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Biomedical subjects

B Marshall

Publications and source records attributed to B Marshall.

At least 19 recordsLinked to original sources

The adnA transcriptional factor affects persistence and spread of Pseudomonas fluorescens under natural field conditions.

A soil plot was inoculated with a mixture of Pseudomonas fluorescens Pf0-2, the wild type, and Pf0-5a, a Tn5 insertion mutant in adnA, at 7.84 log CFU/g of soil. Over a period of 231 days, culturable populations of both strains were measured at selected times below and away from the point of inoculation. Pf0-5a did not spread as fast and attained significantly lower populations than Pf0-2. At sample depths below the inoculation site, the adnA mutant showed a significant decrease in CFU/g of soil as compared to Pf0-2. Pf0-2 was first detected at the 1.5-cm annular site at 3 days after inoculation, whereas Pf0-5a required 7 days to travel the same distance. At this distance, the wild-type strain could be detected at a 21.5- to 25-cm depth, whereas Pf0-5a could be detected only as deep as 15.5 to 18 cm. At 4.5 cm from the site of inoculation and in soil fractions corresponding to 13 to 18 cm, Pf0-2 was the only strain detected. These results suggest that the transcription factor AdnA provides a fitness advantage in P. fluorescens, allowing it to spread and survive in soil under field conditions.

Bacterial Proteins↗

Antiangiogenic scheduling of chemotherapy improves efficacy against experimental drug-resistant cancer.

To reveal the antiangiogenic capability of cancer chemotherapy, we developed an alternative antiangiogenic schedule for administration of cyclophosphamide. We show here that this antiangiogenic schedule avoided drug resistance and eradicated Lewis lung carcinoma and L1210 leukemia, an outcome not possible with the conventional schedule. When Lewis lung carcinoma and EMT-6 breast cancer were made drug resistant before therapy, the antiangiogenic schedule suppressed tumor growth 3-fold more effectively than the conventional schedule. When another angiogenesis inhibitor, TNP-470, was added to the antiangiogenic schedule of cyclophosphamide, drug-resistant Lewis lung carcinomas were eradicated. Each dose of the antiangiogenic schedule of cyclophosphamide induced the apoptosis of endothelial cells within tumors, and endothelial cell apoptosis preceded the apoptosis of drug-resistant tumor cells. This antiangiogenic effect was more pronounced in p53-null mice in which the apoptosis of p53-null endothelial cells induced by cyclophosphamide was so vigorous that drug-resistant tumors comprising 4.5% of body weight were eradicated. Thus, by using a dosing schedule of cyclophosphamide that provided more sustained apoptosis of endothelial cells within the vascular bed of a tumor, we show that a chemotherapeutic agent can more effectively control tumor growth in mice, regardless of whether the tumor cells are drug resistant.

Animals↗

Four novel MSH2 / MLH1 gene mutations in portuguese HNPCC families.

Hereditary non-polyposis colorectal cancer (HNPCC) is considered to be determined by germline mutations in the mismatch repair (MMR) genes, especially MSH2 and MLH1. While screening for mutations in these two genes in HNPCC portuguese families, 3 previously unreported MSH2 and 1 MLH1 mutations have been identified in families meeting strict Amsterdam criteria. Hum Mutat 15:116, 2000.

Adaptor Proteins, Signal Transducing↗

Eleven novel APC mutations identified in Portuguese FAP families.

Germline mutations of the adenomatous polyposis coli (APC) gene are responsible for familial adenomatous polyposis (FAP), an autosomal dominant predisposition to colorectal cancer. In the present study we screened all of the exons of the APC gene in individuals belonging to 85 Portuguese FAP families. We here report eleven novel mutations which are predominantly frameshifts or single base substitutions, resulting in premature stop codons. Hum Mutat 16:178, 2000.

Adenomatous Polyposis Coli↗

Eliminating the cervical esophagogastric anastomotic leak with a side-to-side stapled anastomosis.

