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Biomedical subjects

R A Campbell

Publications and source records attributed to R A Campbell.

At least 19 recordsLinked to original sources
PubMed1992

The action of chelating agents in experimental uranium intoxication in mice: variations with structure and time of administration.

The determination of the relative abilities of 11 chelating agents to enhance the urinary and fecal excretion of uranium when administered 10 min after uranyl acetate dihydrate (UAD) in mice showed that the most effective of these were Tiron, desferrioxamine, and 1,2-dimethyl-3-hydroxypyrid-4-one. An increase in the interval between UAD administration and that of the chelating agent drastically reduces the net mobilization of the uranium by the chelating agents examined. When given shortly after UAD, Tiron produced the greatest reduction in renal and bone levels of uranium. None of the chelating agents were able to affect the bone levels of uranium when administered 24 hr or more after the administration of the UAD.

Animals↗
PubMed1992

Cognitive patterns in school-age children with end-stage liver disease.

Although children with end-stage liver disease (ESLD) have been found to have cognitive delays, the relationship between patterns of cognitive function and diagnostic category, age of onset, duration and severity of disease has not been assessed before transplantation. Verbal and performance IQ (VIQ, PIQ) scores and scores on Bannatyne's cognitive factors for 43 children with ESLD were compared with those of 15 control children with cystic fibrosis (CF) and with existing normative data. Children with biliary atresia had deficits in PIQ, spatial and sequential scores. Children with alpha-1 antitrypsin deficiency did not differ significantly from CF controls but did show deficits compared with normative data. Children with onset of disease in the first year of life had deficits on all cognitive measures compared with both control groups. In contrast, children with later onset differed from the normative population only on VIQ and the acquired knowledge factor. In multiple regression analyses, duration of disease and indexes of liver dysfunction combine to predict cognitive scores. These preliminary findings suggest that children with early onset of liver disease are at high risk for cognitive impairment.

Biliary Atresia↗
PubMed1991

Synthesis of peptide analogues using the multipin peptide synthesis method.

Modification of the multipin peptide synthesis method which allows the simultaneous synthesis of large numbers of different peptide analogues is described. Peptides were assembled on polyethylene pins derivatized with a 4-(beta-alanyloxymethyl)benzoate (beta-Ala-HMB) handle. For comparative purposes, peptides were also assembled on the diketopiperazine-forming handle N epsilon-(beta-alanyl)lysylprolyloxylactate. In model studies it was demonstrated that beta-Ala-HMB-linked peptides were cleaved from polyethylene pins with dilute sodium hydroxide or 4% methylamine/water to yield analogues with beta-Ala-free acid (beta-Ala-CO2H) and beta-Ala-methylamide (beta-Ala-CONHCH3), respectively. To assess the suitability of this approach for T-cell determinant analysis, analogues of a known T-cell determinant were synthesized with the various C-terminal endings. Peptides were characterized by amino acid analysis and fast atom bombardment-mass spectrometry. HPLC of the crude cleaved peptides indicated that 22 of the 24 peptides were greater than 95% pure. These crude peptide solutions were nontoxic in sensitive cell culture assays without further purification. All three cleavage procedures gave comparable activities in T-cell proliferation assays. These results demonstrate the potential of the multipin peptide synthesis method for the production of large numbers of different peptide analogues.

Amino Acid Sequence↗
PubMed1991

Effects of DL-alpha-difluoromethylornithine, 4-deoxypyridoxine and methylglyoxal bis(guanylhydrazone) on allograft prolongation.

DL-alpha-difluoromethylornithine (DFMO), 4-deoxypyridoxine (4-DOP), and methylglyoxal bis (guanylhydrazone) (MGBG) were tested as inhibitors of acute skin graft rejection. Proximal full thickness tail skins were exchanged between C57BL/6 and Balb/C mice. Distal autografts were placed to monitor healing. Inhibitors were given singly or in combination, either orally or by injection, in various schedules to 10 groups of mice. Compared to controls, singly treated mice had significant mean prolongation of allografts ranging from 126% to 141%. Likewise, DFMO plus MGBG extended mean time of complete rejection ranging from 172% to 206%. Autografts remained intact. Some grafts persisted after discontinued immunosuppression. Complete rejection was preceded by a decline in vascularity of the graft bed and/or gradual replacement by host tissue. Graft protection in such stringent circumstances i.e., the use of skin in strains with complete histoincompatibility at the H-2 MHC loci, clearly indicate the anti-rejection effects of polyamine synthesis inhibitors. Moreover, primary and secondary effects of DFMO establish the critical role of polyamine pathway activation in acute rejection. In doses and schedules used, toxicity was encountered when DFMO and 4-DOP were used in combination and when increased amounts of MGBG were administered.

