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T Ward

Publications and source records attributed to T Ward.

At least 73 records · Page 4Linked to original sources
PubMed1994

Contribution of secondaries to the radiation environment on space missions.

Calculations to predict the radiation environment for spacecraft in low earth orbit sometimes ignore the contribution from secondary radiation products. However, the contribution of secondaries, particularly neutrons, on heavy spacecraft or in planetary bodies can be of concern for biological systems. The Shuttle Activation Monitor (SAM) and Cosmic Radiation Effects and Activation Monitor (CREAM) experiments provide valuable data on secondary (as well as primary) radiation effects. Comparisons have been made between induced activity from flight-exposed samples, induced activity in a ground-irradiated sample, and Monte Carlo-derived predictions with and without secondaries. These comparisons show that for a flight-exposed sample, predictions which omit the secondary contribution result in a spectrum that is too low by a factor of 2. The addition of the secondaries results in a predicted spectrum that closely matches the measured data.

Bismuth↗
PubMed1994

The relevance of drug injectors' social and risk networks for understanding and preventing HIV infection.

Focusing on the social environment as well as the individual should both enhance our understanding of HIV transmission and assist in the development of more effective prevention programs. Networks are an important aspect of drug injectors' social environment. We distinguish between (1) risk networks (the people among whom HIV risk behaviors occur) as vectors of disease transmission, and (2) social networks (the people among whom there are social interactions with a mutual orientation to one another) as generators and disseminators of social influence. These concepts are applied to analyses of data from interviews with drug injectors in two studies. In the first study drug injectors' risk networks converge with their social networks: 70% inject or share syringes with a spouse or sex partner, a running partner, or with friends or others whom they know. Qualitative data from interviews with injectors in the second study also show that the social relationships between drug injectors and members of their risk network are often based on long-standing and multiplex relationships, such as those based on kinship, friendship, marital and sexual ties, and economic activity. In the first study the vast majority of injectors, over 90%, have social ties with non-injectors. Injectors with more frequent social contacts with non-injectors engage in lower levels of injecting risk behavior. Risk settings may function as risk networks: injectors in this study who inject at shooting galleries are more likely than those who do not to rent used syringes, borrow used syringes and inject with strangers. Since the adoption of a network approach is relatively new, a number of issues require further attention. These include: how to utilize social networks among drug injectors to reduce risk through peer pressure; how to promote risk reduction by encouraging ties between injectors and non-injectors; and how to integrate biographical and historical change into understanding network processes. Appropriate methodologies to study drug injectors' networks should be developed, including techniques to reach hidden populations, computer software for managing and analyzing network data bases, and statistical methods for drawing inferences from data gathered through dependent sampling designs.

Adult↗
PubMed1994

Time-dependent effects of acute chlorpyrifos administration on spatial delayed alternation and cholinergic neurochemistry in weanling rats.

On postnatal day 21 (PND21), Long-Evans rat pups received a single subcutaneous injection of either 0 (corn oil vehicle), 90, 120, or 240 mg/kg chlorpyrifos and were then tested for T-maze delayed alternation on PND23 or 26. Acetylcholinesterase (AChE) activity and muscaranic receptor density [i.e., quinuclidinyl benzilate (QNB) binding] were determined in hippocampus and cortex of brains taken from pups 15 hours after the end of behavioral testing (i.e., the morning of PND24, and 27). Pups exposed to the 240 mg/kg dose of chlorpyrifos showed signs of overt toxicity that precluded behavioral testing. Exposure to the 120 mg/kg dose produced a selective memory impairment (ie., a deficit in delayed alternation but not position discrimination) relative to the 90 mg/kg and vehicle groups. This impairment was transient, however, as it appeared on PND23 and was absent by PND26. PND21 exposure to chlorpyrifos produced dose-related inhibition and recovery of brain AChE over the PND24-27 age range. A similar pattern was observed in hippocampus. Binding of [3H]QNB was reduced in frontal cortex on PND27 only at the 240 mg/kg dose. No significant effects were observed in the hippocampus. These results suggest that the neurochemical effects of acute chlorpyrifos administration are more transient, and the behavioral effects are smaller and shorter-lived than what has been reported in adult rats.

Acetylcholinesterase↗
PubMed1993

Assessment in severe dementia: the Guy's Advanced Dementia Schedule.