BACKGROUND: Although the acute postoperative complications of a cervical esophagogastric anastomosis are less than those with an intrathoracic esophageal anastomosis, the long-term sequelae of a cervical anastomotic leak are not as minor as initially reported. Nearly 50% of cervical anastomotic leaks result in an anastomotic stricture, and the subsequent need for chronic dilatations negates the merits of an operation intended to restore comfortable swallowing. OBJECTIVE: This study was undertaken to determine whether construction of a side-to-side stapled cervical esophagogastric anastomosis after transhiatal esophagectomy could reliably eliminate the majority of anastomotic leaks. METHODS: In 114 consecutive patients undergoing transhiatal esophagectomy, a functional side-to-side cervical esophagogastric anastomosis was constructed with the Auto Suture Endo-GIA II stapler (United States Surgical Corporation, Auto Suture Company Division, Norwalk, Conn) applied directly through the cervical wound. This side-to-side stapled anastomosis has 3 rows of staples. Early postoperative anastomotic morbidity, subsequent need for anastomotic dilatations, and patient satisfaction with swallowing were evaluated. RESULTS: Before the side-to-side stapled anastomosis, the incidence of cervical esophagogastric anastomosis leak in over 1000 patients undergoing transhiatal esophagectomy having a manually sewn anastomosis varied from 10% to 15%. Among the 111 survivors of transhiatal esophagectomy and a side-to-side stapled anastomosis, there were 3 (2.7%) clinically significant anastomotic leaks. This lowered incidence of leaks has contributed to reduction in the average length of stay after an uncomplicated transhiatal esophagectomy to 7 days and has provided more comfortable swallowing, ease of subsequent esophageal dilatations, and greater patient satisfaction. CONCLUSIONS: Construction of the cervical esophagogastric anastomosis with a side-to-side stapled anastomosis greatly reduces the frequency of anastomotic leaks and later strictures. The side-to-side stapled anastomosis is a major technical advance in the progression of refinements of transhiatal esophagectomy and a cervical esophagogastric anastomosis.

Aged↗

Temperature-dependent germination traits in oilseed rape associated with 5'-anchored simple sequence repeat PCR polymorphisms.

An experiment was conducted to test the hypothesis that phenotypes differing in germination rate and the presence or absence of secondary dormancy at low temperature were not genetically different. Seed of oilseed rape was germinated at 4, 10 and 19 degrees C, where selections were made in the percentile ranges 1-10 (early), 45-55 (intermediate) and 91-100 (late). Secondary dormancy occurred only in the late selections at the two lower temperatures. Thermal weighting of curves of cumulative germination on time gave circumstantial evidence that early percentiles were similar at all three temperatures and that seeds with secondary dormancy came largely from later percentiles above the 50th. To test for genetic differentiation between phenotypes, 5'-anchored simple sequence repeat primers were used to generate DNA marker profiles of seedlings raised from seed from each category. Principal coordinate analysis, and more detailed comparisons using the most discriminating markers, confirmed that the early germinators at the three temperatures were not associated with different banding profiles, but seeds entering secondary dormancy, particularly at 10 degrees C, were genetically distinct from germinators at the same temperature. Secondary dormant seeds at low temperature appear to originate mainly from the late germinating seed at higher temperature. Effects of temperature history and the requirement for alternating temperatures to break secondary dormancy were quantified. The results confirm the existence of genetically discrete sub-populations differing in ecologically significant traits.

Brassica↗

The quality of care for Medicare patients with peptic ulcer disease.

OBJECTIVE: The aim of this study was to examine quality of care for hospitalized Medicare beneficiaries with peptic ulcer disease. METHODS: Collaborating with five Peer Review Organizations, we used 1995 Medicare claim files to select samples of inpatients with a principal diagnosis of peptic ulcer disease. Quality of care indicators developed by content experts included percentages for ulcer patients tested for Helicobacter pylori (H. pylori); biopsied patients who received tissue tests; H. pylori-positive patients who received appropriate therapy; and ulcer patients screened for preadmission nonsteroidal anti-inflammatory drug (NSAID) use and counseled about risks. RESULTS: Of 2,644 patients eligible for medical record review, 56% were tested for H. pylori, and 73% of those testing positive were treated appropriately; 84% of patients with endoscopic biopsies received a tissue test for H. pylori; 74% of patients were screened for preadmission NSAID use, 24% had documented counseling of NSAID use, and only 2% had documented counseling on the ulcer risk of NSAID use. Statistically significant regional variation occurred in four of six quality indicators. Outpatient records were reviewed for 529 patients to document prior outpatient H. pylori in this population; only 2% (n = 12) were tested for H. pylori in the year before admission. CONCLUSIONS: Opportunities exist to improve quality of care by testing for and treating H. pylori in hospitalized Medicare beneficiaries with peptic ulcer disease and to improve screening for NSAIDs and counseling on ulcer risks.

