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Biomedical subjects

D W Hunt

Publications and source records attributed to D W Hunt.

At least 55 records · Page 3Linked to original sources

Effect of porphyrins on the hematopoietic recovery of mice treated with gamma-radiation.

Porphyrins are a group of organic compounds involved in a wide spectrum of fundamental biological processes. Non-metallic, naturally occurring and synthetic porphyrin derivatives may produce cytotoxic effects in malignant or normal tissues exposed to visible light. Supra-clinical doses of the photosensitizing porphyrin, Photofrin are hematostimulatory when administered to normal and immunosuppressed inbred mice. To determine if a non-photosensitizing metalloporphyrin has similar hematostimulatory activity, we have synthesized iron (III) hematoporphyrin chloride (FeHp) and administered it to sub-lethally irradiated mice. FeHp (10 mg/kg) given 1 and 4 days or 1, 4 and 7 days following sub-lethal (7 Gy) whole body irradiation significantly increased spleen colony forming units of progenitor cells of the granulocyte-macrophage lineage (CFU-GM) 14 days post-irradiation, relative to irradiated controls. In addition, total splenocyte numbers were significantly increased 17 days post-irradiation in mice that had received FeHp 1 and 4 days post-irradiation. When FeHp was given 24 hours prior to irradiation and again 48 hours or 48 and 96 hours post-irradiation, significant increases in splenic CFU-GM and spleen cell numbers, relative to control mice, were observed 15 days post-irradiation. A non-metallic photosensitizing monomeric fraction of Photofrin, deuteroporphyrin IX, 2,4 (4,2) hydroxyethyl vinyl (HVD) was compared to Photofrin for its ability to influence the hematopoietic recovery of irradiated mice. Only Photofrin but not HVD given in 3 doses (10 mg/kg) 1, 4 and 7 days following irradiation (4.8 Gy) significantly enhanced the recovery of spleen cellularity and splenic CFU-GM. In addition, Photofrin significantly increased bone marrow CFU-GM 7 and 10 days following the sub-lethal dose of gamma-radiation. The mechanism by which certain porphyrins augment hematopoiesis in the mouse is unknown. However, the identification of FeHp as a non-photosensitizing monomeric porphyrin with hematostimulatory activity in vivo, indicates that further study of metalloporphyrins is warranted and may reveal their clinical potential within the context of therapeutically-induced immunosuppression.

Animals↗

Rail rescue. Putting the multiple injury plan to the test.

When an Amtrak train derailed in Boise, ID, last November, EMS providers implemented the Multiple Injury Plan. EMS recaps the disaster response, chronicling extrication/rescue efforts and patient assessment/management.

Community-Institutional Relations↗

Experimental arthritis and uveitis in rats associated with Mycobacterium butyricum.

OBJECTIVE: To determine if the anterior uveitis associated with adjuvant arthritis (AA) in the rat can be passively transferred with arthritis to syngeneic recipients using spleen cells or T cell lines prepared from animals given complete Freund's adjuvant (CFA) and Mycobacterium butyricum (M. butyricum) in incomplete Freund's adjuvant (IFA). METHODS: Spleen cells from Lewis or Lewis SsN rats given IFA, CFA, type I collagen in IFA (CI-IFA), or type II collagen in IFA (CII-IFA) were administered to naive rats or rats treated with pertussis toxin or bacterial endotoxin. Three CD4+ T cell lines, propagated from CFA injected rats and maintained in vitro with M. butyricum (M-1), bovine proteoglycan (PR-1) or an extract of M. butyricum (MBE-1) were administered to naive or immunosuppressed rats. The arthritogenic and uveitogenic properties of these cell preparations and intradermal MBE-IFA, CII-IFA and intraperitoneal (ip) M. butyricum without adjuvant were evaluated. RESULTS: Uveitis was observed in 15/69 (22%) arthritic rats given CFA. Spleen cells prepared from CFA injected rats caused arthritis in 55 (82%) and uveitis in 2 (3%) of 67 cell recipients. Uveitis occurred in 2/6 cell recipients pretreated with bacterial endotoxin. Neither uveitis nor arthritis was observed in rats given IFA (0/6) or spleen cells prepared from rats given IFA (0/27), CI-IFA (0/6), or CII-IFA (0/28). CII-IFA produced polyarthritis in 5/6 rats, but no uveitis. CII-IFA induced arthritis associated uveitis in 1/15 animals receiving spleen cells from rats given CII-IFA, but not those given CI-IFA (0/3) or IFA (0/13). Uveitis was observed in one recipient of the M-1 T cell line and in 2 recipients of the PR-1 T cell line. Immunization with 400 micrograms of MBE-IFA induced uveitis but not arthritis in 3/11 animals. The MBE specific T cell line was neither arthritogenic nor uveitogenic. A high frequency (5/6) of uveitis accompanied arthritis in male Lewis rats given ip M. butyricum. Arthritis occurred in 4/10 female Lewis rats given ip M. butyricum and 2 arthritic animals also developed uveitis. CONCLUSION: Uveitis occurs infrequently in arthritic rats given spleen cells from CFA injected animals. The ip administration of M. butyricum constitutes a novel disease model in which the immunopathological relationships between arthritis and uveitis may be more reliably studied.

