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Biomedical subjects

L Robertson

Publications and source records attributed to L Robertson.

At least 109 records · Page 6Linked to original sources

The comparative biologic and toxic potencies of polychlorinated biphenyls and polybrominated biphenyls.

Aroclor 1254 and fireMaster BP-6, two commercial polychlorinated biphenyl (PCB) and polybrominated biphenyl (PBB) preparations, exhibit comparable biologic and toxic effects. In the present study the commercial PBB was more active than Aroclor 1254 in causing thymic atrophy in male Wistar rats. However, a direct comparison of the relative effects of bromine vs chlorine substituents is not possible with the commercial PBB and PCB mixtures due to their complex congeneric composition. This study reports the synthesis and biologic and toxic effects of a series of laterally substituted 3,3',4,4'-tetrahalobiphenyls which contain the following variable molecular Cl/Br ratios; Br4, Br3Cl, Br2Cl2 (two isomers), BrCl3, and Cl4. 3,3',4,4'-Tetrabromobiphenyl and 3,4,4'-tribromo-3'-chlorobiphenyl (150 mumol/kg)-pretreated animals significantly inhibited the growth rate of and caused thymic atrophy in immature male Wistar rats whereas those isostereomers with reduced Br (and increased Cl) content were either less active or inactive. Pretreatment of male Wistar rats with 10 mumol/kg of the 3,3',4,4'-tetrahalobiphenyls and determination of their effects as inducers of the hepatic microsomal drug-metabolizing enzymes also illustrated the effects of the relative Cl/Br ratios on induction potencies. Both 3,3',4,4'-tetrabromo- and 3,4,4'-tribromo-3'-chlorobiphenyl maximally induced the cytochrome P-448-dependent monooxygenases, benzo[a]pyrene and 4-chlorobiphenyl hydroxylase; the order of potency of the other isostereomers was 4,4'-dibromo-3,3'-dichloro- congruent to 3,4-dibromo-3',4'-dichlorobiphenyl greater than 4-bromo-3,3',4'-trichloro- greater than 3,3',4,4'-tetrachlorobiphenyl. With few exceptions this order of potency was observed for the induction of benzo[a]pyrene hydroxylase and ethoxyresorufin O-deethylase in rat hepatoma cells in culture and for their relative binding affinities to the rat cytosolic receptor protein. The data clearly demonstrate that the biologic activities of this group of isosteric halogenated biphenyls are enhanced with increasing bromine substitution and also support the hypothesis that the activities of this class of chemicals are mediated through the receptor.

Animals↗

Detection of complement fixation by enzyme linked immunosorbant assay (COMPELISA).

A method is described by which complement fixation is detected with an enzyme linked immunosorbant assay (ELISA) technique. The method obviates the need for sensitised sheep red blood cells as an indicator of complement fixation and the titration of complement is not critical. The dose response curve has the advantage of being steep and the test result is read photometrically. As test serum and complement do not react together serum anticomplementary effects are eliminated. The ELISA complement fixation test (COMPELISA) was more sensitive than the conventional CFT for detecting brucella antibodies.

Antibodies, Bacterial↗

Comparison of selective media for isolation of Campylobacter jejuni/coli.

A comparison of Skirrow's, Butzler's, Blaser's, Campy-BAP and Preston media for Campylobacter spp was made using human, animal and environmental specimens. Butzler's medium gave the lowest isolation rate and Preston medium, which was the most selective, the highest isolation rate. Enrichment culture using Preston enrichment broth gave a higher isolation rate than direct plating onto Preston medium.

Abattoirs↗

Halogenated biphenyls as AHH inducers: effects of different halogen substituents.

4'-Iodo-, 4'-bromo-, 4'-chloro- and 4'-fluoro-2,3,4,5-tetrachlorobiphenyl were administered to immature male Wistar rats and the effects of this homologous series of 4'-halo-2,3,4,5-tetrachlorobiphenyls on the microsomal drug-metabolizing enzymes were determined. All the halogenated biphenyls increased microsomal benzo[a]pyrene hydroxylase (or aryl hydrocarbon hydroxylase, AHH), ethoxyresorufin (ER) O-deethylase and dimethylaminoantipyrine (DMAP) N-demethylase. The effects of the 4'-halo-2,3,4,5-tetrachlorobiphenyls on the microsomal enzyme activities and on the relative peak intensities and spectral shifts of the reduced cytochrome P-450:CO and ethylisocyanide (EIC) binding difference spectra were similar to those observed after coadministration of phenobarbitone (PB) and 3-methylcholanthrene (MC). The relative activities of the halogenated biphenyls were determined using two in vitro assays; namely cytochrome P-448 associated induction in rat hepatoma H-4-II E cells in culture and competitive binding to the hepatic cytosolic Ah receptor protein from male Wistar rats. Dose-response experiments for the iodo, bromo, chloro and fluoro analogs gave EC50(M) values of 8.5 x 10(-9), 6.6 x 10(-8), 5.7 x 10(-7), and 3.3 x 10(-5), and 1.5 x 10(-6), 2.5 x 10(-6), 4.1 x 10(-6) and 2.5 x 10(-5) for the Er O-deethylase induction and receptor binding assays respectively. The relative potencies of the 4'-halo-2,3,4,5-tetrachlorobiphenyls followed the order I greater than Br greater than Cl greater than F for both assays and differences in the EC50 values for the iodo and fluoro analogs were greater than three orders of magnitude for ER O-deethylase induction in rat hepatoma cells in culture. One possible explanation for these effects may be associated with differences in the polarizability of the laterally substituted halogen groups. However, other differences in the physico-chemical properties of the halogen atoms may also be important.

