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Biomedical subjects

J G Williams

Publications and source records attributed to J G Williams.

At least 73 records · Page 4Linked to original sources
PubMed1996

RNGB: a Dictyostelium RING finger protein that is specifically located in maturing spore cells.

The RING finger is a form of zinc finger motif found in proteins of widely varying biological function. The Dictyostelium RNGB protein contains a RING finger and also a K-box, a sequence motif found in several plant homeotic proteins. The rngB mRNA is present at low concentration in growing cells and gradually increases in abundance throughout development. However, the RNGB protein is not detected until culmination and we present evidence that suggests it is translationally regulated. The protein is specifically localised in maturing spore cells and is cytoplasmic, suggesting that the RING finger does not function as a DNA binding domain.

Amino Acid Sequence↗
PubMed1996

Alcoholics' perceptions of cues to intoxication.

This study examined whether alcoholic participants perceive cues to self-judgment of intoxication along the internal-external dichotomy used in the research literature on blood alcohol level discrimination. Twenty-eight participants diagnosed as alcohol dependent participated. Participants rated the perceived similarity of pairs of 18 cues to intoxication. Cluster analysis indicated that participants' ratings formed four clusters: disinhibition, relaxation, impairment, and external cues. These clusters provide some support for the internal-external dichotomy used in previous research.

Adult↗
PubMed1995

Dual role of cAMP during Dictyostelium development.

cAMP plays an essential role during Dictyostelium development both outside and inside the cell. Membrane-bound receptors and adenylyl cyclase are responsible for sensing and producing extracellular cAMP, whereas a phosphodiesterase is responsible for maintaining a low basal level. The molecular events underlying this type of hormone like signalling, which are now beginning to be deciphered, will be presented, in the light of cAMP analogue studies. The importance of intracellular cAMP for cell differentiation has been demonstrated by the central role of the cAMP dependent protein kinase. Mutants as well as strains obtained by reverse genetics will be reviewed which lead to our current understanding of the role of intracelluar cAMP in the differentiation of both stalk and spore cells.

Adenylyl Cyclases↗
PubMed1995

Randomized trial to determine the optimum level of pouch-anal anastomosis in stapled restorative proctocolectomy.

PURPOSE: This study was undertaken to identify the optimum level of stapled ileal pouch-anal anastomosis. METHOD: A prospective, randomized trial was completed to compare double-stapled ileoanal anastomosis placed at the top of anal columns (high, n = 26) with anastomosis at the dentate line (low, n = 21). RESULTS: There was no significant difference in the overall complication rate between operations (high, n = 7, vs. low, n = 8; P < 0.21). Pouch-anal functional score (scale 0-12; 0 = excellent, 12 = poor) was significantly better in the high anastomosis group (median (range): 2 (1-9) vs. 5.5 (1-12); P < 0.05). Incontinence occurred in only two patients randomized to high anastomosis compared with six in the low anastomosis group. Nocturnal soiling was reported in three patients after high anastomosis and in six patients after dentate line anastomosis. Both operations caused a significant but comparable reduction of maximum and resting pressure (31 percent after high anastomosis (P < 0.05); 23 percent after low anastomosis (P < 0.05)). However, a significant fall in functional length of the anal canal was only seen after a low pouch-anal anastomosis (P < 0.05). CONCLUSION: Stapled pouch-anal anastomosis at the top of anal columns gives better functional results compared with a stapled anastomosis at the dentate line.

Adenomatous Polyposis Coli↗
PubMed1995

Randomized trial of internal anal sphincter plication with pelvic floor repair for neuropathic fecal incontinence.

PURPOSE: This study was designed to examine the role of adjuvant internal anal sphincter plication in women with neuropathic fecal incontinence undergoing pelvic floor repair. METHODS: We completed a randomized trial with symptomatic and physiologic assessment before and after surgery. RESULTS: There was no symptomatic advantage of adding internal sphincter plication; the mean improvement of functional score was 3.61 +/- 1.82 (standard deviation; P < 0.01) following pelvic floor repair alone compared with 2.80 +/- 1.66 (standard deviation; P < 0.01) when adjuvant internal and sphincter plication was added. The addition of internal sphincter plication was associated with a significant fall in maximum anal resting and squeezing pressures (P < 0.01). CONCLUSIONS: Addition of internal sphincter plication is not advised in women with neuropathic fecal incontinence treated by pelvic floor repair.

Adult↗
PubMed1995

Interleukin-6 production after thermal injury: evidence for nonmacrophage sources in the lung and liver.

