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Biomedical subjects

S Young

Publications and source records attributed to S Young.

At least 127 records · Page 7Linked to original sources
PubMed1997

Human neutrophils secrete vascular endothelial growth factor.

Vascular endothelial growth factor (VEGF) is a multifunctional cytokine that plays a pivotal role in mediating neovascularization as well as other endothelial cell alterations during inflammation. In this study, we demonstrate that human neutrophils are a source of VEGF. We observed that isolated blood neutrophils released VEGF in response to different stimuli and we demonstrated by immunohistochemistry that neutrophils infiltrating inflamed tissues contain VEGF. These results indicate that neutrophil-derived VEGF may be instrumental in regulating vascular responses during acute and chronic inflammation.

Adult↗
PubMed1997

Toad tadpole aggregation behaviour: evidence for a predator avoidance function

Two sets of experiments were conducted to determine whether aggregation behaviour, commonly observed in tadpoles of the common toad, Bufo bufohad a predator avoidance function. In the first set of experiments, the distribution of toad tadpoles, of single or mixed sibship, was monitored in large artificial pools, one with fish chemical cues and one without. Aggregation behaviour was determined on the basis of the distribution of the tadpoles under these treatments by using two indices of cohesion: variance/mean ratio and a newly developed swarming index. The two indices were highly correlated. Tadpole groups were more cohesive (1) in the presence of fish chemical cues and (2) with other individuals from a single sibship. In the second set of experiments, tadpoles in different densities and distributions were presented to fish predators in a floating arena which allowed strike rate to be monitored but prevented the fish from capturing any tadpoles. Total strike rate per group increased with increasing group size, but strike rate per individual decreased, implying individuals gain from being in a larger group through dilution, but the group as a whole loses. These results are discussed in terms of selfish herd or cooperative group theories on the behaviour of aggregations.Copyright 1997 The Association for the Study of Animal Behaviour1997The Association for the Study of Animal Behaviour

Journal Article↗
PubMed1997

Effects of codon usage and vector-host combinations on the expression of spinach plastocyanin in Escherichia coli.

Spinach plastocyanin has been expressed in Escherichia coli and exported to the periplasmic space. The effects of codon usage, expression system, growth length, and temperature on expression levels in LB medium were investigated. A stretch of codons, rare in E. coli, was identified and replaced with highly expressed codons, increasing the yield by at least 20%. Plastocyanin was more efficiently expressed under the T7 promoter than under the lac promoter. Maximum yields were obtained at 37 degrees C when growing the cells for 16 h after induction. The optimized expression system produced 38 mg holoprotein per liter culture. In this system it was also possible to express plastocyanin in minimal medium, at a yield of 10 mg per liter. N-terminal sequencing and mass spectrometry showed that plastocyanin was correctly processed. The expressed plastocyanin was purified to homogeneity, as shown by an A278/A597 ratio of 1.0, and together with amino acid analysis and the determination of oxidized and total copper contents, both the absorption coefficients for epsilon 278 and for epsilon 597 were determined to be 4700 M-1 cm-1.

Amino Acid Sequence↗
PubMed1997

Intestinal bacterial overgrowth and bacterial translocation in cirrhotic rats with ascites.

