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Biomedical subjects

K Rodgers

Publications and source records attributed to K Rodgers.

At least 37 records · Page 2Linked to original sources
PubMed1997

Effect of acute administration of malathion by oral and dermal routes on serum histamine levels.

Previous studies have shown that acute, oral administration of malathion increased the generation of a humoral immune response, stimulated macrophage function and caused mast cell degranulation and histamine release. In this study, the effect of acute administration of various doses of malathion via oral and dermal routes to mice and rats on serum levels of histamine was evaluated. Oral administration of malathion to mice led to an increase in the level of serum histamine 4 and 8 h after administration. At 4 h after administration, the peak in serum histamine levels was observed at a dose of 10 mg/kg malathion. At 8 h, a maximal effect was observed at a dose of 700 mg/kg and the response was more prolonged than at lower doses. At 12 and 24 h after administration, the level of histamine in the serum of treated mice was comparable to controls. A similar pattern was observed in rats. However, the time point at which histamine levels returned to control was 8 rather than 12 h. After application of malathion to the skin of mice or rats in dimethyl sulphoxide (DMSO), the level of histamine in the blood was also increased. As before, the peak increase was observed at 4 h after administration and the level had returned to control levels within 8 h (slight increase at 8 h in rats) after application. However, after dermal application the maximal levels of histamine in the serum were noted at the highest doses of malathion. The no effect levels for histamine in the blood after malathion administration to these two species by these two routes are as follows: (1) Mice, oral in corn oil, 0.1 mg/kg; (2) Rats, oral in corn oil, 0.1 mg/kg; (3) Mice, dermal in DMSO, 2 mg/kg; (4) Rats, dermal in DMSO--not determined (2 mg/kg low effect level).

Administration, Cutaneous↗
PubMed1997

Immunotoxicity of medical devices. Symposium overview.

Determination of the ability of a medical device to interact with the immune system currently involves assessment of the immunogenic potential and biocompatibility of the device or an extract of the device. However, implants are often in the body for extended periods of time and/or are placed by a surgical procedure that in and of itself will generate an acute inflammatory response. This symposium discussed studies that have been performed to evaluate the immunogenicity of various devices consisting of several different compositions (i.e., silicone, metals, and latex) in contact with different anatomical sites, the ability of a device to modulate an inflammatory response generated by a surgical procedure or trauma, and the response of the body to a material left in place for extended periods of time. This symposium brought together scientists from many different disciplines to begin to identify and fill in the gaps in this area.

Animals↗
PubMed1997

[Animal models used for the evaluation of anti-osteoarthritis drugs].

Naturally occurring osteoarthritis occurs in a variety of animal species including mice, guinea pigs, dogs and cynomolgus macaques and some of these animals have been used to evaluate the ability of anti-osteoarthritis drugs to reduce synovial inflammation and preserve cartilage integrity. However, the genetically determined animal models of osteoarthritis require the establishment of colonies which may take several years to develop and may be influenced by the strain of animal used and ill-defined environmental factors. On the other hand, the injection of irritants or enzymes into joints, or destabilization by surgical means, can rapidly and reproducibly lead to joint arthropathy and has therefore been more widely used. Although small animals, particularly rats and rabbits, have been the favoured target species, large animals such as dogs and sheep offer many advantages including the opportunity to undertake topographical analysis of joint cartilage and serial aspiration of synovial fluid. Meniscectomy is a common orthopaedic procedure which, in man and animals, is known to lead to osteoarthritis. In the past we have used this technique to induce osteoarthritis in pure bred dogs but more recently we have employed pure bred Merino sheep, which were matched for age, sex and weight. Using this ovine model we have been able to monitor the early and intermediate stages of cartilage metabolism, as well as identify key proteinases responsible for the loss of proteoglycans from these tissues in osteoarthritis. The effects of anti-osteoarthritis drugs on inflammatory mediators and cartilage metabolism has been successfully studied using the ovine model of osteoarthritis.

Animals↗
PubMed1996

Fluorescence in situ hybridization analysis of t(3; 12)(q26; p13): a recurring chromosomal abnormality involving the TEL gene (ETV6) in myelodysplastic syndromes.

