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T Dolan

Publications and source records attributed to T Dolan.

At least 19 recordsLinked to original sources
PubMed2006

Infectivity of Theileria parva sporozoites following cryopreservation in four suspension media and multiple refreezing: evaluation by in vitro titration.

Theileria parva sporozoite stabilates are used for immunizing cattle against East Coast fever and in in vitro sporozoite neutralization assays. In this study, we attempted to identify a cheaper freezing medium and quantified the infectivity loss of sporozoites due to refreezing of stabilates, using an in vitro technique. Pools of stabilates prepared using Minimum Essential Medium (MEM), Roswell Park Memorial Institute (RPMI 1640), foetal calf serum (FCS) and phosphate-buffered saline (PBS) were compared. All were supplemented with bovine serum albumin except the FCS. RPMI 1640 was as effective as MEM in maintaining sporozoite infectivity while the infectivity in PBS and FCS reached only 59% and 67%, respectively. In a second experiment, a stabiiate based on MEM was subjected to several freeze-thaw cycles including various holding times on ice between thawing and refreezing. Refrozen stabilate gave an average sporozoite infectivity loss of 35% per cycle. The results indicate that RPMI can be used as a cheaper freezing medium for T. parva stabilates and that refrozen stabilate doses need to be adjusted for the 35% loss of infectivity.

Animals↗
PubMed2005

Comparison of manual and homogenizer methods for preparation of tick-derived stabilates of Theileria parva: equivalence testing using an in vitro titration model.

Theileria parva sporozoite stabilates are used in the infection and treatment method of immunization, a widely accepted control option for East Coast fever in cattle. T. parva sporozoites are extracted from infected adult Rhipicephalus appendiculatus ticks either manually, using a pestle and a mortar, or by use of an electric homogenizer. A comparison of the two methods as a function of stabilate infectivity has never been documented. This study was designed to provide a quantitative comparison of stabilates produced by the two methods. The approach was to prepare batches of stabilate by both methods and then subject them to in vitro titration. Equivalence testing was then performed on the average effective doses (ED). The ratio of infective sporozoites yielded by the two methods was found to be 1.14 in favour of the manually ground stabilate with an upper limit of the 95% confidence interval equal to 1.3. We conclude that the choice of method rests more on costs, available infrastructure and standardization than on which method produces a richer sporozoite stabilate.

Animals↗
PubMed2004

In vitro titration of Theileria parva tick derived stabilates.

Immunization against the protozoan Theileria parva by infection and treatment has proved to be very efficient for the control of East Coast fever, an acute and often-fatal lymphoproliferative tick-borne disease of cattle in Eastern, Central and Southern Africa. The immunizing dose of live T. parva sporozoites used in this method is usually determined by in vivo titration. An alternative in vitro method of quantification of sporozoites in whole tick-derived stabilates is proposed. The method consists of incubating serially diluted T. parva stabilates with bovine peripheral blood lymphocytes, the host cell that is infected naturally. Allowing the cultures to incubate undisturbed for the full cultivation period (10 days) reduced the variability among replicate titrations. Fungal contaminations were avoided by centrifuging stabilates at 400 g prior to the incubation, which did not precipitate sporozoites significantly. Fungistatics, Nystatin and Flucytosine, did not appear to interfere with the in vitro development of T. parva but their effect on fungal growth was limited. In vitro titration data were compared to in vivo infection data for 2 stabilates. In vitro titration of T. parva sporozoites should allow more ethical and efficient research on the preparation and storage of T. parva tick-derived stabilates.

Animals↗
PubMed2003

A common polymorphism of the protein Z gene is associated with protein Z plasma levels and with risk of cerebral ischemia in the young.

BACKGROUND AND PURPOSE: The vitamin K-dependent protein Z (PZ) has been shown to possess anticoagulant as well as procoagulant properties. Plasma levels of PZ show a broad interindividual variation, but it is unknown to which extent this variation is under genetic control. Recent clinical studies revealed contradictory results on the association of PZ plasma levels and the risk of ischemic stroke. METHODS: We performed a case-control study including 200 patients with cerebral ischemia aged < or =50 years and 199 control subjects from the same South German region. We investigated a possible association of 2 common single nucleotide mutations in the PZ gene with the risk of cerebral ischemia. Furthermore, enzyme-linked immunosorbent assay measurements were done in control subjects without vascular disease to detect a potential association of different genotypes with PZ plasma (antigen) levels. RESULTS: In patients, the frequency of the A allele of the intron F polymorphism G79A was significantly lower than in controls (15.7% versus 24.4%; odds ratio, 0.58; 95% CI, 0.39 to 0.86; P=0.007; adjusted for age, sex, and conventional risk factors). The G allele of the promoter polymorphism A-13G tended to be less common in patients (4.2% versus 7.0%; adjusted odds ratio, 0.56; 95% CI, 0.28 to 1.13; P=0.105). In 42 control subjects, the A allele of the intron F polymorphism was associated with lower PZ antigen levels (P=0.0032; Spearman correlation coefficient rs=-0.48). CONCLUSIONS: The A allele of an intron F polymorphism of the PZ gene appears to be a novel protective genetic marker for the risk of cerebral ischemia in young adults. In the context of juvenile stroke, high PZ plasma levels may represent a prothrombotic condition.