Animals↗

A most probable number method for estimating small numbers of campylobacters in water.

A most probable number (MPN) method capable of estimating as few as ten campylobacters per 100 ml of water is described. The method gave results close to those obtained by the viable count method of Miles, Misra & Irwin (1938) with graded suspensions of Campylobacter jejuni. The method was used to test raw water samples: counts were obtained ranging from 10 to 230 campylobacters per 100 ml for 11 49 coastal and estuary water samples, and from 10 to 36 campylobacters per 100 ml for 7 of 44 river samples. Campylobacters were isolated from an additional 24 of the 'negative' samples by testing 200 ml volumes by glass microfibre filtration and enrichment culture methods. The MPN method should prove to be a useful epidemiological tool particularly suited to the enumeration of campylobacters in particulate fluids.

Campylobacter↗

A selective medium for isolating Campylobacter jejuni/coli.

Skirrow's medium is effective for isolating Campylobacters from human faeces but is less suitable for animal and environmental specimens owing to the presence of contaminating species. After determining the sensitivity of 104 strains of Campylobacters to several antimicrobial agents, used singly and in various combinations, a selective medium incorporating polymixin, rifampicin, trimethoprim and actidione, was developed. The medium, called Preston medium, was shown to be more selective than Skirrow's medium and suitable for any kind of specimen.

Agar↗

The role of continuous-flow blood fraction separators in clinical practice.

Continuous-flow blood fraction separators facilitate the efficient exchange of large volumes of plasma or red cells and therefore have clinical application in the rapid correction of abnormalities located predominantly in either of these compartments. Plasmapheresis has been successfully used in managing 2 patients with previously refractory myasthenia gravis, in reducing the antibody titre in a rhesus-sensitized woman, and in diminishing anti-A titre in a patient requiring bone marrow transplantation from an ABO-incompatible but HLA- and MLC-identical sibling. Continuous-flow red cell exchange effectively reduced the haemoglobin S concentration in an individual with sickle cell disease prior to general anaesthesia and abdominal surgery. Complications were not encountered although the procedures were carried out repetitively over prolonged periods of time. All 5 patients tolerated their exchanges without discomfort. As with any new and expensive technique, caution should attend the introduction of continuous-flow plasma or red cell exchange into clinical medicine. Careful evaluation of the safety and the benefits is needed to establish perspective and to distinguish between established and developmental indications.

Acetylcholine↗

Octachloronaphthalene induction of hepatic microsomal aryl hydrocarbon hydroxylase activity in the immature male rat.

Administration of octachloronaphthalene to immature male Wistar rats resulted in a dose-dependent increase in several enzymic, electrophoretic and spectral parameters associated with induction of the hepatic microsomal enzymes. Compared to corn-oil (control)treated animals octachloronaphthalene (150 mumol . kg-1) induced hepatic cytochrome P-450 (1.5-fold), benzo [alpha] pyrene hydroxylase (18-fold) and 4-chlorobiphenyl hydroxylase (18-fold) enzyme activities. In addition to increases in the relative peak intensities of the reduced microsomal cytochrome P-450 : CO and ethylisocyanide (EIC) difference spectra the peak maxima were observed at 448.5 and 452.2/428.0 nm, respectively. The effects of administering octachloronaphthalene to the rat were similar to those observed after pretreatment with 3-methylcholanthrene (MC) and electrophoresis of the induced microsomal proteins showed that both compounds enhance heme-staining peptides with comparable electrophoretic mobilities. Moreover coadministration of MC (3 x 100 mumol . kg-1) and octachloronaphthalene (2 x 150 mumol . kg-1) indicated that their inductive effects were not additive. It was concluded that octachloronaphthalene was an MC-type inducer of hepatic microsomal enzymes.