Animals↗
PubMed1991

Comparative iron mobilizing actions of deferoxamine, 1,2-dimethyl-3-hydroxypyrid-4-one, and pyridoxal isonicotinoyl hydrazone in iron hydroxamate-loaded mice.

A comparison was made of the actions of deferoxamine (DFX), 1,2-dimethyl-3-hydroxypyrid-4-one (L1), and pyridoxal isonicotinoyl hydrazone (PINH) in mobilizing and promoting excretion of iron in mice loaded with iron-acetohydroxamic acid complex. DFX was given ip, while L1 and PINH were given po. Each was given daily for four days at 300 mg/kg/day, and total excreta were collected 24 hr after each administration. Total iron excreted over the 4-day period, expressed as micrograms/mouse, were: Controls, 26; PINH-treated, 31; DFX-treated, 162; and L1-treated, 208. Measurements of iron in selected organs 96 hr after the last administration of each compound revealed that treatment with L1 and DFX induced significant reductions of iron concentrations in kidneys (16% and 17%, respectively) and in pancreas (18% and 19%, respectively). In addition, L1 treatment led to a significant reduction in the liver iron burden (11%), an action not seen after treatment with DFX. None of the compounds reduced iron concentrations in heart, the most critical organ for toxicity of transfusional siderosis. The synthetic routes for preparation of L1 and PINH are described in detail.

Animals↗
PubMed1990

Deep water parasites.

Few geographically local comprehensive studies on deep-sea parasites have been done. A recent study of parasitism in midwater fishes conflicts with broad generalizations previously advanced. Surveys of demersal fishes and macrofaunal invertebrates in the North Atlantic indicate 1) there is little evidence of coherence and continuity of faunal zones around the ocean basin and 2) that the community concept should be abandoned because faunal assemblages only persist on a local scale. Parasitological evidence supports this view. The implications are that the parasite species distributions and character of parasite faunas will vary according to the distribution of the fishes and local faunal assemblages.

Animals↗
PubMed1990

Large histiocytes in the choroid of leukemic patients.

We identified large histiocytes as a prominent feature in the choroid of eyes obtained at autopsy in seven of nine patients who died of leukemia. The eyes of four of the seven patients affected had leukemic choroidal infiltrates, and a majority had similar-appearing histiocytes identified in spleen or bone marrow. The significance of these cells is undetermined; we postulate that these macrophages are ingesting debris of degenerating leukemic cells.

Choroid↗
PubMed1987

Polyamines and uremia.

PAs are intracellular regulators of growth and anabolic processes. Toxic properties of PAs are conferred according to the increasing number of cationic charges. In uremia, PA accumulation occurs both in and outside the cell. Decreased PA synthesis and blunted PA pathway responses suggest PAs may participate in cellular down regulation. This would explain the lack of tissue responses to elevated plasma hormones, a feature of uremia. Such homeostatic control could prevent life-threatening PA toxicity due to an imbalance between production, degradation and excretion. The concurrent rise in plasma PA oxidative activity, while adversely influencing behavior of lymphocytes and neutrophils reduces the likelihood of direct PA toxicity. In addition, preliminary observation of increased glomerular size and capillary area of intact kidneys in PA treated mice suggest there could be a PA dependent adaptive enhancement of renal excretion in circumstances of decreased renal mass due to disease, thus, compensatory renal hypertrophy. It is important to further inspect the non-uremic chronic hyperpolyaminemias as they occur in man. The continued search for parallel adverse systemic and local effects will be useful in strengthening the base for understanding homeostatic consequences of PA accumulation unobserved by the complex mixture of uremic metabolites. In conclusion, we have examined some known regulatory and toxic properties of PAs and related these to features of the uremic syndrome. Available information on the various ramifications of PA dysmetabolism in uremia, as with other suspect toxins, is in part circumscribed and indirect. Caution is to be exercised in evaluating the new and provisional PA related cause and effect relationships suggested here.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Acute, pharmacokinetic, and subchronic toxicological studies of 2,4-dichlorophenoxyacetic acid.