Adult↗
PubMed2001

Molecular and immunological characterisation of Theileria parva stocks which are components of the 'Muguga cocktail' used for vaccination against East Coast fever in cattle.

The 'Muguga cocktail' which is composed of three Theileria parva stocks Muguga, Kiambu 5 and Serengeti-transformed has been used extensively for live vaccination against East Coast fever in cattle in eastern, central and southern Africa. Herein we describe the molecular characterisation of the T. parva vaccine stocks using three techniques, an indirect fluorescent antibody test with a panel of anti-schizont monoclonal antibodies (MAb), Southern blotting with four T. parva repetitive DNA probes and polymerase chain reaction (PCR)-based assays detecting polymorphism within four single copy loci encoding antigen genes. The Muguga and Serengeti-transformed stocks exhibited no obvious differences in their reactivity with the panel of MAbs, whereas Kiambu 5 differed with several MAbs. Kiambu 5 DNA was very distinct from the Muguga and Serengeti-transformed isolates in the hybridisation pattern with all four nucleic acid probes, whereas Muguga and Serengeti-transformed isolates exhibited minor differences and could not be discriminated with one of the probes. PCR amplification in combination with restriction fragment length polymorphism analysis indicated that Kiambu 5 was also markedly divergent from the Muguga and Serengeti-transformed stocks within two of the four antigen coding genes. The T. parva Serengeti-transformed stock did not contain a 130 base pair insert within the p67 sporozoite antigen gene, which has been observed previously in most T. parva parasites isolated from buffalo, and could not be discriminated from T. parva Muguga at any of the four single copy loci. Collectively the data indicate that two of the cocktail components T. parva Serengeti-transformed and Muguga are genetically closely related, while the third component Kiambu 5 is quite distinct. Based on the findings, there may be a need to include only one of the T. parva Muguga and Serengeti-transformed components in the immunising cocktail. The study demonstrates the value of molecular characterisation data for monitoring of live vaccines.

Animals↗
PubMed2001

Theoretical perspectives on language and communication problems in mental retardation and developmental disabilities.

We argue that researchers interested in language and communication problems in mental retardation or any other developmental disorder should view such problems as emerging within the broader context of the behavioral profile, or phenotype, associated with a particular genetic condition. This will require understanding the direct and indirect effects of genes on the development of language and communication and thereby an understanding of the complex relations that exist between language and other dimensions of psychological and behavioral functioning as well as an understanding of the environments in which the developing person acts and is acted upon. We believe that the dominant model for understanding language and communication problems--the nativist approach, which emphasizes the child's innate capacity for acquiring language and characterizes language as consisting of a set of context-free deterministic rules that operate on abstract representations--is inconsistent with an emphasis on indirect genetic effects. We review recent evidence that undermines the nativist approach--evidence concerning the initial state of the language-learning child, the role of environmental input, the competence-performance distinction, and modularity. In place of nativism, we argue for Emergentism, which is a model in which language is seen to emerge from the interaction between the child's biological abilities to map statistical properties of the language input into a distributed representation and the characteristics of the language learning environment and for the purpose of engaging in real-time, meaningful language use.

Child↗
PubMed1999

Is mentoring dead?

Explore the source record for details and available documents.

Hospital Administrators↗
PubMed1990

Treatment of 29 patients with bulky squamous cell carcinoma of the cervix with simultaneous cisplatin, 5-fluorouracil, and split-course hyperfractionated radiation therapy.

