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Biomedical subjects

T Gleason

Publications and source records attributed to T Gleason.

10 recordsLinked to original sources

Evaluation of the efficacy of extrapolation population modeling to predict the dynamics of Americamysis bahia populations in the laboratory.

An age-classified projection matrix model has been developed to extrapolate the chronic (28-35 d) demographic responses of Americamysis bahia (formerly Mysidopsis bahia) to population-level response. This study was conducted to evaluate the efficacy of this model for predicting the population behavior of A. bahia held (for more than three generations) under controlled laboratory exposure conditions. The research involved the performance of a standard life-cycle test and a multigenerational (greater than three mysid generations, 55 d) assay using A. bahia to experimentally evaluate model predictions regarding population-level risks of chemical exposure. The organic compound para-nonylphenol was chosen as the chemical stressor in assays. This compound is a ubiquitous contaminant and suspected endocrine disruptor. Utilizing data obtained during the standard life-cycle test, aggregate estimates of population growth rate (lambda) and measured p-nonylphenol concentration were used to develop an exposure-response model of population-level effects. These estimates provided the basis of predictions for the long-term dynamics of mysid populations exposed to p-nonylphenol. The veracity of the mysid population model was evaluated through quantitative comparisons of model predictions based on the life-cycle test with dynamics of the experimental populations (multigenerational assay results). The results indicate that the population model was able to project within a few micrograms per liter the concentration where population-level effects would begin to occur (projected 16 micrograms/L from the model vs measured 19 micrograms/L from the multigenerational assay).

Aging↗

Biochemical, biophysical, and pharmacological characterization of bacterially expressed human agouti-related protein.

The agouti-related protein gene (Agrp) is a novel gene implicated in the control of feeding behavior. The hypothalamic expression of Agrp is regulated by leptin, and overexpression of Agrp in transgenic animals results in obesity and diabetes. By analogy with the known actions of agouti, these data suggest a role for the Agrp gene product in the regulation of melanocortin receptors expressed in the central nervous system. The availability of recombinant, highly purified protein is required to fully address this potential interaction. A nearly full-length form of AGRP (MKd5-AGRP) was expressed in the cytosolic or soluble fraction of Escherichia coli and appeared as large intermolecular disulfide-bonded aggregates. Following oxidation, refolding, and purification, this protein was soluble, and eluted as a single symmetric peak on RP-HPLC. Circular dichroism studies indicated that the purified protein contains primarily random coil and beta-sheet secondary structure. Sedimentation velocity studies at neutral pH demonstrated that MKd5-AGRP is monomeric at low micromolar concentrations. Mobility shifts observed using SDS-PAGE under reducing and nonreducing conditions for bacterially expressed and mammalian expressed AGRP were identical, an indication of a similar disulfide structure. The purification to homogeneity of a second, truncated form of AGRP (Md65-AGRP) which was expressed in the insoluble or inclusion body fraction is also described. Both forms act as competitive antagonists of alpha-melanocyte stimulating hormone (alpha-MSH) at melanocortin-3 (MC-3) and melanocortin-4 receptors (MC-4). The demonstration that AGRP is an endogenous antagonist with respect to these receptors is a unique mechanism within the central nervous system, and has important implications in the control of feeding.

Agouti Signaling Protein↗

Purification and activation of recombinant p38 isoforms alpha, beta, gamma, and delta.

p38 is a proline-directed serine/threonine kinase that is activated by inflammatory cytokines and cellular stress. At present, four isoforms of p38 have been identified and termed alpha, beta, gamma, and delta. We expressed each p38 homolog in Escherichia coli and purified the recombinant isoforms. p38alpha and C-terminal Flag-tagged p38beta were purified by Q-Sepharose fast flow, hydroxyapatite, and Q-Sepharose high-performance chromatography. His-tagged p38gamma was purified using Ni2+-NTA resin followed by Mono Q chromatography. Glutathione S-transferase-Flag p38delta was purified using M2 affinity agarose and gel-filtration chromatography. Upstream activators of p38, constitutively active (ca) MKK3 and MKK6, were also cloned, purified, and used to activate each p38 isoform. p38 alpha, gamma, and delta were phosphorylated by both MKK6 and caMKK3. p38beta was phosphorylated only by MKK6. Mass spectrometry analysis and kinase assays showed that MKK6 was the superior reagent for phosphorylating and activating all p38 isoforms.

Activating Transcription Factor 2↗

In vivo cytokine response to Escherichia coli alpha-hemolysin determined with genetically engineered hemolytic and nonhemolytic E. coli variants.