BACKGROUND/AIMS: Translocation of indigenous bacteria from the gut lumen of cirrhotic animals to mesenteric lymph nodes appears to be an important step in the pathogenesis of spontaneous bacterial peritonitis. However, the sequence of events leading to translocation remains unclear. One of the most predictable risk factors for translocation is overgrowth of gut bacterial flora. The present study was designed to compare the intestinal aerobic bacterial flora of cecal stools at the time of sacrifice between cirrhotic and normal rats and to evaluate the role of intestinal aerobic bacterial overgrowth in bacterial translocation in cirrhotic rats. METHODS: Thirty-five male Sprague-Dawley rats with carbon tetrachloride-induced cirrhosis and ascites and 10 normal rats were included in this study. Cirrhotic rats were sacrificed when ill and samples of ascitic fluid, mesenteric lymph nodes and cecal stool were taken for detecting quantitatively aerobic bacteria. RESULTS: Total intestinal aerobic bacterial count in cecal stool at the time of sacrifice was significantly increased in cirrhotic rats with bacterial translocation with or without spontaneous bacterial peritonitis compared to cirrhotic rats without bacterial translocation (p<0.001 and p<0.001, respectively) and to normal rats (p<0.001 and p<0.001, respectively). Of the 42 species of bacteria translocating to the mesenteric lymph nodes, 41 (97.6%) were found in supranormal numbers in the stool at the time of sacrifice. CONCLUSIONS: Carbon tetrachloride-induced cirrhotic rats with bacterial translocation have increased total intestinal aerobic bacteria count, and intestinal bacterial overgrowth appears to play an important role in bacterial translocation in this experimental model of cirrhosis in rats.

Animals↗
PubMed1997

Isolated microscopic haematuria in the genitourinary clinic: the value of renal biopsy.

Isolated microscopic haematuria is a common finding in the genitourinary clinic. The conventional approach to investigation includes urological referral for cystourethroscopy if renal imaging is normal. However the diagnostic yield is very low; in particular urothelial malignancy at age < 40 years is rare. Glomerular disease is increasingly recognized as a common cause of microscopic haematuria. In this study 50 patients with persistent microscopic haematuria detected at a genitourinary clinic underwent renal biopsy. Twelve (24%) had an abnormal biopsy--IgA nephropathy 6 (12%), thin membrane nephropathy 3 (6%), other glomerulonephritis 3 (6%). In 7 others no abnormality was found but information was incomplete as electron microscopy was unavailable. It is important to establish these diagnoses since some patients will develop progressive renal disease. In this clinical setting renal biopsy will give diagnostic and prognostic information, protects from repeated urological investigation, and allows reassurance if renal histology is normal. Renal biopsy is recommended for patients age < 40 years with persistent microscopic haematuria. An algorithm for the investigation of microscopic haematuria is presented.

Adult↗
PubMed1997

Research for medical illustrators. Part 2: Trial design, protocols, results and reporting.

Medical illustrators have long been involved in the research projects of other workers, by providing photographic and other visual records. These illustrations may be used for measurement purposes, in which case it is important that medical illustrators understand the requirements for using tested protocols, which ensure that all variables of the recording medium are controlled. Now that there are degree courses in medical illustration an increasing number of medical illustrators in the UK are instigating their own research projects, making it all the more important that they understand the research process. In this second of a two-part article, consideration is given to: the design of experiments and research trials; the production of research protocols; data analysis and interpretation; the writing of the research report or dissertation; and the role of the supervisor or mentor.

Clinical Protocols↗
PubMed1997

Absorbable, delayed-release antibiotic beads reduce surgical wound infection.

Absorbable, polyglycolic acid (PGA) beads were evaluated as a new vehicle for local antibiotic delivery. Incisions on the dorsa of guinea pigs were contaminated with 1 x 10(8) Escherichia coli and 1 x 10(8) Staphylococcus aureus. PGA beads containing either minocycline, amikacin, or no antibiotic (placebo) were placed into these wounds and compared to animals treated with systemic minocycline or amikacin alone. The diameter of wound erythema was measured daily for 7 days. Serial blood and wound quantitative cultures were obtained, and serum and wound antibiotic concentrations were determined. Both minocycline-PGA and amikacin-PGA-treated wounds exhibited less erythema than placebo-PGA wounds (P < 0.05). All minocycline-PGA and amikacin-PGA-treated wounds healed primarily, whereas 67 per cent of placebo-PGA wounds developed purulence, dehisced, and healed secondarily. Local antibiotic delivery was more effective than systemic administration in reducing wound erythema and the number of bacteria in wound quantitative cultures. E. coli and S. aureus were quantitatively reduced (P < 0.05) in wounds of antibiotic PGA-treated animals compared to those in placebo-PGA-treated and systemic minocycline and systemic amikacin-treated animals. Measurable minocycline and amikacin concentrations were present in antibiotic-PGA-treated wounds through day 3, without detectable serum levels. Delayed-release, absorbable, antibiotic-containing PGA beads effectively prevent infection in contaminated wounds and have the advantage of not requiring vehicle removal.

