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S J Walker

Publications and source records attributed to S J Walker.

At least 37 records · Page 2Linked to original sources
PubMed1999

Pretherapeutic laparoscopic staging in advanced gastric carcinoma.

BACKGROUND AND STUDY AIMS: Direct visualization of the abdominal cavity by laparoscopy prior to multimodal treatment may be capable of improving the diagnostic precision of gastric cancer staging. The aim of this study was to evaluate whether diagnostic laparoscopy can influence treatment strategies in gastric cancer staged T3 and T4 by preoperative diagnostic tests. PATIENTS AND METHODS: Extended diagnostic laparoscopy (EDL) was carried out in 111 patients with advanced gastric cancer staged T3 or T4 by computed tomography (CT) and endoluminal ultrasound (EUS). On Lauren's classification of gastric cancer, 46% of the lesions were of the intestinal type and 54% of the nonintestinal type. EDL was carried out with the patients under general anesthesia, and included visual inspection of the abdomen, with surgical exploration of initially inaccessible regions, laparoscopic ultrasound examination, peritoneal lavage, and biopsies. The information provided by laparoscopy was classified as 1) no additional information, 2) important additional findings independent of the tumor stage, 3) downgrading of the tumor to a more favorable stage, and 4) upgrading of the tumor to a less favorable stage. The results of EDL were then compared with those obtained by sonography, CT and EUS in combination. RESULTS: EDL was performed successfully in 107 patients. In 56 of the 111 patients (50.5%), no additional findings were obtained. In 5.4% of cases, additional unforeseen information was found, not connected with the tumor but altering the management. EDL altered the preoperative diagnosis in 51 of the 111 patients (46.0%), leading to changes in management in 45 of them (40.5%). EUS provided additional information in eight cases (7.2% of the whole group, or 15.7% of those in whom the diagnosis had to be changed). Four metastases were detected using EDL. It was possible to rule out peritoneal spread in four patients, but it was newly detected in 26. CONCLUSIONS: Additional information by EDL about the tumor stage in gastric cancer led to a modification of the therapeutic strategy in 40% of patients, in spite of earlier comprehensive diagnostic work-up using modern imaging procedures. EDL should therefore be mandatory if neoadjuvant treatment is planned, in order to avoid either undertreatment or overtreatment of this type of tumor.

Adult↗
PubMed1999

Quantitative RT-PCR: pitfalls and potential.

Reverse transcription PCR (RT-PCR) represents a sensitive and powerful tool for analyzing RNA. While it has tremendous potential for quantitative applications, a comprehensive knowledge of its technical aspects is required. Successful quantitative RT-PCR involves correction for experimental variations in individual RT and PCR efficiencies. This review addresses the mathematics of RT-PCR, choice of RNA standards (internal vs. external) and quantification strategies (competitive, noncompetitive and kinetic [real-time] amplification). Finally, the discussion turns to practical considerations in experimental design. It is hoped that this review will be appropriate for those undertaking these experiments for the first time or wishing to improve (or validate) a technique in what is frequently a confusing and contradictory field.

RNA, Messenger↗
PubMed1999

Mutations of the cathepsin C gene are responsible for Papillon-Lefèvre syndrome.

Papillon-Lefèvre syndrome (PLS) is an autosomal recessive disorder characterised by palmoplantar hyperkeratosis and severe early onset periodontitis that results in the premature loss of the primary and secondary dentitions. A major gene locus for PLS has been mapped to a 2.8 cM interval on chromosome 11q14. Correlation of physical and genetic maps of this interval indicate it includes at least 40 ESTs and six known genes including the lysosomal protease cathepsin C gene (CTSC). The CTSC message is expressed at high levels in a variety of immune cells including polymorphonuclear leucocytes, macrophages, and their precursors. By RT-PCR, we found CTSC is also expressed in epithelial regions commonly affected by PLS, including the palms, soles, knees, and oral keratinised gingiva. The 4.7 kb CTSC gene consists of two exons. Sequence analysis of CTSC from subjects affected with PLS from five consanguineous Turkish families identified four different mutations. An exon 1 nonsense mutation (856C-->T) introduces a premature stop codon at amino acid 286. Three exon 2 mutations were identified, including a single nucleotide deletion (2692delA) of codon 349 introducing a frameshift and premature termination codon, a 2 bp deletion (2673-2674delCT) that results in introduction of a stop codon at amino acid 343, and a G-->A substitution in codon 429 (2931G-->A) introducing a premature termination codon. All PLS patients were homozygous for cathepsin C mutations inherited from a common ancestor. Parents and sibs heterozygous for cathepsin C mutations do not show either the palmoplantar hyperkeratosis or severe early onset periodontitis characteristic of PLS. A more complete understanding of the functional physiology of cathepsin C carries significant implications for understanding normal and abnormal skin development and periodontal disease susceptibility.

