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Biomedical subjects

D Knox

Publications and source records attributed to D Knox.

At least 19 recordsLinked to original sources

Mitochondrial DNA variation in Pleistocene and modern Atlantic salmon from the Iberian glacial refugium.

Current understanding of the postglacial colonization of Nearctic and Palearctic species relies heavily on inferences drawn from the phylogeographic analysis of contemporary generic variants. Modern postglacial populations are supposed to be representative of their Pleistocene ancestors, and their current distribution is assumed to reflect the different colonization success and dispersal patterns of refugial lineages. Yet, testing of phylogeographic models against ancestral genomes from glacial refugia has rarely been possible. Here we compare ND1 mitochondrial DNA variation in late Pleistocene (16,000-40,000 years before present), historical and contemporary Atlantic salmon (Salmo salar) populations from northern Spain and other regions of western Europe. Our study demonstrates the presence of Atlantic salmon in the Iberian glacial refugium during the last 40,000 years and points to the Iberian Peninsula as the likely source of the most common haplotype within the Atlantic lineage in Europe. However, our findings also suggest that there may have been significant changes in the genetic structure of the Iberian refugial stock since the last ice age, and question whether modern populations in refugial areas are representative of ice age populations. A common haplotype that persisted in the Iberian Peninsula during the Pleistocene last glacial maximum is now extremely rare or absent from European rivers, highlighting the need for caution when making phylogeographic inferences about the origin and distribution of modern genetic types.

Animals↗

Vaccination of calves against Ostertagia ostertagi with cysteine proteinase enriched protein fractions.

Cysteine proteinase enriched fractions obtained by thiol-sepharose chromatography of Ostertagia ostertagi membrane-bound protein extract (S3-thiol) or total adult excretory-secretory (ES-thiol) products were tested in a vaccination experiment to evaluate their protective efficacy against O. ostertagi in cattle. Calves were vaccinated three times and subsequently challenged with a trickled infection of 25,000 infective larvae in total over 25 days (1000 L3/day, 5 days/week). Geometric mean cumulative egg counts in the ES-thiol group were reduced by 60% during the 2-month period between the first challenge infection and necropsy, compared to the control group (P < 0.002). No reduction in egg output was observed in the S3-thiol group. At necropsy, calves immunized with ES-thiol had a significantly higher percentage of inhibited L4 larvae (9.8%) and had in total 18% less worms than the control calves, but this reduction was not statistically significant. Both the female and male adult worms were significantly smaller in the ES-thiol group than in the control group. Although no significant difference was observed in the number of eggs per female worm between the groups, there was a trend to less eggs per female worm in the ES-thiol group. Number of worms, size of adult worms and number of eggs per female worm were not significantly different between the S3-thiol group and the control group. Systemic immunization with QuilA as adjuvant induced a significant rise in Ostertagia-specific antibody levels in the abomasal mucosa. Ostertagia-specific local antibody levels showed a significant negative correlation with the size of the adult worms, the number of eggs per female worm and the cumulative faecal egg counts. However, these correlations were quite weak and did not appear to be isotype-specific.

Animals↗

Deception of parents during adolescence.

Two hundred eighty-one undergraduates at a large university in the southeastern United States anonymously completed a 26-item questionnaire about the degree to which they deceived their parents during high school. Only five percent of the respondents reported that they had never lied to their parents about "where I was." "Who I was with," "my alcohol use," and "my sexual behavior" were additional topics about which they lied the most. It was also found that (1) females lied more than males about sexual behavior, (2) the opposite-sex parent was deceived more often, and (3) intact homes were associated with more lying. Respondents also reported more lies when they lived with their parents than when they left for college. The implications of the findings are discussed.

Adolescent↗

Proteinases and associated genes of parasitic helminths.

