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Biomedical subjects

P T Smith

Publications and source records attributed to P T Smith.

At least 19 recordsLinked to original sources
PubMed2003

Fatal, virus-associated peripheral neuropathy and retinopathy in farmed Penaeus monodon in eastern Australia. I. Pathology.

Lesions are described in farmed Penaeus monodon affected with a previously unreported, fatal disease, 'peripheral neuropathy and retinopathy' (PNR). Outbreaks, associated with minor to heavy mortalities, occurred in 22 of 25 ponds on a farm in eastern Australia during the mid to late 1998/99 growout period. Moribund prawns, 5 to 26 g mean body weight, gathered at pond edges and were typically reddish in colour, lethargic, with mild to moderate epibiotic fouling and 1 or more partially amputated appendages. Histologically, there was mild to severe, focal to diffuse degeneration and necrosis of axons and their sheaths, together with associated glial cell apoptosis, in peripheral nerve fibres. Of the 3 appendage types examined systematically, these pathognomonic lesions were most common and severe in proximal antennal nerves and less common and severe in distal antennal nerves, antennular nerves and pereiopod nerves. Mild to severe, acute to chronic retinitis, associated with degeneration and necrosis of retinular cells and their axons, was also present in most clinically affected prawns. Transmission electron microscopy revealed moderate to large numbers of intracytoplasmic rod-shaped, helical nucleocapsids and enveloped virions, morphologically consistent with a yellow head-like virus, in putative glial cells in the antennal nerve, in the fasciculated zone of the eye and in putative sensory nerve cells of antennules. Immunohistochemical examination revealed lesions, but not histologically normal tissues, in peripheral nerves, eyes, lymphoid organ and vas deferens that consistently stained positively for a yellow head-related virus. The findings strongly suggest that a yellow head-related virus such as the Australian gill-associated virus (GAV) is causally associated with PNR. It is likely that PNR was not recognised during earlier investigations of mid-crop mortalities of farmed P. monodon in eastern Australia because appropriate peripheral nerves and eyes were not routinely examined histologically.

Animals↗
PubMed2001

De novo deletion of chromosome 18q in a baby with harlequin ichthyosis.

Harlequin ichthyosis, (MIM 242500), is a rare, autosomal recessive skin disorder due to an inborn error of epidermal keratinization. The gene for this condition has not been localized. We present a case of HI in which there was a de novo deletion of chromosome 18q: the karyotype was 46, XY, del(18)(q21.3). We postulate that the gene for HI may lie at, or distal to 18q21.3 and that the deletion observed in this case may have unmasked this autosomal recessive disorder.

Chromosome Banding↗
PubMed2001

Gene dose effect reveals no Gs-coupled A2A adenosine receptor reserve in murine T-lymphocytes: studies of cells from A2A-receptor-gene-deficient mice.

Agonist binding to extracellular A2A adenosine receptors (A2ARs) inhibits the activation of virtually all tested functions of T-cells and can induce apoptosis in thymocytes. The evaluation of levels of expression of these immunosuppressive receptors is expected to clarify whether the absence of spare A2ARs (no 'receptor reserve') might be one of the mechanisms of attenuation of the effects of extracellular adenosine on T-cells. A2A transcript is found in T-cells and functional receptors can be demonstrated, but the density of receptor on T-cells is too low to be detected by radioligand binding. Studies of direct radioligand binding to murine brain with the selective A2AR agonist [3H]CGS21680 (2-(4-[(2-carboxyethyl)-phenyl]ethylamino)-5'-N-ethylcarboxamidoadenosine) established that striata levels of A2AR are virtually absent from A2A knock-out mice. Mice that are heterozygous (A2AR+/-) for the A2AR express significantly decreased levels of A2AR. To test for the presence of spare receptors in T-cells we took advantage of this gene dose effect and examined whether the decrease in the number of receptors in thymocytes from A2AR+/- mice was proportionately reflected in a decrease in the functional cAMP response of T-cells to adenosine. cAMP accumulation and apoptosis induced by adenosine and by A2AR agonist are of a lower magnitude in T-cells from A2AR+/- heterozygous mice than in T-cells from A2AR+/+ littermate control mice. These results indicate that there is no A2AR reserve in murine T-cells. Strongly decreased adenosine-triggered cAMP increases were detected in thymocytes from A2AR-/- mice, suggesting that A2B adenosine receptors cannot fully compensate for the loss of A2ARs in murine T-cells. We conclude that the number of A2ARs is the limiting factor in determining the maximal cAMP response of T-lymphocytes to extracellular adenosine, thereby minimizing the immunosuppressive effects of extracellular adenosine.

