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S Young

Publications and source records attributed to S Young.

At least 19 recordsLinked to original sources
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

High dose intravitreal ganciclovir injection provides a prolonged therapeutic intraocular concentration.

BACKGROUND: Although intravitreal high dose ganciclovir has previously been found to provide excellent control of cytomegalovirus (CMV) retinitis, little was known about the vitreous concentrations of ganciclovir after a 2 mg intravitreal injection. METHODS: Eleven vitreous samples were taken from seven patients with CMV retinitis at 24 and 72 hours after a 2 mg intravitreal injection of ganciclovir and the concentration of ganciclovir was measured by high performance liquid chromatography. RESULTS: The mean concentration of ganciclovir at 24 hours was 143.8 mg/l (95% confidence interval 97.8-190) and at 72 hours was 23.4 mg/l (95% CI 0-49.7). The half life ranged from 11.9 to 26.3 (mean 18.8) hours in the four patients who had two samples taken. The mean half life calculated from the mean concentrations at 24 and 72 hours was 18.3 hours, so the calculated mean concentration at 7 days was 0.6 mg/l. CONCLUSIONS: This suggests that it takes about 7 days to eliminate the intravitreal ganciclovir, and that it is not likely to accumulate with weekly injections. The intravitreal concentrations achieved with high dose therapy remained above the ID50 for CMV (0.25-1.22 mg/l) for up to 7 days.

Antiviral Agents↗
PubMed1995

The effect of inhaled adrenaline on lung function of recurrently wheezy infants less than 18 months old.

Inhaled bronchodilators have been shown not to improve lung function in infants with wheeze. This observation has led to the suggestion that airway wall edema may be more important than bronchoconstriction in infants with airway narrowing. Inhaled adrenaline is used to relieve upper airway edema in children with croup and has been demonstrated to improve clinical scores and lower pulmonary resistance in some infants with wheeze associated with bronchiolitis. The aim of the present study was to examine the effect of inhaled adrenaline on lung function in a group of infants with recurrent wheeze. Eleven infants aged 10 to 18 months with a history of recurrent wheeze were studied during an asymptomatic interval. Respiratory function was assessed (1) by measuring maximal expiratory flow at functional residual capacity (VmaxFRC) during a forced partial expiratory maneuver and (2) by measuring conductance of the respiratory system (Grs) using a single expiratory occlusion technique. Following baseline measurements, the infants received 0.5 mg/kg adrenaline by nebulizer and serial lung function tests were repeated at 5 min intervals. Ten infants had abnormal baseline lung function (median VmaxFRC 44.2% predicted; median Grs 34% predicted). Using a random effects model, VmaxFRC and Grs declined significantly at 10 and 5 min after adrenaline, respectively. No significant improvements from baseline were observed in either measurement for up to 30 min following adrenaline delivery. It is concluded that inhaled adrenaline did not relieve airways obstruction in this group of asymptomatic infants with recurrent wheeze.

Administration, Inhalation↗
PubMed1995

Posterior thecal lumbar disc herniation mimicking synovial cyst.

We describe a 70 year-old-patient with a rare, misleading presentation of lumbar disc prolapse, which on CT mimicked a synovial cyst. The whole nucleus pulposus had herniated, become sequestrated, and migrated behind the theca adjacent to the L4-5 facet joint. There was no continuity of the disc material with the intervertebral space. A fenestration was performed and the sequestrated disc material was found free of adhesions, and removed completely without difficulty. Histopathological examination confirmed the diagnosis. The patient had complete relief from his pain.

Aged↗
PubMed1995

Surgical delays and outcomes in patients treated with pneumatic antishock garments: a population-based study.

