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Biomedical subjects

J L Shaw

Publications and source records attributed to J L Shaw.

At least 19 recordsLinked to original sources

A neutron scattering and nuclear magnetic resonance study of the structure of GeO2-P2O5 glasses.

Germanophosphate (GeO2-P2O5) glasses were studied with neutron diffraction, phosphorus, and oxygen nuclear magnetic resonance, calorimetry, viscosity measurements, and first-principles calculations. These data sets were combined to propose a structural model of GeO2-P2O5 glasses, which includes tetrahedrally coordinated phosphorus, formation of octahedrally coordinated germanium as P2O5 content increases, an absence of trigonally coordinated oxygen, and hence an absence of rutile-like GeO2 domains. The structural model was then used to propose explanations for both the observed composition dependence of the glass transition temperature and the fragility of the GeO2-P2O5 liquids.

Journal Article↗

Stress, strain, and NMR.

Experimental and ab initio results that demonstrate the effect of stress on the nuclear magnetic resonance spectra of materials are shown. The design of a cell that generates uniaxial compressive stress is presented, and results on gallium phosphide and lead nitrate single crystals that illustrate the observable results of the stress are shown. Tensors that relate stress and strain to changes in the chemical shielding tensors and the electric field gradient tensors are defined formally. The elements of these tensors are then computed by a density functional theory approach that makes use of planewaves and pseudopotentials. The experimental results are interpreted with the aid of the calculations. Extensions to spinning samples and to the interpretation of optical phenomena in materials are discussed.

Algorithms↗

Augmentation of post transplant immunity: antigen encounter at the time of hematopoietic stem cell transplantation enhances antigen-specific donor T-cell responses in the post transplant repertoire.

After transplant, the immune system is reconstituted by cells derived from both hematopoietic stem cells and peripheral expansion from differentiated donor T cells. After transplant, immune function is poor despite transplantation of mature lymphocytes from immune-competent donors. We tested the hypothesis that early antigen encounter at the time of cell transplant would improve the desired donor T-cell responses. Two independent models of peptide-specific T-cell responses were studied. The model for CD4 cells employed T cells from transgenic (Tg) DO11.11 mice that constitutively express the T-cell receptor for the class II-restricted ovalbumin peptide 323-339. The model for CD8 cells employed non-Tg H2-Db-restricted T-cell responses to the influenza nucleoprotein peptide 366-374. As measured both functionally and by direct imaging of T cells using clonotypic reagents, encounter with specific antigen at the time of T-cell transplantation led to clonal expansion of donor T cells and preservation of donor T-cell function in the post transplant immune environment. Antigen-specific donor T-cell function was poor if antigen encounter was delayed or omitted. Severe parent>F1 graft-versus-host reactions blocked the effect of early antigen exposure. Vaccination of transplant recipients against microbial or leukemia antigens may be worthy of study.

Animals↗

Comparative affinity of duloxetine and venlafaxine for serotonin and norepinephrine transporters in vitro and in vivo, human serotonin receptor subtypes, and other neuronal receptors.

The blockade of serotonin (5-HT) and norepinephrine (NE) transporters in vitro and in vivo by the dual 5-HT/NE reuptake inhibitors duloxetine and venlafaxine was compared. Duloxetine inhibited binding to the human NE and 5-HT transporters with K(i) values of 7.5 and 0.8 nM, respectively, and with a K(i) ratio of 9. Venlafaxine inhibited binding to the human NE and 5-HT transporters with K(i) values of 2480 and 82 nM, respectively, and with a K(i) ratio of 30. Duloxetine inhibited ex vivo binding to rat 5-HT transporters and NE transporters with ED(50) values of 0.03 and 0.7 mg/kg, respectively, whereas venlafaxine had ED(50) values of 2 and 54 mg/kg, respectively. The depletion of rat brain 5-HT by p-chloramphetamine and depletion of rat hypothalamic NE by 6-hydroxydopamine was blocked by duloxetine with ED(50) values of 2.3 and 12 mg/kg, respectively. Venlafaxine had ED(50) values of 5.9 and 94 mg/kg for blocking p-chloramphetamine- and 6-hydroxydopamine-induced monoamine depletion, respectively. Thus, duloxetine more potently blocks 5-HT and NE transporters in vitro and in vivo than venlafaxine.

Animals↗

Identification of a mutation cluster in mevalonate kinase deficiency, including a new mutation in a patient of Mennonite ancestry.

