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Biomedical subjects

S O'Neil

Publications and source records attributed to S O'Neil.

At least 19 recordsLinked to original sources

Complete genome sequence of the model actinomycete Streptomyces coelicolor A3(2).

Streptomyces coelicolor is a representative of the group of soil-dwelling, filamentous bacteria responsible for producing most natural antibiotics used in human and veterinary medicine. Here we report the 8,667,507 base pair linear chromosome of this organism, containing the largest number of genes so far discovered in a bacterium. The 7,825 predicted genes include more than 20 clusters coding for known or predicted secondary metabolites. The genome contains an unprecedented proportion of regulatory genes, predominantly those likely to be involved in responses to external stimuli and stresses, and many duplicated gene sets that may represent 'tissue-specific' isoforms operating in different phases of colonial development, a unique situation for a bacterium. An ancient synteny was revealed between the central 'core' of the chromosome and the whole chromosome of pathogens Mycobacterium tuberculosis and Corynebacterium diphtheriae. The genome sequence will greatly increase our understanding of microbial life in the soil as well as aiding the generation of new drug candidates by genetic engineering.

Bacterial Proteins↗

The genome sequence of Schizosaccharomyces pombe.

We have sequenced and annotated the genome of fission yeast (Schizosaccharomyces pombe), which contains the smallest number of protein-coding genes yet recorded for a eukaryote: 4,824. The centromeres are between 35 and 110 kilobases (kb) and contain related repeats including a highly conserved 1.8-kb element. Regions upstream of genes are longer than in budding yeast (Saccharomyces cerevisiae), possibly reflecting more-extended control regions. Some 43% of the genes contain introns, of which there are 4,730. Fifty genes have significant similarity with human disease genes; half of these are cancer related. We identify highly conserved genes important for eukaryotic cell organization including those required for the cytoskeleton, compartmentation, cell-cycle control, proteolysis, protein phosphorylation and RNA splicing. These genes may have originated with the appearance of eukaryotic life. Few similarly conserved genes that are important for multicellular organization were identified, suggesting that the transition from prokaryotes to eukaryotes required more new genes than did the transition from unicellular to multicellular organization.

Base Sequence↗

Parameter estimation for suspended sediment transport processes under random waves.

This paper presents a parameter estimation method for suspended sediment transport processes subject to random wave environments. An objective function was constructed based on measurements of suspended sediment concentration profiles and the governing equation of sediment transport. The Chebyshev least square method was employed to approximate the process parameters, i.e. vertical eddy diffusivity (epsilon) and net vertical velocity (w). The objective function of sediment transport processes with Chebyshev's parameters is well posed and does not require boundary conditions. First, second, and third order epsilon and w Chebyshev orthogonal functions were determined for monochromatic (MONO), narrow-banded (NBR) and broad-banded (BBR) random wave conditions. In the BBR and NBR conditions, the best fit Chebyshev approximations of epsilon and w were 2nd degree, while the best approximations in the MONO condition were 2nd degree for epsilon and 1st degree for w. The Chebyshev method provides a quick, accurate and direct estimation of two prime parameters in sediment transport dynamics.

Journal Article↗

Pancreaticogastrostomy following pancreaticoduodenectomy: review of 102 consecutive cases.

Disruption of the pancreatic anastomosis with resultant sepsis is the cause of nearly 50% of deaths following pancreaticoduodenectomy (PD). Traditionally, the pancreatic remnant is anastomosed to the jejunum. Pancreaticogastrostomy (PG) was introduced as an alternative by Waugh and Clagett in 1946 and by Park, Mackie, and Rhoads in 1967. The purpose of this retrospective review was to assess the safety of PG at a single institution. Between 1986 and 1998 a total of 102 patients underwent PG following PD. The indications for PD were periampullary carcinoma (n = 89), pancreatitis (n = 7), and miscellaneous (n = 6). Altogether, 80 patients underwent the traditional Whipple procedure and 22 the pylorus-preserving Whipple (PPW) procedure. The PG was performed by a single-layer invagination technique to the posterior gastric wall using interrupted silk sutures. Leaks from the pancreatic anastomosis were detected by measuring amylase in fluid obtained from surgically placed drains. Operative mortality was 3.9% (4/102). The cause of death was uncontrolled upper gastrointestinal hemorrhage, sepsis, pulmonary embolus, and cardiac failure secondary to myocardial infarction. The mean operating time was 6.8 hours. Blood transfusion was given in 43 patients (42%), and the mean amount of the transfusion was 2.6 units. Nonfatal complications occurred in 35 patients (34%), and included leaks from the pancreatic anastomosis in 9 (8.8%), leaks from the biliary-enteric anastomosis in 4 (3.9%), and gastric paresis 7 (6.9%). Other complications included abscess, wound infection, colitis, delirium tremens, and hyperbilirubinemia. Discharge occurred 6 to 47 days (median 12 days) postoperatively and was prolonged in patients suffering from a complication. PD is associated with significant morbidity. PG is a safe alternative to pancreaticojejunostomy for managing the pancreatic remnant.

