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Biomedical subjects

J Walker

Publications and source records attributed to J Walker.

At least 199 records · Page 11Linked to original sources

A novel cystathionine beta-synthase from Panagrellus redivivus (Nematoda).

The free-living nematode Panagrellus redivivus can be used as a biochemical model for parasitic nematodes in the search for new chemotherapeutic agents. A novel cystathionine beta-synthase has been purified 3600-fold from the cytosol of P. redivivus. The enzyme catalyses the synthesis of cystathionine from homocysteine plus serine or cysteine. The enzyme, native M(r) 71.7 kDa, pI 4.7, is a dimer and also catalyses the replacement of the beta-SH group of cysteine with 2-mercaptoethanol to yield a thioether, S-(2-hydroxyethyl) cysteine and H2S. This reaction proceeds much faster than cystathionine synthesis and L-cysteine cannot be replaced by D-cysteine, L-cystine, N-acetyl L-cysteine, cysteamine of D,L-homocysteine. 2-Mercaptoethanol in the assay can be replaced by monothiolglycerol and to a lesser extent by cysteamine. The absolute K(m) values for L-cysteine and 2-mercaptoethanol were 0.13 +/- 0.05 mM and 1.72 +/- 0.24 mM, respectively, the absolute V(max) was 55 +/- 4.9 mumol.min(-1).mg protein(-1). The enzyme had a pH optimum of approx. 8.5 and did not require metal ions for activity. The enzyme was inhibited by a series of substrate analogues, anthelmintics and plant phenols. The P. redivivus enzyme differs markedly from its mammalian equivalent and suggests distinctive differences in sulphur amino acid metabolism in nematodes.

Animals↗

Smoking multiple high- versus low-nicotine cigarettes: impact on resting energy expenditure.

The thermic effect of smoking multiple cigarettes varying substantially in nicotine yield was investigated. Three treatments were imposed: nonsmoking at baseline, smoking six low-nicotine (0.8 mg nicotine) cigarettes (LOW), and smoking six high-nicotine (1.74 mg nicotine) cigarettes (HIGH). An initial increase of 6.8% in resting energy expenditure (REE) above baseline REE occurred after consumption of two consecutive cigarettes for both the HIGH and LOW treatments. With consumption of more cigarettes, the peak increase for the HIGH treatment was 9.3%, significantly greater than the peak of 5.9% for the LOW. Averaged over 2 hours, the HIGH treatment significantly increased REE by 6.9% and the LOW treatment significantly increased REE by 5.2%. Expired carbon monoxide (CO) measurements indicated that LOW cigarettes were smoked more aggressively than HIGH cigarettes. It was concluded that, initially, the nicotine yield of cigarettes is not an important influence on the thermic effect of smoking. But over a longer period and after multiple cigarettes, the nicotine yield may become an important influential factor.

Adolescent↗

A comparison of hemolysis rates using intravenous catheters versus venipuncture tubes for obtaining blood samples.

OBJECTIVE: The primary purpose of this study was to compare the rate of hemolysis in blood samples obtained by an i.v. catheter versus the rate in samples obtained by venipuncture (Vacutainer tubes and needles; Becton Dickinson Vacutainer Systems, Franklin Lakes, N.J.). Subsequently, variance in i.v. catheter diameter was reviewed to determine its influence on hemolysis rate of i.v. catheter aspirate. DESIGN: A randomized, prospective study was used to evaluate hemolysis differences between the two blood sampling methods. A descriptive, retrospective review of study data was used to evaluate the importance of the variable i.v. catheter diameter. METHODS: The study group consisted of patients who came to the emergency department and required both an i.v. infusion and blood sampling for determination of electrolyte levels and complete blood cell count. Pediatric patients (younger than 16 years) were excluded. The ED patients who qualified for the study were randomly assigned to either group A or B. The blood samples for patients in the A group were obtained through the i.v. catheter at the time of insertion. The i.v. catheters ranged in size from 24 gauge to 14 gauge. Patients in the B group also had insertion of an i.v. line, but their blood samples were obtained by Vacutainer venipuncture at a separate site. The Vacutainer needle was standardized at 21 gauge. All blood samples were collected by one of seven experienced ED nurses. The nurse who collected the blood sample for an study patient was responsible for result follow-up. RESULTS: A total of 165 patients participated in the study; 87 patients were assigned to the A (i.v.) group, and 78 patients participated in the B (venipuncture) group. In group A a total of 12 of 87 (13.7%) blood samples hemolyzed. Hemolysis occurred in 3 of 78 (3.8%) of group B samples. These findings were statistically significant (p < 0.05). When we examined the variable i.v. catheter diameter, we noted a lower incidence of hemolysis with larger catheter diameters: 24 gauge (100%), 22 gauge (25%), 20 gauge (15%), 18 gauge (10%), 16 gauge (0%), 14 gauge (0%). This findings was statistically significant (p < 0.05). CONCLUSIONS: Hemolysis of blood samples obtained by an i.v. catheter was significantly higher than when blood was obtained through Vacutainer venipuncture. There is an inverse correlation between i.v. catheter diameter and the rate of hemolysis.

