Search PubMedSearch

Biomedical subjects

J R Thomas

Publications and source records attributed to J R Thomas.

At least 19 recordsLinked to original sources

Refined structure of the lipophosphoglycan of Leishmania donovani.

The primary structure of the major surface glycoconjugate of Leishmania donovani parasites, a lipophosphoglycan, has been further characterized. The repeating PO4-6Galp beta 1-4Man disaccharide units, which are a salient feature of the molecule, are shown to terminate with one of several neutral structures, the most abundant of which is the branched trisaccharide Galp beta 1-4(Manp alpha 1-2)Man. The phosphosaccharide core of lipophosphoglycan, which links the disaccharide repeats to a lipid anchor, contains 2 phosphate residues. One of the core phosphates has previously been localized on O-6 of the galactosyl residue distal to the lipid anchor; the second phosphate is now shown to be on O-6 of the mannosyl residue distal to the anchor and to bear an alpha-linked glucopyranosyl residue. Also, the anomeric configuration of the unusual 3-substituted Galf residue in the phosphosaccharide core is established as beta. The complete structure of the core is thus PO4-6Galp alpha 1-6Galp alpha 1-3Galf beta 1-3[Glcp alpha 1-PO4-6]Manp alpha 1-3Manp alpha 1-4GlcN alpha 1-. This further clarification of the structure of lipophosphoglycan may prove beneficial in determining the structure-function relationships of this highly unusual glycoconjugate.

Animals

Purification and characterization of an extracellular phosphoglycan from Leishmania donovani.

An extracellular phosphoglycan (exPG), present in the culture medium of the promastigote form of Leishmania donovani, was purified and structurally characterized. The purification scheme included ethanol precipitation of the culture medium, anion exchange chromatography, hydrophobic chromatography on phenyl-Sepharose, and preparative polyacrylamide gel electrophoresis. Structural analysis by 1H-1H NMR, methylation linkage analysis, and glycosidase digestion revealed that the exPG consisted of the following structure: (CAP)----[PO4-6Galp beta 1-4Manp alpha 1]10-11-PO4-6Galp beta 1-4Man. The cap was found to be one of several small, neutral oligosaccharides, the most abundant of which was the trisaccharide Galp beta 1-4(Manp alpha 1-2)Man. The results indicated structural analogy to the cellular-derived lipophosphoglycan (LPG) from L. donovani. The important exceptions are a lack of the lipid anchor, the entire phosphosaccharide core, and several of the repeating disaccharide units. Although the function of exPG is presently unknown, it may play a protective role for the promastigote in the insect vector or during infection of a mammalian host.

Animals

Relative effects of intraoperative tissue expansion and undermining on wound closing tensions.

Intraoperative tissue expansion is advocated as a technique to facilitate closure of soft-tissue wounds with less tension than if they were closed primarily without expansion or, presumably, simple undermining. Few objective studies have been done, however, to validate the technique. We specifically questioned the relative effects of intraoperative tissue expansion and undermining on wound closing tensions in an animal model. Our data showed statistically significant reduction in the force required to close a wound after acute intraoperative tissue expansion when compared with baseline. However, when the degree of undermining achieved by the expander was matched in an equivalent defect, no difference in the resultant wound closing tensions could be discerned between techniques. This study should be viewed as an initial effort to understand the role of intraoperative tissue expansion in reconstructive surgery.

Animals

Tyrosine pretreatment alleviates suppression of schedule-controlled responding produced by corticotropin releasing factor (CRF) in rats.

Disruption of performance observed when animals are exposed to physical stressors which deplete brain catecholamines can be alleviated by pretreatment with the catecholamine precursor tyrosine. Central administration of the stress hormone corticotropin releasing factor (CRF) has been shown to affect a variety of behaviors and also to potently increase the release of central catecholamines. Since CRF-induced disruption of behavior may involve CRF-induced depletion of brain catecholamines, the present study examined whether tyrosine would alleviate suppression of schedule-controlled responding in rats resulting from ICV administration of CRF. Administration of CRF (1.0 microgram-10 micrograms) produced dose-dependent suppression of response rate and total number of earned reinforcers in rats responding on a multiple fixed-interval 60 s/fixed-ratio 20 schedule for food reinforcement. Pretreatment with 200 mg/kg tyrosine (IP) administered with ICV saline decreased response rate but did not lower total reinforcers, whereas 400 mg/kg of tyrosine decreased both. Injection of 400 mg/kg tyrosine reduced, but did not completely restore, CRF-induced suppression of behavior. The 200 mg/kg tyrosine dose was less effective in alleviating CRF-induced suppression of performance. These data indicate that pretreatment with the catecholamine precursor tyrosine can partially ameliorate performance decrements resulting from CRF administration.