Adenocarcinoma↗

Men and osteoporosis.

BACKGROUND: While strict criteria have been developed for defining osteoporosis in women (bone mineral density measurements more than 2.5 standard deviations below the mean for young adult normal women, i.e. t-score value < -2.5), there still remains a controversy regarding the definition in men. Spinal fractures occur in 5% and hip fractures in 6% of men older than 50 years. There are significant differences between men and women with respect to the pathogenesis of osteoporosis, underlying medical conditions and postfracture sequelae. OBJECTIVE: To provide an overview of the pathogenesis, diagnosis and prevention of osteoporosis in men. DISCUSSION: Osteoporosis is increasingly recognised. Data from the Dubbo Osteoporosis Epidemiology Study suggests that 30% of men in Australia aged over 60 years will suffer from an osteoporotic fracture. It is estimated that 30-60% of men presenting with spinal fractures will have another illness contributing to their bone loss. Osteoporotic fractures in men are associated with higher morbidity and mortality than in women. Lifestyle changes together with daily calcium supplementation should be implemented and vitamin D3 should be considered in men with osteopenia.

Bone Density↗

Guidelines for treatment of osteoporosis in men.

BACKGROUND: Osteoporosis is associated with significant morbidity and mortality in men. Published randomised controlled trials assessing the benefits of therapy in men with osteoporosis are limited, but those available need to be used to develop management guidelines. OBJECTIVE: To present evidence based guidelines for the treatment of osteoporosis in men. DISCUSSION: It is estimated that 30-60% of men presenting with spinal fractures have another illness contributing to their bone disease. Therefore assessment and treatment of coexisting medical conditions is a vital part of management of osteoporosis. While primary prevention of fractures remains crucial, treatment to ensure further fractures do not occur is equally important. Alendronate is the treatment of choice for men with osteoporosis and fractures, with cyclical etidronate an appropriate alternative and testosterone replacement therapy is indicated in hypogonadal men presenting with osteoporosis.

Calcitriol↗

Successful nonoperative management of bleeding hepatic artery pseudoaneurysm following pancreaticoduodenectomy.

BACKGROUND/AIMS: To report the management of a hepatic artery pseudoaneurysm presenting 35 days following a Whipple procedure. METHODS: The case study of a patient with a bleeding pseudoaneurysm is presented. RESULTS: Computed tomography demonstrated a pseudoaneurysm which was successfully embolized. CONCLUSIONS: Acute gastrointestinal bleeding from a pseudoaneurysm in the hepatic artery following Whipple procedure can be successfully managed with transcatheter embolization.

Aged↗

Phylogeny and PCR-based classification of Wolbachia strains using wsp gene sequences.

Wolbachia are a group of intracellular inherited bacteria that infect a wide range of arthropods. They are associated with a number of different reproductive phenotypes in their hosts, such as cytoplasmic incompatibility, parthenogenesis and feminization. While it is known that the bacterial strains responsible for these different host phenotypes form a single clade within the alpha-Proteobacteria, until now it has not been possible to resolve the evolutionary relationships between different Wolbachia strains. To address this issue we have cloned and sequenced a gene encoding a surface protein of Wolbachia (wsp) from a representative sample of 28 Wolbachia strains. The sequences from this gene were highly variable and could be used to resolve the phylogenetic relationships of different Wolbachia strains. Based on the sequence of the wsp gene from different Wolbachia isolates we propose that the Wolbachia pipientis clade be initially divided into 12 groups. As more sequence information becomes available we expect the number of such groups to increase. In addition, we present a method of Wolbachia classification based on the use of group-specific wsp polymerase chain reaction (PGR) primers which will allow Wolbachia isolates to be typed without the need to clone and sequence individual Wolbachia genes. This system should facilitate future studies investigating the distribution and biology of Wolbachia strains from large samples of different host species.

Animals↗

Home intervention for in utero drug-exposed infants.