Blood Specimen Collection↗

Enlarged blind spots in chorioretinal inflammatory disorders.

PURPOSE: This study was undertaken to better characterize patients with multifocal choroiditis and panuveitis (MCP), punctate inner choroidopathy (PIC), multiple evanescent white dot syndrome (MEWDS), and diffuse subretinal fibrosis syndrome. The specific aim was to determine whether these disorders were different entities or part of a spectrum of diseases with similar features. METHODS: Seventy-nine patients were included in this study. Most of the patients have been followed up prospectively since July 1980 with some found retrospectively. RESULTS: Forty-one patients had MCP, 16 had PIC, 6 had diffuse subretinal fibrosis syndrome, and 16 had MEWDS. Patients with MCP had visual loss and visual field defects caused directly by visible lesions or recurrent inflammation around old lesions. In particular, clustering of lesions around the optic nerve and nasal periphery was seen in patients with MCP and appeared to be related to visual field loss. Patients with PIC also had enlarged blind spot and other field defects explained by fundus lesions. Patients with PIC and MCP did not have recurrent lesions on extended follow-up. Patients with diffuse subretinal fibrosis syndrome represented a subset of patients characterized with lesions in the posterior pole, sever scarring, and visual loss. Patients with MEWDS had the least inflammation with symmetrically distributed lesions. Minimal permanent chorioretinal scarring was seen in patients with MEWDS. Visual field defects improved in most patients with MEWDS and PIC, whereas most patients with MCP and diffuse subretinal fibrosis syndrome did not improve. CONCLUSIONS: Although enlarged blind spots are a feature of all four disorders, other clinical, angiographic, and electroretinographic evidence suggest that these are different entities.

Adolescent↗

Restricted B-cell responses to microbial challenge of the respiratory tract.

The local B-cell response in the respiratory tract to infectious challenge has been analyzed in pigs and calves using two techniques: flow cytometry and antibody secreting cell (ASC) probes. Pneumonia in pigs caused by experimental infection with Mycoplasma hyopneumoniae resulted in a 25-fold increase in the B-cell population in BAL and lung parenchyma 28 days post infection. ASC probes revealed that the B-cell response of immune pigs to a large challenge infection was localized to lung parenchyma and tracheobronchal lymph nodes. Naive calves infected with Pasteurella multocida had a 5-fold increase in the B-cell blast population in lung parenchyma and BAL, and a greater than 60-fold increase in the draining lymph node at 9 days post infection. The ASC probes prepared post challenge from immune calves showed the response to be localized to the draining lymph nodes, with little response in lung parenchyma. A major finding was that ASC probes prepared from lung parenchyma and from pulmonary lymph nodes of both calves and pigs recognized a restricted range of bacterial antigens, particularly compared to the range of antigens recognized by concurrently circulating sera. The use of ASC probes demonstrates that there is a restricted B-cell repertoire in the respiratory tract.

Animals↗

The use of oral midazolam in accident and emergency to reduce anxiety in children.

The injured child can react to a visit to the Accident and Emergency (A & E) department in many ways. The strange noise, people, environment or their frightened parents may be overwhelming for the child. The screaming, uncooperative child can be as hard to manage as the silent unpredictable child, and there are also the smiling, laughing 'you can do anything to me within reason' children. As all these children present at our triage stations, the vast majority can be assessed quickly and efficiently with regard to their anxiety. As experienced A & E nurses we know which child will probably have to endure a painful procedure, which ones will cope well and which will not. This article aims to discuss one method of reducing anxiety for our paediatric clientele, oral midazolam. There is a need for sedation in some children; this will be further explained. The pharmacology of midazolam will be briefly looked at, within this article further detail is not necessary. The main discussion will be the introduction and the current use of oral midazolam in A & E at Leeds General Infirmary (LGI, UK). Some concerns and worries will be considered.

Administration, Oral↗

Antibiotic prophylaxis for infantile pyloromyotomy.

