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Biomedical subjects

J E Nixon

Publications and source records attributed to J E Nixon.

At least 19 recordsLinked to original sources

The Giardia genome project database.

The Giardia genome project database provides an online resource for Giardia lamblia (WB strain, clone C6) genome sequence information. The database includes edited single-pass reads, the results of BLASTX searches, and details of progress towards sequencing the entire 12 million-bp Giardia genome. Pre-sorted BLASTX results can be retrieved based on keyword searches and BLAST searches of the high throughput Giardia data can be initiated from the web site or through NCBI. Descriptions of the genomic DNA libraries, project protocols and summary statistics are also available. Although the Giardia genome project is ongoing, new sequences are made available on a bi-monthly basis to ensure that researchers have access to information that may assist them in the search for genes and their biological function. The current URL of the Giardia genome project database is www.mbl.edu/Giardia.

Animals↗

Phylogenomic analysis of the alpha proteasome gene family from early-diverging eukaryotes.

We employed a phylogenomic approach to study the evolution of alpha subunits of the proteasome gene family from early diverging eukaryotes. BLAST similarity searches of the Giardia lamblia genome identified all seven alpha proteasome genes characteristic of eukaryotes from the crown group. In addition, a PCR strategy for the amplification of multiple alpha subunit sequences generated single alpha proteasome products for representatives of the Kinetoplastida (Leishmania major), the Parabasalia (Trichomonas vaginalis), and the Microsporidia (Vairimorpha sp., Nosema sp., Endoreticulata sp., and Spraguea lophii). The kinetoplastid Trypanosoma cruzi and the eukaryote crown group Acanthamoeba castellanii yielded two distinct alpha proteasome genes each. The presence of seven distinct alpha proteasome genes in G. lamblia, one of the earliest-diverging eukaryotes, indicates that the alpha proteasome gene family evolved rapidly from a minimum of one gene in Archaea to seven or more in Eukarya. Results from the phylogenomic analysis are consistent with the idea that the Diplomonida (as represented by G. lamblia), the Kinetoplastida, the Parabasalia, and the Microsporidia diverged after the duplication events that originated the alpha proteasome gene family. A model for the early origin and evolution of the proteasome gene family is presented.

Base Sequence↗

Influence of body weight restriction in a body-weight-selected line of turkeys on response to challenge with Pasteurella multocida.

Previous research has shown that a line (F) of turkeys selected long-term for increased 16-wk BW was more susceptible to challenge with washed Pasteurella multocida (PM) than a randombred control line (RBC2), the base population of the F line. Published research indicated that the mortality of the F line following challenge with PM was similar to that of two commercial sire lines. The purpose of the present study was to determine the influence of reducing BW of the F line to that of the RBC2 line by nutrient restriction on resistance to PM. Four challenge trials were conducted over a 2-yr period. The BW of a group of F line birds was restricted to that of the RBC2 line by limiting access to feed from 1 to 6 wk of age. The F line restricted birds and full-fed RBC2 and F line birds were challenged with a field isolate of washed PM (1.2x10(7) organisms/bird of capsular serogroup A and somatic serotype 3, 4) at 6 wk of age. Birds were checked twice daily for 14 d. Resistance to PM was measured by days to death of those that died and percentage mortality. The BW of the restricted group of the F line did not differ from full-fed RBC2 birds for males or females. In males, the restricted F line birds had similar mortality (48.0%) to the full-fed RBC2 line birds (44.3%), and the mortalities in both groups were significantly lower than that observed for the full-fed F line birds (81.3%) following challenge with PM. The mortality following challenge in females did not differ significantly among groups, even though mortality of the full-fed F line birds (64.1%) and restricted F line birds (63.3%) was more than 9% higher than that (54.2%) observed for the full-fed RBC2 line birds. Days to death was not a sensitive indicator of resistance to PM, as no differences among the three groups of birds were observed for either sex.

Animals↗

Thrombo-embolic prophylaxis in total knee replacement. Evaluation of the A-V Impulse System.