We have identified a new recurrent reciprocal translocation between chromosome 3 and 12 with breakpoints at bands 3q26 and 12p13, t(3;12)(q26;p13) in the malignant cells from five patients with acute transformation of myelodysplastic syndrome or blast crisis of chronic myelogenous leukemia. t(3;12)(q26;p13) appears as a rare but nonrandom event present in various myeloid leukemia subtypes, which is frequently associated with dysplasia of megakaryocytes, multilineage involvement, short duration of any blastic phase, and a very poor prognosis. Here, we report the molecular cytogenetic analysis of the t(3;12). Fluorescence in situ hybridization results indicate that the 3q26 breakpoints are quite heterogeneous and occur 5' of MDS1, 3' of EVI1, or between MDS1 and EVI1. Our results are very similar to those observed in other 3q26 rearrangements in which breakpoints were shown to occur over considerable distances 5' and 3' of EVI1. Fluorescence in situ hybridization investigations proved that, in three myelodysplastic syndrome cases with t(3;12)(q26;p13), the 12p 13 breakpoint occurred within the TEL gene.

Adult↗
PubMed1996

Effects of malathion on humoral immunity and macrophage function in mast cell-deficient mice.

Malathion, when administered at noncholinergic doses, was previously shown to enhance the humoral immune response to a T-dependent antigen, sheep red blood cells (SRBC), and macrophage function. In addition, malathion was shown to cause mast cell degranulation. The hypothesis that mast cells contribute to the observed alterations in humoral immunity and macrophage function was determined by examination of the effects of acute administration of malathion to mast cell-deficient mice on macrophage function and the generation of a humoral immune response to SRBC. Initial studies in two strains of mast cell-deficient mice (6-7 weeks old) indicated that oral administration of malathion reduced macrophage function in these mice, but enhanced macrophage function in the wild-type strain. Because both strains reacted in a similar fashion and the defect in the WBB6F1-W/WV strain allowed reconstitution, further studies were conducted with this strain. Exposure of either wild-type mice or mast cell-deficient mice with reconstituted with bone marrow-derived mast cells (BMMC) from the wild-type mice to malathion enhanced macrophage function and the production of circulating IgM, but not IgG, antibodies to SRBC on Days 3 and 5 after immunization. In contrast, administration of malathion to older mast cell-deficient mice suppressed the generation of IgM and IgG antibodies to SRBC on Days 3 and 5 after immunization, but did not affect macrophage function. In summary, the results presented indicate that the presence of mast cells was necessary for the increases in macrophage function and humoral immunity observed after acute oral administration of malathion to mice.

Animals↗
PubMed1996

Contribution of mast cell mediators to alterations in macrophage function after malathion administration.

Previous studies showed that acute administration of noncholinergic doses of malathion increased macrophage function and the generation of a primary humoral immune response to a T-dependent antigen and caused mast cell degranulation. Recent studies using mast cell-deficient mice showed that the presence of mast cells was necessary for the increase in macrophage function observed after oral administration of malathion, and reconstitution with bone marrow-derived mast cells restored the ability of malathion to increase macrophage function. In the present study, the contribution of mast cell mediators to alterations in macrophage function after oral administration of malathion was examined. Controls in this study included the effect of the agent to be examined on resident peritoneal macrophages and macrophages elicited with pristane, an agent that can stimulate macrophages in the absence of mast cells. Coadministration of intraperitoneal cromolyn, a stabilizer of mast cell membranes, with oral malathion blocked the ability of malathion to increase macrophage function as measured by the generation of respiratory burst activity, the phagocytosis of opsonized yeast, and the production of cathepsin D. On the other hand, administration of cromolyn to mice whose macrophage function was stimulated with pristane did not affect the observed increases in macrophage function. As oral administration of malathion caused histamine release, the ability of a histamine receptor antagonist, pyrilamine, to alter the response of peritoneal macrophages to oral administration of malathion was also examined. Intraperitoneal administration of pyrilamine partially blocked the effects of oral administration of malathion on peritoneal macrophage function, but did not affect the function of resident or pristane-elicited peritoneal macrophages. These data suggest that mediators from mast cells contribute to the elevation in macrophage function observed after oral malathion administration.

Administration, Oral↗
PubMed1995

The immunotoxicity of pesticides in rodents.

Many pesticides that are widely used and have great potential for occupational and public exposure have received only a cursory examination with regards to their immunotoxic potential. Many of the studies that are available were done during the early period of immunotoxicology and many reports do not state whether or not any other toxic signs were observed and the dose-response relationships were not generally examined. Most studies were done in multiple species, through various routes of administration and using a variety of assays of immune function and do not allow a comparison. For the compounds extensively studied, the site of action has been determined at the cellular and perhaps the biochemical level, but the molecular site of action has not been determined. The approach to evaluate the mechanism of action will vary from compound to compound.

Animals↗
PubMed1994

The preparation and use of biotinylated trypsin in western blotting for the detection of trypsin inhibitory proteins.