Animals↗
PubMed2001

Adenosine deaminase deficiency increases thymic apoptosis and causes defective T cell receptor signaling.

Adenosine deaminase (ADA) deficiency in humans results in a severe combined immunodeficiency (SCID). This immunodeficiency is associated with severe disturbances in purine metabolism that are thought to mediate lymphotoxicity. The recent generation of ADA-deficient (ADA(-/-)) mice has enabled the in vivo examination of mechanisms that may underlie the SCID resulting from ADA deficiency. We demonstrate severe depletion of T and B lymphocytes and defects in T and B cell development in ADA(-/-) mice. T cell apoptosis was abundant in thymi of ADA(-/-) mice, but no increase in apoptosis was detected in the spleen and lymph nodes of these animals, suggesting that the defect is specific to developing thymocytes. Studies of mature T cells recovered from spleens of ADA(-/-) mice revealed that ADA deficiency is accompanied by TCR activation defects of T cells in vivo. Furthermore, ex vivo experiments on ADA(-/-) T cells demonstrated that elevated adenosine is responsible for this abnormal TCR signaling. These findings suggest that the metabolic disturbances seen in ADA(-/-) mice affect various signaling pathways that regulate thymocyte survival and function. Experiments with thymocytes ex vivo confirmed that ADA deficiency reduces tyrosine phosphorylation of TCR-associated signaling molecules and blocks TCR-triggered calcium increases.

Adenosine↗
PubMed2000

Diseases of the eye of farmed shrimp Penaeus monodon.

Lesions were found in the eyes of cultured shrimp Penaeus monodon that displayed non-specific signs of disease, including lethargy, dark pigmentation, brown gills, empty midgut, anorexia, white tail muscle, necrosis of uropods and fouled cuticle. Eye lesions were associated with sexual development in moribund shrimp in at least 1 disease event. Suppurative inflammation, granuloma and malacia were observed in histological examination of the eye and the causative agents of lesions appear to be Vibrio spp. and a rod-shaped virus (similar to Lymphoid Organ Virus, Gill-Associated Virus [GAV] and Yellow-Head Virus). Suppurative inflammation was characterised by edema, infiltration of haemocytes and local sites of abscesses. Eyes with granuloma usually appeared white in pond-side examinations, and histology showed that fibrous tissue replaced ommatidia, ganglia and internal structures of the eye. Malacia of the eye was characterised by necrosis of nervous tissue, vacuolation and vascular proliferation in the medulla ganglia. Levels of presumptive Vibrionaceace were high in moribund specimens and Gram-negative rods were observed in some specimens as free particles in the interstitial fluid and haemolymph in the eye. Transmission electron microscopy showed that nerve cells in the fasciculated zone (near the basement membrane) contained cytoplasmic vesicles (1 to 3 microm in diameter) with particles (15 to 26 nm in diameter) and rod-shaped nucleocapsids. The rods were similar to those of GAV and were 130 to 260 nm long, 10 to 16 nm in diameter and had helical symmetry with a screw-like thread (2.4 to 3.5 nm pitch). Also, unidentified enveloped virions, averaging 74 nm in diameter, were observed in cytoplasmic vesicles in the fasciculated zone. In conclusion, it is suggested that bacterial and viral infections of the eye could result in impaired neuroendocrine functions, which may cause a range of clinical signs of disease.

Animals↗
PubMed2000

Study of A(2A) adenosine receptor gene deficient mice reveals that adenosine analogue CGS 21680 possesses no A(2A) receptor-unrelated lymphotoxicity.

