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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↗
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↗
PubMed1979

Parathyroid autotransplantation in renal osteodystrophy.

Severe renal osteodystrophy with metaphyseal fractures developed in two children with hypoplastic-dysplastic kidneys and chronic renal failure despite therapy with vitamin D, CaCO3, phosphate-binding agents, and protein restriction. Serum immunoreactive parathyroid hormone (iPTH) levels were elevated to 709 and 1,537 pg/mL (N = 255 +/- 92 pg/mL). Total parathyroidectomy and then autotransplantation of a small portion of parathyroids into the left brachioradialis muscle resulted in complete healing of renal osteodystrophy with the same dose of vitamin D. Serum iPTH and histological studies have demonstrated functioning parathyroid autotransplants, 19 and 20 months postoperatively in these two patients. Advantage of such a procedure over 3 3/4 parathyroidectomy is that this transplanted parathyroid tissue is easily accessible for partial removal in case of recurrence of uncontrollable hyperparathyroidism. We believe that total parathyroidectomy and autotransplantation can be successfully performed even in small children.

Child, Preschool↗
PubMed1979

Polyamine-pyridoxal Schiff bases in urine.

Schiff bases of the diamines 1,3-diaminopropane, putrescine, and cadaverine and the polyamines spermidine and spermine with pyridoxal or pyridoxal phosphate occur in human urine, as shown by gas chromatographic/mass spectrometric selected ion-monitoring techniques. By use of synthetic standards, procedures were devised for conversion of the Schiff bases to stable derivatives amenable to gas chromatographic/mass spectrometric analysis. These procedures involve borohydride reduction of the C = N double bond, hydrolytic removal of the phosphate group, chromatographic separation from the bulk of urinary constituents, and trifluoroacetylation of polar functional groups. The levels of the polyamine-pyridoxal Schiff bases were estimated to be in the range of pmol/ml or urine.

Adult↗
PubMed1979

Purification of rabbit antispermine antiserum by affinity chromatography.

Immunoglobulins G were isolated from a crude rabbit antispermine antiserum using a protein A-Sepharose CL-4B column. Affinity chromatography coupling spermine to the Sepharose matrix was employed for separation of antispermine antibodies from these immunoglobulins. Four fractions of antispermine antibodies were isolated by stepwise elution with solutions at pH range from 4 to 1. Binding constants were determined and cross-reactivity with other polyamines was tested for each fraction of antibodies. Highly specific antispermine antibodies were found in fraction IV.

Animals↗
PubMed1978

1-N-Acetylspermidine: occurrence in normal human serum.

Using gas chromatography mass spectrometry following derivatization (N-trifluoroacetylation), 1-N-acetylspermidine was found to occur in normal human serum at a level of approximately 0.008--0.5 nmol ml(-1), i.e. about two orders of magnitude lower than the corresponding spermidine level. No evidence for the occurrence in serum of the isomeric 8-N-acetylspermidine was found. Mass spectra of authentic samples of trifluoroactylated 1-N- and 8-N-acetylspermidine are presented.

Acetylation↗
PubMed1978

Ontogeny of behavioral arousal: the role of environmental stimuli.

During the course of ontogenesis the developing rat has been reported to pass through a transient period of intense behavioral arousal which peaks at 15 days of age, a phenomenon that has been interpreted to reflect a sequential caudal to rostral development of excitatory and inhibitory systems in the mammalian brain. In a series of four experiments it was shown (a) that this period of intense hyperactivity occurs only when the animal is tested alone in an unfamiliar environment, that the degree of arousal is proportional to the dissimilarity between the home cage and the test environment, and that isolation per se is insufficient to elicit the arousal response; (b) that environmental temperature has a minimal influence on the degree of behavioral arousal seen in either familiar of unfamiliar environments; (c) that unlearned responses to pheromonal or other naturally occurring nest odors do not suppress the high levels of locomotor activity evoked by unfamiliar environments in the 15-day old rat pup; and (d) that it is fear or distress evoked by the unfamiliar environment rather than curiosity that underlies this developmental phenomenon. It is concluded that the sequential increase and decrease in locomotor activity that occurs during ontogenesis cannot be used to support the principle of caudal to rostral development of excitatory and inhibitory centers in the central nervous system.

Age Factors↗
PubMed1978

Radioimmunoassay of spermidine in human serum.

Specific antispermidine antibodies were produced following immunization of New Zealand white rabbits with a spermidine-thyroglobulin conjugate of high (greater than 200:1) hapten-carrier molar ratio. The harvested antispermidine rabbit antiserum was characterized and a radioimmunoassay procedure developed. The specificity of this antibody was tested against cadaverine, putrescine, spermine, monoacetylputrescine, N-8-acetylspermidine and other compounds of similar molecular structure. Negligible cross-reactivity was observed with putrescine (2.1%), cadaverine (0.6%), spermine (0.3%), diaminopropane (less than 0.1%), and no cross-reaction was found with monoacetylputrescine, N-8-acetylspermidine, histamine, L-lysine and L-ornithine. The spermidine values on serum of five healthy volunteers were determined by RIA and compared with values by gas chromatographymass spectrometry. Statistical evaluation of the results were highly agreeable. Antibody titer, intra-assay precision and analytical accuracy were tested. The assay requires only 20 microliter of serum and has picomole sensitivity. The sensitivity, specificity and small sample requirement make this procedure an effective tool for spermidine analysis.

Animals↗