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Biomedical subjects

D G Baker

Publications and source records attributed to D G Baker.

At least 37 records · Page 2Linked to original sources

Experimental infection of inbred mouse strains with Spironucleus muris.

Four inbred mouse strains: BALB/c ByJ, 129/J, C3H/HeJ, and DBA/lJ, differing in major histocompatibility type, were orally inoculated with 2 x 10(5) infectious cysts of Spironucleus muris. Fecal samples were collected for fecal cyst output prior to infection, and on days 2, 6, 7, 8, 9, 11, 13, 15, and 17 after infection. Following necropsy, formalin-fixed intestinal sections were examined for the presence of trophozoites. On post-inoculation days 6 and 8, mice of the 129/J strain shed significantly (p<0.05) fewer cysts than other strains. This pilot study suggests that major histocompatibility haplotype may influence susceptibility of inbred mouse strains to S. muris.

Animals↗

Natural pathogens of laboratory mice, rats, and rabbits and their effects on research.

Laboratory mice, rats, and rabbits may harbor a variety of viral, bacterial, parasitic, and fungal agents. Frequently, these organisms cause no overt signs of disease. However, many of the natural pathogens of these laboratory animals may alter host physiology, rendering the host unsuitable for many experimental uses. While the number and prevalence of these pathogens have declined considerably, many still turn up in laboratory animals and represent unwanted variables in research. Investigators using mice, rats, and rabbits in biomedical experimentation should be aware of the profound effects that many of these agents can have on research.

Animals↗

Interpersonal trauma and animal-related experiences in female and male military veterans: implications for program development.

Exposure to trauma is more frequent than was previously recognized. The prevalence and impact of trauma events, including trauma involving animals, was assessed in age-matched male and female veterans. High rates of exposure to at least one trauma event were reported by males (95%) and females (97%). Females were more likely to report sexual and physical abuse by a significant other. Both genders experienced higher trauma rates in the military than in civilian settings. A survey of animal-related experiences showed similar rates of losing a special pet, being frightened or hurt by an animal, witnessing or perpetrating violence toward animals, and having sexual interactions with animals. Almost one-third of the veterans showed evidence of post-traumatic stress disorder symptoms, highlighting the potential benefit of trauma screening to identify veterans in need of further evaluation and treatment.

Animals↗

Acute gouty arthritis is seasonal.

OBJECTIVE: Information regarding effect of weather conditions on gout is sparse. We conducted a study in the USA to examine whether gout is seasonal. METHODS: We reviewed synovial fluid (SF) analyses from our laboratory during 1990-1995 and identified 359 patients who had acute gouty attacks. All fluids of patients with acute gout had intracellular monosodium urate crystals and SF leukocyte counts > 2000/mm3 or more than 10 leukocytes per high power field (HPF). Retrospective chart review of all patients was performed to confirm a clinical picture of acute gout. A control group included 76 patients with acute pseudogout whose SF were analyzed during the same period and who had intracellular calcium pyrophosphate crystals and inflammatory leukocyte counts as in patients with gout. RESULTS: Acute gout was most common during the spring; n = 115 (32%). Ninety (25%) patients had acute gout attacks in the fall; 81 (23%) had acute attacks during the summer; 73 (20%) had acute attacks in the winter. One-way analysis of variance (ANOVA) was used to compare the overall frequency of acute gout during the months and seasons. Using ANOVA, there was no overall statistically significant difference in the incidence of gout per season (p = 0.07), although it approached statistical significance. Acute gouty attacks were more common in the spring compared with winter (p = 0.002) and summer (p = 0.015). There was a trend but no statistically significant difference compared with fall. Winter was the season in which the fewest acute gouty cases were seen, although it was not statistically significant. No seasonal difference was seen in the pseudogout group. There was no correlation between either mean monthly temperature or humidity and the incidence of acute gouty attacks. CONCLUSION: Acute gout attacks are significantly more common in the spring. No seasonal variation was seen in patients with acute pseudogout attacks.

Acute Disease↗

Relationship between posttraumatic stress disorder and self-reported physical symptoms in Persian Gulf War veterans.

BACKGROUND: While prior studies show that combat veterans with posttraumatic stress disorder (PTSD) report more physical symptoms than veterans without PTSD, the link between PTSD and somatic complaints in Persian Gulf War veterans (PGWVs) is yet to be evaluated. METHODS: A questionnaire booklet was completed by 188 PGWVs, of whom half were patients in a veterans health screening clinic and half were non-treatment-seeking volunteers on active duty. The booklet included the Combat Exposure Scale, the Mississippi Post-Traumatic Stress Disorder Scale (MPTSD), and a subjective symptom-based health questionnaire. RESULTS: The 24 PGWVs (12.8%) with PTSD (MPTSD score > or = 116) reported more combat exposure (P = .02) and a greater number of physical symptoms (P = .001) than other PGWVs. Fatigue, nausea, muscle aches, dizziness, back pain, stomach ache, and numbness were much more likely to be reported by those with PTSD (MPTSD score > or = 116) than by those without PTSD (MPTSD score < or = 95). CONCLUSIONS: Physicians examining PGWVs should be alert to the possibility of PTSD in this group and that those with PTSD are more likely to report physical symptoms that may overlap with those in Persian Gulf syndrome. Consequently, mental health screening is essential, since for those veterans with PTSD diagnosis of other coexisting conditions may be confounded and early effective treatment of their PTSD may be delayed. Also, given the increased reporting of certain symptoms by those with PTSD, those seeking the cause of Persian Gulf syndrome should control for PTSD when determining the symptom cluster that may constitute this condition.