Methods were developed for the preparation of biotinylated trypsin of high specific activity. This was used as a probe for the detection of serine proteinase inhibitory proteins which had been separated by sodium dodecyl sulfate-polyacrylamide gradient slab gel electrophoresis and electroblotted to nitrocellulose. The method was extremely sensitive and specific and could detect 0.15 ng of the serine proteinase inhibitor, trasylol (0.023 pmol active inhibitor). The method was also widely applicable and could be used to detect a range of serine proteinase inhibitors in human serum with molecular weights of 50 to approximately 180 kDa, soybean trypsin inhibitor variants, and secretory leukocyte proteinase inhibitor extracted from human intervertebral disc and articular cartilage. The identity of several of the serine proteinase inhibitors detected using biotinylated trypsin was verified by Western blotting using specific antibodies. Under the conditions used, electrotransfer of trasylol was quantitative; densitometric examination of blots indicated that there was a linear relationship between the amount of active trasylol electrophoresed (1-50 ng) and the intensity of the blot obtained with biotinylated trypsin as probe, indicating that serine proteinase inhibitory proteins may also be quantified by this technique using densitometric scanning.

Animals↗
PubMed1992

Mechanism of the modulation of murine peritoneal cell function and mast cell degranulation by low doses of malathion.

Malathion is a widely used organophosphate pesticide that modulates immune function at noncholinergic doses. Previous studies showed that this alteration in immune function was the result of enhanced macrophage function. In the present study, the effects of low doses of purified malathion (as low as 0.25 mg/kg malathion) administered orally to mice enhanced the respiratory burst of peritoneal cells. Microscopic examination of the peritoneal cells showed that mast cells were degranulated within 4 hr after malathion administration. The amount of beta-hexosaminidase, an enzyme released upon immunologic degranulation of mast cells, in the peritoneal lavage fluid of malathion-treated mice was also significantly elevated with 4 hours after malathion administration. Treatment of RBL-1, a rat basophilic cell line, cells with malathion, parathion or paroxon in vitro also led to the release of beta-hexosaminidase with paraoxon being the most potent. Further examination of the peritoneal cells of malathion-treated mice showed that the percentage of phagocytic peritoneal cells ingesting mast cell granules and the number of granules ingested per cell were elevated. These data suggest that malathion may enhance the respiratory burst of peritoneal cells through degranulation of peritoneal mast cells and the subsequent exposure to peritoneal cells to mast cell mediators.

Animals↗
PubMed1990

Dramatic electrocardiographic T-wave changes associated with gastric dilatation.

A case report is presented of a 54-year old female patient with a history of acute-onset sharp retrosternal chest pain. Clinical examination was unremarkable, but the 12-lead ECG showed anterior T-wave inversion and the chest x-ray film showed gaseous dilatation of the stomach. The patient's symptoms and electrocardiographic abnormalities resolved immediately after gastric decompression. Further investigations revealed no evidence of coronary artery disease. This case report documents marked T-wave changes and atypical chest pain with gastric dilatation. The possible causes of the ECG changes and chest pain are discussed.

Acute Disease↗
PubMed1988

Effects of tolmetin sodium dihydrate on normal and postsurgical peritoneal cell function.

Recent studies utilizing intraperitoneal (i.p.) administration of NSAIDs to rabbits after surgical injury to the parietal peritoneum demonstrated macrophage involvement. NSAIDs are known to inhibit the metabolism of arachidonic acid to prostaglandins, which in turn modulate a variety of macrophage functions. Studies presented here examine the effects of tolmetin administration on peritoneal resident and post-surgical leukocyte functions, such as phagocytosis, the release of superoxide anion and tumoricidal activity. Rats, either non-surgical or following peritoneal surgery, were injected i.p. with tolmetin. At various times after treatment, the rats were sacrificed and peritoneal cells collected by lavage. The phagocytic capability of peritoneal leukocytes was transiently decreased 5-7 days after the administration of tolmetin to normal animals. However, administration of tolmetin during surgery extended the length of time that phagocytic capability was enhanced. In non-surgical controls, there was an elevation in superoxide anion release and tumoricidal activity 24 h after tolmetin administration. Superoxide anion release was suppressed at days 5 and 7 after treatment, but returned to control levels by day 14. Intraoperative administration of tolmetin significantly elevated superoxide anion release at days 3 and 5, phagocytosis at days 7 and 14 and tumoricidal activity at day 3. These studies suggest that compounds which suppress prostaglandin synthesis can modulate the function of resident and post-surgical peritoneal cells.

Animals↗
PubMed1988

Determination of follicle regulatory protein levels in urine during the normal menstrual cycle using an enzyme-linked immunosorbant assay.