Amikacin↗
PubMed1997

Dog attacks.

BACKGROUND: An estimated 100,000 Australians each year will seek medical attention after a dog attack. Such attacks have the potential to cause significant morbidity especially with regard to soft tissue injury and infection. Proper wound assessment and early intervention will reduce this morbidity. OBJECTIVE: To review the epidemiology, assessment and treatment of soft tissue wounds caused by dog bites. DISCUSSION: Any patient who has been attacked by a dog requires a primary survey for any immediate life threatening problems, a careful assessment of tissue wounds and a treatment regimen that will promote tissue healing and reduce the likelihood of infection. Wounds must be carefully examined for skin loss, joint penetration, and tendon, nerve and vascular injuries, and appropriate action taken if any of these points are detected. The chance of a wound infection will be reduced by thorough cleansing of wounds, debridement and/or delayed primary closure of selected wounds and the judicious use of antibiotics.

Animals↗
PubMed1996

Effects of mutations in plastocyanin on the kinetics of the protein rearrangement gating the electron-transfer reaction with zinc cytochrome c. Analysis of the rearrangement pathway.

We study, by flash kinetic spectrophotometry on the microsecond time scale, the effects of ionic strength and viscosity on the kinetics of oxidative quenching of the triplet state of zinc cytochrome c (3Zncyt) by the wild-type form and the following nine mutants of cupriplastocyanin: Leu12Glu, Leu12Asn, Phe35Tyr, Gln88Glu, Tyr83Phe, Tyr83His, Asp42Asn, Glu43Asn, and the double mutant Glu59Lys/Glu60Gln. The unimolecular rate constants for the quenching reactions within the persistent diprotein complex, which predominates at low ionic strengths, and within the transient diprotein complex, which is involved at higher ionic strengths, are equal irrespective of the mutation. Evidently, the two complexes are the same. In both reactions, the rate-limiting step is rearrangement of the diprotein complex from a configuration optimal for docking to the one optimal for the subsequent electron-transfer step, which is fast. We investigate the effects of plastocyanin mutations on this rearrangement, which gates the overall electron-transfer reaction. Conversion of the carboxylate anions into amide groups in the lower acidic cluster (residues 42 and 43), replacement of Tyr83 with other aromatic residues, and mutations in the hydrophobic patch in plastocyanin do not significantly affect the rearrangement. Conversion of a pair of carboxylate anions into a cationic and a neutral residue in the upper acidic cluster (residues 59 and 60) impedes the rearrangement. Creation of an anion at position 88, between the upper acidic cluster and the hydrophobic patch, facilitates the rearrangement. The rate constant for the rearrangement smoothly decreases as the solution viscosity increases, irrespective of the mutation. Fittings of this dependence to the modified Kramers's equation and to an empirical equation show that zinc cytochrome c follows the same trajectory on the surfaces of all the plastocyanin mutants but that the obstacles along the way vary as mutations alter the electrostatic potential. Mutations that affect protein association (i.e., change the binding constant) do not necessarily affect the reaction between the associated proteins (i.e., the rate constant) and vice versa. All of the kinetic and thermodynamic effects and noneffects of mutations consistently indicate that in the protein rearrangement the basic patch of zinc cytochrome c moves from a position between the two acidic clusters to a position at or near the upper acidic cluster.

Animals↗
PubMed1996

Carvedilol produces dose-related improvements in left ventricular function and survival in subjects with chronic heart failure. MOCHA Investigators.