Animals

Radioiodinated 2-hydroxy-3-(4-iodophenyl)-1-(4-phenylpiperidinyl)propane: potential radiotracer for mapping central cholinergic innervation in vitro.

Radioiodinated 2-hydroxy-3-(4-iodophenyl)-1-(4-phenylpiperidinyl)propane, 5 (4-HIPP), was synthesized and evaluated as a simple vesamicol-like radiotracer for mapping cholinergic pathways in the brain. Both enantiomers of 5 exhibit significant accumulation (approx. 2% of injected dose) and prolonged retention (t1/2 greater than 3 h) within the rat brain. The accumulation of radioiodinated 5 in the rat brain was reduced by up to 70% in the presence of vesamicol and its analogs. The levorotary isomer (-)-4-[123I]HIPP exhibits significant accumulation in the monkey brain, with a half-life of about 9 h. Radioiodinated 5 may therefore be a useful tool for studying cholinergic pathways in the brain.

Animals

Role of leukocyte CD11/CD18 complex in endotoxic and septic shock in rabbits.

Two models of sepsis were investigated using rabbits. In the first model, rabbits given lipopolysaccharide (LPS) were treated with saline (group II) or CD18 monoclonal antibody (MAb) 60.3 (group III). Group I animals received no LPS. Cardiac output was maintained by infusion of lactated Ringer solution with group II (95 +/- 68 ml/kg) requiring significantly more than group I (0 +/- 0 ml/kg) or group III (39 +/- 27 ml/kg). Lung permeability indexes in groups II (median 0.002, range 0.023) and III (median 0.0035, range 0.053) were not different but were significantly greater than group I (median 0.0007, range 0.001). In the second model, peritonitis was produced by devascularizing the appendix, leaving it in situ for 19 h, and then performing an appendectomy. Saline or MAb 60.3 treatment was at appendectomy and every 12 h for 3 days. Survival was significantly greater in the MAb 60.3-treated group at day 10 (90 vs. 40%). Lung permeability was increased at day 2 and was not different between groups. Day 1 fluid requirements were greater in the saline-treated group. These data are consistent with MAb 60.3 protection of systemic but not pulmonary circulation in two models of sepsis.

Animals

Scurvy in a nonalcoholic person in the United States.

Scurvy is rarely diagnosed in our society today. The authors describe the case of a 31-year-old man with weakness, gingival pain, and a rash over the lower extremities. He had a history of poor nutritional intake, no alcohol consumption, and a 13 pack-year history of cigarette smoking. Laboratory studies revealed an extremely deficient serum ascorbic acid level. Treatment was begun with oral ascorbic acid tablets and, within 3 days after discharge, all clinical symptoms of scurvy had resolved. Scurvy is an easily treated disease and should be considered when there is an appropriate history and classic clinical findings. Because vitamin C deficiency can be seen in many chronic disease states, it is important to recognize some of the early features and clinical manifestations of such nutritional deficiencies.

Adult

Structural characterization of a novel glycosyl-phosphatidylinositol from the protozoan Tetrahymena mimbres.

A glycolipid metabolically labelled with [14C]GlcN was isolated from the free-living protozoan Tetrahymena mimbres. The glycolipid was sensitive to a bacterial phosphatidylinositol-specific phospholipase C, and the headgroup was shown to contain a phosphorylated Man alpha 1-2Man alpha 1-4Man alpha 1-4GlcN glycan. The Tetrahymena glycolipid is structurally unique among the glycosylphosphatidylinositols that have so far been characterized, including those from several protozoan parasites of humans.

Animals

Rapid intraoperative tissue expansion for closure of facial defects.

Rapid intraoperative tissue expansion (RITE) has been shown to have definite applicability to reconstruction in the head and neck. However, widespread use of this modality has yet to be adopted by the otolaryngologic community. Believing that RITE might offer some advantages in the reconstruction of soft-tissue facial defects following Mohs micrographic surgery for cutaneous malignant neoplasms, we evaluated 30 consecutive patients referred for cosmetic reconstruction after Mohs micrographic surgery for the use of RITE. Eight patients were selected and underwent reconstruction using a total of 10 tissue expanders. Herein, we describe our experience with this initial series as well as some background and future applications of RITE.

