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Biomedical subjects

G Evans

Publications and source records attributed to G Evans.

At least 91 records · Page 5Linked to original sources
PubMed1999

Vaccine injury compensation programs worldwide.

Approximately a dozen countries provide some form of compensation for injuries (or deaths) following vaccination. More than anything else, they were instituted in the belief governments have a special responsibility to those injured by properly manufactured and administered vaccines used in public health programs. Administratively, most are managed through the national government, including decisions on eligibility for and amount of compensation. Eligibility may depend on the recipient's age, citizenship or residency status, category of vaccine (e.g., recommended, compulsory), the location it is administered (public vs private ambulatory setting), or satisfying certain time frames for filing a claim. Since few vaccine-related injuries have a clinical or laboratory marker, proving actual causation is difficult. Causation decisions are usually based on the balance of probabilities standard of more likely than not. All countries require that the effects be long lasting (e.g., greater than 6 months), and nearly all provide coverage for medical costs, disability pensions, and death benefits, while noneconomic damages (pain and suffering) are included much less frequently. Funding is generally from the national treasury, with some programs receiving support from lower governmental entities or vaccine manufacturers. After nearly 4 decades of operation, vaccine injury compensation program appears to be an increasingly accepted component of immunization programs today. While we have a much better understanding of their statutory purpose, frame work, process and outcome, there is much more to be learned. Future research should focus on vaccine compensation programs and (1) decision-making at the administrative level; (2) the utilization of outcome indicators in order to gauge effectiveness, including immunization acceptance; (3) the knowledge and attitudes of the public and medical community in host countries; and (4) the overall perspective of vaccine manufacturers. Insight into these and other areas will no doubt aid other countries as they consider implementing programs of their own.

Humans↗
PubMed1999

Potentiation of methicillin activity against methicillin-resistant Staphylococcus aureus by diterpenes.

Totarol is a diterpene compound extracted from the totara tree. Totarol and eight other diterpenes were found to potentiate methicillin, one reducing the minimum inhibitory concentration of methicillin against resistant Staphylococcus aureus 256-fold. Totarol did not inhibit the synthesis of DNA or peptidoglycan in S. aureus, but reduced the respiration rate by 70%. Under potentiation conditions, diterpenes had only a slight effect on the respiration rate, but had a significant effect on expression of PBP 2a. We conclude that the primary staphylococcal target for totarol is the respiratory chain, but that potentiation of methicillin by diterpenes is by interference with PBP 2a expression.

Bacterial Proteins↗
PubMed1999

Characteristics and crystal structure of bacterial inosine-5'-monophosphate dehydrogenase.

IMP dehydrogenase (IMPDH) is an essential enzyme that catalyzes the first step unique to GTP synthesis. To provide a basis for the evaluation of IMPDH inhibitors as antimicrobial agents, we have expressed and characterized IMPDH from the pathogenic bacterium Streptococcus pyogenes. Our results show that the biochemical and kinetic characteristics of S. pyogenes IMPDH are similar to other bacterial IMPDH enzymes. However, the lack of sensitivity to mycophenolic acid and the Km for NAD (1180 microM) exemplify some of the differences between the bacterial and mammalian IMPDH enzymes, making it an attractive target for antimicrobial agents. To evaluate the basis for these differences, we determined the crystal structure of the bacterial enzyme at 1.9 A with substrate bound in the catalytic site. The structure was determined using selenomethionine-substituted protein and multiwavelength anomalous (MAD) analysis of data obtained with synchrotron radiation from the undulator beamline (19ID) of the Structural Biology Center at Argonne's Advanced Photon Source. S. pyogenes IMPDH is a tetramer with its four subunits related by a crystallographic 4-fold axis. The protein is composed of two domains: a TIM barrel domain that embodies the catalytic framework and a cystathione beta-synthase (CBS) dimer domain of so far unknown function. Using information provided by sequence alignments and the crystal structure, we prepared several site-specific mutants to examine the role of various active site regions in catalysis. These variants implicate the active site flap as an essential catalytic element and indicate there are significant differences in the catalytic environment of bacterial and mammalian IMPDH enzymes. Comparison of the structure of bacterial IMPDH with the known partial structures from eukaryotic organisms will provide an explanation of their distinct properties and contribute to the design of specific bacterial IMPDH inhibitors.