BACKGROUND: We conducted a multicenter, placebo-controlled trial designed to establish the efficacy and safety of carvedilol, a "third-generation" beta -blocking agent with vasodilator properties, in chronic heart failure. METHODS AND RESULTS: Three hundred forty-five subjects with mild to moderate, stable chronic heart failure were randomized to receive treatment with placebo, 6.25 mg BID carvedilol (low-dose group), 12.5 mg BID carvedilol (medium-dose group), or 25 mg BID carvedilol (high-dose group). After a 2- to 4-week up-titration period, subjects remained on study medication for a period of 6 months. The primary efficacy parameter was submaximal exercise measured by two different techniques, the 6-minute corridor walk test and the 9-minute self-powered treadmill test. Carvedilol had no detectable effect on submaximal exercise as measured by either technique. However, carvedilol was associated with dose-related improvements in LV function (by 5, 6, and 8 ejection fraction [EF] units in the low-, medium-, and high-dose carvedilol groups, respectively, compared with 2 EF units with placebo, P < .001 for linear dose response) and survival (respective crude mortality rates of 6.0%, 6.7%, and 1.1% with increasing doses of carvedilol compared with 15.5% in the placebo group, P < .001). When the three carvedilol groups were combined, the all-cause actuarial mortality risk was lowered by 73% in carvedilol-treated subjects (P < .001). Carvedilol also lowered the hospitalization rate (by 58% to 64%, P = .01) and was generally well tolerated. CONCLUSIONS: In subjects with mild to moderate heart failure from systolic dysfunction, carvedilol produced dose-related improvements in LV function and dose-related reductions in mortality and hospitalization rate.

Adrenergic beta-Antagonists↗
PubMed1996

Interleukin-8 regulation of the Ras/Raf/mitogen-activated protein kinase pathway in human neutrophils.

Interleukin-8 (IL-8), the prototypic member of the CXC subfamily of chemokines, induces in neutrophils chemotaxis, the respiratory burst, granule release, and increased cell adhesion. The IL-8 receptor is a seven-transmembrane spanning receptor coupled to specific heterotrimeric G proteins including Gi and G16. IL-8 stimulation of its receptor on neutrophils activates Ras GTP loading and the mitogen-activated protein kinase (MAPK) pathway including Raf-1 and B-Raf. The properties of IL-8 stimulation of the MAPK pathway differ from those observed for chemoattractants such as C5a. Even though Ras GTP loading is similar for IL-8 and C5a, the maximal activation of Raf-1 and B-Raf is approximately 2-fold and 3-7-fold, respectively, less for IL-8 than that observed for C5a. Raf-1 activation is rapid but transient, returning to near basal levels by 10 min. B-Raf activation is slower in onset and does not return to basal levels for nearly 30 min. IL-8 activation of MAPK follows a time course suggesting an involvement of both Raf-1 and B-Raf. Surprisingly, wortmannin, at low concentrations, inhibits Raf-1, B-Raf, and MAPK activation in response to IL-8 and C5a demonstrating a role for phosphatidylinositol 3-kinase in the activation of Raf kinases in G protein-coupled receptor systems in human neutrophils. Furthermore, wortmannin inhibits IL-8 stimulated granule release and neutrophil adherence. These findings demonstrate the control of Raf kinases, the MAPK pathway and specific neutrophil functions by phosphatidylinositol 3-kinase enzymes.

Androstadienes↗
PubMed1996

Structural dynamics in the plastocyanin-photosystem 1 electron-transfer complex as revealed by mutant studies.