Many parasites have deployed proteinases to accomplish some of the tasks imposed by a parasitic life style, including tissue penetration, digestion of host tissue for nutrition and evasion of host immune responses. Information on proteinases from trematodes, cestodes and nematode parasites is reviewed, concentrating on those worms of major medical and economical importance. Their biochemical characterization is discussed, along with their putative biological roles and, where available, their associated genes. For example, proteinases expressed by the various stages of the schistosome life-cycle, in particular the well-characterized cercarial elastase which is involved in the penetration of the host skin and the variety of proteinases, such as cathepsin B (Sm31), cathepsin L1, cathepsin L2, cathepsin D, cathepsin C and legumain (Sm32), which are believed to be involved in the catabolism of host haemoglobin. The various endo- and exoproteinases of Fasciola hepatica, the causative agent of liver fluke disease, are reviewed, and recent reports of how these enzymes have been successfully employed in cocktail vaccines are discussed. The various proteinases of cestodes and of the diverse superfamilies of parasitic nematodes are detailed, with special attention being given to those parasites for which most is known, including species of Taenia, Echinococcus, Spirometra, Necator, Acylostoma and Haemonchus. By far the largest number of papers in the literature and entries to the sequence data bases dealing with proteinases of parasitic helminths report on enzymes belonging to the papain superfamily of cysteine proteinases. Accordingly, the final section of the review is devoted to a phylogenetic analysis of this superfamily using over 150 published sequences. This analysis shows that the papain superfamily can be divided into two major branches. Branch A contains the cathepin Bs, the cathepsin Cs and a novel family termed cathepsin Xs, while Branch B contains the cruzipains, cathepsin Ls, papain-like and aleurain/cathepsin H-like proteinases. The relationships of the helminth proteinases, and similar proteinases from protozoan parasites and other organisms, within these groups are discussed.

Amino Acid Sequence↗

Implementing a congestive heart failure disease management program to decrease length of stay and cost.

Congestive heart failure (CHF) is the most common reason for a hospital admission in the Medicare age group and is nearly double the rate of pneumonia, the next highest volume diagnosis. The economic burden of this debilitating, chronic disease demands a mechanism to improve quality of care while preventing unnecessary hospitalizations. Beginning in 1995, Evanston Northwestern Healthcare (ENH) created a disease management program involving a multidisciplinary team designed to decrease length of stay (national average = 6.2 days; ENH = 4 days), reduce costs, prevent readmissions (national 30-day readmission rate = 23%; ENH CHF Program = 2.3%), and improve compliance with the treatment regimen. Compliance monitoring through an automated telemanagement program reinforces education, identifies early warning signs and reduces the likelihood of hospitalization. After 18 months, telemanagement participants' compliance rate averages 89.5%. CHF hospitalization rates are 0.6/patient/year compared with the national benchmark of 1.7/patient/year. A disease management program consists of inpatient consultation, education, outpatient CHF clinic, cardiac home care, and compliance monitoring. Throughout this continuum, education must be communicated consistently by all team members. A CHF Assessment Guide assists the multidisciplinary team to thoroughly complete all education and address unique solutions to patients' needs.

Ambulatory Care↗

Prophylactic oral dolasetron mesylate reduces nausea and vomiting after abdominal hysterectomy. The Canadian Dolasetron Study Group.

PURPOSE: The incidence of postoperative nausea and vomiting (PONV) varies from 50% to 75% after gynaecological surgery under general anaesthesia. This study evaluates the dose-response relationships, safety, and efficacy of the new 5-HT3 antagonist, dolasetron mesylate, in the prevention of PONV in women undergoing total abdominal hysterectomy (TAH). METHODS: Three hundred and seventy four women scheduled for TAH under general anaesthesia were studied at 13 Canadian centres. Patients received in a randomized, double-blind manner 25, 50, 100, or 200 mg dolasetron or placebo po one to two hours before induction of anaesthesia. The anesthetic protocol was standardized. Efficacy was evaluated for 24 hr after surgery by comparing the number of emetic episodes, administration of rescue medication, severity of nausea, and patient satisfaction. RESULTS: Analysis of complete response (no emetic episodes and no rescue for 24 hr) revealed a linear dose-response relationship across dolasetron groups (P < 0.002). Dolasetron 100 mg (P < 0.003) and 200 mg (P < 0.01) were superior to placebo. The percentage of patients with no emetic episodes increased from 29.3% (placebo) to 54.1 % (100 mg). Subgroup analysis revealed ASA status (I > II), previous history of PONV, previous history of motion sickness, and total morphine dose (> 55 mg associated with less PONV than < 55 mg) influenced the incidence of emetic symptoms, but did not alter the results of the primary analysis. CONCLUSION: Prophylactic dolasetron (100 mg and 200 mg) reduces the incidence of PONV in patients having total abdominal hysterectomy.

Adolescent↗

The isolation and purification of a proteinase with chymotrypsin-like properties from ovine mucosal mast cells.

A mast cell granule proteinase was purified from isolated ovine mucosal mast cells by cation exchange chromatography, which defined the conditions for enzyme purification from sheep gastric mucosae. Antibodies raised against the proteinase were used in subsequent purification procedures which yielded 78 micrograms of enzyme per 5 g wet wt of abomasal tissue. Immuno-histochemistry confirmed that mucosal mast cells were the source of the enzyme. The proteinase had chymotrypsin-like esterase activity, with a molecular weight between 19,000 and 25,000.