Adult↗
PubMed1998

Allelotype analysis of oesophageal adenocarcinoma: loss of heterozygosity occurs at multiple sites.

Deletions of tumour-suppressor genes can be detected by loss of heterozygosity (LOH) studies, which were performed on 23 cases of adenocarcinoma of the oesophagus, using 120 microsatellite primers covering all non-acrocentric autosomal chromosome arms. The chromosomal arms most frequently demonstrating LOH were 3p (64% of tumours), 5q (45%), 9p (52%), 11p (61%), 13q (50%), 17p (96%), 17q (55%) and 18q (70%). LOH on 3p, 9p, 13q, 17p and 18q occurred mainly within the loci of the VHL, CDKN2, Rb, TP53 and DCC tumour-suppressor genes respectively. LOH on 5q occurred at the sites of the MSH3 mismatch repair gene and the APC tumour-suppressor gene. 11p15.5 and 17q25-qter represented areas of greatest LOH on chromosomes 11p and 17q, and are putative sites of novel tumour-suppressor genes. LOH on 9p was significantly associated with LOH on 5q, and tumours demonstrating LOH at both the CDKN2 (9p21) and MSH3 (5q11-q12) genes had a significantly higher fractional allele loss than those retaining heterozygosity at these sites. Six of nine carcinomas displaying microsatellite alterations also demonstrated LOH at CDKN2, which may be associated with widespread genomic instability. Overall, there are nine sites of LOH associated with oesophageal adenocarcinoma.

Adenocarcinoma↗
PubMed1998

New Zealand epidemic of meningococcal disease identified by a strain with phenotype B:4:P1.4.

New Zealand is experiencing an epidemic of serogroup B meningococcal disease, which has taken the rate of disease from an average of 1.5/100,000 population in the preepidemic years of 1989 and 1990 to 14.0/100,000 in 1996. Sterile-site isolates of Neisseria meningitidis from cases of invasive disease have been phenotypically characterized by serogrouping, serotyping, and serosubtyping, revealing the involvement of a strain with phenotype B:4:P1.4. Macrorestriction analysis using pulsed-field gel electrophoresis on 667 meningococci isolated from cases during the epidemic has identified the clonal relationship of meningococci expressing the PorA P1.4 antigen. Multilocus enzyme electrophoresis has shown the epidemic strain B:4:P1.4 to belong to lineage III. The recorded characteristics of New Zealand's epidemic are consistent with previous serogroup B epidemics in other parts of the world.

Adolescent↗
PubMed1997

Review article: controversy in the therapy of gastro-oesophageal reflux disease--long-term proton pump inhibition or laparoscopic anti-reflux surgery?

The treatment of gastro-oesophageal reflux disease is controversial. Whilst medical treatment is successful in patients with mild to moderate disease, the threshold of severity above which an operation should be contemplated remains a matter for debate. Laparoscopic anti-reflux surgery may be lowering this threshold, as this form of therapy provides several advantages over its open counterpart, but it is not without risk, and few long-term results are available. This article reviews treatment options for reflux disease and examines the relative position of current medical and surgical therapies.

Gastroesophageal Reflux↗
PubMed1996

Spigelian herniae: presentation, diagnosis and treatment.