Adult↗

A comparison of the inflammatory potential of particulates derived from two composite materials.

In order to develop total joint prostheses with moduli of elasticity close to bone while retaining excellent strength characteristics, composite materials are being developed. Composites consist of graphite fibers embedded in a polymer matrix. We studied the inflammatory potential of particulates derived from two composites with different matrix components, polysulfone (PFS) and polyetherketoneketone (PEKK), in the rat subcutaneous air pouch model. Neat components of the composites were studied separately in the air pouch. Particulates also were studied in culture using the macrophage cell line RAW 264.7, adherent synovial cells (ASC), and human polymorphonuclear neutrophils (PMNs). Particles derived from the PEKK-containing composite material consistently were less inflammatory than the PFS composite-derived particles, as measured by PMN infiltration, neutral metalloprotease activity, tumor necrosis factor (TNF) activity, and prostaglandin E2 (PGE2) accumulation. Results from the neat materials confirmed the findings in the composite-derived material. PEKK composite-derived material produced less TNF from macrophage cultures, but there were no significant differences noted in PGE2 production from ASC or in superoxide anion generation from PMNs. Particles from both PSF and PEKK produced minimal inflammatory responses in the rat subcutaneous air pouch. PEKK elicited a response virtually the same as the saline control and significantly less than that produced by particles of PSF.

Animals↗

Cerebrospinal fluid and plasma beta-endorphin in combat veterans with post-traumatic stress disorder.

Opioid-mediated analgesia develops in experimental animals following traumatic stress and increased opioid-mediated analgesia has been observed in combat veterans with post-traumatic stress disorder (PTSD). These observations have led to the hypothesis that increased central nervous system (CNS) opioidergic activity exists in patients with PTSD. However, direct CNS data on opioid peptide concentrations and dynamics in patients with PTSD are lacking. We withdrew cerebrospinal fluid (CSF) via a flexible, indwelling subarachnoid catheter over a 6-h period and determined hourly CSF concentrations of immunoreactive beta-endorphin (ir beta END) in 10 well-characterized combat veterans with PTSD and nine matched normal volunteers. Blood was simultaneously withdrawn to obtain plasma for ir beta END. PTSD symptom clusters, as measured by the CAPS, were correlated with neuroendocrine data. Mean CSF ir beta END was significantly greater in patients with PTSD compared with normals and there was a negative correlation between the ir beta END and PTSD intrusive and avoidant symptoms of PTSD. No intergroup difference between plasma ir beta END was found, nor was there a significant correlation between CSF and plasma ir beta END. Immunoreactive beta-lipotropin (ir beta LPH) and pro-opiomelanocortin (irPOMC), both precursors of beta END, were much more plentiful in human CSF than was beta-endorphin itself, as has been previously reported. It remains to be determined whether the increased CNS opioid concentrations predate traumatic stress, thereby conferring a vulnerability to dissociative states and PTSD itself, or result from the trauma. The negative correlation between CSF ir beta END and avoidant and intrusive symptoms suggests that CNS hypersecretion of opioids might constitute an adaptive response to traumatic experience. Poor correlation between CSF and plasma ir beta END limits use of plasma measures to assess CNS opioid activity.

Adrenocorticotropic Hormone↗

Monosodium urate, hydroxyapatite, and calcium pyrophosphate crystals induce tumor necrosis factor-alpha expression in a mononuclear cell line.

OBJECTIVE: Tumor necrosis factor-alpha (TNF-alpha) is thought to be important in chronic inflammation of joints characteristic of crystal induced arthritis. Monocytes are instrumental in maintaining that inflammation. We investigated production of mRNA and protein for TNF-alpha in vitro in a murine mononuclear cell line, after exposure to relevant crystal types. METHODS: Using the cell line designated RAW 264.7, cells were grown in standard medium and exposed to varying amounts of monosodium urate (MSU), hydroxyapatite (HA), and calcium pyrophosphate dihydrate (CPPD) crystals for differing time periods. Analysis of TNF-alpha mRNA induced by such exposure was by Northern hybridization; analysis of TNF-alpha protein was by ELISA: RESULTS: RNA analyses of cells treated with various levels of MSU, HA, and CPPD crystals showed strong induction of TNF-alpha transcripts. ELISA on culture supernatants confirmed high level TNF-alpha peptide secretion resulting from that transcriptional upregulation. Time course studies showed peak accumulation of TNF-alpha mRNA 1-6 h post-treatment. Study of the signalling pathway involved in TNF-alpha transcriptional upregulation indicated that increased phospholipase A2 activity was required. CONCLUSION: These observations suggest that crystals in joints can directly stimulate production of TNF-alpha, and that the source of that cytokine may be the monocytes known to be present and playing an important role in chronic joint disease.

