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Biomedical subjects

C D Anderson

Publications and source records attributed to C D Anderson.

At least 19 recordsLinked to original sources

A review of causal factors and control measures for bloat in farmed salmonids with a suggested mechanism for the development of the condition.

A mechanism for the development of bloat in salmonids is proposed and explained in terms of the physiology of digestion and osmoregulation in fish. Understanding the causal factors for bloat enables control measures to be identified. In farmed salmonids, the chyme produced during the digestion of nutrient-rich pelleted foods that rapidly disintegrate in the stomach will be a potent activator of a negative feedback mechanism (enterogastric control), which slows stomach emptying to protect the small intestine from nutrient overload. In saline environments salmonids continuously drink sea water to replace fluid lost across the gills. Fluid loss is increased during periods of stress caused by factors such as low oxygen levels, elevated temperature or high salinity. When ingestion of nutrient-rich food results in prolonged activation of enterogastric control, slowed stomach emptying leads to decreased absorption of water, thirst and increased drinking. This further exacerbates stomach distention. The proposed mechanism for the development of bloat is supported by on-farm experience where measures to control bloat include reducing food intake, altering the composition of the diet and using appropriate strategies to reduce stress.

Air Sacs↗

Microdialysis and response during regional chemotherapy by isolated limb infusion of melphalan for limb malignancies.

This study sought to use a microdialysis technique to relate clinical and biochemical responses to the time course of melphalan concentrations in the subcutaneous interstitial space and in tumour tissue (melanoma, malignant fibrous histiocytoma, Merkel cell tumour and osteosarcoma) in patients undergoing regional chemotherapy by Isolated Limb Infusion (ILI). 19 patients undergoing ILI for treatment of various limb malignancies were monitored for intra-operative melphalan concentrations in plasma and, using microdialysis, in subcutaneous and tumour tissues. Peak and mean concentrations of melphalan were significantly higher in plasma than in subcutaneous or tumour microdialysate. There was no significant difference between drug peak and mean concentrations in interstitial and tumour tissue, indicating that there was no preferential uptake of melphalan into the tumours. The time course of melphalan in the microdialysate could be described by a pharmacokinetic model which assumed melphalan distributed from the plasma into the interstitial space. The model also accounted for the vascular dispersion of melphalan in the limb. Tumour response in the whole group to treatment was partial response: 53.8% (n = 7); complete response: 33.3% (n = 5); no response: 6.7% (n = 1). There was a significant association between tumour response and melphalan concentrations measured over time in subcutaneous microdialysate (P< 0.01). No significant relationship existed between the severity of toxic reactions in the limb or peak plasma creatine phosphokinase levels and peak melphalan microdialysate or plasma concentrations. It is concluded that microdialysis is a technique well suited for measuring concentrations of cytotoxic drug during ILI. The possibility of predicting actual concentrations of cytotoxic drug in the limb during ILI using our model opens an opportunity for improved drug dose calculation. The combination of predicting tissue concentrations and monitoring in microdialysate of subcutaneous tissue could help optimise ILI with regard to post-operative limb morbidity and tumour response.

Adult↗

Surgical treatment of chronic lower extremity neuropathic pain.

The current authors retrospectively reviewed 147 lower extremity peripheral nerve procedures in 114 patients (average age, 42 years) with chronic lower extremity neuropathic pain to determine whether surgical treatment based on an empirically derived algorithm could reduce pain and improve function. This algorithm assigns crush, stretch, and chronic transection injuries to treatment with transection and containment. Peripheral nerve stimulation was used in conjunction with transection and containment for patients with more chronic presentations for whom previous transections had been unsuccessful. Patients with adhesive neuralgia underwent revision neurolysis with vein wrapping. Patients with repetitive nerve trauma (overuse) underwent primary or revision neurolysis. Duration of symptoms averaged 37 months, and mechanisms of nerve injury included chronic transection, crush, adhesive neuralgia, stretch, repetitive trauma, and idiopathic etiology. Time to followup averaged 38 months. Pain and dysfunction were ranked from 0 points (no pain or dysfunction) to 10 points (pain prompting request for amputation or functional deficit warranting wheelchair use); preoperative and followup work status were documented. Average pain and dysfunction scores improved: 8.8 to 5.6 points and 7.6 to 5.0 points, respectively. Of the 114 patients, 52 (46%) patients improved their work status, including 35 of 87 (40%) involved in workers' compensation. There were no statistically significant differences in outcome based on mechanism of nerve injury or type of procedure. The consistent average improvement suggests this algorithm assigns the appropriate procedure to a given mechanism of injury.