BACKGROUND: Thermal injury induces circulating levels of interleukin-6 (IL-6). The liver and lung have been proposed as major sources of IL-6 after injury; however, multiple cell types within these organs are capable of IL-6 production. In these experiments we further characterize cellular sources of IL-6 after thermal injury by examining tissue macrophage response in the liver and lung and IL-6 production of cultured pulmonary microvascular endothelial cells (PMECs). METHODS: Serum, liver and lung tissue, and tissue macrophage IL-6 response was determined in Wistar rats subjected to a 35 to 40% total body surface area scald injury. Cultured PMEC IL-6 production was determined after treatment with serum from the burned animals. IL-6 bioactivity was assayed by 7TD1 proliferation, and IL-6 messenger RNA levels were determined by reverse transcriptase-polymerase chain reaction. Alveolar macrophages were obtained by bronchoalveolar lavage. Kupffer cells and PMECs were obtained by enzyme digestion of liver and lungs. RESULTS: Burn increases circulating IL-6 activity through postburn day 3 (388 +/- 50 units/0.1 ml versus 80 +/- 12 units/0.1 ml in controls). Burn increases lung and liver IL-6 messenger RNA without concurrent increase in the alveolar macrophages or Kupffer cells and persists in the lung after bronchoalveolar lavage. PMECs cultured in the presence of postburn day 3 serum (10% vol) release more IL-6 activity (1118 +/- 333 units/culture versus sham rat serum with 288 +/- 146 units/culture) than control cultures and have more readily detectable levels of IL-6 messenger RNA. CONCLUSIONS: Non-tissue macrophage sources including microvascular endothelium may be a contributing source of IL-6 in the lung after thermal injury.

Animals↗
PubMed1995

Protein kinase A is a positive regulator of spore coat gene transcription in Dictyostelium.

The cotA, cotB, and cotC genes encode the major spore coat proteins of Dictyostelium. All three cot genes are coordinately expressed as aggregation is nearing completion. Induction and maintenance of their expression is dependent upon the presence of extracellular cAMP. We show that expression of a dominant inhibitor of the cAMP dependent protein kinase (PKA) in prespore cells greatly reduces the transcription rates of the cotB and cotC genes. All three cot genes contain, in their upstream regulatory regions, short sequence elements that have a high content of cytosine and adenosine residues. These CA-rich sequences are essential for optimal cot gene transcription. We show that expression of the dominant PKA inhibitor results in a greatly reduced level of the binding activity that recognizes the CA-rich sequences upstream of the cotB gene. Thus PKA acts, either directly or indirectly, to control expression of the cot genes and it may do so by modulating the activity of a DNA binding protein. However, we find that mutant cells where PKA is constitutively active still require exogenous cAMP for optimal cot gene expression in dissociated cells, suggesting that a separate, PKA-independent, signalling pathway is also involved in the regulation of cot gene expression by extracellular cAMP.

Animals↗
PubMed1995

Perioperative blood transfusion does not prevent recurrence in Crohn's disease. A pooled analysis.

The effect of perioperative blood transfusion on the recurrence of Crohn's disease is controversial. Various studies have suggested that perioperative blood transfusions reduce the risk of recurrence; others have failed to find a protective effect. Since all the studies are based on relatively small numbers, we performed a pooled analysis. We contacted the senior authors of seven previously published studies and asked for the original data. Four authors provided their data. The pooled database included 622 patients with a primary and complete resection of macroscopic disease. Recurrence was defined as the need for repeat surgery for disease control. Kaplan-Meier life table analysis was performed. Of the study sample, 366 cases (59%) were female. Disease distribution was as follows: small bowel (47%), small/large bowel (35%), and large bowel only (18%). Three hundred thirty-one patients (53%) received blood in the perioperative period. Mean follow-up was 72.8 months. For the overall sample, the 5-year recurrence rates were 26.9% for the transfused group and 25.2% for the nontransfused (p = 0.456). When the data were stratified by age, gender, disease location, and length of resection, no difference in 5-year recurrence rates between transfused and nontransfused cases could be detected. In this pooled analysis of four retrospective studies on the effect of blood transfusions on the risk of recurrence in Crohn's disease, we were unable to document a protective effect.

Adolescent↗
PubMed1995

Integrated case studies and medical decision making: a novel, computer-assisted bridge from the basic sciences to the clinics.

This article describes a novel course that was designed to bridge the gap between the basic science years and clinical experiences in medical school by using information science and computer technology as major components of problem-based learning (PBL) sessions. The course, Integrated Case Studies and Medical Decision Making, was first given to second-year students at the University of Pittsburgh School of Medicine in the spring of 1994. It consists of 13 PBL exercises, each of which explores a clinical case. The cases, including images and gated access to information, are housed on a computer. Using one of 16 networked terminals in specially designed small-group rooms, groups of nine students progress through the cases with a faculty facilitator. The responses of students and faculty to the initial year of the course were favorable. In comparison with traditional PBL sessions, enhanced quality of and access to images and accountability for accessing case information in sequential fashion were cited as major strengths of the course. Juxtaposition of basic science and clinical material and utility in reviewing for the United States Medical Licensing Examination were also cited as strengths. The diversity of the basic science material involved in completing the cases drew overwhelming enthusiasm from students and facilitators alike. In conclusion, the course successfully employs computer and information science technology, which will be of increasing importance to future physicians. The course also serves as an effective bridge to the clinical years of medical school and as a study adjunct for the USMLE.

Clinical Competence↗
PubMed1994

Absorption of non-haem iron from food during normal pregnancy.