Acetophenones↗

Uncoupling of serotonergic and noradrenergic systems in depression: preliminary evidence from continuous cerebrospinal fluid sampling.

We used the technique of continuous cerebrospinal fluid (CSF) sampling to test the following hypotheses regarding CNS monoaminergic systems in depression: (1) absolute concentrations of the informational substances tryptophan and 5-hydroxyindoleacetic acid (5-HIAA) are altered in the CNS of depressed patients (2) abnormal rhythms of tryptophan and/or 5-HIAA, or defective conversion of tryptophan to serotonin (5HT), exist in the CNS of depressed patients, and (3) the relationship between the CNS 5HT and norepinephrine (NE) systems is disrupted in depressed patients. We obtained 6-h concentration time series of tryptophan, 5-HIAA, NE, and 3-methoxy-4-hydroxyphenylglycol (MHPG) in the CSF of 10 patients with major depression and in 10 normal volunteers. No significant differences in CSF tryptophan, 5-HIAA, NE, or MHPG concentrations or rhythms were observed between normal volunteers and depressed patients. Neither were there differences in the mean tryptophan-to-serotonin ratio. However, a negative linear relationship was observed between mean concentrations of 5-HIAA and NE in the CSF of the normal volunteers (r = 0.916 [r2 = 0.839], df = 9, P < 0.001) while, in contrast, depressed patients showed no such relationship (r = +0.094 [r2 = 0.00877], df = 9, n.s.). Furthermore, the correlation coefficients expressing the relationship between CSF MHPG and CSF 5-HIAA within the normal and depressed groups were significantly different. These data support the hypothesis that a disturbance in the interaction between the serotonergic and noradrenergic systems can exist in depressive illness in the absence of any simple 5HT or NE deficit or surplus.

Adult↗

Serum IgE levels in dairy calves: evaluation of parasite and pasture exposure as possible determinants of IgE response.

Immunoglobulin E (IgE) has been regarded as an antibody isotype important in the host response to helminth infection and allergic conditions. Level of parasitic infection has been associated with serum total IgE level and the highest levels have been observed during the spring when environmental allergen levels are also high. Two groups of five parasite-native calves were maintained in a barn and one of the groups received an experimental gastrointestinal nematode infection. One group of five parasite-native calves was placed on clean pasture and another group of five was placed on a nematode-contaminated pasture. The contaminated pasture group acquired an acute gastrointestinal nematode infection, compared with a relatively low infection in the experimentally infected group. The only difference between the groups was a significant change (increase) in IgE level in calves on contaminated pasture, compared with the other three groups. This suggested that the infection acquired on pasture and not the experimental infection or environmental allergens encountered while grazing or in the barn stimulated an IgE response.

Allergens↗

In vivo inflammatory response to silicone elastomer particulate debris.

Silicone elastomer particles (Silastic silicone elastomer, Dow Corning, Midland, MI), polymethylmethacrylate particles, and monosodium urate particles smaller than 10 microns were injected into a rat subcutaneous air pouch lined with synovial membrane-like cells. Inflammatory exudate from the air pouch was retrieved at 6 hours, 24 hours, 48 hours, and 72 hours after injection. White blood cell count, tumor necrosis factor, and prostaglandin E2 were measured in the exudate. White blood cell and tumor necrosis factor levels in the exudate were the highest for the silicone group at 6 and 24 hours. Prostaglandin E2 was also significantly higher in the silicone group at 24 hours. We conclude that the acute inflammation is particle-type specific and that Silicone elastomer particles are acutely inflammatory.

Animals↗

Clinical assessment of the 1987 American College of Rheumatology criteria for rheumatoid arthritis.

The 1987 American College of Rheumatology (ACR) criteria for the classification of rheumatoid arthritis (RA) were clinically assessed. These criteria do not include findings of synovial fluid (SF) analysis and require no exclusion criteria. We have studied sequential patients with arthritis seen in four rheumatology centers in the Philadelphia area. Classifications by the ACR criteria were compared with our clinical diagnoses. Two hundred ninety eight patients were evaluated, 113 with RA and 185 with other diagnoses. Classifications as RA by the ACR criteria corresponded to our clinical diagnosis in 95% of the cases, corroborating the high sensitivity previously reported. However, we found a lower specificity (73%) than that reported (89%). False positive classifications as RA were found in 71% of patients with psoriatic arthritis, 48% of patients with SLE, and 31% of patients with gout. The specificity could be improved to 89% by excluding disorders with obvious distinguishing extraarticular features such as psoriasis or by SF findings of monosodium urate crystals. Awareness of these possible sources of confusion will further increase the teaching and epidemiologic value of these useful simplified criteria.

Adult↗