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Biomedical subjects

T P Sullivan

Publications and source records attributed to T P Sullivan.

16 recordsLinked to original sources

Endogenous versus exogenous fatty acid availability affects lysosomal acidity and MHC class II expression.

Although the immune system, inflammation, and cellular metabolism are linked to diseases associated with dyslipidemias, the mechanism(s) remain unclear. To determine whether there is a mechanistic link between lipid availability and inflammation/immune activation, we evaluated macrophage cell lines incubated under conditions of altered exogenous and endogenous lipid availability. Limiting exogenous lipids results in decreased lysosomal acidity and decreased lysosomal enzymatic activity. Both lysosomal parameters are restored with the addition of oleoyl-CoA, suggesting that fatty acids play a role in the regulation of lysosomal function. Cell surface expression of major histocompatibility complex (MHC)-encoded molecules is also decreased in the absence of exogenous lipids. Additionally, we observe decreased gamma-interferon stimulation of cell surface MHC class II. Using cerulenin to limit the endogenous synthesis of fatty acids results in decreased cell surface expression of MHC class II but does not appear to alter lysosomal acidity, suggesting that lysosomal acidity is dependent on exogenous, but not endogenous, fatty acid availability. Testing these conclusions in an in vivo mouse model, we observed statistically significant, diet-dependent differences in lysosomal acidity and MHC class II cell surface expression. Collectively, these data demonstrate a mechanistic link between lipid availability and early events in the immune response.

Animals↗

Infliximab for hidradenitis suppurativa.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic disease characterized by significant morbidity. Current medical therapies are only minimally effective at treating the disease. Infliximab is a chimeric monoclonal antibody with high affinity for tumour necrosis factor (TNF)-alpha. TNF-alpha is known to induce proinflammatory cytokines and may play an important role in the therapy of a number of disparate inflammatory disorders. Infliximab has shown promise for the therapy of rheumatoid arthritis and psoriasis. OBJECTIVES: Retrospectively to evaluate the effectiveness of infliximab for the treatment of HS. METHODS: A retrospective chart review was performed for patients who received infliximab at the University of Miami Department of Dermatology. Patients were contacted and asked retrospectively to rate their disease activity immediately prior to and after therapy. RESULTS: Patients' self-reported disease activity scores were significantly decreased (P = 0.0001, paired t-test) following infliximab infusion. This correlated with physician-observed clinical improvement. CONCLUSIONS: Infliximab is a promising agent for the treatment of HS. These initial results suggest that infliximab is associated with objective and subjective improvement in HS. Further controlled studies of the efficacy of infliximab and its effect on the course of the disease are warranted.

Adult↗

Follow-up of conservatively managed epidural hematomas: implications for timing of repeat CT.

BACKGROUND AND PURPOSE: Small asymptomatic epidural hematomas (EDHs) are frequently managed nonoperatively with good neurologic outcome. Our goals were to determine the frequency and timing of enlargement of acute traumatic EDHs that are not immediately surgically evacuated as well as to identify factors associated with rehemorrhage. METHODS: Of 252 consecutive patients with acute traumatic EDH who were treated over a 5-year period, 160 were managed nonoperatively. Their CT scans, imaging reports, and medical records were reviewed retrospectively. Parameters analyzed as possible predictors of rehemorrhage during nonoperative management were size of the EDH, presence of an associated fracture, contralateral brain injury, midline shift, coagulopathy, and neurologic and physiological injury as measured by the Revised Trauma Score. We compared discharge discharge disposition as a proxy for neurologic condition at discharge. RESULTS: The EDH enlarged in 37 (23%) of the 160 patients during conservative management. Mean enlargement was 7 mm, and the mean time to enlargement was 8 hours after injury and 5.3 hours after CT diagnostics. EDH enlargement occurred within 36 hours after injury in all cases. Of the parameters analyzed, only a high Revised Trauma Score correlated significantly with EDH rehemorrhage, suggesting that intubation and chemical paralysis may prevent rehemorrhage through the restriction of head movement and the control of blood pressure. The subgroup of patients with rehemorrhage experienced no difference in neurologic outcome despite a higher rate of clinical deterioration. CONCLUSION: EDH enlargement occurs frequently, but early. Repeat imaging with CT is most appropriate within 36 hours after injury.