We performed a prospective randomised controlled trial of a new mechanical method of prophylaxis for venous thrombo-embolism in 60 patients undergoing knee replacement surgery. The method uses the A-V Impulse System to produce cyclical compression of the venous reservoir of the foot. The overall incidence of deep-vein thrombosis was 68.7% in patients receiving no prophylaxis and 50% in those using the device. The difference was not significant. There was, however, a reduction of the extent of thrombosis in the treated group. There were 13 major calf-vein thrombi and six proximal-vein thrombi in the control group compared with only five major calf-vein thrombi in the treated group. This difference was significant (p = 0.014). No patient developed clinical features of a pulmonary embolism.

Aged↗

Does sublaminar wiring produce spinal stenosis?

Sublaminar wiring provides strong and effective fixation of the scoliotic or unstable spine, but its long-term effects on the spinal canal remain unknown. An animal model was developed to observe these effects on the growth and development of the immature spine over a two-year period. Laminar overgrowth occurred both longitudinally to produce a kyphoscoliosis and in the transverse plane to cause significant laminar thickening and growth into the spinal canal. However, the cross-sectional area of the spinal canal was not significantly compromised.

Animals↗

Annular protrusion: pathophysiology and roentgenographic appearance.

The degenerative changes of the lumbar spine in 100 patients with symptomatic low-back pain were reviewed using plain roentgenograms and computed tomographic scans in order to determine the relationship between degeneration and annular protrusion. Additionally, the lumbar spinal units of 25 fresh cadavers were roentgenographed, injected with a mixture of methylene blue and renografin-60, dissected, and studied. The state of degeneration of each of the intervertebral units of both groups was graded on a four-point scale based on the roentgenographic presence or absence of osteophytes and facet joint changes, and the intervertebral disc height. The degree of annular protrusion was measured by dividing the anteroposterior diameter of the intervertebral disc by the anteroposterior diameter of the vertebral plate as determined on the radiographic studies. In the clinical group, 39 intervertebral discs having Grade II and III degeneration exhibited a statistically higher annular/vertebral diameter ratio (A/V index) of 1.30 as compared to the normal invertebral discs, with an A/V index of 1.12 (P less than 0.001). The dissection of the disc spaces of the cadavers with radiographic evidence of disc space narrowing and marginal osteophytosis, Grade II and III degeneration, displayed significant interruption and tearing of the annular fibers and peripheral migration of collagenized nuclear fragments. In both the clinical and pathologic groups, there was a direct correlation between the size of the annular bulge, as indicated in the A/V index, and the degree of narrowing of the disc space. Therefore, this study indicated that annular protrusion is an intricate part of the degeneration process.

Adult↗

Enhancement of carcinogenesis by the natural anticarcinogen indole-3-carbinol.

Indole-3-carbinol (I3C), a natural constituent of cruciferous vegetables, is an inhibitor in several experimental animal models of carcinogenesis by polynuclear aromatic hydrocarbons or aflatoxin B1 (AFB1) when administered prior to or during carcinogen exposure. For assessment of the postinitiation effects of I3C, rainbow trout were exposed to dietary I3C in two different protocols--before and during AFB1 exposure or after AFB1 exposure only. Preinitiation exposure to I3C reduced AFB1-initiated hepatocellular carcinomas in trout as previously reported, but post-initiation I3C exposure strongly enhanced the tumor incidence above the positive AFB1 control. These results reveal the need for additional research to elucidate the overall effect of I3C on chemical carcinogenesis.

Aflatoxin B1↗

Copying for fun and profit.

We have found our office copier an indispensible aid to the department's work production. Our savings in both time and production costs more than offset the copier's limitations. This article highlights only a few of the ways we utilize our copier. Further experimentation by others, we believe, should uncover even more advantages to these machines.

Copying Processes↗

Impaired clearance, elimination, and metabolism of plasma cholesterol esters associated with hypercholesteremia in mice fed cyclopropenoid fatty acids.