Previous findings suggest that severely demented subjects are often capable of responding in some ways to stimulation. This study describes the development of a schedule which can discriminate between subjects on the basis of their responses to a range of objects of varying familiarity. The schedule includes extensive prompting to elicit a range of responses from simple taking of objects through to naming and using. The measure was found to be reliable and valid against the Clifton Assessment Procedures for the Elderly and the Mini-Mental State Examination. Scores were able to discriminate between subjects scoring 0 on the Mini-Mental State Examination. It is suggested that scores on the schedule may reflect residual cognitive capacities and orientation to the environment and as such this measure could prove useful to a range of future studies.

Aged↗
PubMed1993

A comparison of 5-fluorouridine and 5-fluorouracil in an experimental model for the treatment of vitreoretinal scarring.

5-Fluorouridine (5-FUR), a ribonucleotide metabolite of 5-Fluorouracil (5-FU), is a more potent inhibitor of cellular proliferation and cell-mediated contraction in vitro than 5-FU. We compared the efficacy of these two drugs in a cell injection model of proliferative vitreoretinopathy using New Zealand albino rabbits. Forty-five eyes were divided into three groups and injected intravitreally with homologous fibroblasts. Eyes were examined at the time of injection and 7, 14, 21 and 28 days thereafter. By day 28, 70.5% (12 of 17) of 5-FUR treated eyes demonstrated no appreciable proliferative or tractional activity compared with 41.7% (5 of 12) of 5-FU treated eyes and 10% (1 of 10) of control eyes (p < 0.006). Medullary ray puckers developed in 29.4% (5 of 17) and 25% (3 of 12) of 5-FUR and 5-FU treated eyes respectively. No 5-FUR treated eye developed extensive tractional or combined tractional and rhegmatogenous retinal detachment compared with 33.3% (4 of 12) of 5-FU treated eyes and 80% (8 of 10) of control eyes (p < 0.001). These results suggest that 5-Fluorouridine may be more effective than 5-FU for the treatment of vitreoretinal scarring.

Animals↗
PubMed1992

The abstinence violation effect in sex offenders: a reformulation.

It is argued that the central issue in the treatment of sexually aggressive behavior is the tendency to relapse shown by offenders. A model of the relapse process is presented along with what is described as its central feature, the abstinence violation effect (AVE). This construct is critically examined and its shortcomings identified. A brief description of Weiner's attributional theory is provided and this is used to reformulate the AVE. The advantages of the reformulated AVE are described, as are the clinical implications. Suggestions are then made for future research.

Aggression↗
PubMed1992

Applications and limitations of vitreoretinal biopsy techniques in intraocular large cell lymphoma.

The cases of 4 patients with clinical signs of intraocular large cell lymphoma are described. Initial cytopathologic examination of vitrectomy specimens failed to establish the malignant character of the vitreous infiltrates. Three of the four patients eventually developed solid central nervous system tumors, intracranial biopsy samples of which revealed large cell lymphoma, 13 months to 42 months after initial examination. In one patient, transscleral retinochoroidal biopsy confirmed the diagnosis at the same time as negative vitreous cytologic examination. Results of cytopathologic examination alone of vitreous biopsy specimens may not be sufficient to make a diagnosis in certain cases of large cell lymphoma that are subsequently documented by CNS biopsy. Careful attention should be paid to the handling, processing, and interpretation of vitrectomy specimens from patients suspected of having intraocular large cell lymphoma. Consideration should be given to immunocytologic staining and interpretation by centers that are highly experienced in vitreous cytopathology.

Biopsy↗
PubMed1991

Fine mapping of probes in the adenomatous polyposis coli region of chromosome 5 by in situ hybridization.