Animals↗

Relationship between collagen-induced and adjuvant arthritis in the Lewis rat.

Adjuvant arthritis (AA) and type II collagen (CII)-induced arthritis (CIA) in the rat serve as models of chronic human arthritis. Adoptive transfer of AA was observed in 21 of 25 Lewis rats given concanavalin A (Con A)-treated spleen cells prepared from animals immunized with Mycobacterium butyricum in mineral oil (complete Freund's adjuvant, CFA). No arthritic changes were noted in rats given spleen cells obtained from donors that had received incomplete Freund's adjuvant (IFA, 0/22), type I collagen in IFA (CI-IFA, 0/6) or CII-IFA (0/28). Administration of spleen cells from IFA, CI-IFA or CII-IFA-injected animals did not modify the development of CIA when these rats were subsequently challenged with CII-IFA. However, partial protection against induction of AA was provided by the transfer of spleen cells prepared from rats immunized with CII-IFA (6/11) but not by those obtained from rats injected with IFA (1/15) or CI-IFA (0/3). Rats that did not develop clinically evident arthritis following the administration of spleen cells prepared from CFA-injected rats were also resistant to AA induction by CFA. Pre-treatment of rats with a synthetic peptide, corresponding to amino acids 180-188 of the Mycobacterium 65 kD heat shock protein (65 kD HSP), significantly delayed the onset of AA, but not that of CIA. Disease-specific resistance to AA, provided by spleen cells prepared from rats injected with CII-IFA and by pre-treatment with the 65 kD HSP 180-188 peptide, may result from the induction of protective tolerance to arthritogenic epitopes present in the Mycobacterium and CII preparations.

Amino Acid Sequence↗

Iris protein antibodies in serum of patients with juvenile rheumatoid arthritis and uveitis.

Homogenates of bovine iris were fractionated by gel filtration chromatography, and the column-eluted proteins were probed with pooled sera obtained from patients with pauciarticular juvenile rheumatoid arthritis (JRA). The serum pool prepared from patients with pauciarticular JRA and a history of anterior uveitis, but not from those without the eye disease, contained IgG antibodies which bound a low molecular weight iris antigen (LMW-IA) as measured by a modified ELISA. LMW-IA was protease-sensitive and contained at least four proteins of approximate molecular weights of 16, 13, 9 and 6.5 kD with no uronic acid or carbohydrate. Analysis of individual patient sera for IgG anti-LMW-IA antibody demonstrated that 1/20 (5%) pediatric non-rheumatic disease controls (NRDC), 1/19 (5.3%) non-uveitic pauciarticular JRA patients and 6/21 (28.6%) uveitic pauciarticular JRA patients were positive by ELISA. Levels of anti-LMW-IA antibody did not correlate with serum IgG concentration, the presence of IgG antibody to soluble retinal S antigen (S antigen) or reactivity to the low molecular weight fraction of bovine choroid (LMW-C). Ten of 21 (47.6%) children with pauciarticular JRA and uveitis had serum antibody that reacted with LMW-IA and/or retinal S antigen as compared to 1/20 (5%) NRDC patients and 3/19 (15.8%) patients with pauciarticular JRA uncomplicated by uveitis. Analysis of patient immunoreactivity to proteins of the anterior uveal tract may provide a greater understanding of pathogenic features related to arthritis-associated eye disease.