Adolescent↗

Complex salvage procedures for severe lower extremity nerve pain.

From 1995 to 1999, the senior author did revision nerve release and vein wrapping (58 limbs in 58 patients) or peripheral nerve stimulation (62 limbs in 62 patients) to relieve intractable lower extremity nerve pain. Vein wrapping was done if the patient had temporary relief after a previous nerve release, if there was evidence of scarring around the nerve, and if nerve pain was triggered by mechanical stimulation. Peripheral nerve stimulation was done when previous nerve operations provided no relief or if the nerve pain was more constant and spontaneous without mechanical provocation. The duration of symptoms preoperatively averaged 52 months, and the number of previous peripheral neurosurgical interventions averaged 2.5. Postoperatively, the average pain improvement was rated as 60% for the patients who had vein wrapping and 41% for the patients who had peripheral nerve stimulation. Of the patients who had vein wrapping, 53% were satisfied, 14% were somewhat satisfied, and 33% were dissatisfied. Of the patients who had peripheral nerve stimulation, 61% were satisfied, 21% were somewhat satisfied, and 18% were dissatisfied. Most patients (78%) stated they would undergo the procedures again.

Adult↗

Subtalar distraction bone block arthrodesis.

This retrospective study analyses the results of subtalar bone block distraction arthrodesis used in the treatment of late complications of calcaneal fractures, acute severely comminuted fractures, nonunion (and malunion) of attempted subtalar arthrodeses, avascular necrosis of the talus, and club-foot deformity. Of 39 patients (41 feet) who had this procedure, 35 (37 feet) returned for follow-up after a mean of 70 months (26 to 140). There were 24 men (25 feet) and 11 women (12 feet) with a mean age of 41 years (16 to 63). Each completed a standardised questionnaire, based on the hindfoot-scoring system of the American Orthopaedic Foot and Ankle Society and were reviewed both clinically and radiologically. Of the 37 operations, 32 (87%) achieved union. The mean hindfoot score (maximum of 94 points) increased from 21.1 points (8 to 46) preoperatively to 68.9 (14 to 82) at the final follow-up. The mean talocalcaneal and calcaneal pitch angles were 20.5 degrees and 4.9 degrees before operation, 25.9 degrees and 8.3 degrees immediately after, and 24.6 degrees and 7.7 degrees at the final follow-up, respectively. The mean talar declination angle improved from 6.5 degrees (-10 to 22) before operation to 24.8 degrees (14 to 32) at the final follow-up. The mean talocalcaneal height increased from 68.7 mm before operation to 74.5 mm immediately after and 73.5 mm at the final follow-up. Of the 37 arthrodeses available for review, 32 were successful; 29 patients (30 arthrodeses) were satisfied with the procedure. Minimal loss of hindfoot alignment occurred when comparing radiographs taken immediately after operation and at final follow-up.

Adolescent↗

Luminous vibriosis in rock lobster Jasus verreauxi (Decapoda: Palinuridae) phyllosoma larvae associated with infection by Vibrio harveyi.

Studies were conducted to determine the cause of outbreaks of luminous vibriosis in phyllosoma larvae of the packhorse rock lobster Jasus verreauxi reared in an experimental culture facility. On 2 separate occasions mortalities of up to 75% over a period of 4 wk were observed in 4th to 5th and 8th to 10th instar phyllosomas at water temperatures of 20 and 23 degrees C, respectively. Affected larvae became opaque, exhibited small red spots throughout the body and pereiopods, and were faintly luminous when viewed in the dark. Histopathology showed that the gut and hepatopancreas tubules of moribund phyllosomas contained massive bacterial plaques. The hepatopancreas tubules of moribund larvae were atrophic and some contained necrotic cells sloughed into the lumen. Dense, pure cultures of a bacterium identified as Vibrio harveyi were isolated from moribund larvae. The disease syndrome was reproduced by in vivo challenge and V. harveyi was successfully reisolated from diseased larvae after apparently healthy larvae were exposed by immersion to baths of more than 10(4) V. harveyi ml(-1) at 24 degrees C. Injured larvae were more susceptible to infection than were healthy larvae. Survival of larvae experimentally and naturally exposed to V. harveyi was improved when antibiotics were administered via bath exposures.