The single-dose oral LD50 values in Fischer 344 rats for technical-grade, 2,4-dichlorophenoxyacetic acid (2,4-D), esters, and salts ranged from 553 mg/kg (isobutyl ester in females) to 1090 mg/kg (dimethylamine salt in males). The LD50 values for the acid, esters, or salts, when expressed as acid equivalents, were consistent which suggests that the acute toxicity was due to 2,4-D per se. Acute dermal LD50 values in rabbits for the acid, esters, and salts were greater than 2000 mg/kg. Overall, these results indicate that the acute oral and dermal toxicity of 2,4-D are low. Pharmacokinetics were evaluated in male Fischer 344 rats given single oral doses of 10, 25, 50, 100, or 150 mg 2,4-[14C]D/kg. The amount of 2,4-D in the plasma, kidney, and urine 6 hr postdosing indicated that the urinary elimination of 2,4-D was saturated in male rats given oral doses in excess of 50 mg/kg. Subchronic dietary studies in male and female Fischer 344 rats used dose levels of 0, 15, 60, 100, or 150 mg/kg/day of purified or technical-grade 2,4-D acid for 13 weeks. Body weight gains were decreased for both sexes at the higher dose levels of purified and technical-grade 2,4-D acid. Kidney weights were increased in all treated male rats and in females given the higher three dose levels of purified 2,4-D. Treatment-related cytoplasmic alterations were present in the renal proximal tubules of most rats given 60 mg/kg/day and higher of purified or technical-grade 2,4-D; a few females given 15 mg/kg/day also had slight alterations in the cytoplasm of the proximal tubules. A dose-related degenerative change was identified in the descending proximal renal tubules of all male rats given the highest three dose levels of either test material and some given 15 mg/kg/day. Dose levels of 100 or 150 mg/kg/day of either compound for both sexes produced minimal swelling and increased staining homogeneity in the liver cells and were associated with a slight elevation of liver weight and serum glutamic pyruvic transaminase activity. Higher dose levels of technical-grade and purified 2,4-D decreased total serum tetraiodothyronine levels in female rats, however, the morphology of the thyroid gland was normal. The no-observed-effect level (NOEL) was less than 15 mg/kg/day for both purified and technical-grade 2,4-D acid.

2,4-Dichlorophenoxyacetic Acid↗
PubMed1987

Dietary toxicity of picloram herbicide in rats.

The toxicity of orally administered technical-grade picloram was evaluated in male and female Fischer 344 rats. Dietary dose levels were up to 2000 mg/kg body weight (bw) X d for 2 wk, 500 mg/kg bw X d for 13 wk, or 200 mg/kg bw X d for 12 mo. Routine indices of toxicity were evaluated at all of the respective time periods. Body weight, food consumption, clinical chemistries, urinalyses, and hematological determinations were considered unaffected by treatment. The only treatment-related effect, regardless of the duration of exposure, was in the liver of both male and female rats. This was generally manifested as an increase in the liver-to-body weight ratio and slight hypertrophy and pallor of the centrilobular hepatocytes. These effects were consistently present in rats receiving 1000 mg/kg bw X d for 2 wk, 300 mg/kg bw X d for 13 wk, or 200 mg/kg bw X d for 6 or 12 mo. Similar effects were marginally evident for rats receiving 500 mg/kg bw X d for 2 wk, 150 mg/kg bw X d for 13 wk, or 60 mg/kg bw X d for 6 or 12 mo. At 60 mg/kg bw X d, the effects were not progressive from 6 to 12 mo. The no-observable-effect level (NOEL) was 20 mg/kg bw X d for male and female rats fed picloram for 12 mo.

Administration, Oral↗
PubMed1986

Chronic toxicity and oncogenicity study on acrylamide incorporated in the drinking water of Fischer 344 rats.

Male and female Fischer 344 rats were maintained on treated drinking water providing dosages of 0 (controls), 0.01, 0.1, 0.5, or 2.0 mg acrylamide/kg body wt/day for 2 years to assess the chronic toxicity and oncogenic potential of the chemical. The mean body weights of male and female rats receiving 2.0 mg/kg/day and of male rats receiving 0.5 mg/kg/day were minimally decreased when compared with controls. During the last 4 months of the study, there was an increase in mortality among male and female rats receiving 2.0 mg/kg/day. A target organ effect, characterized by degeneration of peripheral nerves, was observed in rats receiving 2.0 mg/kg/day. The incidence of several tumor types was increased in the rats receiving 2.0 mg/kg/day when compared with controls. In females, increased tumor incidences were observed in the mammary gland, central nervous system, thyroid gland-follicular epithelium, oral tissues, uterus, and clitoral gland. In males the incidence of tumors of the thyroid gland-follicular epithelium and scrotal mesothelium was increased. Male rats receiving 2.0 mg/kg/day also had increased incidence of central nervous system tumors when compared to historical controls but not when compared to concurrent controls. The only tumor incidence which was significantly increased at the 0.5 mg/kg/day level was scrotal mesothelioma. There was no statistically significant increase of any tumor type at the 0.1 or 0.01 mg/kg/day dose levels. However, the incidence of scrotal mesothelioma at the 0.1 mg/kg/day level was greater than that observed in the control group or historically reported in this laboratory.