Catalytic Domain↗
PubMed1999

Successful in vitro fertilization of in vivo matured oocytes aspirated laparoscopically from red deer hinds (Cervus elaphus).

Most current protocols of in vitro fertilization in ruminants are based on in vitro maturation of oocytes derived from abattoir material. For application of IVF technology to captive endangered species, however, noninvasive techniques are required which allow repeated collection of oocytes from live females. The aim of this study was to develop a method for embryo production from mature oocytes collected laparoscopically from red deer hinds. Follicular development was synchronized in red deer hinds by the insertion of intravaginal progesterone-releasing devices for 10 d, and ovarian stimulation was induced with 1000 IU, i.m. PMSG 48 h before progesterone device removal. Oocytes were harvested by laparoscopy under xylazine/ketamine sedation 24 h after progesterone device removal and then co-incubated with frozen-thawed red deer spermatozoa for 24 h. In Experiment 1, oocytes and embryos were fixed and stained at different developmental timepoints. Their external morphological changes (cumulus expansion, extrusion of the second polar body and cytokinesis) paralleled their nuclear developmental changes (formation of the 2nd metaphase spindle of meiosis, pronuclear formation and nuclear division, respectively). In Experiment 2, embryos were maintained in vitro until they ceased to undergo cell division. A total of 39 aspiration procedures was carried out on 14 red deer hinds. Forty-four cumulus-oocyte complexes (COC) were aspirated from 95 large Graafian follicles; of these, 27 were classed as mature/nondegenerated on the basis of cumulus/cytoplasmic morphology. Seventeen oocytes cleaved following in vitro fertilization, yielding six 2-cell embryos, six 4-cell embryos, four 8-cell embryos and one 16-cell embryo. The results indicate that laparoscopic aspiration of mature oocytes from hormone-treated females offers a valuable source of genetic material for assisted deer breeding programs.

Animals↗
PubMed1999

A MAD experiment performed at the white line of the iridium LIII absorption edge in lysozyme.

A multiple-wavelength anomalous diffraction (MAD) experiment was performed on an iridium derivative of hen egg-white lysozyme. Diffraction data were measured at five wavelengths on the X31 EMBL beamline on the DORIS III storage ring and at two further wavelengths on the X11 beamline. Four iridium-binding sites were located from the dispersive anomalous differences between two wavelengths at the rising and falling inflection points of the Ir LIII-edge white line using direct methods. All other attempts to determine the heavy-atom positions failed. The results demonstrate an experimental method whereby systematic error in MAD data due to sample absorption can be reduced where a white line is present in the absorption spectrum of a heavy atom.

Animals↗
PubMed1999

The Belt mutation in pigs is an allele at the Dominant white (I/KIT) locus.

A white belt is a common coat color phenotype in pigs and is determined by a dominant allele (Be). Here we present the result of a genome scan performed using a Hampshire (Belt)/Pietrain (non-Belt) backcross segregating for the white belt trait. We demonstrate that Belt maps to the centromeric region of pig Chromosome (Chr) 8 harboring the Dominant white (I/KIT) locus. Complete cosegregation between Belt and a single nucleotide polymorphism in the KIT gene was observed. Another potential candidate gene, the endothelin receptor type A gene (EDNRA), was excluded as it was assigned to a different region (SSC8q21) by FISH analysis. We argue that Belt is a regulatory KIT mutation on the basis of comparative data on mouse KIT mutants and our previous sequence analysis of the KIT coding sequence from a Hampshire pig. Quantitative PCR analysis revealed that Belt is not associated with a KIT duplication, as is the case for the Patch and Dominant white alleles. Thus, Belt is a fourth allele at the Dominant white locus, and we suggest that it is denoted I(Be).