Swiss-Webster mice were fed corn oil control diet or 0.7% cyclopropenoid fatty acid (CPFA) for 8 weeks and dosed iv with an equimolar suspension of [3H]cholesteryl palmitate and [14C]cholesteryl palmitoleate. Blood decline of labeled sterol was biphasic. There were no differences in vivo plasma cholesterol ester metabolism, elimination kinetics, or fecal elimination rate for labeled sterol from [3H]cholesteryl palmitate or [14C]cholesteryl palmitoleate within CPFA or control groups. However, compared to controls, CPFA animals diverted significantly more labeled sterol into saturated and diunsaturated cholesterol esters, less into mono- and tetraunsaturated esters, and showed decreased blood clearance and fecal elimination of labeled sterol. Biliary elimination was probably not impaired by depressed hepatic cholesterol esterase activity in CPFA-fed mice. The fundamental effect of CPFA on serum cholesterol concentration appears to reside in a severely imbalanced cholesterol ester profile. Results indicate that CPFA alter normal fatty acid profile of serum cholesterol esters by proportionally altering the C-2 fatty acyl composition of serum phospholipid, which is the substrate for lecithin:cholesterol acyltransferase, the major source of plasma cholesterol esters.

Animals↗

Altered lipid metabolism and impaired clearance of plasma cholesterol in mice fed cyclopropenoid fatty acids.

Swiss-Webster mice fed a diet containing 0.5% cyclopropenoid fatty acids (CPFA) for 6 weeks showed depressed growth rates and developed hypercholesteremia and increased concentrations of serum phospholipid and free cholesterol compared to control mice. No depression of cytochromes P-450 and b5 or microsomal mixed-function oxidase activities occurred to indicate impaired oxidative catabolism of serum cholesterol. Elimination of intragastrically administered [3H]cholesterol from blood was biphasic; there was no significant difference in first-order rate constants for absorption, distribution, and elimination processes between control and CPFA-fed animals. However, the area under the blood clearance curve for CPFA-fed animals was significantly increased (p less than or equal to 0.01) by 29% over controls, demonstrating a net increase in clearance time for exogenous cholesterol in CPFA-fed animals, thus contributing to their hypercholesteremia. In the CPFA-fed mice, the percentage of saturated fatty acid residues increased at the expense of monounsaturates in the cholesterol ester, triglyceride, and phosphatidyl choline fractions of serum lipids. Total polyene content of serum lipid was not altered; however, CPFA-fed animals demonstrated increased linoleic acid at the expense of arachidonic acid in all serum lipid fractions. Excessively saturated serum lipids may impede clearance of serum cholesterol in CPFA-fed animals by inhibited plasma lecithin-cholesterol acyltransferase (LCAT) and hepatic cholesterol esterase activities.

Animals↗

Age-related changes in proprioception and sensation of joint position.

With a clinical goniometer we measured the ability of 29 normal women to (a) reproduce the perceived position of each knee with that of the other knee, and (b) reproduce from memory the perceived resting position of each knee following its return to rest. Fifteen subjects were under 30 years old and 14 were over 60. The younger group scored higher in all trials. This study suggests the existence of an age-related change in proprioception and static joint position sensation in women and provides a basis for further investigation of contributory factors of musculoskeletal trauma in the elderly.

Adult↗

Glucuronides in bile of rainbow trout (Salmo gairdneri) injected with [3H]aflatoxin B1 and the effects of dietary beta-naphthoflavone.

Rainbow trout Salmo gairdneri were fed a diet containing the mixed-function oxidase system inducer, beta-naphthoflavone or were fed a control diet. For the two respective diets, as much as 50 and 12% of an i.p.-injected dose of [3H]aflatoxin B1 was recovered in the bile. The major product in the bile of beta-naphthoflavone-fed trout was an aflatoxicol-M1 glucuronide, whereas the major product in the control bile was an aflatoxicol glucuronide.

Aflatoxin B1↗

Comparative activation of aflatoxin B1 to mutagens by isolated hepatocytes from rainbow trout (Salmo gairdneri) and coho salmon (Oncorhynchus kisutch).

Isolated hepatocytes from rainbow trout readily activated aflatoxin B1 (AFB1) to mutagens detectable by S. typhimurium TA 98. Characterization studies demonstrated that activation efficiency was essentially linear with respect to hepatocyte concentration (5 X 10(5)-2 X 10(7) cell/ml) and AFB1 dose (0-10 micrograms/ml). This system was employed to assess possible differences in AFB1 activation in hepatocytes from rainbow trout and coho salmon, two species which have been shown in in vivo studies to differ widely in sensitivity to AFB1 carcinogenesis. Activation efficiency was approximately three times greater in trout hepatocytes compared with salmon hepatocytes. This difference was more marked when S20 liver fractions from the two species were used. Analysis of unbound [3H]AFB1 metabolites performed on supernatants of hepatocyte incubations revealed that under the normal conditions of assay, addition of bacteria does not perturb the various pathways of AFB1 metabolism within hepatocytes. These results support other studies which suggest that the greater sensitivity of trout to AFB1 carcinogenicity resides largely in increased initial DNA damage, compared with coho salmon.