Acrylamide↗
PubMed1984

Turnover of proteoglycans in cultures of bovine articular cartilage.

Proteoglycans in cultures of adult bovine articular cartilage labeled with [35S]sulfate after 5 days in culture and maintained in medium containing 20% fetal calf X serum had longer half-lives (average 11 days) compared with those of the same tissue maintained in medium alone (average 6 days). The half-lives of proteoglycans in cultures of calf cartilage labeled after 5 days in culture and maintained in medium with serum were considerably longer (average 21 days) compared to adult cartilage. If 0.5 mM cycloheximide was added to the medium of cultures of adult cartilage, or the tissue was maintained at 4 degrees C after labeling, the half-lives of the proteoglycans were greater, 24 and greater than 300 days, respectively. Analyses of the radiolabeled proteoglycans remaining in the matrix of the tissue immediately after labeling the tissue and at various times in culture revealed two main populations of proteoglycans; a large species eluting with Kav of 0.21-0.24 on Sepharose CL-2B, of high bouyant density and able to form aggregates with hyaluronate, and a small species eluting with a Kav of 0.63-0.70 on Sepharose CL-2B, of low buoyant density, containing only chondroitin sulfate chains, and unable to form aggregates with hyaluronate. The larger proteoglycan had shorter half-lives than the smaller proteoglycan; in cartilage maintained with serum, the half-lives were 9.8 and 14.5 days, respectively. Labeling cartilage with both [3H]leucine and [35S]sulfate showed the small proteoglycan to be a separate synthetic product. The size distribution of 35S-labeled proteoglycans lost into the medium was shown to be polydisperse on Sepharose CL-2B, the majority eluting with a Kav of 0.27 to 0.35, of high buoyant density, and unable to aggregate with hyaluronate. The size distribution of glycosaminoglycans from 35S-labeled proteoglycans appearing in the medium did not differ from that associated with labeled proteoglycans remaining in the matrix.

Aging↗
PubMed1983

Suppression of postoperative pain by preoperative administration of ibuprofen in comparison to placebo, acetaminophen, and acetaminophen plus codeine.

The analgesic effect of preoperatively administered ibuprofen was evaluated in 107 dental outpatients undergoing the removal of impacted third molars. Subjects were given 800 mg ibuprofen prior to the procedure and 400 mg ibuprofen 4 and 8 hours later. Comparison was made to groups receiving either placebo at all three doses, 600 mg acetaminophen administered on the same schedule, or preoperatively administered placebo followed by two doses of postoperatively administered 600 mg acetaminophen plus 60 mg codeine. Ibuprofen pretreatment resulted in significantly less pain than placebo or acetaminophen pretreatment as the local anesthetic wore off. Ibuprofen also resulted in less postoperative pain than acetaminophen plus codeine following the second dose. Side effects were similar across drug treatments and placebo with the exception of greater reports of drowsiness following the opiate-analgesic combination. These findings indicate that pretreatment with a nonsteroidal antiinflammatory drug, such as ibuprofen, results in a suppression of postoperative pain when compared to standard therapy without an increase in side effects.

Acetaminophen↗
PubMed1979

Polyamines: an unrecognised cardiovascular risk factor in chronic dialysis?

The significance of raised polyamine (P.A.) levels in chronic-dialysis patients is unknown. Since these biologically active substances have hormone-like properties and promote cell-growth in plant and animal tissues, it is possible that they stimulate proliferation of arterial smooth-muscle cells (S.M.C.)--a central process in atherogenesis--and thereby contribute to the rapidly accelerated cardiovascular disease observed during dialysis. Such a role for P.A. is supported by tissue-culture studies, which show not only that P.A.-rich serum from dialysis patients stimulates S.M.C. growth, but also that this mitogenic effect is lost when P.A. are selectively removed from uraemic serum and restored by their addition. Although these observations provide new insights into possible mechanisms of atherogenesis, they are not surprising in view of the many known biological actions of P.A.

Arteries↗