Acute Disease↗

Colchicine in dermatology.

Colchicine is a medication most often used to treat symptoms of gout. This drug has also been shown to have beneficial effects on cutaneous conditions, including leukocytoclastic vasculitis, psoriasis, and Sweet's syndrome. Colchicine inhibits the function of polymorphonuclear leukocytes, and dermatoses with a strong presence of these cells may benefit the most from the administration of this medication. A review of the pharmacology, mechanism of action, and adverse reactions of colchicine is also presented.

Colchicine↗

Case report 828: Plexiform neurofibroma of the tibial nerve invading the medial and lateral gastrocnemius muscles and plantaris muscle.

A 5-year-old boy presented with a several-year history of swelling of his calf and muscular weakness. MRI demonstrated abnormal signal and diffuse enlargement of the gastrocnemius muscle. Pathological examination revealed plexiform neurofibroma, and the diagnosis of neurofibromatosis was subsequently made. The manifestations of neurofibromatosis and the peripheral nerve sheath tumors encountered in this disease are discussed. Special attention is paid to the MR features of the plexiform neurofibroma which is characteristic of this disorder.

Child, Preschool↗

Cloning of the cDNA and gene for mouse mast cell protease 4. Demonstration of its late transcription in mast cell subclasses and analysis of its homology to subclass-specific neutral proteases of the mouse and rat.

Based on the amino-terminal amino acid sequence of the mature form of mouse mast cell protease 4 (MMCP-4), previously identified in peritoneal connective tissue mast cells (CTMC) and Kirsten sarcoma virus-immortalized mast cells (KiSV-MC), a 26-mer oligonucleotide probe was constructed and used to clone cDNAs for MMCP-4 from a KiSV-MC1 cDNA library. MMCP-4 is the first secretory granule serine protease of CTMC to be molecularly cloned. Using a cDNA probe derived from the 3'-untranslated portion of the MMCP-4 cDNA, the gene for MMCP-4 and a second highly related gene (mouse mast cell protease-like, MMCP-L) were cloned from a BALB/c mouse genomic DNA library and sequenced entirely, including approximately 2 kilobases of the 5'-flanking region. MMCP-4 and MMCP-L have five exons of identical length, four introns of nearly identical length, and approximately 900 base pairs of 5'-flanking DNA with sequence similarity by dot matrix analysis. By RNA blot analysis with gene-specific probes for MMCP-4 (bases 497-633 of the cDNA) and MMCP-L (bases 502-638 of the cDNA), mRNA for MMCP-4 was present in KiSV-MC5, CTMC, and the intestine of a mouse infected with the parasite Nippostrongylus brasiliensis markedly enriched for mucosal mast cells (MMC); MMCP-L mRNA was detected only in the intestine of the N. brasiliensis-infected mouse. MMCP-4 mRNA was not expressed in normal mouse intestine or in interleukin 3-dependent bone marrow-derived mast cells, which can serve as precursors to both MMC and CTMC. This finding suggests that MMCP-4 is transcribed relatively late in the development of both the CTMC and MMC subclasses and underscores the fact that mouse bone-marrow-derived mast cells are immature mast cells, rather than tissue culture equivalents of the MMC subclass.

Amino Acid Sequence↗

Cocaine abuse during pregnancy: peripartum prevalence and perinatal outcome.