Mevalonate kinase (MKase) deficiency (MKD) is a rare autosomal recessive disorder in the pathway of cholesterol and nonsterol isoprenoid biosynthesis. Thus far, two disease-causing missense alleles have been identified, N301T and A334T. We report four additional mutations associated with MKD: L264F, T243I, L265P, and I268T, the last found in a patient of Mennonite ancestry. Electrophoretic analysis of bacterially expressed wild-type and mutant MKase indicated that I268T and T243I mutants produced normal or somewhat reduced amounts of MKase protein; conversely, L264F and L265P mutations resulted in considerably decreased, or absent, MKase protein. Immunoblot analysis of MKase from all patients suggested that the MKase polypeptide was grossly intact and produced in amounts comparable to control levels. Three mutations resulted in significantly diminished MKase enzyme activity (<2%), whereas the I268T allele yielded approximately 20% residual enzyme activity. Our results should allow more-accurate identification of carriers and indicate a mutation "cluster" within amino acids 240-270 of the mature MKase polypeptide.

Alleles↗

Eradication of a new focus of Amblyomma variegatum in Puerto Rico.

In May 1992 an infestation with the tropical bont tick appeared in a small dairy heifer replacement herd in Camuy, Puerto Rico, a completely new site located near Puerto Rico's northwest coast. This finding occurred after some three years of no infestation in either Puerto Rico or the U.S. Virgin Islands and is not suspected of being associated with any previous infestations. The methods used to eradicate this tick include spray treatment at a two-week interval of all domestic livestock, with amitraz at 0.025% and permethrin at 0.055%. Dogs and chickens are also inspected. Owners are encouraged to reduce numbers of these species. All livestock on adjoining farms are inspected and treated on a frequent basis. There has been no evidence of any spread and the infestation is expected to be eliminated within 18 months.

Animals↗

Effects of the caecal nematode Trichostrongylus tenuis on egg-laying by captive red grouse.

Captive hen red grouse infected with Trichostrongylus tenuis larvae started to lay later in spring and laid fewer eggs at a slower rate than uninfected hens. March-infected hen grouse showed greater effects than December-infected ones, probably because developing larvae were more pathogenic than adult worms. The mechanism by which parasites interfered with egg production involved reduction in food intake. Infected hens also gained less weight than controls before laying.

Analysis of Variance↗

The role of parasite fecundity and longevity in the success of Trichostrongylus tenuis in low density red grouse populations.

The prevalence of the caecal threadworm Trichostrongylus tenuis in red grouse in the north of Scotland was high despite low grouse densities. Prevalence, intensity and aggregation of threadworms was higher in old than in young grouse. Infections were long-lasting: populations of adult worms could survive for over 2 years in grouse, with little mortality. Parasite egg output decreased with the age of a worm population, largely as a result of a decrease in the fecundity of ageing female worms. Seasonal variations in worm fecundity were also evident. However, there was no evidence of an intensity-dependent decrease of worm fecundity with increasing worm numbers in either captive or wild grouse. The long life and high reproductive capacity of T. tenuis probably contribute to its effective transmission and high prevalence.

Animals↗

Factors affecting the establishment of the caecal threadworm Trichostrongylus tenuis in red grouse (Lagopus lagopus scoticus).

The resistance of captive reared red grouse to Trichostrongylus tenuis was measured as the proportion of ingested infective 3rd-stage larvae which failed to develop to adult worms. Individual grouse showed wide, repeatable variations in resistance. Seasonal variations may also have occurred. Red grouse acquired little or no effective immunity to reinfection after challenge with a single dose of infective larvae. In trickle-dosed grouse, however, adult worms weakly inhibited the establishment of incoming larvae in an intensity-dependent fashion. Despite this, the proportion of larvae established in trickle infections was similar to that in single-dose challenges.

Analysis of Variance↗

Development and survival of the free-living stages of Trichostrongylus tenuis, a caecal parasite of red grouse Lagopus lagopus scoticus.

In the laboratory, yields of infective 3rd-stage larvae of Trichostrongylus tenuis were determined by temperature when moisture was adequate. On the moor, eggs in caecal faeces did not develop to infective larvae during the winter. In summer, development did occur and yields of infective larvae were related to temperature: greatest yields were obtained when mean monthly soil surface temperatures ranged between 7.6 and 10.3 degrees C. Rainfall was unimportant, as was desiccation. During summer the mean monthly mortality of infective larvae was 44% but over winter survival was negligible.

Animals↗

Arrested development of Trichostrongylus tenuis as third stage larvae in red grouse.