Aged↗

Calcium hydroxylapatite deposition disease in a Great Dane Puppy.

A 10-week-old male Great Dane Puppy was presented for sudden onset tetraataxia and severe paresis of the front legs. Mineral deposits were detected radiographically, at gross postmortem examination, and light microscopically between the vertebral arches of multiple cervical and lumbar vertebrae. These deposits were associated with the interarchial ligaments (ligamentia interarcualia), along the interfaces of the synovium and articular cartilage of multiple cervical, thoracic, and lumbar facets, on the dorsal aspect of several thoracic intervertebral discs, and at the insertion of muscles at the lateral aspect of several cervical and thoracic vertebral bodies. The mineral deposits were associated with a granulomatous inflammation and synovial fibrocartilaginous metaplasia and proliferation, which was focally exuberant. X-ray diffraction analyses of the mineral deposits revealed calcium hydroxylapatite as the major component. The clinical signs in this puppy were due to focal compression of the spinal cord by marked extraarticular ligament-associated fibrocartilaginous proliferation.

Animals↗

Evolution of a laboratory based system for investigating outbreaks of infectious intestinal disease.

In 1995 Preston Public Health Laboratory introduced an incident logging system intended to improve the investigation of suspected outbreaks of infectious intestinal disease. A unique incident log (Ilog) number assigned and issued to the reporting individual and other interested parties when the laboratory is informed of a potential outbreak is used to identify all associated specimens submitted to the laboratory and is quoted in all communications about the incident. The results are reviewed formally each month. Between January 1995 and December 1998, 349 potential outbreaks of infectious intestinal disease were investigated, 325 of which were considered to be general outbreaks. Small round structured viruses were identified in 45% of these outbreaks, salmonellas in 8%, and no pathogens in 35%. Data from the national surveillance scheme for general outbreaks of infectious intestinal disease included 104 general outbreaks in 1996 and 1997 for the entire North West region, but our laboratory alone reported 184 general outbreaks during that period. The Ilog system is a simple and effective means for reviewing data from outbreaks, and helps to coordinate their investigation.

Clinical Laboratory Techniques↗

Systemic Weber-Christian disease complicated by partial transverse myelopathy.

Weber-Christian disease is an inflammatory disorder of fatty tissue which usually presents with raised red tender nodules in the skin. Although there may be additional systemic upset, there are very few reports of neurological features associated with this condition. We report a patient with biopsy-confirmed systemic Weber-Christian disease in whom a transient partial myelopathy, of probable inflammatory origin, was the most prominent feature. Based on recent reports of the effects of immune mediators on neuronal function, a possible pathogenetic explanation for this syndrome is suggested.

Adult↗

Differential response to dietary fat in large (LG/J) and small (SM/J) inbred mouse strains.

The "large" (LG/J) and "small" (SM/J) inbred mouse strains differ for a wide variety of traits related to body size and obesity. Ninety-three LG/J and SM/J mice were divided into two treatment categories and fed a moderately high-fat diet (21% kcal fat) or a low-fat diet (12% kcal fat) from weaning to necropsy. Strain differences in obesity-related traits and differential response to dietary fat increases were analyzed using ANOVA. LG/J animals grow faster from 3 to 10 wk, have longer tails, and have heavier body weight, liver weight, and fat pad weight than SM/J animals. SM/J animals grow faster after 10 wk of age and have higher fasting glucose levels than LG/J animals. SM/J mice were more responsive to increased dietary fat than LG/J mice for growth after 10 wk, necropsy weight, liver weight, fat pad weights, and fasting glucose levels (in males). The growth from 3 to 10 wk had a much greater response in the LG/J strain, whereas tail length had no response. This pattern of dietary response is similar to that expected under the "thrifty" phenotype hypothesis. Genes affecting strain differences and the differential response of the strains to dietary fat can be successfully mapped in the intercross of the LG/J and SM/J strains. This intercross provides an excellent multigenic model for the genetic basis of complex traits and diseases related to body size and obesity.