A personal series of 19 patients (8 males), mean age 62.4 years (range 21-83 years) with a spigelian hernia [right-sided in eight patients (42.1%)] is presented. The defect was confirmed in 18 patients undergoing surgery, extending between the internal and external oblique layers in 15 of those 18 patients (83.3%) and passing through the external oblique layer in three of the 18 (16.7%). Four uncommon variants were encountered in these 18 patients. The sac was empty in six (33.3%), contained small bowel in six (33.3%), greater omentum in five (27.8%), caecum in one (5.6%) and sigmoid colon in one (5.6%). Four of 19 patients (21.1%) presented acutely with a tender irreducible mass. Thirteen of 19 patients (68.4%) presented electively. All had a palpable swelling which was reducible in 11 of these 13 (84.6%). Local pain and tenderness was inconstant. A spigelian hernia was an incidental finding in two of the 19 patients (10.5%). In only nine out of 17 patients (52.9%) was the diagnosis suspected pre-operatively, and treatment was frequently delayed. Predisposing factors were present in 15 of the 19 patients (78.9%).

Abdominal Muscles↗
PubMed1995

Acute appendicitis: does removal of a normal appendix matter, what is the value of diagnostic accuracy and is surgical delay important?

A prospective study with long-term follow-up was undertaken of 248 patients (137 males, median age 18 years (range 6-81 years), undergoing emergency appendicectomy during a 12-month period. Acute inflammation was present in 182 patients (73.4%) (males 86.1%, females 57.8%; P < 0.001). Before surgery, the positive predictive value of diagnostic accuracy was 82.0% (males 91.2%, females 67.7%). Delaying surgery did not significantly increase the proportion of perforated appendices (22.0%), hospital stay, or frequency of postoperative complications (overall 49.6%). Hospital complications were significantly more common among patients with a perforated appendix. There was no significant difference in the complication rate between patients with or without appendicitis while in hospital, during the first 18 months after operation or 8 years after operation. At 18 months, 17 of 238 patients (7.1%) continued to experience their original pain. After 8 years the original pain was still present in 10 of 155 patients (6.5%). Continued pain was more likely in patients having undergone removal of a normal appendix (P < 0.001)

Abdominal Pain↗
PubMed1994

Catalytic core of rat tyrosine hydroxylase: terminal deletion analysis of bacterially expressed enzyme.

Tyrosine hydroxylase (TH) catalyzes the rate-limiting step in catecholamine biosynthesis. This enzyme is hypothesized to consist of an amino-terminal regulatory domain and a carboxy-terminal catalytic domain. In the present studies, we have utilized recombinant DNA techniques to map the boundaries of the regulatory and catalytic domains of TH. We have isolated a full-length cDNA clone for rat pheochromocytoma TH and have expressed the enzyme in bacteria. Utilizing this bacterial expression system and polymerase chain reaction technology, we have constructed and subcloned genes for five amino-terminal deletion mutants (N delta 40, N delta 155, N delta 165, N delta 175 and N delta 200; N delta denotes amino-terminal deletion and the numerical value denotes the number of amino acids deleted) and two carboxy-terminal deletion mutants (C delta 19 and C delta 50). The catalytic core of rat tyrosine hydroxylase has been identified to include the region from amino acid #165 to amino acid #479. The amino-terminal deletion mutants, N delta 40, N delta 155 and N delta 165 are from 1.85 to 2.5-fold more active than unmodified recombinant TH, while the removal of 19 amino acids from the C-terminus (C delta 19) results in a 70% reduction in enzyme activity. Removal of additional sequences (ten more residues from the N-terminus [N delta 175]; or an additional 31 amino acids from the C-terminus [C delta 50]) results in protein that is totally without enzyme activity. As expected, removal of 40 (or more) N-terminal amino acids abolishes the ability of the catalytic subunit of the cAMP-dependent protein kinase to phosphorylate the recombinant enzyme; serine-40 is the phosphorylation site on TH for PKA. We conclude that the N-terminal boundary for the TH catalytic domain resides between residues 165 and 175 and that removal of this N-terminal domain (totally or partially) increases the activity of the enzyme. These findings confirm previous reports that proteolytic cleavage at amino acid #158 produces an active (and activated) catalytic fragment.

Amino Acid Sequence↗
PubMed1994

Inverse electrocardiographic transformations: dependence on the number of epicardial regions and body surface data points.