Alleles↗
PubMed1999

Intraarterial catheter-directed thrombolysis: urokinase versus tissue plasminogen activator.

The purpose of this study was to evaluate the differences between tissue plasminogen activator (TPA) and urokinase (UK) in the management of ischemic limbs. A total of 58 limbs (24 in the TPA group and 34 in the UK group) in 53 patients were studied prospectively. The two groups were based on the surgeon's preference for lytic agent. The dose regimen for UK was 150,000 IU/hr over 1/2 to 2 hr followed by a continuous infusion of 50,000 IU/hr. TPA was given as a 5-mg bolus followed by 1 mg/hr. Both groups received heparin at a rate of 400 IU/hr through the side arm of the arterial sheath. There was no significant difference in efficacy between UK and TPA, but TPA acted faster and had a higher incidence of bleeding complications.

Aged↗
PubMed1999

Residential detoxification for substance abusers with HIV/AIDS. Walden House Detoxification Program.

Substance abusers with HIV/AIDS have a complex array of problems that are not easily addressed in outpatient or long-term residential programs. A new but promising treatment modality is residential detoxification for substance abusers with HIV/AIDS, such as described by this paper. The purpose of the program is profiled, as well as its general components and the aspects that address the special needs of HIV clients. Data indicating the successes and limitations of the program are presented, along with recommendations for further addressing the needs of substance abuses with HIV/AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Solvent/detergent fresh frozen plasma as primary treatment of acute thrombotic thrombocytopenic purpura.

Three patients with acute thrombotic thrombocytopenic purpura (TTP) (one associated with E. coli infection) received as primary treatment pooled fresh frozen plasma (FFP) virus inactivated by the solvent/detergent (SD) method, plus prednisolone. All three patients attained platelet counts of > 50 x 10(9)/l by days 7, 3 and 10, respectively. Serum creatinine became corrected in parallel. Neurological features were slow to resolve in one patient, and developed de novo during plasma infusion in another with rapid reversal once intensive plasma exchange with SDFFP was instituted. All patients are in stable remission > 1 years later. SDFFP was well tolerated with no febrile or other reactions, and all patients remained negative for markers of infection with HIV, hepatitis B and hepatitis C viruses. One patient was positive for antibodies for hepatitis A virus and parvovirus B19 prior to treatment. The other two patients remained antibody negative at the end of therapy.

Adult↗
PubMed1999

Previous maternal experience potentiates the effect of parturition on oxytocin receptor mRNA expression in the paraventricular nucleus.

In sheep, central oxytocin release at parturition induces maternal behaviour which is thought to be mediated by changes in the expression of central oxytocin receptors. The distribution, effects of parturition, previous maternal experience and hormonal status on the distribution of an oxytocin receptor was investigated using immunocytochemistry and in situ hybridization. In ewes with no previous maternal experience, parturition induced significant increases in oxytocin receptor mRNA expression in the anterior olfactory nucleus, medial preoptic area, ventromedial hypothalamus, lateral septum, medial amygdala, bed nucleus of the stria terminalis and diagonal band of Broca. In maternally experienced ewes, parturition induced additional increases in two areas, the paraventricular nucleus and the Islands of Calleja. The changes in progesterone and oestrogen that occur during late pregnancy and parturition appear to contribute to increases in expression in the anterior olfactory nucleus, Islands of Calleja, medial preoptic area, ventromedial hypothalamus, bed nucleus of the stria terminalis and diagonal band of Broca, but not in the paraventricular nucleus, lateral septum and medial amygdala. These results demonstrate that progesterone and oestrogen priming enhance oxytocin receptor mRNA expression in a number of regions in the olfactory system, hypothalamus and limbic brain. These effects appear to be independent of maternal experience. Parturition increases oxytocin receptor mRNA expression in all the areas influenced by hormonal priming and the lateral septum, medial amygdala and paraventricular nucleus. Maternal experience also enhances expression of oxytocin receptor mRNA in the paraventricular nucleus and the Islands of Calleja. Because the paraventricular nucleus is the main source of oxytocin release in the brain, this upgrading of autoreceptors as a result of maternal experience may serve to enhance release of this peptide in projection sites regulating maternal behaviour.

