosol spray in outpatient hysteroscopy: a randomized double-blind placebo-controlled trial.

OBJECTIVE: To assess the efficacy of lignocaine spray during outpatient hysteroscopy in reducing the need for additional anesthesia and reducing the discomfort of the procedure. DESIGN: A randomized double-blind, placebo-controlled trial. SETTING: An undergraduate university teaching hospital in London. PATIENT(S): One hundred twenty patients undergoing outpatient hysteroscopy. INTERVENTION(S): Application of lignocaine spray to the cervix, cervical canal, and uterine cavity during outpatient hysteroscopy. MAIN OUTCOME MEASURE(S): The need to use additional anesthesia and the pain experienced at various steps of the procedure. RESULT(S): Women treated with active spray experienced significantly less pain when the cervix was grasped with a tenaculum at the start of hysteroscopy. There were no other significant differences in the outcome of hysteroscopy between the placebo and lignocaine groups, although there was a significant reduction in the use of additional anesthesia in both groups compared with historical controls. CONCLUSION(S): Lignocaine spray has beneficial effects on cervical but not uterine sensation. Pretreatment with either lignocaine or placebo seems to reduce the need for additional intracervical anesthesia during hysteroscopy.

Adult↗
PubMed1997

Indications and alternatives to hysterectomy.

Hysterectomy is the commonest major operation performed by gynaecologists and is the definitive cure for many of it's indications which include dysfunctional uterine bleeding, fibroids, utero-vaginal prolapse, endometriosis and adenomyosis, pelvic inflammatory disease, pelvic pain, gynaecological cancers and obstetric complications. It is a successful operation in terms of relieving women of their presenting symptoms and high levels of satisfaction are reported by patients. However, it has a high risk of complications, involves a prolonged convalescence, is expensive and to some women represents a loss of femininity. It should only be employed after trying conservative treatments first if appropriate. If this fails, currently only endometrial ablation and myomectomy are valid alternatives to hysterectomy. If ultimately hysterectomy is required, there is considerable evidence that patient care can be improved by increasing the proportion of operations that are done vaginally and laparoscopically and decreasing the number of laparotomies.

Endometriosis↗