A retrospective study of 50 patients with infantile hypertrophic pyloric stenosis (IHPS) showed wound infection in six patients. In an attempt to assess the value of antibiotic prophylaxis in infantile pyloromyotomy 150 patients with infantile hypertrophic pyloric stenosis were entered in a prospective randomized controlled study. The infants were allocated to receive a dose of Cefuroxime (30 mg/kg) at induction of anaesthesia or no antibiotic. Eight infants developed wound infection, five in the control group and three in the antibiotic prophylaxis group. Although the difference between the two groups was not statistically significant there was an overall reduction of wound infection (6.5%) compared with pre-trial figures (12%). In order to study the bacterial flora in the umbilicus in these infants, culture swabs were taken from the umbilicus on admission, immediately prior to surgery and from the wound prior to skin closure. It was shown that the umbilicus was not the source of infection.

Antibiotic Prophylaxis↗

Antilymphocyte induction immunosuppression in the post-Minnesota anti-lymphocyte globulin era: incidence of renal dysfunction and delayed graft function. A single center experience.

Between 4/91 and 12/93, 262 patients received cadaveric (CRT) (n = 205) or living donor (LRT) (non-HLA identical) renal transplants. All patients were treated with the same sequential induction immunosuppression protocol, with the exception of different forms of antilymphocyte sera: either Minnesota antilymphocyte globulin (MALG), antithymocyte globulin (ATG), orthoclone antibody (OKT3), d 1 postoperatively, or OKT3 intraoperatively. With the withdrawal of MALG from the market, we wished to prospectively analyze the influence of these other antilymphocyte therapies on the incidence of delayed graft function (DGF) (the requirement for hemodialysis within the first week postoperatively) and renal function during the first 3 d postoperatively and during the subsequent .6 months post-transplantation and compare that with our MALG experience. Of the 205 CRT, 76 received MALG with a DGF rate of 18.4%, 50 received ATGAM with a DGF rate of 22.0%, 38 received OKT3 postoperatively with a DGF rate of 39.5%, and 41 received OKT3 intraoperatively with a DGF rate of 39%. Of the 57 LRT, only two patients, one receiving intraoperatively OKT3 (secondary to graft thrombosis), and one MALG patient, suffered DGF. Serum creatinine values were obtained from postoperative d 1 through postoperative d 4 for 185 patients. Each of the four groups showed similar mean decrements in serum creatinine. The number of grafts functioning at 1, 2, 3 and 6 months postoperatively and serum creatinine values were not statistically different between the groups. We conclude that induction immunosuppression with MALG and ATGAM is associated with a lower DGF rate than OKT3 given either intraoperatively or postoperatively. However, with 6 months of follow-up, we do not observe any difference in the incidence of rejection or graft function between the therapies. Consequently, we have chosen ATGAM as our preferred inductive therapy in the absence of MALG owing to its lower associated DGF rate.

Adult↗

Historical population movements in Europe influence genetic relationships in modern samples.

We have newly constructed an ethnohistorical database consisting of 3460 records of ethnic locations and movements in Europe since 2200 B.C. Using this database, we computed vectors of proportions that peoples speaking various language families contributed to the gene pools of 2216 1 degree x 1 degree land-based quadrats of Europe. From these vectors we computed ethnohistorical distances as arc distances between all pairs of quadrats. We used these distances as predictors of genetic distances, which we calculated independently from 26 genetic systems. We find significant partial correlations between ethnohistorical and genetic distances when geographic distance, a common causative factor, is held constant. Ethnohistorical distances explain a significant amount of the genetic variation observed in modern populations. These results are highly robust to simulated errors in and omissions from the ethnohistorical database. Randomization tests show that the historical sequence of the movements does not affect estimates of the ethnohistory-genetics correlation, but the geographic locations of movements do. We track the development of the ethnohistory-genetics correlation through time and show it to be gradual and cumulative over the past 4200 years.

Ethnology↗

Chemical modification of a cloned glutathione S-transferase from Schistosoma japonicum: evidence for an essential histidine residue.

Diethylpyrocarbonate (DEP) inhibits the catalytic activity of a cloned glutathione S-transferase from Schistosoma japonicum (Sj26GST) with a second-order rate constant of 474 M-1 min-1 at pH 7.0 and 25 degrees C. There is an accompanying increase in absorbance at 242 nm due to the formation of N-carbethoxyhistidyl derivatives. There was no evidence that tyrosine or cysteine residues were modified by DEP treatment nor did the enzyme undergo any major conformational change. Activity can be restored by treating the DEP-modified enzyme with hydroxylamine and the pH curve for inactivation indicates involvement of a residue with a pKa of 7.3. Complete inactivation of Sj26GST requires the modification of six histidine residues per subunit. Statistical analysis of residual enzyme activity versus number of groups modified showed that of the six modifiable groups, only one is critical for activity. Substrate protection suggests that this essential histidine residue is at or near the active site.

Animals↗