Each year in the United States, around 5.5% (or 230,000) infants are born to mothers who used illicit drugs during pregnancy. The untoward effects of in utero drug exposure (IUDE) include significant decreases in birthweight and length and head circumference, prematurity, and developmental problems. Intensive early intervention, including home-based interventions, is recognized as an effective method to improve cognitive development and reduce health problems in these high risk infants and children. Examination of home visit records of 20 IUDE infants during their first year of life revealed frequent health and social problems. Infectious disease symptoms were the most frequent problem encountered in the home during the physical assessment of the infants. Of note was the mothers' lack of basic parenting information (understanding signs of illness, basic nutrition, and infant development) which was then provided by the nurse during each home visit. Of concern was the lack of drug treatment sought by these mothers. Findings support the view that home visiting should be incorporated into the discharge planning of any IUDE infant in order to maintain these infants in the health care system and monitor their safety.

Adult↗

Obstructive jaundice in rats results in exaggerated hepatic production of tumor necrosis factor-alpha and systemic and tissue tumor necrosis factor-alpha levels after endotoxin.

BACKGROUND: Obstructive jaundice (OJ) predisposes patients to postoperative sepsis. We determined whether OJ led to an increased endotoxin stimulated tumor necrosis factor-alpha (TNF-alpha) production by macrophage-rich organs and whether a lack of intraluminal gut bile contributed to this increased sensitivity. METHODS: Rats underwent laparotomy and common bile duct ligation and division (CBDL) or sham operation after they were given low-dose endotoxin or saline solution (NS). TNF-alpha levels in plasma, perfusate from the isolated perfused rat liver, and tissue from lung, spleen, and liver were measured 90 minutes later. An additional group underwent creation of a choledochal-vesical fistula and endotoxin administration. RESULTS: The plasma TNF-alpha, liver perfusate TNF-alpha, and the tissue TNF-alpha levels in liver, lung, and spleen were significantly elevated in the CBDL + endotoxin (CBDL + ETX) group compared with the SHAM + ETX and CBDL + NS groups (p < 0.05). The choledochal-vesical fistula group after endotoxin had plasma TNF-alpha levels only 27% that of the CBDL + ETX group (p < 0.05). CONCLUSIONS: OJ sensitizes macrophage-rich organs to produce larger amounts of TNF-alpha in response to endotoxin. This sensitization is not solely due to decreased intraluminal gut bile.

Animals↗

Fine-needle aspiration of 697 palpable breast lesions with histopathologic correlation.

BACKGROUND: Fine-needle aspiration breast biopsy has been used increasingly as an alternative to excisional biopsy. The purpose of this study is to evaluate the accuracy of fine-needle aspiration with histopathologic confirmation. METHODS: A retrospective study was performed using a computer database over a 5-year period. All women who had had fine-needle aspiration breast biopsy with histopathologic confirmation of the diagnosis were included. Fine-needle aspirations were interpreted as malignant, suspicious, or benign. Histopathologic diagnosis included core-needle biopsy, open excisional biopsy, or mastectomy specimen. RESULTS: A total of 697 patients fulfilled the criteria. Only 5 (0.7%) of the specimens were inadequate for study. There were 401 total malignant fine-needle aspiration diagnoses, with only 3 false-positive specimens. All three were ductal hyperplasia, one from a previously radiated breast. There were 125 suspicious readings; 84 of these were malignant and 41 were false-suspicious specimens. Most of the false-suspicious lesions were fibrocystic disease. Of the 166 lesions interpreted as benign, there were 13 false-negative specimens. The test had a 97% sensitivity, 78% specificity, 92% positive predictive value, and 92% negative predictive value. CONCLUSIONS: Fine-needle aspiration is a sensitive test that can be useful as an adjunct in the diagnosis of breast cancer. "Malignant" and "benign" interpretations are highly predictive but must be used only in the context of other diagnostic modalities. "Suspicious" lesions require further investigation.

Biopsy, Needle↗

Creating tobacco control policy at the local level: implementation of a direct action organizing approach.

This article describes the community activation and policy change process in seven Minnesota communities involved in the Tobacco Policy Options for Prevention (TPOP) study. The study's intervention employed a direct action organizing model, which relies on mobilizing large numbers of people to alter decision making and leverage the power of elites. As part of the organizing process, TPOP organizers and teams made 1,319 personal contacts with community members, generated 309 media stories, and initiated 445 public events related to tobacco use. These actions resulted in the establishment of comprehensive tobacco ordinances in all seven communities. The authors discuss the goals, training, activities and political factors relevant to four phases of the TPOP intervention: information gathering and team recruitment, community awareness building and ordinance development, preparing for city council, and ordinance establishment and enforcement. Included are suggestions for practitioners interested in using policy change and community-based advocacy to resolve public health problems.

