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Biomedical subjects

D Knox

Publications and source records attributed to D Knox.

At least 19 recordsLinked to original sources
PubMed1999

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↗
PubMed1999

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↗
PubMed1997

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↗
PubMed1986

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↗
PubMed1984

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↗
PubMed1981

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↗
PubMed1981

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↗
PubMed1981

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↗
PubMed1980

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↗
PubMed1978

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↗
PubMed1977

Alloxan diabetic neuropathy: electron microscopic studies.

Peripheral nerves of diabetic rats were studied 2 years after alloxan injection. We observed demyelination and remyelination, axonal degeneration and regeneration, reduplication of basal laminae around vessels and Schwann's cells, as well as onion bulb formation by proliferated Schwann's cells. Crystalline deposits composed of aggregates of fibrillary electron dense material often occurred in vessel walls and endoneurium of diabetic animals but rarely were seen in nerves from age-matched control animals. Glycogen accumulated in myelinated and unmyelinated axons within mitochondria. Axoplasmic inclusions resembling Lafora's bodies and the inclusions of glycogenosis type IV were frequent and often were accompanied by deposits of particulate glycogen. The findings suggest that the neuropathy in alloxan diabetes is caused by metabolic impairment of anxons, Schwann's cells, and vessels, leading to segmental demyelination and axonal degeneration.

Animals↗
PubMed1976

Coping with fatherhood: the first year.

Fantasy (thinking back to prebaby times) and holidays (going out alone with the wife) are examined here as methods of coping with parenthood for 93 white, first-time fathers. Results suggest that only the holiday coping mechanism is associated with maintaining or improving marital satisfaction. The use of fantasy actually decreases marital satisfaction. These data suggest that the discrepancies in the conclusions of previous "parenthood as crisis" studies may be accounted for through the analysis of coping mechanisms that various fathers utilize.

Adaptation, Psychological↗
PubMed1975

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

1. Seven groups of young turbot (Scophthalmus maximus) were given diets containing graded levels of thiamin (0-19--50 mg/kg) for 16 weeks and their growth rate was measured during this period. 2. Good growth was obtained on all these treatments except in the group given the lowest dietary thiamin level (0-19 mg/kg). These fish grew normally until the 12th week but thereafter their weight did not increase. 3. Measurements of erythrocyte transketolase (sedoheptulose-7-phosphate: D-glyceraldehyde-3-phosphate glycolaldehydetransferase; EC 2.2.1.1) activity at the end of the experiment and of percentage stimulation of erythrocyte transketolase by thiamin pyrophosphate indicated that the apoenzyme was saturated with coenzyme at a dietary thiamin level of 2-6 mg/kg, but not at 1-1 mg/kg. 4. An 8th group of turbot given the thiamin antagonist pyrithiamin (40 mg/kg diet) grew normally for 6 weeks. Thereafter mortalities began to occur and all fish died by the 10th week. No clear-cut signs of thiamin deficiency were observed. 5. The dietary thiamin requirement of turbot is much lower than published requirements of freshwater fish other than carp (Cyprinus carpio) and appears to be between 0-6 and 2-6 mg/kg diet.

Animal Nutritional Physiological Phenomena↗
PubMed1975

Long term studies of pancreas transplantation in experimental diabetes mellitus.

Alloxan diabetes was induced in inbred rats that then were divided into four groups consisting of unoperated diabetic controls, sham-operated diabetic controls, rats given pancreaticoduodenal isografts, and rats given duct-ligated pancreas isografts. The animals were studied for from 18 months (controls) to two years (transplants) and the following important results were obtained: 1) In striking contrast to the diabetic controls, pancreas transplants of both types produced immediate and permanent relief of hyperglycemia, immediate and lasting elevation of serum insulin levels, a normal weight and growth curve, and good health for two years. Removal of the graft was followed by recurrence of severe diabetes. 2) Pancreas transplants of both types prevented the widespread and severe renal, ophthalmic and neural lesions of diabetes that were found in the diabetic controls. 3) The duct-ligated pancreas graft and pancreaticoduodenal transplant were equally effective in controlling diabetes. Ligation of the pancreatic duct was not followed by significant morphologic or clinical evidence of pancreatitis or by loss of endocrine function. 4) Portal venous drainage of the pancreas transplant was unnecessary for good endocrine function.

Animals↗