OBJECTIVE: To determine whether the increased iron demands of pregnancy could be met by increased absorption from dietary sources. DESIGN AND SETTING: Longitudinal prospective study in the research unit of a maternity hospital. SUBJECTS: 12 normal pregnant women. INTERVENTIONS: At 12, 24, and 36 weeks' gestation (within one week) and 16-24 weeks after delivery women ate a breakfast of meat, bread, and orange juice (3.2 mg iron), extrinsically labelled with the stable isotope iron-54 (2.8 mg); the stable isotope iron-57 (200 micrograms) was given intravenously. MAIN OUTCOME MEASURES: Serum samples were taken for 10 hours after administration of the isotopes; ratios of the isotopes were measured by inductively coupled plasma mass spectrometry, and the absorption of oral iron was calculated. RESULTS: The geometric mean (95% confidence interval) absorption of iron at 12, 24, and 36 weeks' gestation was 7% (5% to 11%), 36% (28% to 47%), and 66% (57% to 76%) respectively. At 16-24 weeks after delivery the absorption was 11% (6% to 21%). The mean increase in absorption at 36 weeks (compared with that at 12 weeks) was 9.1 times (6.0 to 13.7). One pregnant woman developed iron deficiency anaemia but was otherwise indistinguishable from the others. CONCLUSIONS: An increase in the absorption of iron from food is a physiological consequence of normal pregnancy, not the result of developing anaemia during pregnancy, and such an increase is large enough to meet the increased requirements of pregnancy provided that the dietary intake is adequate.

Female↗
PubMed1994

Augmented tumor necrosis factor response to lipopolysaccharide after thermal injury is regulated posttranscriptionally.

BACKGROUND AND OBJECTIVE: Thermal injury has been shown to enhance macrophage sensitivity to lipopolysaccharide (LPS), resulting in augmented tumor necrosis factor alpha (TNF-alpha) production. This study was designed to examine whether enhanced TNF-alpha response after thermal injury and LPS stimulation is regulated at the level of transcription. DESIGN: Tumor necrosis factor alpha release in alveolar macrophages harvested from sham- or thermal-injured Wistar rats was determined using an L929 cytotoxicity bioassay on days 1, 3, and 5 following 40% scald burn and incubation for 24 hours with LPS (0 or 10 micrograms/mL). Separate groups of rats underwent intraperitoneal injection of LPS (5 mg/kg) 3 days following sham or thermal injury. Lung tissue RNA was isolated and probed for TNF-alpha messenger RNA (mRNA), using nuclease protection analysis. Finally, pooled alveolar macrophages were harvested 3 days following sham or thermal injury and cultured in the presence or absence of LPS (10 micrograms/mL) for 4 hours. The RNA from the pooled alveolar macrophages was extracted and probed for TNF-alpha mRNA levels. RESULTS: Thermal injury alone did not significantly increase alveolar macrophage TNF-alpha bioactivity, whole-lung TNF-alpha mRNA levels, or pooled alveolar macrophages TNF-alpha mRNA levels when compared with levels in sham-injured rats. However, alveolar macrophages from postburn day 3 (PBD 3) demonstrated increased sensitivity to LPS (10 micrograms/mL) compared with alveolar macrophages from sham-injured animals undergoing similar LPS treatment (2365 +/- 1011 vs 169 +/- 79 ng/mL; P < .05). Whole-lung mRNA levels in both sham-injured and PBD-3 rats receiving intraperitoneal LPS, while elevated approximately 2.5-fold from those of non-LPS treated rats, were not different from each other. Finally, pooled alveolar macrophages from sham-injured and PBD-3 rats cultured in the presence of LPS had approximately 1.7-fold and threefold increased TNF-alpha mRNA levels, respectively, compared with alveolar macrophages not cultured with LPS. CONCLUSIONS: Thermal injury induces priming of alveolar macrophages, resulting in significant increases in macrophage TNF-alpha production after exposure to LPS. The majority of this effect appears to be regulated at a posttranscriptional level, since there were only moderate increases in TNF-alpha mRNA levels after LPS stimulation, which did not coincide with large differences in bioactivity.

Animals↗
PubMed1994

A method for predicting the volume of an ileo-anal pouch.

Functional outcome following restorative proctocolectomy depends, in part, on the volume of the pouch. This study investigates the relationship between the length of ileum and volume of saline required to distend the ileum to a set pressure, and the possibility of predicting the volume of an ileoanal pouch using these measurements. Measurements were made on the ileum of 8 mongrel dogs. There was a linear relationship between the length of ileum and volume of saline infused to produce an intraluminal pressure of 20 mmHg (r = 0.94-0.99). However, the capacity of ileum varied widely from animal to animal (100 cc of saline filled 15.5 cm to 43 cm of ileum). Twenty-four pouches (15J, 9S) were constructed from segments of ileum of known capacity. The capacity of a J pouch was 1.71 +/- 0.11 times greater than the capacity of the original length of bowel and an S pouch had a capacity 2.14 +/- 0.25 times greater. These changes in capacity are similar to a theoretical calculation of change in volume of ileum after pouch construction. This technique is a simple, quick method of predicting the volume of an ileo-anal pouch which will be useful in a clinical trial to compare function of pouches of different volumes.

Animals↗