The inverse problem of electrocardiography, the computation of epicardial potentials from body surface potentials, is influenced by the desired resolution on the epicardium, the number of recording points on the body surface, and the method of limiting the inversion process. To examine the role of these variables in the computation of the inverse transform, Tikhonov's zero-order regularization and singular value decomposition (SVD) have been used to invert the forward transfer matrix. The inverses have been compared in a data-independent manner using the resolution and the noise amplification as endpoints. Sets of 32, 50, 192, and 384 leads were chosen as sets of body surface data, and 26, 50, 74, and 98 regions were chosen to represent the epicardium. The resolution and noise were both improved by using a greater number of electrodes on the body surface. When 60% of the singular values are retained, the results show a trade-off between noise and resolution, with typical maximal epicardial noise levels of less than 0.5% of maximum epicardial potentials for 26 epicardial regions, 2.5% for 50 epicardial regions, 7.5% for 74 epicardial regions, and 50% for 98 epicardial regions. As the number of epicardial regions is increased, the regularization technique effectively fixes the noise amplification but markedly decreases the resolution, whereas SVD results in an increase in noise and a moderate decrease in resolution. Overall the regularization technique performs slightly better than SVD in the noise-resolution relationship. There is a region at the posterior of the heart that was poorly resolved regardless of the number of regions chosen. The variance of the resolution was such as to suggest the use of variable-size epicardial regions based on the resolution.

Adult↗
PubMed1994

Mathematical modelling of the growth, survival and death of Yersinia enterocolitica.

This paper discusses the development of a novel mathematical equation capable of handling the growth, survival and death of microorganisms. The equation was used in combination with second-order polynomials to fit a response surface to data representing the growth, survival and death of Yersinia enterocolitica as affected by temperature (0-30 degrees C), sodium chloride (0-10.5% w/v), pH (3.5-7.0) and undissociated lactic acid (0-9.63 g/l). The resulting predictive model showed a good correlation over the entire range of the experimental data. Predictions from the model have been compared with independent data from both published literature and inoculated food studies. Analysis of the results showed a good correlation, particularly for data from milk and meat products.

Hydrogen-Ion Concentration↗
PubMed1994

A phase II study of mitomycin, ifosfamide and cisplatin in operable and inoperable squamous cell carcinoma of the oesophagus.

We have evaluated the effect of mitomycin 6 mg/m2, ifosfamide 3 g/m2, and cisplatin 50 mg/m2 (MIC) in two groups of patients with squamous or undifferentiated carcinoma of the oesophagus, as either preoperative or primary treatment. Response was assessed by barium swallow, CT scan, and measurement of metastases where present. Toxicity was acceptable and there were no chemotherapy related deaths. In the operated group, five of 23 patients (22%) showed a complete response (three confirmed histologically) and nine (39%) showed a partial response following two courses of MIC. Resection was completed in 21 patients, with three hospital deaths (14%). Of the 18 patients who were discharged from hospital, eight have died at 4-24 months (median 13) from the start of treatment and 10 are alive at 5-35 months, with known recurrence in one. In the non-operated group, five of 20 patients (25%) showed a response, one complete, following one to four (mean 2.6) courses of MIC. Nineteen patients have died (at median 5 months), and one, who had a complete response, is alive and free from disease at 29 months. Neo-adjuvant therapy with MIC in squamous carcinoma of the oesophagus has shown encouraging early results, with acceptable toxicity.

Aged↗
PubMed1994

A carboxyl terminal leucine zipper is required for tyrosine hydroxylase tetramer formation.

Tyrosine hydroxylase catalyzes the rate-limiting reaction in the biosynthesis of the catecholamine neurotransmitters and hormones (dopamine, norepinephrine, and epinephrine). Rat tyrosine hydroxylase exists, in its native form, as a tetramer composed of identical 498 amino acid subunits. There is currently no information describing the molecular interactions by which the four monomeric tyrosine hydroxylase subunits assemble into an active tetramer. Mutational analysis was performed on bacterially expressed enzyme to assess the role of a putative C-terminal leucine zipper in the assembly of subunits into the tetrameric holoenzyme. Deletion of the C-terminal 19 amino acids, or mutation of a leucine residue (to an alanine), converts the enzyme from a tetrameric to a dimeric form that exhibits greater structural heterogeneity. This change in macromolecular form is accompanied by a 75% (deletion mutation) to 20% (Leu-->Ala mutation) reduction in specific activity of the enzyme. This represents the first report of the functional involvement of a region containing a leucine zipper motif in the assembly and activity of a neuronal enzyme.

Amino Acid Sequence↗