Alpha-hemolysin is an Escherichia coli exotoxin that enhances bacterial virulence, has profound effects on leukocytes in vitro, and induces the release of interleukin-1 (IL-1) but not tumor necrosis factor (TNF) from human monocytes in vitro. The purpose of this study was to examine alpha-hemolysin's influence on virulence and TNF and IL-1 production in vivo. Two genetically engineered, isogeneic strains of E. coli were used; one variant produces alpha-hemolysin, and the other does not. Male BALB/c mice were injected with either of the two variants and serum TNF and IL-1 were assayed. These results were compared with those obtained from the injection of either of two serotypes of lipopolysaccharide (LPS). The nonhemolytic E. coli strain produced no mortality and no significant elevation of serum TNF or IL-1 levels. In contrast, equal inocula of the hemolytic E. coli strain produced significant mortality and elevation of serum IL-1 levels. No significant elevation of TNF levels was detected in this group despite high-level mortality. A pattern of induction of mortality and elevation of serum IL-1 levels without elevation of serum TNF levels is distinct from the pattern typical of LPS. In these experiments, both serotypes of LPS caused elevations of TNF and IL-1 levels whether or not mortality was induced. Thus, alpha-hemolysin produces a cytokine response in vivo that is similar to that previously demonstrated in vitro by Bhakdi et al. (S. Bhakdi, M. Muhly, S. Korom, and G. Schmidt, J. Clin. Invest. 85:1746-1753, 1990) and appears to induce mortality independently of serum TNF.

Animals↗

Thermal balloon angioplasty in a canine model: preliminary results.

Preliminary results suggest that thermal balloon angioplasty (BA) may produce plaque welding, decreased elastic recoil, and increased luminal caliber. The authors report results of a simple method of thermal BA in a canine model. Seven mongrel dogs (15-25 kg) underwent conventional BA of each iliac artery with balloons that were 1-2 mm larger than the vessel lumen. The balloons were then perfused with a mixture of saline and contrast material at either 25 degrees C (control) or 100 degrees C for 1 minute. Compared with baseline measurements, thermal BA produced greater lumen enlargement (+16.7%) than control BA (+3.4%) immediately after the procedure (P less than .05). This trend persisted in vessels studied after a delay of 2, 4, or 12 weeks. Histologic sections from specimens studied after a delay demonstrated intimal hyperplasia in both the thermally treated and control arteries. Medial sclerosis was consistently seen in the thermally treated arteries. The authors conclude that thermal BA results in immediate and delayed increases in arterial diameter compared with conventional BA due to decreased elastic recoil and medial sclerosis.

Angioplasty, Balloon↗

Aneurysmal bone cyst of the thoracic spine: treatment by excision and segmental stabilization with Luque rods.

Preoperative radiological evaluation with magnetic resonance imaging and computed tomography was valuable in planning the surgical management of a destructive lesion of the posterior elements of the thoracic spine that was causing spinal cord compression in an 18-year-old woman. Preoperative recognition of bilateral involvement of the pedicles in addition to the laminae and spinous process led to use of prophylactic segmental stabilization of the spine with Luque rods after successful excision of an aneurysmal bone cyst. This case provides an example of the usefulness of computed tomographic scanning and magnetic resonance imaging in assessing the distribution and location of vertebral tumor and its potential effect on spinal stability. The efficacy of combining radical excision with stabilization for treatment of aneurysmal bone cysts of the spine is emphasized.

Adolescent↗

Tricuspid valve myxoma infected with dysgonic fermenter-2.

We have described a patient with an infected myxoma attached to the tricuspid valve. Unlike those previously reported, our patient had a significant underlying disease, chronic lymphocytic leukemia, and presented the problem of multiple pulmonary infiltrates in an immunosuppressed host, with persistently negative blood cultures. The infecting bacterium, isolated only at operation, was a recently described fastidious gram-negative rod belonging to the CDC group dysgonic fermenter-2.

Bacterial Infections↗

Tuberculosis of the duodenum.

At present, tuberculosis of the intestinal tract is rare in the United States. When gastrointestinal disease is seen, 85--90% of cases involve the ileocecal area. A case of tuberculosis of the duodenum unassociated with pulmonary disease is described. Although fiberoptic enndoscopy, abdominal ultrasonography and computerized axial tomography were used, the diagnosis required laprotomy with biopsy. The clinical manifestations, diagnostic investigations and treatment of the 49 previously reported cases of duodenal tuberculosis are also reviewed.

Adult↗

Quit rates at one year follow-up of Alaska Native Medical Center Tobacco Cessation Program.

The prevalence of tobacco use in the Alaska Native population is unusually high, as high as 50% in both adult men and women. In June of 1992, the Alaska Native Medical Center and the Alaska Area Native Health Service began a tobacco cessation program using behavioral modification classes and transdermal nicotine patches. Patients were subsequently followed at three month intervals for a year to assess smoking status. To date, 193 people have completed the program with at least three months having elapsed since completion of classes. The quit rates at three, six, nine, and twelve months were 31%, 30%, 24%, 21% respectively. The long-term quit rates for this tobacco cessation program are comparable to the rates of other studies which have included both behavioral modification and transdermal nicotine.

Administration, Cutaneous↗