Arthritis, Juvenile↗

Secretory patterns of growth hormone and insulin-like growth factor-I during peripubertal period in intact and castrate male cattle.

Fifteen Angus bulls and 15 Angus steers 9 months of age and 275 kg of body weight were bled at 20-min intervals over a 6-hr period and serum GH and IGF-I concentrations were measured by RIA. There were no differences between bulls and steers in the mean GH concentration, pulse frequency and amplitude when analyzed by the computer program PULSAR. Mean IGF-I concentration was not different between the two sex phenotypes, nor was there a significant correlation between the integrated IGF-I and GH concentrations. Subsequently, five bulls and five steers were selected from the 30 animals, full-fed a diet for growth in individual pens for 3 months and bled at 15-min intervals over a 24-hr period. Bulls tended to show a greater weight gain and feed conversion efficiency (P less than .10) than steers during the 3-month period. Serum GH concentrations had a pulsatile pattern in all animals with no apparent diurnal rhythm during the 24-hr bleeding. Although mean GH concentration was not different between the two sex phenotypes, bulls tended to have lower baseline levels (P less than .10) and greater peak amplitudes than steers. Serum IGF-I concentrations fluctuated within a two-fold concentration range, with no obvious pulsatility similar to that of GH. Mean IGF-I concentrations of each of the 10 animals were correlated with mean peak GH amplitudes (r = .79), but not with mean GH. These results suggest that gonadal hormone(s) modulates the GH secretory pattern and increases IGF-I secretion which may be related to the greater growth rate of bulls compared with steers.

Age Factors↗

Use of trenbolone acetate and estradiol in intact and castrate male cattle: effects on growth, serum hormones, and carcass characteristics.

The effects of anabolic implant on growth, carcass characteristics, and serum hormones were examined in 30 young bulls and steers fed a growing diet then a finishing diet. In a 2 X 3 factorial arrangement, steers and bulls received an implant of trenbolone acetate (TBA), TBA and estradiol-17 beta (E2), or no implant. Blood samples were taken serially (every 20 min for 6 h) at intervals during the growing and finishing phases. Percentage of DM, fat, protein, and ash and Warner-Bratzler shear test were measured and taste panel evaluations of the 9-10-11 rib section were obtained. Treatment with TBA and E2 increased weight gain in steers but not in bulls. There were no differences in feed efficiency, serum growth hormone (GH), and cortisol concentrations between bulls and steers or between treated groups and controls in bulls or steers, although during the finishing phase mean GH concentrations in treated steers were twofold higher than in controls and were similar to those in the bull groups. Serum insulin-like growth factor-I (IGF-I) increased twofold during the growing phase, then remained at that level. Steers implanted with TBA and E2, which had the highest gains among the steer groups, had the highest serum GH and IGF-I. Longissimus steaks from bulls treated with TBA alone or TBA and E2 were comparable to steaks from steers in the shear test. Taste panelists found steaks from TBA- and E2-treated bulls to be similar in tenderness and connective tissue to steaks from steers.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗

Psoriatic arthritis in children.

A proposed definition of juvenile psoriatic arthritis (JPsA) was used to identify definite or probable JPsA in 35 children. Definite JPsA (24 patients) was defined as arthritis associated, but not necessarily coincident, with a typical psoriatic rash, or arthritis plus at least 3 of 4 minor criteria: dactylitis, nail pitting, psoriasis-like rash, or family history of psoriasis. Probable JPsA (11 patients) was defined as arthritis plus 2 of the minor criteria. In 33 of 35 patients, the onset of arthritis was pauciarticular, but the disease followed a polyarticular course in 23 of 35. Chronic anterior uveitis (6 of 35), antinuclear antibodies (22 of 35), anticollagen antibodies (10 of 35), HLA-DR4 (2 of 28), and HLA-DR8 (5 of 28) occurred with frequencies similar to those seen in patients with juvenile rheumatoid arthritis. JPsA may have more in common with juvenile rheumatoid arthritis than with the seronegative spondylarthropathies with which it is traditionally associated.