Worms were counted in red grouse (Lagopus lagopus scoticus) in north east Scotland in March, April, August, September, November and December 1986. Immature worms occurred as third (L3) and fourth (L4) stage larvae throughout. Two kinds of evidence suggest that L3 larvae spent much of the winter in a state of arrested development. First, recently acquired L3 larvae could be distinguished by the fact that they retained outer L2 cuticles for a few days; these were present only in the August and September samples. Secondly, the mean proportion of larvae (L3 and L4) present as L3 was less than 15 per cent in August and September, but increased to 92 per cent by December and then decreased to 71 per cent by March and April. During March and April the proportion of L4 increased as overwintering L3 resumed their development.

Animals↗

Cysteamine induces cataracts in newborn rats.

Daily subcutaneous injections of cysteamine (CSH) administered to neonatal rats for 6 to 11 days cause dense bilateral cataracts that are evident at eye opening and that are permanent. CSH has been previously shown to induce protein cross-linking by the formation of abnormal disulfide bonds. It is hypothesized that the same mechanism underlies its cataractogenic effect; as such, CSH may be a useful agent in the study of models of senile cataract formation in humans.

Animals↗

Prostacyclin production by isolated rat adipocytes: evidence for cyclic adenosine 3',5'-monophosphate-dependent and independent mechanisms and for a selective effect of insulin.

The rat adipocyte contains two separate mechanisms for prostaglandin (PG) production. Norepinephrine stimulates prostacyclin (PGI2) and PGE2 production and triglyceride lipolysis in isolated rat adipocytes. In contrast, the vasoactive peptides angiotensin II, vasopressin, and bradykinin stimulate PGI2 production, but not PGE2 production or triglyceride lipolysis, in these cells. In this study, we characterized the two separate mechanisms of PG production with respect to the time course, the role of cAMP, the identity of the adrenergic receptor, and the effects of insulin and glucocorticoids. Angiotensin II stimulated PGI2 production rapidly (at 5 min) and independently of cAMP. beta-Adrenergic stimulation with isoproterenol produced a rapid 11-fold increase in the cAMP concentration and stimulated PGI2 production more slowly (at 120 min). The phosphodiesterase inhibitor 1-methyl-3-isobutylxanthine (0.2 and 0.5 mM) and the adenylate cyclase activator forskolin (10 microM) also stimulated cAMP production rapidly and PGI2 production more slowly. 1-Methyl-3-isobutylxanthine (5.0 mM) further stimulated cAMP levels, but prevented the increase in PGI2 production and blunted the increase in glycerol release seen at lower concentrations. beta-Adrenergic blockade with propranolol or timolol completely inhibited the norepinephrine- or isoproterenol-stimulated production of PGI2 and triglyceride lipolysis, respectively. Insulin selectively inhibited isoproterenol-stimulated PGI2 production and triglyceride lipolysis at physiological concentrations, but had no effect on angiotensin II-stimulated PGI2 production. In contrast, dexamethasone inhibited PGI2 production induced by both isoproterenol and angiotensin II. We conclude that: angiotensin II stimulates PGI2 production rapidly and independently of cAMP, but isoproterenol stimulates PGI2 production more slowly, an effect that is cAMP dependent; insulin inhibits the cAMP-dependent beta-adrenergic stimulation of PGI2 production (and triglyceride lipolysis), but not the cAMP-independent angiotensin II-induced stimulation of PGI2 production (this suggests that the former effect is mediated by a decrease in cAMP levels in the adipocyte); and dexamethasone inhibits both mechanisms of PGI2 production. Both mechanisms of PGI2 production by rat adipocytes are exquisitely sensitive to hormonal regulation.

1-Methyl-3-isobutylxanthine↗

Sucrose taste functions and dental caries in children.

Sweetness detection threshold, suprathreshold estimation, and preference were evaluated in caries-free and caries-susceptible children aged 7 to 15 years. The two caries groups appeared similar on all measures. This report contrasts with previous adult studies indicating a relationship between sweet taste sensitivity and caries status.

Adolescent↗

Localized ureteral fibrosis: an unrecognized complication of radiation therapy for prostatic carcinoma.

Complications of radiation therapy for prostatic carcinoma are frequent but usually minor. A patient is described in whom localized ureteral fibrosis developed following curative radiation therapy, which subsequently required a reconstructive operation. An analogous situation regarding patients with carcinoma of the cervix is examined and possible etiologies are discussed. This complication should be recognized so that proper management can be instituted.

Adenocarcinoma↗