Until mid-1991, our emergency medical services (EMS) system required the routine application of pneumatic antishock garments (PASGs) in all trauma cases, and inflation of the garment if the patient was hypotensive (systolic blood pressure < 90 mm Hg). The findings in 398 trauma patients who underwent emergency surgery when PASG was still being routinely applied were compared with the findings in 590 trauma patients who underwent emergency surgery after routine PASG application had been discontinued. Since the discontinuation of routine PASG application, scene time intervals for "intermediate" blunt and penetrating trauma activations have not changed, but scene times for "full-activation" blunt trauma have actually increased (6.4 minutes with PASG and 9.5 minutes without PASG, P = .0004). Transport times were found to be a function of the type of trauma; patients with penetrating injuries were transported more rapidly (P < .0001) than patients with blunt trauma, even after controlling for injury severity and point of origin. Total time elapsed from EMS activation to the start of surgery for "full" activations, both blunt and penetrating, was unchanged (52.8 minutes with PASG and 53.8 minutes without PASG for penetrating trauma, 117.9 minutes with PASG and 105.1 minutes without PASG for blunt trauma). Times for "intermediate" activations did not change significantly. Length of intensive care unit (ICU) stay did not change. Within the subgroup of patients with femoral but not pelvic fractures, time spent at the scene of injury was shorter for patients treated with PASG than for those treated without (9.5 minutes v 14.5 minutes, P = .0066). Predicted and actual mortality rates were unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Cohort Studies↗
PubMed1995

Feminizing Sertoli cell tumors in boys with Peutz-Jeghers syndrome.

We report the pathology findings in two cases of multicentric Sertoli cell testicular tumors in two young boys with probable Peutz-Jeghers syndrome. Four cases of such tumors occurring in boys with Peutz-Jeghers syndrome were previously reported. Each of the two boys reported in this paper had prominent gynecomastia, rapid growth, and advanced bone age. Serum levels of estradiol were markedly elevated. Anti-müllerian hormone was measured in the serum of one of the boys and was in the normal range for age. Bilateral orchiectomy was performed in each case because the neoplastic growth would most likely result in sterility, and curtailment of height potential was threatened from continued elevation of estradiol levels. Microscopically, greatly enlarged seminiferous tubules packed with ovoid Sertoli-like cells were present. Prominent eosinophilic basement membrane surrounded the tubules and intersected between the cells, forming hyalinized ovoid globules and microcalcifications. Ultrastructure revealed lamination of basement membranes surrounding adjacent cells, ovoid cells with abundant cytoplasm, and limited smooth endoplasmic reticulum. Studies of testicular tumor tissue from both cases revealed increased transcription of the aromatase cytochrome P450 gene using promoter II, the promoter directing aromatase expression in the normal ovary and testis. The levels of transcripts were comparable to corpus luteum, thus resulting in increased estrogen synthesis. Transcripts specific for placental-type aromatase promoters (I.1 and I.2) were not detected in significant levels in these tumors.

Anti-Mullerian Hormone↗
PubMed1995

Lung function, airway responsiveness, and respiratory symptoms before and after bronchiolitis.

Acute viral respiratory illness during infancy has been implicated as a precursor for subsequent lower respiratory morbidity in childhood. A prospective, longitudinal study of respiratory function, airway responsiveness, and lower respiratory illness during early childhood was performed in a cohort of 253 healthy infants to characterise those who experienced bronchiolitis. Seventeen infants (7% of the cohort), were given a diagnosis of bronchiolitis during the first two years of life with two (1%) requiring hospital admission. Seventy one per cent of those infants with bronchiolitis had a family history of atopy, 53% of asthma, and 29% had a mother who smoked cigarettes. These family history characteristics in this group with bronchiolitis were not different from the rest of the cohort. There were also no differences in the number of older siblings, the number breast fed, the duration of breast feeding, or socioeconomic status of the families between those that did and did not get bronchiolitis. Respiratory function was assessed at 1, 6, and 12 months of age. Maximum flow at functional residual capacity (VmaxFRC) was measured using the rapid thoracic compression technique. Resistance (Rrs) and size corrected compliance (Crs/kg) were obtained from a single brief occlusion at end inspiration. Airway responsiveness was assessed by histamine inhalation challenge and the provocation concentration of histamine resulting in a 40% fall on VmaxFRC from baseline (PC40) was determined. Respiratory measurements were ranked into terciles to assess the distribution of infants who developed bronchiolitis through the cohort. Cough and wheeze were noted to be frequent before the episode of bronchiolitis. This study has demonstrated that infants who develop bronchiolitis have evidence of pre-existing reduced respiratory function and lower respiratory symptoms. It is proposed that bronchiolitis, although potentially contributory, is not usually causative of subsequent lower respiratory morbidity.