Animals↗
PubMed1999

Normal fertility in ewes after cervical insemination with frozen-thawed spermatozoa supplemented with seminal plasma.

The effect of seminal plasma (SP) on the motility, capacitation status, penetration through cervical mucus and fertility of frozen-thawed ram spermatozoa was examined. In the presence of SP, motility of frozen-thawed spermatozoa was better (P<0.001) and there were more uncapacitated and less acrosome-reacted cells in comparison with controls (P<0.001). Frozen thawed spermatozoa were also better able to penetrate cervical mucus after addition of SP. Addition of SP increased the percentage of ewes pregnant after insemination of frozen-thawed (39/94, 41.5% v. 51/92, 55.4%; P<0.05) but not fresh spermatozoa (34/55, 61.8% v. 42/58, 72.4% for 0 v. 30% SP in the resuspension medium). Moreover, SP improved pregnancy rates after cervical (14/50; 28% v. 25/49; 51%; P<0.05) but not intrauterine insemination (25/44; 56.8 v. 26/43; 60.5%) with frozen-thawed spermatozoa. In a second experiment, pregnancy rates were 30/45 (66.7%), 9/37 (24.3%) and 24/40 (60.0%) for ewes inseminated with frozen-thawed spermatozoa in the uterus (control), cervix without SP and cervix after supplementation with SP, respectively (P<0.01 for unsupplemented v. supplemented spermatozoa). These experiments demonstrate that impaired function of cryopreserved spermatozoa can be overcome by addition of SP, resulting in normal fertility after cervical AI.

Animals↗
PubMed1999

Reproductive cycles of farmed female chital deer (Axis axis).

Studies were conducted on chital deer hinds (Axis axis) living in a temperate region to advance the understanding of the patterns of reproduction of a tropical cervid species. The hinds exhibited regular patterns of oestrus cyclicity throughout the year as evidenced by concentrations of serum progesterone monitored over a 14-month period, and detection of behavioural oestrus by vasectomized stags. The mean length of the oestrous cycle was 18.0+/-0.7 days (range, 12-23 days). Profiles of serum progesterone showed concentrations of <0.5 ng mL(-1) at the time of oestrus, which rose to a peak (range 1.5-5.0 ng mL(-1)) about Day 13, and then declined to low concentrations at the next oestrus. Observations following parturition showed that the first detected oestrus occurred at a mean (+/- SEM) time of 26.9+/-3.0 days later for seven of nine hinds. The mean length of the oestrous cycle after the first post-partum oestrus was 16.6+/-1.0 days (range 7-20 days). The presence of a stag may influence the length of the post-partum period in chital deer hinds, and hinds in contact with a stag in this study had a significantly shorter interval from parturition to first ovulation (P<0.01) compared with hinds not in contact with a stag. By 7 weeks post partum a corpus luteum was detected in 93% of hinds. In comparison only 43% of hinds with no stag contact had a corpus luteum by 7 weeks post partum. It is suggested that the tendency towards seasonal calving in the study population may be related more to male than female factors.

Animals↗
PubMed1999

Fate and functional integrity of fresh and frozen-thawed ram spermatozoa following intrauterine insemination.