Adipose Tissue↗

Alternative splicing and hypermutation of a nonproductively rearranged TCR alpha-chain in a T cell hybridoma.

Like Ig genes, TCR genes are formed by somatic rearrangements of noncontiguous genomic V, J, and C regions. Unlike Ig genes, somatic hypermutation of TCR V regions is an infrequent event. We describe the occurrence of spontaneous hypermutation in a nonproductively rearranged TCR alpha-chain gene in a clonal T cell hybridoma that had lost its productively rearranged alpha-chain. The mutating hybridoma was eventually supplanted in culture by a nonmutating variant that had restored an open reading frame in the nonproductively rearranged TCR alpha-chain through the use of cryptic splice sites in the V alpha region. Evidence is presented for the presence of cDNA reverse transcripts of the TCR alpha-chain within the hybridoma, suggesting a role for reverse transcriptase in the generation of mutations.

Alternative Splicing↗

Socioeconomic status, social mobility and cancer occurrence during working life: a case-control study among French electricity and gas workers.

OBJECTIVES: A case-control study within a cohort of the workers employed by Electricité de France and Gaz de France between 1988 and 1992 was carried out to investigate relationships between cancers and socioeconomic status, including the effects of social mobility, by studying three professional career points. METHODS: All the incident cases of breast cancer in women and all the incident cases of upper respiratory and digestive tract cancer (comprising cancers of the larynx, pharynx, buccal cavity and esophagus), lung cancer, hematopoietic system cancers and colon cancer in men were extracted from the Cancer Register of the Social Security Department. The controls were matched for age (men) and for age and length of employment in the company (women). Socioeconomic status was measured at three professional career points (beginning, midpoint (about 35), and time of diagnosis (about 48)) by two types of socio-professional variables: employee category (low, medium, high) and a variable based on the French socioeconomic status classification system. An estimation of social mobility was done between career beginning and midpoint. Cases and controls were compared for socioeconomic status at the three career points. They were also compared for social mobility. RESULTS: The differences between the social categories were larger at the start than later in the career for breast cancer in women. The category of operations staff was used as a reference, and this analysis shows a difference between the risks associated with supervisors (OR = 2.0) and managers and specialist professions (OR = 1.5). There were large differences according to the type of cancer in men. A socioeconomic gradient in the incidence of cancers of the upper respiratory and digestive tract was observed at every career stage. The gradient was largest at the moment of diagnosis. The odds ratio was 3.4 for supervisors, 7.8 for operations staff and 14.8 for production staff. There was a socioeconomic gradient in lung cancer at all points in the career and in the incidence of the hematopoietic system cancers at mid-career and at diagnosis. No association between socioeconomic status and colon cancer was found. Social mobility accentuated all these results. CONCLUSION: Socioeconomic status is involved in the development of cancers. Our study suggests that the transition from social to biological processes could act via specific lifestyle and/or work-related risk factors. When there is a social gradient in the incidence of a cancer, an individual's social change is at least as important as his/her original social status in the relationship between cancer and social class.

Adult↗

The spatial distribution of larvae of Culicoides impunctatus biting midges.