The gene for adenomatous polyposis coli has been localized to 5q21-22. We have mapped six probes from this region using isotopic or nonisotopic in situ hybridization. Using tritium-labeled probes we localized II227 (D5S37) to 5q14-15 and ECB27 (D5S98) to 5q21. Following hybridization with biotin-labeled probes, the positions of signals along the chromosomes were measured as fractional length relative to the length of the chromosome arm from centromere to qter (FLcen-qter). Ninety-five percent confidence limits, compared with standard karyotypes, provided the corresponding band localization. By this method we localized Cllpll (D5S71) to FLcen-qter 0.407-0.452 (5q21.1-21.3), ECB27 to FLcen-qter 0.426-0.473 (5q21.3), YN5.48 (D5S81) to FLcen-qter 0.459-0.496 (5q21.3-22.2), and ECB134 (D5S97) to FLcen-qter 0.509-0.533 (5q22.3-23.1). ECB220 had three sites of hybridization, a major site at FLcen-qter 0.460-0.492 (5q21.3-22.1) and minor sites at FLcen-qter 0.299-0.339 (5q14.3-15) and FLcen-qter 0.629-0.691 (5q23.3-31.2). We have shown that the chromosome 5 breakpoint in a t(5;15) translocation from a patient with Gardner's syndrome (GM03314) is between Cllpll and ECB27. Linkage data are presented suggesting that ECB27 is located on the same side of the APC locus as II227. These and published results including data on several constitutional deletions (M, SD, and brothers PW and ND) give a probable order of [cen] - [II227, proximal SD breakpoint] - [Cllpll] - [proximal PW/ND, M breakpoint(s), GM03314 breakpoint] - [ECB27] - [APC] - [YN5.48] - [distal PW/ND breakpoint] - [ECB134] - [distal M breakpoint] - [qter]. The major site of ECB220 appears to be between ECB27 and the distal PW/ND breakpoint; the distal SD breakpoint is distal to YN5.48.

Adenomatous Polyposis Coli↗
PubMed1991

Functional assessment in severely demented patients.

The Brighton Clinic Adaptive Behaviour Scale was administered to a group of severely demented patients, resulting in a range of scores. The scale was found to be reliable and validated against the Clifton Assessment Procedures for the Elderly Behaviour Rating Scale and psychiatric ratings. The scale is likely to prove useful to clinicians and researchers.

Aged↗
PubMed1991

Liposome suppression of proliferative vitreoretinopathy. Rabbit model using antimetabolite encapsulated liposomes.

The effects of the antimetabolites, cytarabine (Ara-C) and 5-fluorouridine 5'-monophosphate (FUMP), encapsulated in multivesicular liposomes on formation of vitreous fibroproliferative membranes in New Zealand white (NZW) rabbits were studied. In pharmacokinetic studies, the drug half-life in the vitreous cavity was 124 hr after intravitreal administration of 1.0 mg of FUMP in liposomes. By contrast, the drug half-life after a single injection in nonliposome-treated controls was only 4.5 hr. In a heterologous dermal fibroblast model of proliferative vitreoretinopathy (PVR), there was a 92% decrease in frequency of tractional retinal detachments in rabbits receiving a single intravitreal injection of liposome-encapsulated 0.1 mg of FUMP compared with controls receiving liposomes without drug. A dose of 1 mg of Ara-C in liposome-treated rabbits was associated with only a 46% reduction in tractional detachment compared with controls. Multivesicular liposome-encapsulated FUMP may be useful for inhibiting formation of fibroproliferative membranes in the vitreous after vitreoretinal surgery.

Animals↗
PubMed1991

Behavioral and neurochemical changes in rats dosed repeatedly with diisopropylfluorophosphate.

Behavioral effects of organophosphates (OPs) typically decrease with repeated exposure, despite persistence of OP-induced inhibition of acetylcholinesterase (AChE) and downregulation of muscarinic acetylcholine (ACh) receptors. To characterize this tolerance phenomenon, rats were trained to perform an appetitive operant task which allowed daily quantification of working memory (accuracy of delayed matching-to-position), reference memory (accuracy of visual discrimination) and motor function (choice response latencies and inter-response times during delay). Daily s.c. injections of 0.2 mg/kg of diisopropylfluorophosphate (DFP) caused no visible cholinergic signs, did not affect body weight or visual discrimination, but progressively impaired matching accuracy and lengthened response latencies and interresponse times. These effects recovered in seven of eight treated rats after termination of DFP treatment. Resumption of daily DFP at 0.1 mg/kg caused smaller impairments of both matching accuracy and response latency. After 21 injections of 0.2 mg/kg/day of DFP, rats were subsensitive to the hypothermia induced by acute oxotremorine (0.2 mg/kg i.p.), as expected after OP-induced downregulation of muscarinic ACh receptors. Evidence for supersensitivity to scopolamine (0.03 and 0.056 mg/kg i.p.) in DFP-treated rats was mixed, with additive effects predominating on both the cognitive and motor aspects of the task. After 18 days of 0.1 mg/kg of DFP, AChE was inhibited 50 to 75% and muscarinic ACh receptor density was reduced 15 to 20% in hippocampus and frontal cortex. Progressive declines in AChE activity in hippocampus and frontal cortex across 15 daily doses with DFP at 0.1 and 0.2 mg/kg were observed in other rats; quinuclidinyl benzilate binding was significantly reduced in hippocampus after 15 doses at both levels of DFP. These results indicate that animals showing a definitive sign of tolerance to OP administration (subsensitivity to a cholinergic agonist) were also functionally impaired on both the mnemonic and motoric demands of a working memory task. The nature of this impairment suggests further that it results from compensatory changes in the central nervous system, e.g., muscarinic receptor downregulation, considered to produce "tolerance" to OPs in exposed animals.