Adolescent↗

Immunity to ocular and collagen antigens in childhood arthritis and uveitis.

Humoral and cellular immunity to ocular antigens (S antigen and alpha, beta heavy, beta light, and gamma crystallins) and connective tissue antigens (type I, II, III, and IV collagens) were studied in children with juvenile rheumatoid arthritis (JRA) with or without uveitis and in controls. There was no association between the presence of uveitis and antibody to any collagen type or of lymphocyte transformation to type II collagen. Antibodies to all crystallins were more common in children with JRA than in controls, and antibodies to BH crystallins were more frequent in children with JRA and uveitis than in those with JRA alone. Such reactivity did not appear to represent antibody cross-reactive with collagen antigens. Lymphocyte proliferation to alpha crystallin was increased in JRA with or without uveitis, whereas lymphocyte response to S antigen was associated with the presence of uveitis.

Antigens↗

Toothpick foreign body in the foot. A case report.

A case report of a wooden toothpick as a foreign body in the foot was presented. Such lesions are visualized poorly, if at all, on standard radiographs, and localization of the foreign body may not be possible. Computed tomography, with its superior soft tissue imaging capabilities, can detect this otherwise radiolucent wood material and make accurate localization of the foreign body possible.

Aftercare↗

Uveitis and arthritis induced by adjuvant: clinical, immunologic and histologic characteristics.

The intradermal administration of complete Freund's adjuvant (CFA) containing Mycobacterium butyricum to Sprague-Dawley (SD) and Lewis strain rats results in polyarthritis and uveitis. Over 90% of the eyes examined from the SD rats given CFA had histologic evidence of anterior uveitis, clinically evident in only 20 to 28%. Many rats developed arthritis without clinical uveitis, but uveitis was rare in the absence of arthritis. Histologically, the ocular inflammation was characterized by a polymorphonuclear, and later, a lymphocytic infiltration of the iris and ciliary body with cells and fibrinous exudate in the anterior chamber and cells in the vitreous. Antibodies and cellular immunity to ocular (S antigen, alpha crystallin), articular (type II collagen, proteoglycan) and bacterial components (MDP), were demonstrated in some rats, but positive tests did not correlate with either articular or ocular disease. Ten percent of rats given type II collagen in incomplete Freund's adjuvant developed uveitis. Thus, the pathogenesis of the arthritis and uveitis in the adjuvant model may be mediated by lymphocytes which exhibit crossreactivity with antigens in these structures, although the specificity of such antigens has not been identified in our studies.

Animals↗

Immunity to soluble retinal antigen in patients with uveitis accompanying juvenile rheumatoid arthritis.

Studies of immunity to bovine soluble retinal antigen (antigen S) were carried out using serum and peripheral blood lymphocytes from children with juvenile rheumatoid arthritis and chronic anterior uveitis (JRA-uveitis), children with JRA alone, children with nonrheumatic diseases, and controls who had no ocular or rheumatic disease. Enzyme-linked immunosorbent assay and the lymphocyte transformation assay were used to determine immunity. Antibody to antigen S was present significantly more frequently in children with JRA-uveitis than in children with JRA alone, children with nonrheumatic disorders, or controls. These latter groups did not differ in positivity for this antibody. Lymphocyte transformation occurred more frequently in children with JRA-uveitis than in children with JRA alone or controls. Children with JRA alone and controls had similar frequencies of lymphocyte transformation positivity. Enzyme-linked immunosorbent assay positivity and lymphocyte transformation positivity tended to occur in different children. Children with JRA-uveitis who had HLA-B35 had the highest frequency of antibody to antigen S. Immunity to antigen S may be the result of ocular damage by mechanisms other than a pathogenic mechanism per se.

Adult↗

Antibodies to type IV collagen in rheumatic diseases.