Asthma↗
PubMed1995

High dose intravitreal ganciclovir for CMV retinitis: a shelf life and cost comparison study.

BACKGROUND: It was previously found that high dose intravitreal ganciclovir provided superior treatment of cytomegalovirus retinitis compared with intravenous treatment. This study examined the stability and solubility of the ganciclovir solution to determine the shelf life of prepared solution, and compared the cost of intravitreal with intravenous therapy. METHODS: For the solubility studies high performance liquid chromatography was used to determine the ganciclovir concentration in various solutions. Measurements were taken of freshly made 20 mg/ml solution, the same solution stored at room temperature or frozen for 10, 17, and 24 days, after the solution was filtered, and after it was heated at 56 degrees C. For the cost comparison analysis the cost of 22 patients treated exclusively with intravitreal high dose ganciclovir was compared with cost estimates for the same patients treated with a standard intravenous therapy regimen over the same time. RESULTS: There was little variation in the concentration of ganciclovir regardless of the storage conditions, suggesting that the 20 mg/ml solution was very stable. The heating and filtering experiments suggest that maximum solubility was achieved both in the freshly prepared and thawed frozen stored solution. The total cost of the intravitreal treatment was Aus $172,435 and the estimate of intravenous treatment was Aus $490,521. This represents a total saving of $318,086 (65%), or $14,458 per patient. The average number of weeks of treatment for each patient was 27.9 (613 weeks/22 patients), so the saving per patient per year was $29,946. CONCLUSION: High dose intravitreal ganciclovir therapy may be administered in a very cost effective way, which along with its acceptability, safety, and clinical efficacy make it an attractive method of treatment of CMV retinitis.

Cytomegalovirus Retinitis↗
PubMed1995

Myocardial hypertrophy and coronary artery disease in male cocaine users.

We compared the heart weights and the incidence of atherosclerotic lesions in trauma fatalities testing positive for cocaine with the hearts of cocaine negative trauma fatalities, with the hearts of decedents dying from cocaine overdose, and with historic controls derived from the literature. There were 116 trauma victims, 83 men and 33 women, aged 20-50 years, and 26 men with cause of death listed as cocaine toxicity. The 32 cocaine (+) male trauma fatalities had a mean age 34 +/- 10 years and a mean heart weight of 375 +/- 82 grams. The 51 cocaine free males had a mean age 31 +/- 9 years, and mean heart weight 337 +/- 54 grams (P = .01). Heart weights in the cocaine using group were also significantly greater than historical controls from World War I, Korea, and Vietnam. The incidence of atherosclerotic changes was similar in both groups, but cocaine (+) men had more frequent coronary artery lesions involving multiple vessels (P = .01). Comparisons between 16 cocaine (+) females and 17 cocaine (-) female controls disclosed no significant differences in heart weight or the frequency of atherosclerotic lesions. The 26 men dying of cocaine overdose also had larger hearts than the controls (379 +/- 64 g, P = .004), and more severe CAD (30% had involvement of 2 or more vessels, P = .02). The degree of myocardial hypertrophy documented in this study was highly significant, but because the increase is modest (around 10%), it is likely to go unrecognized at autopsy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Perimalleolar tendon transfer to the os calcis for triceps surae insufficiency in patients with postpolio syndrome.