Acetylcholinesterase↗
PubMed1990

Effects of a diabetogenic strain of encephalomyocarditis (EMC) virus on protein synthesis in mouse islets of Langerhans.

The effects of a diabetogenic strain of encephalomyocarditis (EMC) virus on total protein and insulin biosynthesis in mouse islets of Langerhans have been studied in tissue culture. In dispersed mouse islets, the rates of protein biosynthesis were assessed by measuring the incorporation of [3H]leucine into proteins. In infected dispersed islets incubated in 20 mM-glucose, both insulin and total protein biosynthesis were decreased at 6 h; only insulin biosynthesis was significantly decreased at 3 h. In whole islets, EMC virus brought about a decrease in glucose-stimulated protein and insulin biosynthesis as early as 2 h after infection without concomitant effects on insulin release. This inhibition of protein biosynthesis was still apparent at 20 h post-infection, at which time insulin release was found to be markedly elevated, and the islet insulin content was moderately decreased. At 44 h post-infection, glucose-induced insulin biosynthesis was preferentially inhibited. Infected islets at this later time point also displayed elevated levels of insulin release, and a marked loss of islet insulin content. When insulin mRNA and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA levels were assessed by dot-blot hybridization using appropriate cDNA probes, levels of insulin mRNA were shown to decrease steadily during the first 20 h of infection, in contrast with the levels of GAPDH mRNA. At 44 h post-infection, both types of mRNA were markedly decreased. It is suggested that there is an initial early 'shut-off' of protein synthesis without other detectable changes in islet function. This is followed by a phase where both insulin mRNA levels and insulin synthesis are dramatically decreased.

Animals↗
PubMed1990

The RAD50 gene, a member of the double strand break repair epistasis group, is not required for spontaneous mitotic recombination in yeast.

Mutations in the RAD50 gene of Saccharomyces cerevisiae have been shown to reduce double strand break repair, meiotic recombination, and radiation-inducible mitotic recombination. Several different point mutations (including ochre and amber alleles) have been previously examined for effects on spontaneous mitotic recombination and did not reduce the frequency of recombination. Instead, the rad50 mutations conferred a moderate hyper-rec phenotype. This paper examines a deletion/interruption allele of RAD50 that removes 998 of 1312 amino acids and adds 1.1 kb of foreign DNA. The results clearly indicate that spontaneous mitotic recombination can occur in the absence of RAD50; in fact, the frequency of recombination is elevated over the wild-type cell. One possible interpretation of these observations is that the initiating lesion in spontaneous recombination events in mitosis might not be a double strand break.

Alleles↗
PubMed1990

Coxsackie B4 viruses with the potential to damage beta cells of the islets are present in clinical isolates.

Infections with Coxsackie viruses (especially Coxsackie B4) are thought to be involved in the pathogenesis of diabetes. Many interdependent variables determine the outcome of an infection with a Coxsackie virus, one of them being the tropism of the virus for a specific tissue. The extent to which Beta cell tropic variants of Coxsackie B4 virus occur naturally was assessed. Human isolates of this virus were tested in an in vitro system in which elevated insulin release from infected islets incubated at a non-stimulatory (2 mmol/l) glucose concentration appears to be related to viral attack. Using this technique, 8/24 isolates tested, impaired secretory function in mouse islets. Some strains of Coxsackie B4 virus, therefore, will directly infect mouse islets in vitro leading to changes in islet cell function. In conclusion, these findings confirm that variants of Coxsackie B4 virus with the potential to damage Beta cells occur quite frequently in the natural population. In certain circumstances the damage they inflict on Beta cells may cause destruction of these cells, or precipitate overt diabetes.

Animals↗