Abomasum↗

The effects of dietary tryptophan levels on growth and metabolism of rainbow trout (Salmo gairdneri).

Groups of rainbow trout (Salmo gairdneri) (mean weight 14 g) were given diets containing 0.8, 1.3, 2, 3, 4 or 6 g tryptophan/kg diet for 12 weeks. By analysis of the growth results, the dietary requirement of tryptophan was found to be 2.5 g/kg diet (equivalent to 50 mg/kg biomass per d). Carbon dioxide expired by trout following intraperitoneal injection of [14COOH]tryptophan contained little radioactivity when dietary tryptophan level was low but, above 2.0 g/kg diet, it increased rapidly with increasing dietary tryptophan level. The break point in the dose-response curve did not, however, coincide with that from the growth results. Changes in concentrations of free tryptophan in blood and liver and activity of hepatic tryptophan pyrrolase (EC 1. 13. 11. 11) in response to changes in dietary tryptophan concentration did not provide reliable indicators for quantifying dietary requirement. Unlike the situation in mammals, blood tryptophan was not protein-bound to any appreciable extent. Tryptophan pyrrolase of trout has properties which suggest it has no apoenzyme form. In fish given adequate levels of tryptophan injected intraperitoneally with a tracer dose of [14COOH]tryptophan, 60% of the dose was incorporated into body protein within 1 d. The turnover of the label in this protein is very slow. Those trout given diets deficient in tryptophan suffered from severe scoliosis and lordosis as well as having increased liver and kidney levels of calcium, magnesium, sodium and potassium.

Animals↗

The effect of low dietary manganese intake on rainbow trout (Salmo gairdneri).

1. Rainbow trout (Salmo gairdneri) of mean initial weight 15 g were given either a low-manganese or control diet containing 1.3 and 33 mg Mn/kg dry diet respectively. 2. Weight gains over a 24-week feeding period were the same for both groups of trout. 3. Hepatosomatic index, blood packed cell volume and haemoglobin concentration, plasma protein and the activities of aspartic aminotransferase (EC 2.6.1.1) and alanine aminotransferase (EC 2.6.1.2) were unaffected by dietary Mn intake. 4. Plasma potassium and iron levels were increased in the trout given the low-Mn diet. 5. The hepatic levels of magnesium, sodium, K, zinc, copper, Mn and phosphorus were significantly reduced in the fish given the low-Mn diet. 6. In those trout given the low-Mn diet the levels of Mn and calcium in the vertebral ash were significantly reduced. 7. The hepatic activity of Cu-Zu superoxide dismutase (EC 1.15.1.1; Cu-ZnSOD) and of Mn superoxide dismutase (EC1.15.1.1; MnSOD) in cardiac muscle and liver was reduced in the group of trout given the low-Mn diet. The fall in Cu-ZnSOD and MnSOD activities coincided with reduced tissue levels of their respective metal components.

Animals↗

Studies on the nutrition of salmonid fish. The magnesium requirement of rainbow trout (Salmo gairdneri).

1. Rainbow trout (Salmo gairdneri) of mean initial weight 35 g were given one of five experimental diets for 20 weeks. The diets contained (g/kg dry diet) 15 calcium, 10 phosphorus and graded levels of magnesium from 0.04 (diet no. 1) to 1.0 (diet no. 5). In a second experiment rainbow trout of mean initial weight 16 g were given one of six experimental diets for 20 weeks. The diets contained (g/kg dry diet): Ca (40), P (30) and levels of Mg from 0.06 (diet no. 6) to 2.0 (diet no. 11). 2. In both experiments weight gains were lowest in those trout given diets containing the basal levels of Mg (diet no. 1 and diet no. 6) but increased with increasing dietary Mg concentration. In neither experiment was there any further increase in weight gain once the Mg concentration reached 0.25-0.5 g/kg dry diet; weight gain reached a plateau at this dietary MG level. 3. The following trends occurred in serum electrolyte concentrations as dietary Mg increased. Mg increased in both experiments, in Expt 2 it reached a maximum of 1 mmol/l when the diet contained 0.5 g Mg/kg and did not increase further; sodium was positively correlated in both experiments; potassium decreased and in Expt 2 reached a plateau minimum of 1.7 mmol/l at a dietary Mg concentration of 0.5 g/kg; Ca and P altered little in either experiment. 4. In both experiments renal Ca concentrations were greatly increased in trout given diets lacking supplementary Mg; they fell to low levels (3-5 mmol/kg) when diets contained 0.15 g Mg/kg or more. Renal K and P concentrations were negatively correlated with dietary Mg in Expt 2; other electrolytes measured were not altered in concentration by the treatments used. 5. Extracellular fluid volume (ECFV) of muscle was negatively correlated with dietary Mg. In Expt 2 it reached a minimal or normal value at 0.5 g Mg/kg diet and did not decrease further. Muscle Mg concentration increased with diet Mg in both experiments and muscle K concentration was also correlated with diet Mg in Expt 2. These changes were related to the shift in muscle water. In Expt 1, P concentration was decreased with increasing diet Mg but in Expt 2 its concentration increased, these changes may have been connected with the three-fold difference in dietary P in the two experiments. 6. By contrast with skeletal muscle, Mg levels in cardiac muscle increased at low dietary Mg intakes. 7. Concentrations of electrolytes in liver did not alter with the dietary treatments used. 8. The results show that Mg requirement of rainbow trout is met by a diet containing 0.5 gMg/kg diet.