Rheumatic disease sera were examined by a sensitive and specific enzyme linked immunosorbent assay (ELISA) for antibodies to native and to denatured type IV collagen from basement membranes of bovine anterior lens capsules or human placenta. The frequency of antitype IV collagen antibodies depended on the antigen and the disease studied. No controls had human type IV collagen antibodies and only 5.6% had antibody to bovine type IV collagen. Antibody to one or more of our 4 antigens was seen in 20% of children with juvenile rheumatoid arthritis (JRA), 35% of patients with mixed connective tissue disease (MCTD), 40% of those with juvenile dermatomyositis (DM), 52% of adults with rheumatoid arthritis (RA), 56% of patients with scleroderma and 60% of patients with systemic lupus erythematosus (SLE). Antibodies to native human type IV collagen were rare (0-10%) except in SLE (45%). Antibodies to denatured human type IV collagen were commoner in RA, scleroderma and SLE. Antibodies to native bovine type IV collagen occurred in 8-20% of patient sera, and to denatured antigen in 25-26% of scleroderma, MCTD and DM patients. Antibovine type IV collagen activity measured by ELISA could be absorbed from positive sera by preincubation of the sera with bovine type IV collagen but not bovine type I collagen or native human placental type IV collagen, indicating that the antibodies were specific for bovine type IV collagen.

Adult↗

Antibodies to native type I collagen in childhood rheumatic diseases.

The sera of 116 children with a variety of rheumatic diseases were assayed for the presence of antibodies to bovine native type I collagen by an enzyme-linked immunosorbent assay. For comparison, the sera of 69 children without rheumatic diseases, 50 healthy adult blood donors and 23 adults with rheumatoid arthritis (RA) were similarly assayed. Twenty-four % of the 90 children with juvenile rheumatoid arthritis (JRA) had antibodies to native type I collagen. Eleven of 26 (42%) with polyarticular onset, 5 of 53 (9%) with pauciarticular onset and 6 of 11 (55%) with systemic onset JRA had such antibodies. Seven of 10 children with spondyloarthropathies and 8 of 16 children with a variety of connective tissue diseases had antibodies to native type I collagen. Among children with nonrheumatic diseases, 12 of 69 (17%) were anticollagen antibody positive. Anticollagen antibodies were found in 4% of adult blood donors and 70% of adults with RA. Thus, antibodies to native type I collagen occur in a wide variety of childhood rheumatic diseases and their presence is not confined exclusively to rheumatic disorders.

Adolescent↗

Antibodies to native and denatured type II collagen in children with rheumatic diseases.

Sera of 153 children with rheumatic diseases were assayed by an enzyme-linked immunosorbent assay (ELISA) for the presence of antibodies to native (n) and to denatured (d) type II collagen (IIC). Among the study population, antibodies to nIIC were detected in 47% with juvenile rheumatoid arthritis (JRA), 21% with spondyloarthropathies, 37% with other rheumatic diseases, 70% with adult onset rheumatoid arthritis (RA), and in less than 1% of nonrheumatic disease control groups. Antibodies to dIIC were detected in 42% of children with JRA, 41% with spondyloarthropathies, 37% of children with other rheumatic diseases, 67% with adult onset RA, and in less than 6% of nonrheumatic disease control groups. These results indicate that, when compared to nonrheumatic disease control groups, antibodies to both nIIC and dIIC occur significantly more frequently in children with a variety of rheumatic diseases.

Adolescent↗

The binding of DNA to native type II collagen.

The demonstration that free DNA binds to collagen suggests that the local formation of collagen bound DNA-anti-DNA complexes might be important in the pathogenesis of some autoimmune disorders. We explored the interaction of single and double-stranded DNA (ssDNA and dsDNA) with native type II collagen. Each of 6 sera, known to contain antibodies to dsDNA and ssDNA, was employed in an enzyme linked immunosorbent assay as an antibody reagent for the detection of collagen bound DNA. Six sera without such antibodies served as controls. Our results indicate that significant binding of ssDNA (t = 3.22; p less than .005) and dsDNA (t = 3.06; p less than .01) to type II collagen occurs.

Animals↗