Cell surface A(2A) adenosine receptor (A(2A)R) mediated signalling affects a variety of important processes and adenosine analogues possess promising pharmacological properties. Demonstrating the receptor specificity of potentially lymphotoxic adenosine-based drugs facilitates their development for clinical applications. To distinguish between the receptor-dependent and -independent lymphotoxicity and apoptotic activity of adenosine and its analogues we used lymphocytes from A(2A)R-deficient mice. Comparison of A(2A)R-expressing (+/+) and A(2A)R-deficient (-/-) cells in cyclic AMP accumulation assays confirmed that the A(2A)R agonist CGS 21680 is indeed selective for A(2A) receptors in T-lymphocytes. Incubation of A(2A)R-expressing thymocytes with extracellular adenosine or CGS 21680 in vitro results in the death of about 7-15% of thymocytes. In contrast, no death was induced in parallel assays in cells from A(2A)R-deficient mice, providing genetic evidence that CGS 21680 does not display adenosine receptor-independent intracellular cytotoxicity. The A(2A) receptor-specific lymphotoxicity of CGS 21680 is also demonstrated in a long-term (6-day) in vitro model of thymocyte positive selection where addition of A(2A)R antagonist ZM 241,385 did block the effects of CGS 21680, allowing the survival of T cells. The use of cells from adenosine receptor-deficient animals is proposed as a part of the screening process for potential adenosine-based drugs for their receptor-independent cytotoxicity and lymphotoxicity.

Adenosine↗
PubMed2000

Modality effects and the development of the word length effect in children.

Two experiments investigated the development of the word length effect in children aged 4 to 10 years, comparing auditory and visual stimuli. The question addressed was whether word length effects emerged earlier with auditory presentation or visual presentation, or whether they emerged at the same age regardless of presentation modality. Results provided evidence that word length effects emerge earlier with visual than auditory presentation. The implication of our results is that with visual presentation, 4-year-olds engage in some form of verbalization strategy that involves obtaining phonological representations of picture names and mapping them on to articulatory output plans. This strategy is clearly verbal in nature, but is not necessarily characterised as cumulative verbal rehearsal.

Acoustic Stimulation↗
PubMed2000

A jigsaw puzzle theory of memory.

The principal novel feature of this paper is the notion that a coherent memory can be synthesised from a set of partially coherent memory fragments by maximising a particular function, Harmony (Smolensky, 1986). The appeal of Harmony is that it fulfils two functions: it is at the heart of the synthesis algorithm and it provides a natural measure for "feeling-of-knowing". The model is applied to feeling-of-knowing data, flashbulb memories, flashbacks, repression, dissociation, memory stability across repeated recalls, and the effects of cue size on retrieval.

Cues↗
PubMed2000

The development of the use of long-term knowledge to assist short-term recall.

The influence of item familiarity upon memory span was examined in adults and children aged 5, 7, and 10 years by comparing the recall of words and nonwords. Using a probed recall task, both item recall and position recall were tested. The effect of familiarity upon item recall was found to develop with age, from no effects in the 5-year-olds to significant effects in the older children and adults. By contrast, no effect of familiarity was found at any age when recall of position was required. Dissociations between word length effects and familiarity effects supported the conclusion that the familiarity effect does not result from rehearsal. Several explanations for the source of the familiarity effect were examined, and the familiarity effect was attributed to a strategic redintegration or reconstruction process, which is necessary for item recall but not for position recall.

Adult↗
PubMed1999

A phylogeny of aphid parasitoids (Hymenoptera: Braconidae: Aphidiinae) inferred from mitochondrial NADH 1 dehydrogenase gene sequence.

Wasps of the braconid subfamily Aphidiinae are solitary endoparasitoids of aphids. Several aspects of their biology have been the focus of intuitive evolutionary hypotheses which could be tested with a robust phylogeny. Phylogenetic hypotheses have been proposed previously for aphidiines based on morphology, embryology, and DNA sequences. However, many of them are based on a limited number of characters and/or taxa and lack congruence. In addition, many of the inferred phylogenies have not been based upon cladistic analysis. Therefore, a phylogenetic study of Aphidiinae was undertaken, utilizing 465 bp of DNA sequence of the mitochondrial NADH1 dehydrogenase gene. DNA sequences were obtained from 40 taxa, including 14 genera and three outgroups. It is suggested that in agreement with most of the previously proposed phylogenies, the aphidiines, each of the three recognized tribes (Praini, Ephedrini, Aphidiini), and most genera are monophyletic. In contrast to previously proposed phylogenies, the clade of Praon + Dyscritulus (=Praini), rather than Ephedrini, is basal among the aphidiines.