Age Factors↗

Polychlorinated biphenyls as inducers of hepatic microsomal enzymes: structure-activity rules.

A number of highly purified polychlorinated biphenyl (PCB) isomers and congeners were synthesized and administered to male Wistar rats at dosage levels of 30 and 150 mumol . kg-1. The effects of this in vivo treatment on the drug-metabolizing enzymes were determined by measuring the microsomal benzo[a]pyrene (B[a]P) hydroxylase, dimethylaminoantipyrine (DMAP) N-demethylase and NADPH-cytochrome c reductase enzyme activities, the cytochrome b5 content and the relative peak intensities and spectral shifts of the reduced microsomal cytochrome P-450 CO and ethylisocyanide (EIC) binding difference spectra. The results were compared to the effects of administering phenobarbitone (PB), 3-methylcholanthrene (MC) and PB plus MC (coadministered) to the test animals. The synthetic PCB congeners used in this study included 3,4,4',5-tetrachlorobiphenyl (TCBP-1), 2,3',4,4'-tetrachlorobiphenyl (TCBP-2), 2,3',4,4',5'-pentachlorobiphenyl (PCBP-1), 2,3,4,-4',5-pentachlorobiphenyl (PCBP-2), 2,3,3',4,4',5-hexachlorobiphenyl (HCBP-1) 2,3',4',5,6-hexachlorobiphenyl (HCBP-2), 2,3,3',5,5',6-hexachlorobiphenyl (HCBP-3), 2,2',3,5,5',6-hexachlorobiphenyl (HCBP-4) and 2,3,3',4,5,5'-hexachlorobiphenyl (HCBP-5) and were used to reappraise the structure-activity rules for PCBs as hepatic microsomal enzyme inducers. The results suggested that (a) PCBs which induce MC or mixed-type activity must be substituted at both para positions, at least two meta positions but not necessarily on the same phenyl ring and can also contain one ortho chloro substituent; (b) due to the considerable structural diversity of the PB-type inducers the rules for induction of this activity by PCB congeners are not readily defined.

Animals↗

Campylobacter enteritis associated with consumption of unpasteurised milk.

In October and November 1978 two outbreaks of enteritis occurred in the north of England. Symptoms lasted two to over eight days but in no case necessitated admission to hospital. Faecal specimens from most of the patients were found to contain thermophilic Campylobacter sp. Inquiry disclosed that all patients had consumed unpasteurised milk from local farms. Examination of rectal swabs from the cattle concerned and milk socks yielded strains of Campylobacter sp indistinguishable from those isolated from the patients. It was therefore concluded that, since campylobacters are not known to be excreted in milk, faecal contamination of the milk had probably occurred and had led to these outbreaks. Evidence suggests that thermophilic Campylobacter sp is an occasional contaminant of milk. So long as unpasteurised milk continues to be distributed further outbreaks will probably occur.

Animals↗

Adolescent blood pressure in Richmond, Virginia, schools.

The blood pressure of 3,166 adolescents was measured periodically in Richmond during the period 1974-1977. The subjects were students in public and private schools and ranged in age from 14 to 18 years. Analysis of the readings showed minimal differences relating to age, sex, school and race but a strong correlation with obesity. Only two organic renal causes of hypertension were discovered. A 3 1/2-year followup of 902 students indicated significant tracking, with a correlation coefficient of .385 for systolic and .305 for diastolic pressure. At the conclusion of the study, 340 students (10.7%) were identified as needing followup for hypertension.

Adolescent↗

A simple method for determining bacterial susceptibility to aminoglycosides.

A method is described of determining the susceptibility of enterobacteria to four amino-glycosides by means of an antibiotic diffusion method. The results are exose obtained by a method that involved titration in agar plates and the use of a multi-point inoculator. A statistical analysis showed that the diffusion method gave accurate reproducible results. The antibiotic can be incorporated into paper disks, paper strips or agar ditches and the calculation converting the measured zones of inhibition to MIC values is easily performed. The appropriate equation is derived from another--obtained from observations on a single strain of known sensitivity--describing the diffusion of the antibiotic from the reservoir.

Anti-Bacterial Agents↗

Sensitivity of Brucella spp to tetracycline and its analogues.

The sensitivity to eight tetracyclines of 100 strains of brucellae, comprising strains of Brucella abortus, Br. melitensis, and Br. suis, was determined. Demethylchlortetracycline was the most effecitve against all the groups of brucellae, whereas oxytetracycline and chlortetracycline were the least effective. The mean MIC value for demethylchlortetracycline, doxycycline, lymecycline, and tetracycline was less than or equal to 1 mug/ml. Strains of Br. abortus biotype 2 and Br. suis were the most sensitive strains examined.

Brucella↗