Attempting to improve local disease control in bulky (greater than 8 cm) primary or recurrent pelvic tumors, 29 patients with squamous cell carcinoma of the cervix (stage II, 4; III, 10; IV, 6; recurrent, 9) were treated with concomitant chemotherapy and split-course hyperfractionated radiation therapy between April 1983 and August 1988. Cisplatin (CDDP) and 5-fluorouracil (5-FU) have been shown to be radiation enhancers; furthermore, CDDP, radiation therapy, and continuous-infusion 5-FU have elicited high local response rates in head and neck squamous cell carcinoma. A pilot study of cyclical week on/week off CDDP, continuous-infusion 5-FU, and hyperfractionated radiation therapy was developed. Radiation was administered at 116 cGy twice daily, Days 1-5, every other week for a median dose of 4600 cGy to a pelvic field, with paraaortic extension if indicated. Concomitant chemotherapy included CDDP 60 mg/m2 IV Day 1 and 5-FU 600 mg/m2 IV continuous infusion for 96 hr following CDDP infusion. Patients received a median of four cycles of combined treatment, and intracavitary or interstitial brachytherapy followed in 21 patients. Local pelvic response was achieved in 29 of 29 (100%): complete response (CR) in 19 of 29 (66%), partial response (PR) in 10 of 29 (34%). Among CR patients 10 of 19 (53%) were without evidence of disease at a mean follow-up of 29 (range 12-76) months. Five-year actuarial disease-free survival among complete responders was 65%. Of the 10 CR patients 2 failed in the pelvis, for a local control rate of 17/19 (89%). Chemotherapy-related and acute radiation morbidity was minimal but 2 patients required surgical correction of radiation injury. Aggressive combination of split-course hyperfractionated radiation therapy with radiation enhancers resulted in promising local control of bulky pelvic tumor, with an acceptable complication rate, in this otherwise very poor prognostic group of patients.

Adult↗
PubMed1989

Improved characterization of Theileria parva isolates using the polymerase chain reaction and oligonucleotide probes.

Theileria parva DNA was purified from piroplasms isolated from cattle infected with 5 different East African isolates of the parasite, including the East Coast fever reference stock T. p. parva Muguga. Total cellular DNA was prepared from T. parva schizont-infected bovine lymphoblastoid cell cultures (11 isolates). Two probes, previously isolated from T. p. parva Muguga repetitive genomic DNA, were hybridized to restriction digests; closely similar restriction fragment length polymorphism (RFLP) patterns were produced, and no two isolates had the same RFLP pattern. The DNA sequences of probe PMB3, two further copies of the repeated sequence from T. p. parva Muguga, and homologous regions from T. p. parva Kiambu 4 and T. p. lawrencei 3081, were determined. Oligonucleotides were synthesized corresponding to two conserved sections flanking a region which varied between isolates. These oligonucleotides were used as primers in the polymerase chain reaction to amplify the variable region. Further oligonucleotides corresponding to sequences in this variable region were able to distinguish between isolates and no sample hybridized to both oligonucleotides. This is the first unequivocal plus/minus discrimination between groups of isolates to be achieved for T. parva.

Animals↗
PubMed1989

Frequency resolution in children.

The auditory frequency resolving ability of preschool children, school-aged children, and adults was assessed in a standard forced-choice masking experiment. Thresholds for pure-tone signals at 500 Hz, 2000 Hz, and 4000 Hz were obtained in two masking conditions. In one condition, the masker was a 4000-Hz-wide band of noise centered at the signal frequency; in the other, there was a notch in the noise spectrum, approximately one-half octave wide and 50 dB deep, centered at the signal frequency. Frequency resolving ability was inferred from the difference in signal threshold between the two masking conditions. The adaptive forced-choice psychophysical procedure was embedded in a video game in order to obtain rigorous psychophysical data within the attentional limits of young children. This procedure produced data from children as young as 3 years old that were qualitatively indistinguishable from adult data. However, the threshold estimates from the children were more variable from run to run than were the estimates obtained from adults. The mean data from this experiment suggest that frequency resolving ability improves at all frequencies with increasing age.

Adult↗
PubMed1989

Temporal resolution in children.

The auditory temporal resolving power of young children was measured using an adaptive forced-choice psychophysical paradigm that was disguised as a video game. 20 children between 3 and 7 years of age and 5 adults were asked to detect the presence of a temporal gap in a burst of half-octave-band noise at band center frequencies of 400 and 2,000 Hz. The minimum detectable gap (gap threshold) was estimated adaptively in 20-trial runs. The mean gap thresholds in the 400-Hz condition were higher for the younger children than for the adults, with the 3-year-old children producing the highest thresholds. Gap thresholds in the 2,000-Hz condition were generally lower than in the 400-Hz condition and showed a similar age effect. All the individual adaptive runs were "adult-like," suggesting that the children were generally attentive to the task during each run. However, the variability of threshold estimates from run to run was substantial, especially in the 3-5-year-old children. Computer simulations suggested that this large within-subjects variability could have resulted from frequent, momentary lapses of attention, which would lead to "guessing" on a substantial portion of the trials.

Attention↗