Animals↗
PubMed1999

Performance characteristics of three serum iron and total iron-binding capacity methods in acute iron overdose.

Accurate serum iron and total iron binding capacity (TIBC) measurements may be useful in acute iron overdoses. Two alumina column TIBC methods were found to measure increased TIBC when free iron was present. A homogeneous TIBC method gave consistent results until iron concentrations exceeded 500 micrograms/dL (90 mumol/L), when it began to underestimate the TIBC. Serious iron overdoses require chelation therapy with deferoxamine. Iron recovery was reduced by up to 50% for all 3 methods with clinically achievable concentrations of deferoxamine 8,400 micrograms/dL (150 mumol/L). TIBC measurements by both alumina column methods were reduced by deferoxamine in the presence of free iron and unaffected when the iron concentration was less than the TIBC. The homogeneous TIBC method yielded falsely elevated results in the presence of free deferoxamine. Procedures that measure TIBC by addition of excess ferric iron followed by alumina adsorption are not suitable for monitoring TIBC in acute iron overdose. The homogeneous TIBC assay can be used in acute iron overdose but underestimates TIBC when iron concentrations exceed 500 micrograms/dL (90 mumol/L). None of the methods examined are useful for measuring iron or TIBC in the presence of deferoxamine.

Acute Disease↗
PubMed1998

Papular-purpuric gloves and socks syndrome associated with acute parvovirus B19 infection: case report and review.

The papular-purpuric gloves and socks syndrome (PPGSS) was first described in 1990. This syndrome is characterized by fever, acral pruritus, edema, petechiae, and oral erosions. Subsequently, parvovirus B19 has been implicated, in most cases, as the causative agent of this syndrome. To date, with two exceptions, all published cases of PPGSS have been from Europe and the Middle East and have been mainly reported in the dermatology literature. Herein, we report what we believe to be only the second case of documented parvovirus B19-associated PPGSS occurring in the United States. The patient presented with the typical clinical syndrome, and the diagnosis of acute parvovirus B19 infection was documented by serial serologies that demonstrated development of IgM antibody to virus during the acute phase of infection and seroconversion to IgG antibody in the convalescent period. We then review the existing literature on this unusual syndrome and its association with parvovirus B19.

Acute Disease↗
PubMed1998

Suitability of patient education materials for cardiac catheterization.

Changes in healthcare delivery for such diagnostic procedures as cardiac catheterization have resulted in an emphasis on patient self-study, using booklets and videotapes given to them before the procedure. This transition mandates an evaluation of the appropriateness and effectiveness of these materials. The purpose of this study was to systematically assess the suitability of materials used to prepare patients for cardiac catheterization. Three videotapes and four booklets were evaluated using the Suitability Assessment of Materials instrument. Concrete objective information (procedural and sensation information) was also evaluated. Scores revealed only one video and two booklets suitable for patient education. None received a superior rating. These results suggest that some patient educational materials used to prepare patients for cardiac catheterization are unsuitable. Clinicians should augment current suitable materials to enhance their effectiveness.

Cardiac Catheterization↗
PubMed1997

Implementing a self care program. Effect on employee health care utilization.

1. One way to reduce health care costs is to reduce the demand for health care services. This can be accomplished by teaching employees to make better decisions about when they should see the health care provider or go to the emergency department versus treating themselves at home using self care. 2. In an effort to reduce health care costs, a manufacturing company implemented a self care program using a publication called the HealthyLife Self Care Guide. The guide was distributed to employees during a 50 minute workshop. 3. Analysis of claims data 1 year prior to distribution of the Guide and 1 year after distribution showed a savings of $39.65 per employee (a 24.4% decrease in costs) due to reduced health care provider and emergency department visits. This amounted to a return on investment of 2.6:1. 4. It appears that implementing a self care program in a worksite setting can be an effective way to reduce employer health care costs.

Adult↗
PubMed1996

Phosphorylation of extracellular domains of T-lymphocyte surface proteins. Constitutive serine and threonine phosphorylation of the T cell antigen receptor ectodomains.