Aflatoxins↗

Inhibition of aflatoxin B1 carcinogenesis in rainbow trout by flavone and indole compounds.

Several compounds such as flavonoids, selenium, antioxidants and retinoids reportedly reduce the induction of cancer in experimental animals, and some have been suggested to function by affecting the mixed-function oxidase (MFO) system. The following compounds: 50 and 500 p.p.m. beta-naphthoflavone (BNF), 1000 p.p.m. flavone, 1000 p.p.m. of a tangeretin - nobilitin mixture, 1000 p.p.m. beta- ionone , 1000 p.p.m. indole-3-carbinol ( I3C ) and 2000 p.p.m. quercetin were examined for protection against aflatoxin B1 (AFB1) hepatocarcinogenesis, induction of the MFO system and metabolism of AFB1 in rainbow trout. These compounds were fed to fingerling rainbow trout for 8 weeks. At that time the activity of several MFO enzymes and cytochrome P450 content were measured and the trout were exposed for 2 weeks to 20 p.p.b. AFB1 in the same diets. After feeding the test diets without AFB1 for another 6 weeks and basal diet for another 52 weeks, the tumor incidence was determined. The effect of BNF and I3C on in vivo binding of AFB1 to DNA was also measured in separate groups of trout. BNF induced the trout MFO system in a dose-dependent manner, tangeretin - nobilitin was less effective and I3C did not induce. BNF showed significant alterations in the metabolism of AFB1 to aflatoxicol and aflatoxin M1 using cell fractions from pretreated fish. None of the other compounds, including I3C showed such an effect. Despite the apparent lack of in vitro effect of I3C , both BNF and I3C reduced AFB1 - DNA binding in vivo. I3C and BNF provided marked protection against AFB1-induced hepatocarcinogenesis, while the other compounds were less effective. The 58 weeks tumor incidences were 4% for 1000 p.p.m. I3C , 6% for 500 p.p.m. BNF and 18% for 50 p.p.m. BNF, compared to 38% for the AFB1-positive control. These data demonstrate that gross induction of the MFO system was not necessarily required for alterations in DNA adduct formation in vivo or protection against AFB1 carcinogenesis. Both BNF and I3C provided marked protection but only BNF induced the MFO system.

Aflatoxin B1↗

Undergraduate education in the accident unit.

The present system of undergraduate education in trauma has evolved over the past 15 years. As with orthopaedic teaching in Oxford (Dickson, Houghton & Duthie, 1979) an intensive 4-week course is provided for small groups of students. The subject is covered by personal teaching illustrated by practical problems together with a basis of seminars and tutorials.

Curriculum↗

The sensitivity of rainbow trout and other fish to carcinogens.

Systematic design of replacement chemicals with reduced toxicities will require knowledge of mechanisms of action of parent compounds, especially in species which occupy the environment of most likely exposure. For aquatic systems, the rainbow trout has proven a valuable model for studying mechanisms of carcinogenicity. By comparison, small aquarium species show great potential as in situ field monitors of aquatic contamination by toxic chemicals but are less developed for mechanism studies. Fish species, especially rainbow trout, have also proven useful alternatives to traditional rodent models for comparative studies on mechanisms of action of nonaquatic carcinogens. These kinds of comparative studies form an essential basis for extrapolation of animal studies to man. Carcinogenicity testing of individual compounds and their replacements can provide only limited information on the expected impact of such chemicals on natural populations, since these populations are unavoidably exposed to potent modulators of the carcinogenic response. Hence any program which aims at redesign of commercial chemicals with reduced toxicities must have as a prior aim the full understanding of the mechanisms of joint carcinogen-inhibitor-promotor interactions. Because of their high sensitivity, low cost per individual, and low background tumor incidences, fish models such as the rainbow trout may be the only vertebrate models in which it is economically practical to initiate such complex studies.

Aflatoxin B1↗