Adolescent↗

Dysfibrinogenemia or afibrinogenemia in a Border Leicester lamb.

Hereditary fibrinogen deficiency is a rare condition in all species. Measurement of plasma fibrinogen should indicate low levels. Specific factor assays and pedigree analysis are essential in establishing a definitive diagnosis of the hereditary deficiency. Differentiation between afibrinogenemia, hypofibrinogenemia, and dysfibrinogenemia requires sophisticated techniques and assistance from a specialized laboratory.

Afibrinogenemia↗

Clinical ehrlichiosis in a cat.

Clinical ehrlichiosis was diagnosed in a cat from Colorado on the basis of cytologic, serologic, and clinical findings. Clusters of gram-negative organisms that were morphologically similar to morulae of Ehrlichia spp were found only in mononuclear cells. The cat had clinical signs that were referable to infection by a rickettsial organism, and antibodies against E canis (titer, 1:80) and E risticii (titer, 1:40) were detected in serum. Exclusion of other obvious causes inducing similar clinical signs, and positive clinical response to doxycycline, an antibiotic with known antirickettsial actions, aided in diagnosis. The cat was clinically normal within days following initiation of treatment, and was clinically normal, as well as seronegative for antibodies against E canis and E risticii, 1,365 days after discharge.

Animals↗

Separation of isoenzymes of citrate synthase and isocitrate dehydrogenase by fast protein liquid chromatography.

Fast protein liquid chromatography (FPLC) has been shown to be a rapid and effective method of separating isoenzymes of citrate synthase and isocitrate dehydrogenase in extracts of Pseudomonas aeruginosa and Acinetobacter calcoaceticus. The advantages of FPLC over conventional methods of fractionation are discussed and it is suggested that this may be a valuable and more general technique for isoenzyme resolution.

Acinetobacter↗

Brain dopamine and serotonin receptor sites revealed by digital subtraction autoradiography.

Autoradiography combined with image analysis permitted quantitative visualization of dopamine (D2) and serotonin (S2) binding sites in rat brain. Forebrain sections were incubated with tritiated spiroperidol alone or with tritiated spiroperidol plus unlabeled compounds that saturated the D2 or S2 sites. By subtracting the digitized image of an autoradiograph derived from the latter sections from that of the former, the D2 or S2 sites were specifically revealed. The resulting quantitative images demonstrate the differing anatomical distributions of these sites. The D2 site is largely restricted to the striatal complex (caudate-putamen, nucleus accumbens septi, and olfactory tubercle), whereas the S2 site is enriched in layer 5 of motor cortex, the perirhinal and cingulate cortices, and the claustrum.

Animals↗

Sensorimotor impairment and elevated levels of dopamine metabolites in the neostriatum occur rapidly after intranigral injection of 6-hydroxydopamine or gamma-hydroxybutyrate in awake rats.

The unilateral injection of 6-hydroxydopamine (8 micrograms) into the ventral tegmental area of awake rats produced a rapidly developing and irreversible sensory neglect to contralateral tactile stimuli. This neglect developed in a caudal to rostral direction on the affected body surface and coincided with significant elevation in the concentrations of dopamine and two of its metabolites, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the ipsilateral neostriatum. The unilateral injection of procaine or gamma-hydroxybutyric acid (GHB) into the substantia nigra of awake animals also produced a contralateral neglect that developed in a caudal to rostral direction, but the behavioral effect of these drugs diminished within 1 hr. Concentrations of dopamine, dihydroxyphenylacetic acid and homovanillic acid in the neostriatum were markedly elevated during continuous infusions of procaine or gamma-hydroxybutyric acid. The extent of sensory neglect and changes in dopamine metabolism in the neostriatum varied according to the amount of gamma-hydroxybutyric acid injected into the nigra and according to the proximity of injections of gamma-hydroxybutyric acid to the pars compacta. The rapid onset of sensory neglect following microinjections of 6-hydroxydopamine, procaine or gamma-hydroxybutyric acid is consistent with the ability of each of these drugs to block the conduction of impulses in mesostriatal neurons and suggests that concomitant increases in levels of dopamine, dihydroxyphenylacetic acid and homovanillic acid in the neostriatum resulted from decreases in the release of dopamine coupled with increased synthesis of dopamine. These findings also indicate that the catabolism of dopamine to dihydroxyphenylacetic acid or homovanillic acid may originate intraneuronally, without prior release of dopamine and its recapture by mesostriatal terminals, if the flow of impulses in this pathway has been blocked.

3,4-Dihydroxyphenylacetic Acid↗