Adult

Thermal stress modulates temporal patterns of responding on a multiple DRL-FR schedule.

To investigate temporal changes in behavior induced by moderate cold temperatures, rats performing on a multiple differential-reinforcement-of-low-rate (DRL) fixed-ratio (FR) schedule were exposed to ambient temperatures of 2, 8, 16, and 24 degrees C. DRL response rates markedly increased with decreasing cold temperatures, while FR response rates remained unchanged. In addition, as ambient temperatures decreased, the interresponse time (IRT) distribution of DRL responses shifted toward shorter times and short IRT bursts increased. Compared with cold effects, exposure to 38 degrees C heat induced decreases in both DRL and FR response rates which were associated with increases in long IRTs. Decreases in reinforcement frequency was associated only with the DRL schedule in cold, and with both DRL and FR schedules during heat exposures. The distinct effects of cold and heat on both DRL and FR responding suggest that the increases in DRL response rates and shifts in IRT distribution are unique to cold, and are not due to general effects of nonspecific thermal change in the ambient environment.

Animals

Hippocampal and body temperature changes in rats during delayed matching-to-sample performance in a cold environment.

In order to study the effects of temperature changes induced by cold stress on working memory, telemetry thermistor probes were implanted into the hippocampal region of the brain and into the peritoneal cavity of rats. Temperatures in these regions were monitored while rats performed on a delayed matching-to-sample (DMTS) task at ambient temperatures of 23 degrees C and 2 degrees C. Matching accuracy was significantly decreased during exposure to 2 degrees C, indicating a marked impairment of short-term or working memory. Temperature in the hippocampus increased 2 degrees C during exposure to 23 degrees C, but only 1 degrees C when the environmental temperature was 2 degrees C. Body temperature showed a similar but less pronounced pattern in that cold exposure attenuated the increase in temperature observed when animals performed the DMTS task. These results suggest that cold-induced impairment of working memory may be associated with subtle temperature changes in the brain.

Animals

Neuropeptide-Y both improves and impairs delayed matching-to-sample performance in rats.

Neuropeptide-Y (NPY) was administered intracerebroventricularly to rats performing on delayed matching-to-sample (DMTS) to determine if NPY modulates short-term (working) memory. Rats administered saline demonstrated a characteristic DMTS delay gradient in which accuracy decreased as the delay interval between sample and comparison stimuli increased from 2 to 8 to 16 seconds. At 8- and 16-second delays, low doses of NPY (0.25 and 0.5 nmol/kg) increased matching accuracy. As doses increased from 1 to 16 nmol/kg, accuracy decreased in a dose- and delay-dependent manner. NPY effects were specific to working memory, since NPY did not affect accuracy of responses to the sample stimulus (reference memory). At higher doses, a greater decline in accuracy occurred when the correct stimulus was on the opposite side from the response on the previous trial compared to accuracy when the previous response was on the same side. These data show NPY may both improve and impair accuracy on DMTS and that some portion of impairment is due to proactive interference resulting from previous trials.

Animals

Cold-induced impairment of delayed matching in rats.

Exposure to moderate, nonhypothermic cold temperature has been reported to affect a variety of behavioral and neural functions. To elucidate the effects of mild cold stress on short-term (working) memory, Long-Evans rats were exposed to an ambient temperature of either 2 degrees or 23 degrees C while performing a delayed matching task. At the beginning of each trial, rats were required to respond on one of two levers cued by a light. Following a delay of 2, 8, or 16 s, a response on the lever previously cued produced food reinforcement. Relative to performance at 23 degrees C, exposure to 2 degrees C occasioned no change in matching accuracy at the 2-s delay, a modest decrement at the 8-s delay, and a larger decrement at the 16-s delay. The cold exposure did not decrease colonic temperature. In addition to accuracy decrements, matching response times were consistently shorter during cold exposures. Cold-induced impairments were absent during removal of the memory component from the task, indicating the observed cold effects on memory were not due to impaired attentional, sensory, or motor processes. These data suggest that mild cold stress may impair active maintenance of information in working memory but not processes related to reference memory.

Animals