Ewes in a synchronized oestrus were inseminated (intrauterine) with fresh and frozen-thawed spermatozoa and the spermatozoa were either recovered from each section of the reproductive tract after the animal was killed (Experiments 1a and 1b) or after they were voided from the cervix (Experiment 2). In Experiment 1a, only 1.2+/-0.27% of the original inseminate was recovered. Placing a ligature at the base of the uterine horn in Experiment 1b led to the recovery of 3.0+/-0.33% of the original inseminate, located mainly in each uterine horn (33.1+/-5.48%), and each isthmic and ampullary region of the oviduct (2.9+/-5.48% and 4.0+/-5.48%, respectively). A higher proportion of spermatozoa recovered from the isthmus were uncapacitated when observed by chlortetracycline staining than those recovered from the uterus (26.4+/-1.92% and 15.6+/-1.92%, respectively, P<0.05). Experiment 2 showed that large proportions of spermatozoa were voided from the tract through the vagina, with similar numbers of fresh and frozen-thawed spermatozoa lost from the tract. However, frozen thawed spermatozoa were lost at a faster rate than fresh (P<0.05) and with a more advanced membrane state (66.8+/-1.30% and 53.2+/-1.30% were acrosome reacted respectively; P<0.001). Large numbers of recovered spermatozoa had lost their tails, with frozen-thawed spermatozoa more susceptible to tail loss than fresh spermatozoa (55.0+/-0.96% and 45.5+/-0.96% respectively; P<0.05).

Animals↗
PubMed1999

The genetic epidemiology of early-onset epithelial ovarian cancer: a population-based study.

We conducted a population-based study to determine the contribution of germline mutations in known candidate genes to ovarian cancer diagnosed at age <30 years. Women with epithelial ovarian cancer were identified through cancer registries. DNA samples were analyzed for mutations in BRCA1, the "ovarian cancer-cluster region" (nucleotides 3139-7069) of BRCA2, and the mismatch-repair genes hMSH2 and hMLH1. Probable germline mutations in hMLH1 were identified in 2 (2%; 95% confidence interval 1%-8%) of 101 women with invasive ovarian cancer diagnosed at age <30 years. No germline mutations were identified in any of the other genes analyzed. There were no striking pedigrees suggestive of families with either breast/ovarian cancer or hereditary nonpolyposis colorectal cancer (HNPCC). There was a significantly increased incidence of all cancers in first-degree relatives of women with invasive disease (relative risk [RR] = 1.6, P=.01) but not in second-degree relatives or in relatives of women with borderline cases. First-degree relatives of women with invasive disease had increased risks of ovarian cancer (RR = 4.8, P=.03), myeloma (RR = 10, P=.01), and non-Hodgkin lymphoma (RR = 7, P=.004). Germline mutations in BRCA1, BRCA2, msh2, and mlh1 contribute to only a minority of cases of early-onset epithelial ovarian cancer. Our data suggest that early-onset ovarian cancer is not associated with a greatly increased risk of cancer in close relatives.

Adaptor Proteins, Signal Transducing↗
PubMed1999

What are the occupational implications of thalassaemia?

The thalassaemias are a heterogeneous group of inherited haemoglobin disorders. With modern treatment, most patients with severe disease survive to adult life. If they have no complications, and their general health is good, then the condition should have little impact on their fitness for work, though exposure to agents that are toxic or suppress the bone marrow should be avoided. Most patients with thalassaemia have minor disease and are asymptomatic. Their condition generally has no effects on their fitness to work. Pre-employment screening for thalassaemia is not justified.

Adult↗
PubMed1999

Taking MAD to the extreme: ultrafast protein structure determination.

Multiwavelength anomalous diffraction data were measured in 23 min from a 16 kDa selenomethionyl substituted protein, producing experimental phases to 2.25 A resolution. The data were collected on a mosaic 3 x 3 charge-coupled device using undulator radiation from the Structural Biology Center 19ID beamline at the Argonne National Laboratory's Advanced Photon Source. The phases were independently obtained semiautomatically by two crystallographic program suites, CCP4 and CNS. The quality and speed of this data acquisition exemplify the opportunities at third-generation synchrotron sources for high-throughput protein crystal structure determination.

Base Sequence↗