Twelve patients (14 feet) with the diagnosis of postpolio syndrome underwent patients-specific transfer of perimalleolar tendons to the os calcis for triceps surae insufficiency. One to 5 tendons were transferred, for a resulting mean muscle strength of Grade 3 at a mean followup of 2.7 years. At final followup, 7 patients were restudied with ankle plantar flexion torque measurements, range of motion, and gait analysis. Patients reported subjective improvements in endurance (86%), pain (90%), and ambulatory distance (50%). No progression of foot deformity was noted. Three of 5 patients became brace free. After tendon transfer, patients recorded increased ankle plantar flexion torque strength (80%) and an increase in 1 grade of muscle strength (29%). There was no significant change in gait velocity, stride length, or heeloff time between pre- and postoperative gait analysis. No tenodesis effect was observed. In conclusion, perimalleolar tendon transfers for triceps surae insufficiency in postpolio patients was effective in decreasing subjective complaints, arresting progressive foot deformity caused by muscle imbalance, and increasing plantar flexion strength, whereas the results of gait analysis failed to show significant improvement.

Adult↗
PubMed1995

Developing a course on principles of stoma care.

Hospital and community nurses may see relatively few patients with stomas and thus feel unprepared to care for them. The first short course on stoma care available in Scotland has been set up by specialist nurses to help their colleagues to understand the principles of care. The aim of the course is to produce a network of informed nursing professionals in this field.

Community Health Nursing↗
PubMed1995

Antibiotic penetration of experimental intra-abdominal abscesses.

Intra-abdominal abscess is seldom adequately treated by systemic antibiotics alone and often requires surgical or computed tomography-guided drainage for resolution. Abscess penetration of six currently used antibiotics was examined in a murine intra-abdominal abscess model. Ampicillin/sulbactam, cefmetazole, clindamycin, and trospectomycin penetrated intra-abdominal abscesses to a greater degree than cefoxitin and ceftriaxone. Abscess pus antibiotic levels were not significantly higher after multiple doses than after a single dose. Pus antibiotic levels below the MIC90 for Bacteroides and E. coli within intra-abdominal abscess were observed for most antibiotics with the doses used in this study. Selection of antibiotics with a greater ability to penetrate abscess may be important in optimally treating patients with abdominal infection.

Abdominal Abscess↗
PubMed1995

Effect of selective bowel decontamination with norfloxacin on spontaneous bacterial peritonitis, translocation, and survival in an animal model of cirrhosis.

Selective bowel decontamination with the orally administered quinolone antibiotic, norfloxacin, has been shown to suppress gut gram-negative bacteria and help prevent gram-negative infections in cirrhotic patients who are at high risk of bacterial infection. Because this drug does not eradicate gram-positive organisms, it is conceivable that gram-positives could replace the suppressed gram-negatives in the gut and lead to subsequent infection. Also the effect of norfloxacin on translocation (as defined by culture positivity of mesenteric lymph nodes) has received little attention. In this study, the effect of oral norfloxacin on translocation, bacterial peritonitis, and survival was investigated in an animal model of carbon tetrachloride-induced cirrhosis and ascites. Treated rats received daily doses of orally administered norfloxacin from the onset of cirrhosis until they died or were killed. Controls received no antibiotic. Norfloxacin led to a reduction in bacterial peritonitis from 70% in untreated cirrhotic controls to 28% in treated cirrhotic rats; these data were statistically significant (P = .012). There was no effect on overall translocation rate (28% with norfloxacin vs. 50% without norfloxacin) (P > .1). Gram-positives were isolated in 100% of the bacterial peritonitis episodes and in 71.4% of culture-positive mesenteric lymph nodes in treated animals compared with only 25% of peritonitis episodes and 10% of culture-positive mesenteric lymph nodes of untreated cirrhotic controls (P < .01 for peritonitis and P < .05 for translocation). The survival rate was not different between groups (P > .1).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