The extracellular accumulation of ATP after activation of T-lymphocytes, as well as the presence of ecto-protein kinases in these cells, led us to propose that T cell surface receptors could be regulated through the reversible phosphorylation of their extracellular domains (ectodomains). Here, in a model system, we used T cell transfectants which express T cell antigen receptor chains lacking intracellular and transmembrane protein domains and 32Pi metabolic labeling of cells to definitively demonstrate phosphorylation of ectodomains of T cell surface proteins. We show that alphabetaTCR ectodomains were phosphorylated intracellularly and constitutively on serine and threonine residues and were then expressed on the T cell surface in phosphorylated form. TCR ectodomains also could be phosphorylated at the cell surface when extracellular [gamma-32P]ATP or [gamma-32P]GTP were used as phosphate donors with the same cells. Consensus phosphorylation sites for serine and threonine protein kinases were found to be strongly evolutionary conserved in both alpha and beta TCR chains constant regions. These results are consistent with the hypothesis, where T cell surface proteins which are phosphorylated intracellularly on their ectodomains, could subsequently be expressed at the cell surface and then be reversibly modified by ectoprotein phosphatase(s) and by ectokinase(s). Such modifications may change T cells cognate interactions by, e.g. affecting TCR-multimolecular complex formation and antigen binding affinity. It is suggested that alphabetaTCR ectodomain phosphorylation could serve as a potential mechanism for regulation of alphabetaTCR-mediated T-lymphocytes response.

Adenosine Triphosphate↗
PubMed1996

Toxic effects of blooms of marine species of Oscillatoriales on farmed prawns (Penaeus monodon, Penaeus japonicus) and brine shrimp (Artemia salina).

Benthic and planktonic blooms of species of Oscillatoriales coincided with mortalities of Penaeus monodon during four episodes at Australian prawn farms. Oscillatoria corakiana was the dominant planktonic species at 65-90,000 cells/ml, but Spirulina sp., Lyngbya sp., Oscillatoria sp. and Nodularia sp. were also identified from the water column, benthic layers or surface mats. The levels and variety of Vibrionaceae in prawn tissue, suggest that mortalities were caused by secondary infections of bacteria. However, experimental results indicate that toxicity of the blooms of Oscillatoriales was the primary cause of disease. Pond water and extracts from a tank culture of benthic Oscillatoriales caused mortalities when injected into P. monodon and P. japonicus. Immersion of artemia in extracts from the tank culture also caused mortalities, with L.D50 values for the supernatant extract of 70 mg/litre for artemia cysts and 50 mg/litre for adult artemia, and LD50 values for the pellet extract of 110 mg/litre for artemia cysts and 200 mg/litre for adult artemia. Experiments with artemia suggested the blooms of Oscillatoriales produced water-soluble, heat-labile toxin/s. Mortalities may have been caused by a neurotoxin because: (a) there was a lack of histopathological evidence of damage to the digestive tracts of prawns during each episode; and (b) artemia cysts immersed in extracts of Oscillatoriales died before they developed digestive tracts. PSP toxin, anatoxin-a, homoanatoxin-a and microcystins were not detected when pond water from a diseased pond was tested. It is proposed that sub-lethal levels of toxin weakened the prawns, causing reduced feeding behaviour and an impaired immune system. As a result, prawns were prone to secondary infection by pathogenic bacteria. Because Oscillatoriales are ubiquitous in prawn farms, the findings have significant implications for the assessment of disease in the prawn farming industry.

Animals↗
PubMed1995

Short-term reproductive diapause by Culex tarsalis (Diptera: Culicidae) in the Coachella Valley of California.

Culex tarsalis Coquillett from the Coachella Valley in southeastern California enter a short-term reproductive diapause that is terminated by changes in photoperiod at or shortly after the winter solstice. Reproductively active and unfed resting females exhibited respective increases and decreases in parity rates during December that were characteristic of diapause induction, although reproductively active females, larvae, and males were collected during every month throughout winter. Laboratory experiments demonstrated that females from Coachella Valley enter and maintain a facultative reproductive diapause similar to females from the more northern San Joaquin Valley when exposed to simulated winter conditions. In environmental chambers, diapause termination was not related to temperature accrual because females terminated diapause at approximately the same time regardless of temperature regimens. A field experiment showed that female cohorts emerging in the Coachella Valley from late October through December entered a reproductive diapause that was terminated synchronously by changing photoperiod in late December.

Animals↗