A series of plastocyanin mutants have been constructed by site-directed mutagenesis and expressed in Escherichia coli to elucidate the interaction between plastocyanin and photosystem 1 in the photosynthetic electron-transfer chain. Leu-12 has been replaced with alanine, asparagine, glutamate, and lysine, while Tyr-83 has been exchanged for histidine, phenylalanine, and leucine. Phe-35, Asp-42, and Gln-88 have been mutated to tyrosine, asparagine, and glutamate, respectively. The mutations that have been introduced do not seem to place any strain on the tertiary structure according to optical absorption and electron paramagnetic resonance (EPR) spectroscopic studies. However, there are changes in the reduction potential for the Leu-12 mutants that cannot be accounted for by electrostatic interactions alone. For some of the mutants, the pI shifts, in accordance with the changes in the number of titratable groups. Only the Leu-12 mutants show any major change in their photosystem 1 kinetics, while the mutants in the acidic patch show minor changes, suggesting that both the hydrophobic and acidic patches make contact with photosystem 1 but that the electron transfer occurs at the hydrophobic interface, most probably via the His-87 residue. The kinetics are best described with a model in which a rate-limiting conformational change occurs in the plastocyanin-photosystem 1 complex [Bottin, H., & Mathis, P. (1985) Biochemistry 24, 6453-6460; Sigfridsson, K., Hansson, O., Karlsson, B.G., Baltzer L., Nordling, M., & Lundberg, L. G. (1995) Biochim. Biophys. Acta 1228, 28-36], where the changes observed are attributed to changes in the dynamics within the electron-transfer complex.

Electron Spin Resonance Spectroscopy↗
PubMed1996

Amino acid residues on the I-Ak alpha-chain required for the binding and stability of two antigenic peptides.

The class II molecules of the MHC bind processed Ag fragments (peptides) for presentation to T cells, but the role of individual MHC residues in binding these peptides has not been entirely defined. A panel of 27 mutant I-Ak transfectants was analyzed for the capacity to bind 2 unrelated peptides. The main peptides examined were hen egg lysozyme residues 48-62 and heat shock protein (hsp70) to residues 28-41. Alanine substitutions of sites in the alpha-helical region of the I-Ak alpha-chain altered the ability of this class II protein to bind both peptides. Of the 27 substitutions tested, nine caused a decrease in peptide binding while only three caused an increase in peptide binding. The stabilities of these altered I-Ak-peptide complexes were also examined on SDS-Page. Complexes with lowered stabilities were observed after only four substitutions, and in all four cases this loss of stability was accompanied by a loss in hen egg lysozyme or hsp70 peptide-binding ability. Further, three of these residues lie in the short extended strand at the N terminus of the alpha-helix of the alpha 1 domain, suggesting that this region of I-Ak molecule may be critical for the formation of stable peptide-MHC complexes.

Alanine↗
PubMed1996

Heterogeneous expression of carcinoembryonic antigen in the normal colon and upregulation in active ulcerative colitis.

Using a technique of tolerization, a murine monoclonal antibody (MAb 2E8) has been raised which displays regional differences in reactivity in the epithelium of the normal human colon and increased reactivity in active ulcerative colitis. MAb 2E8 (IgG1) was highly colon-specific and gave higher immunoperoxidase staining scores in the proximal colonic mucosa compared with paired rectal sections (P < 0.02). Expression of the antigen reactive with MAb 2E8 was enhanced in active ulcerative colitis compared with quiescent ulcerative colitis (P < 0.05) and normal controls (P < 0.001). Western blotting and indirect immunofluorescent screening on transfected cell lines established that MAb 2E8 was reactive with carcinoembryonic antigen (CEA). This is the first demonstration of regional differences in the expression of CEA in the normal colon and indicates upregulation of this molecule in active ulcerative colitis.

Adult↗
PubMed1996

Field intubation of trauma patients: complications, indications, and outcomes.

Neither the success nor the complication rate for field intubation of trauma patients is known with any certainty. A retrospective audit of 94 severely injured patients who required field intubation was undertaken. Fifty percent (13 of 26) of survivors and 67% (37 of 71) of nonsurvivors were successfully intubated in the field (not significant). Mechanism of injury was similar in both groups, but survivors were younger (27 v 60 years, P= .049) and less critically injured, as reflected by their Injury Severity Scale scores, their Trauma Scores, and their field Glasgow Coma Scale scores (22.1 v 30.8, P = .0035; 7.7 v 4.2, P < .0002; and 6.3 v 3.3, P < .0001). When compared with previously published studies of medical patients with cardiac arrest, the success rate was lower in our trauma patients. When compared with patients having similar injuries intubated at the trauma center, field intubation was three times more likely to be associated with the development of nosocomial pneumonia than was hospital intubation.

Emergency Medical Services↗