Animal Nutritional Physiological Phenomena↗

Tissue distribution, uptake, and requirement for alpha-tocopherol of rainbow trout (Salmo gairdneri) fed diets with a minimal content of unsaturated fatty acids.

The metabolism of and requirements for alpha-tocopherol in rainbow trout fed diets containing 1% linolenic acid as sole source of unsaturated fat and graded levels of tocopherol (0.06-10 mg/100 g) were examined. Fish grew 5-fold over a 16-week period. In liver, tocopherol was concentrated in mitochondria with little in cytosol. Orally administered [3H]-tocopherol was rapidly taken up by plasma and liver but uptake into erythrocytes and white muscle was much slower; in most tissues radioactivity reached a plateau after about 3 days but in red muscle radioactivity increased over a 10-day period. Activities of enzymes that prevent free radical initiated tissue damage did not change in tocopherol deficiency. Tocopherol-deficient trout had no gross or subcellular pathologies even though liver and muscle were severely depleted of the vitamin. Ascorbic acid-stimulated lipid peroxidation in liver organelles indicated a tocopherol requirement of 2-3 mg/100 g diet; the molar ratios of polyunsaturated fatty acids to tocopherol in livers of trout fed diets lacking or supplemented with tocopherol (100 mg/100 g) were 980 and 170, respectively.

Animals↗

Bilateral gaze paralysis with positive computerized tomography findings. A clinicoanatomic correlation.

The subacute development of an almost isolated bilateral gaze paralysis in a patient with mycosis fungoides allowed a unique opportunity for in vivo clinicoanatomical correlation when enhanced computerized tomography (CT) scan revealed two extremely small lesions of the pontine tegmentum. The larger lesion involved the region occupied by the medial longitudinal fasciculus and the paramedian pontine reticular formation (PPRF) bilaterally, and was alone sufficient to account for the eye movement disorder.

Brain Neoplasms↗

Studies on the nutrition of marine flatfish. The pyridoxine requirement of turbot (Scophthalmus maximus).

1. Diets containing graded levels of pyridoxine hydrochloride (to supply 0.26--30 mg pyridoxine/kg) were given to seven duplicate groups of turbot (Scophthalmus maximus) for 12 weeks and their growth rate was measured during this period. 2. Good growth was obtained on all treatments except those groups given less than 1.0 mg pyridoxine/kg diet. These fish grew normally until weeks 8--10 but thereafter their weight gain was significantly less than that for other treatments. 3. Measurements of aspartate aminotransferase (EC 2.6.1.1) in muscle and liver and of alanine amino-transferase (EC 2.6.1.2) in liver of the turbot showed that the activities of these enzymes increased with increasing dietary pyridoxine intake up to a level of 2.5 mg pyridoxine/kg. The activities of these enzymes were not further enhanced by additional dietary pyridoxine. 4. Percentage stimulation of these enzymes by pre-incubation of extracts with pyridoxal phosphate was minimal with those groups of turbot given 2.5 mg pyridoxine/kg diet or more. 5. It is concluded that the dietary requirement of turbot for vitamin B6 can be safely met with a diet containing between 1.0 and 2.5 mg pyridoxine/kg. 6. An eighth group of turbot given the pyridoxine antagonist 4-deoxypyridoxine hydrochloride (20 mg/kg) showed retarded growth after 2 weeks, together with a high mortality rate.

Alanine Transaminase↗