The spatial distribution of Culicoides impunctatus Goetghebuer (Diptera: Ceratopogonidae) larvae was sampled at a site in western Scotland, and geostatistical analyses were used to quantify spatial dependencies. Nested sampling and analysis indicated that most of the spatial variance occurred within distances of 160-640 cm, levelling off at distances >640 cm. Semivariograms for transformed data from three 100 m x 100 m grids showed similar, isotropic patterns for larval counts, soil organic content, soil water content and the distribution of Juncus spp. rushes, with the variance increasing with separation distance. High levels of significance were associated with power models used to describe the semivariograms, which was indicative of the absence of a plateau (or 'sill') in the respective data. Correlation analysis of transformed data revealed significantly positive relationships between larval counts and soil pH, soil percentage organic content, soil percentage water content and also the distribution of Sphagnum spp., Juncus spp. and Myrica gale. There were also significantly negative relationships between larval counts and the distribution of Pteridium aquilinum and all mosses other than Sphagnum spp. The results suggest a far more structured and predictable pattern of C. impunctatus larval sites than previous studies and are discussed in relation to their application in localized Culicoides control and to studies of the mechanisms determining the spatial distribution of C. impunctatus larvae.

Animals↗

Photobactericidal activity of methylene blue derivatives against vancomycin-resistant Enterococcus spp.

The toxicities and phototoxicities of methylene blue and its two methylated derivatives were measured against one standard and three vancomycin-resistant pathogenic strains of Enterococcus spp. Each of the compounds was bactericidal and the derivatives exhibited photobactericidal activity on illumination at a 'light' dose of 6.3 J/cm(2) against one or more of the strains. Increased bactericidal and photobactericidal activity in the methylated derivatives is thought to be due to their higher hydrophobicities allowing greater interaction with the bacterial cell wall. In addition, the derivatives exhibited higher inherent photosensitizing efficacies.

Enterococcus faecalis↗

Transhiatal esophagectomy: clinical experience and refinements.

OBJECTIVE: To review the authors' clinical experience with transhiatal esophagectomy (THE) and the refinements in this procedure that have evolved. BACKGROUND: Increased use of THE during the past two decades has generated controversy about the merits and safety of this approach compared with transthoracic esophageal resection. The authors' large THE experience provides a valuable basis for benchmarking data regarding the procedure. METHODS: The results of THE were analyzed retrospectively using the authors' prospectively established esophageal resection database and follow-up information on these patients. RESULTS: From 1976 to 1998, THE was performed in 1085 patients, 26% with benign disease and 74% with cancer. The procedure was possible in 98.6% of cases. Stomach was the esophageal substitute in 96%. The hospital mortality rate was 4%. Blood loss averaged 689 cc. Major complications were anastomotic leak (13%), atelectasis/pneumonia (2%), intrathoracic hemorrhage, recurrent laryngeal nerve paralysis, chylothorax, and tracheal laceration (<1% each). Actuarial survival of patients with carcinoma equaled or exceeded that reported after transthoracic esophagectomy. Late functional results were good or excellent in 70%. With preoperative pulmonary and physical conditioning, a side-to-side stapled cervical esophagogastric anastomosis (<3% incidence of leak), and postoperative epidural anesthesia, the need for an intensive care unit stay has been eliminated and the length of stay reduced to 7 days. CONCLUSION: THE is possible in most patients requiring esophageal resection and can be performed with greater safety and fewer complications than the traditional transthoracic approaches.

Adolescent↗

Oral fluid antibody detection in the diagnosis of Helicobacter pylori infection.

The aim of this study was to evaluate an enzyme-linked immunosorbent assay (ELISA) for the detection of anti-Helicobacter pylori specific IgG antibodies in specimens of oral fluid. Antral biopsy specimens, serum and oral fluid samples were collected from 81 patients attending for upper gastrointestinal endoscopy. The presence or absence of current H. pylori infection was determined by culture, histology and urease detection. Anti-H. Pylori specific IgG was detected in serum by an established in-house ELISA and in oral fluid by an ELISA developed for this study. In all, 34 (42%) of 81 patients were positive for H. pylori by one or more of the 'gold standard' tests (culture, histology and urease detection). The oral fluid ELISA had a sensitivity of 94% and specificity of 85% with regard to current H. pylori infection. The serum ELISA had a sensitivity and specificity of 91%. There was an overall agreement of 88% between serum and oral fluid antibody detection. The detection of anti-H. pylori specific IgG in oral fluid by ELISA is comparable in sensitivity and specificity with serum-based methods. Oral fluid-based ELISA could provide a reliable, non-invasive method for the diagnosis of H. pylori infection, and may be of particular benefit for population surveys.

Adult↗