A protein from follicular fluid [referred to as follicle regulatory protein (FRP)] which inhibits aromatase activity in granulosa cells was recently isolated and partially characterized. The purified FRP was used to produce a monoclonal antibody which was used to develop an enzyme-linked immunosorbant assay suitable for quantitation of FRP in urine. Twelve normal premenopausal women underwent daily collection of blood and first morning urine samples, beginning on the 1st day of menses, as well as daily ultrasonographic evaluation of follicular diameter, beginning on the 10th day of the menstrual cycle, until the onset of the next menses. Serum estradiol, progesterone, LH, and FSH levels were determined by RIA. Urinary FRP levels increased in the midfollicular phase, reached their zenith in the midluteal phase [mean, 0.38 +/- 0.03 (+/- SE) immunoreactive units; 1 immunoreactive unit = approximately 1 ng FRP/mL.mg creatinine], and then declined to reach their nadir (not detectable) during the early follicular phase. Immunohistochemical evaluation of ovarian tissue demonstrated that anti-FRP localized to mural granulosa cells in viable follicles, to all follicular epithelial cells in atretic follicles, and to the large cells of the corpus luteum. These findings indicate that immunoreactive FRP levels in urine change during the menstrual cycle and suggest a relationship among FRP, follicular maturation, and corpus luteum formation.

Adult↗
PubMed1987

Pediatric maxillofacial trauma: unique features in diagnosis and treatment.

The purpose of this study was to review mechanisms, etiologies, associated injuries, and treatment of maxillofacial trauma in children and to compare them to similar adult injuries. Thirty blunt injuries (1984-1986) comprised the children's group, and 176 injuries, the adult group. Multiple associated injuries were more common in children, the most frequent being CNS and orthopedic injuries. Detailed anatomy of mandibular fractures required pleuridirectional tomography in 63% of the pediatric cases compared to 12% in adults. In the children's group, the mandibular fractures were favorable in 56% of cases compared to 15% in adults. Children required shorter periods of intermaxillary fixation with no child requiring reapplication of fixation. Based on these comparisons, a protocol for the management of pediatric maxillofacial injuries has been developed.

Accidents, Traffic↗
PubMed1986

Phosphorylation downregulates the DNA-binding activity of simian virus 40 T antigen.

Proteolytic fragments of simian virus 40 tumor (T) antigen and T antigen that was dephosphorylated with alkaline phosphatase bound between 1.5 to 2 times more origin-containing simian virus 40 DNA than did intact T antigen in DNA saturation experiments. Kinetic experiments showed that these treatments also enhanced the rate at which T antigen bound to the DNA. The enhanced binding of T-antigen fragments correlated with the generation of DNA-binding fragments that lacked the NH2-terminal region. Dephosphorylation of T antigen in vitro resulted in the removal of phosphate groups from the NH2-terminal region as well as from the COOH-terminal region. To test the effects of dephosphorylation on the size of the protein, immunoaffinity-purified T antigen was subjected to sedimentation with and without prior treatment with alkaline phosphatase. Most of the purified protein sedimented as a monomer and no significant effect was observed after dephosphorylation, indicating that the enhanced DNA-binding activity was probably not due to the uncovering of additional binding sites buried specifically in oligomerized T antigen. Taken together, these results indicate that in vivo phosphorylation of the NH2-terminal region (residues 106 to 124) decreases the binding of the protein to the DNA origin. The effect is reversed by in vitro dephosphorylation or by proteolysis which removes the highly phosphorylated NH2-terminal arm of the polypeptide. We suggest that phosphorylation inactivates one of two distinct DNA-binding activities on the polypeptide chain perhaps corresponding to two separate regions in T antigen.

Antigens, Viral, Tumor↗
PubMed1985

The interaction of zinc and cadmium in the synthesis of hepatic metallothionein in rats.

The interaction of injected zinc salts (Zn) and cadmium salts (Cd) with regard to the synthesis of metallothionein (MT) in adult rat liver was investigated. Male rats received an i.p. injection of Zn (20 mg/kg) or Cd (0.6 mg/kg) with or without pretreatment with Zn (20 mg/kg 16 h prior to the second injection). It was found that both metals, when administered singly, induced the synthesis of significant levels of hepatic MT, but that, when the Cd injection followed the Zn injection, synthesis of MT was not additive. When Zn pretreatment was followed by a second Zn injection, MT accumulation was additive (approx. 2-fold of that observed after a single Zn injection). Also, a highly significant positive correlation, (r = 0.97, P less than 0.01) was noted between hepatic Zn concentration and hepatic MT concentration, a relationship which was independent of the mode of MT induction. The results of the investigation indicate that: (1) in the presence of pre-existing hepatic Zn--MT, the ability of Cd to induce new MT synthesis is greatly reduced; rather, Cd is sequestered by the pre-existing MT; and (2) Zn may play a major role in the induction of MT synthesis both after Zn administration and after Cd administration.

Animals↗