The frequency of cocaine abuse during pregnancy has increased markedly in recent years. Cocaine abuse during pregnancy has been associated with significant perinatal morbidity and mortality. In this study a large population of pregnant women were tested for drug use at the time of their admission to the hospital for labor and delivery. During the study period a total of 138 (8%) of 1776 patients who were delivered of infants had positive urine toxicologic screening tests for cocaine. Moreover, the prevalence of peripartum cocaine abuse increased considerably during the study period. The perinatal outcomes of the 138 patients whose urine samples yielded positive test results for cocaine were compared with those of the 88 control patients with negative results. Cocaine use was associated with lower gestational age at delivery and higher incidences of preterm delivery, premature rupture of the membranes, and small-for-gestational-age infants. When compared with control infants, infants of mothers who used cocaine had more instances of neonatal morbidity and longer hospitalizations. In this study peripartum cocaine abuse was common, increased during the study period, and was associated with perinatal morbidity.

Abnormalities, Drug-Induced↗

Liposome-encapsulated hemoglobin as an artificial red blood cell: characterization and scale-up.

Encapsulation methods using high pressure extrusion and homogenization were developed which produce hemoglobin-containing liposomes, approximately one micron or less in diameter with an oxygen-carrying capacity of more than half that of red blood cells (RBCs). These methods were developed for scaling-up liposome-encapsulated hemoglobin (LEH) production. Previously, the lack of adequate scale-up methods has been a serious barrier to full scale efficacy and toxicity testing for all the researchers engaged in such investigations. The scale-up methods and characterization of the resulting LEH preparations are presented.

Blood Substitutes↗

Experimental studies of rainbow trout populations exposed to field applications of Roundup herbicide.

This paper reports the effects of Roundup herbicide (MON 02139) on rainbow trout viability and behavior in several field experiments at the University of British Columbia Research Forest. Laboratory and field 96-hr LC50 values were similar: 54.8 and 52.0 mg/L. Avoidance-preference data indicated that fish would avoid lethal levels of Roundup. Operational application of Roundup at the recommended field dose of (2.2 kg a.e./ha), as well as 10x and 100x field dose resulted in no mortality to rainbow trout in field streams. Results indicate that operational spraying with this herbicide for weed control should not be detrimental to rainbow trout populations. Improper use or accidental spills of Roundup could be avoided by rainbow trout and should not be lethal if diluted in a moderately-flowing stream.

Animals↗

The pig as a model for human wound healing.

The medical literature describes numerous in vitro and in vivo wound-healing models. The selection of an animal model depends on a number of factors including availability, cost, ease of handling, investigator familiarity, and anatomical/functional similarity to humans. Small mammals are frequently used for wound healing studies, however, these mammals differ from humans in a number of anatomical and physiological ways. Anatomically and physiologically, pig skin is more similar to human skin. The many similarities between man and pig would lead one to believe that the pig should make an excellent animal model for human wound healing. The purpose of this paper is to review the existing literature for evidence of this supposition and determine how well the various models correlate to human wound healing. Studies of wound dressings, topical antimicrobials, and growth factors are examined. Over 180 articles were utilized for this comparative review. Our conclusion is that the porcine model is an excellent tool for the evaluation of therapeutic agents destined for use in human wounds.

Animals↗

Modeling magnetic fields in residences: validation of the resicalc program.

RESICALC is a computer program that models magnetic fields due to currents on arbitrary arrays and configurations of electric transmission lines, primary and secondary distribution lines, and ground and neutral return pathways. The program conducts network analyses of ground/neutral currents in neighborhoods based on residential loads and impedances in the current path. Experiments were conducted at the Magnetic Field Research Facility (MFRF) in Lenox, Massachusetts to validate the program's field computation. MFRF has a simulated residential electric distribution system that permits the testing of scenarios with a broad range of electrical characteristics. The results demonstrate that the program accurately models fields from complex combinations of supply and ground/neutral currents, and shows how estimated fields may be sensitive to impedance values assigned to the ground and neutral currents. The program has usefulness as an exposure assessment tool when access to residences is not possible, and as a means to estimate fields when planning electrical facility or residential development. Careful mapping of power line and residential coordinates in the program, as well as acquiring the highest quality load and grounding data available, are critical for modeling valid exposure estimates.

Computer Simulation↗