Animals↗

Hydropic degenerating leiomyoma presenting as pseudo-Meigs syndrome with elevated CA 125.

BACKGROUND: Leiomyomas rarely cause pseudo-Meigs syndrome. Increased levels of CA 125 often are associated with some types of malignancy. No reported case of pseudo-Meigs syndrome presenting with hydropic degeneration of uterine leiomyoma and an elevated CA 125 level could be found on a MEDLINE search. CASE: A 46-year-old woman presented with a pleural effusion and a pelvic mass measuring 30 x 18 cm. Preoperative evaluation was remarkable for a CA 125 level of 254 U/mL. At laparotomy, the diagnosis was a benign leiomyoma with focal hyaline and extensive hydropic degeneration. Her pleural effusion resolved completely by 4 months postoperatively. CONCLUSION: Pseudo-Meigs syndrome can present with an elevated CA 125 level.

CA-125 Antigen↗

Purification and kinetic characterization of Haemophilus parasuis malate dehydrogenase.

Haemophilus parasuis malate dehydrogenase ((S)-malate:NAD+ oxidoreductase; EC 1.1.1.37) isolated from cell sonicates was purified 584-fold to electrophoretic homogeneity with a 19% recovery and a specific activity of 222 units/mg protein. SDS-polyacrylamide gel electrophoresis and molecular exclusion chromatography indicated the purified enzyme to be a dimer composed of 34,600 molecular weight subunits. Kinetic parameters for all four substrates in the forward and reverse reactions indicated a sequential mechanism for this enzymic process. Product and dead-end inhibition studies were consistent with an ordered bi-bi mechanism in which NAD is the first substrate bound to the enzyme and NADH the second product released. Protection against thermodenaturation of the enzyme by NAD and not by malate was supportive of this mechanism. A pronounced product inhibition by NADH (K(i) = 9.0 microM) was observed. Although NADP did not serve as a coenzyme, a number of analogs of NAD structurally altered in the nitrogen base moieties were observed to function as coenzymes in the oxidation of malate catalyzed by the purified malate dehydrogenase. Coenzyme-competitive inhibition of the malate dehydrogenase was observed with five adenosine derivatives and six structural analogs of NAD. Of the NAD analogs studied as inhibitors, 3-pyridylcarbinol adenine dinucleotide was the most effective (K(i) = 18 microM). Although inhibition of growth of H. parasuis by this analog was observed, it was less effective (K(i) = 136 microM) than the inhibition of the purified dehydrogenase.

Adenosine↗

Azotobacter vinelandii glucose 6-phosphate dehydrogenase properties of NAD- and NADP-linked reactions.

Glucose 6-phosphate oxidation, catalyzed by purified Azotobacter vinelandii glucose 6-phosphate dehydrogenase, was studied with respect to the selective utilization of NAD, NADP, thionicotinamide adenine dinucleotide or thionicotinamide adenine dinucleotide phosphate as coenzyme. A sigmoidal relationship was observed for the effect of substrate concentration on initial velocities when either NAD, NADP or thionicotinamide adenine dinucleotide was used as coenzyme, with N values from the Hill equation equalling 2.0, 1.7, and 1.7, respectively. The thionicotinamide analogs of NAD and NADP both functioned as coenzyme-competitive inhibitors of the enzyme-catalyzed NAD- and NADP-linked reactions. A dual wavelength assay, using a combination of NADP and thio-NAD, was established and was used to demonstrate that increasing glucose 6-phosphate concentration did not change the enzyme preference for the coenzyme form used. Sigmoidal relationships were observed for reduction of both dinucleotides, and N values were the same as those observed when each dinucleotide was studied as the only coenzyme form present in reaction mixtures. Using the dual wavelength assay, inhibition by isocitrate, 6-phosphogluconate, ATP, and palmitoyl-CoA was shown to be equally effective in both NAD- and NADP-linked reactions. An enzyme activator, glucosamine 6-phosphate, altered the glucose 6-phosphate sigmoidicity through activation at low substrate concentrations.

Azotobacter vinelandii↗

Deep loop excision for prehysterectomy endocervical evaluation.

OBJECTIVE: Our purpose was to determine whether office deep loop excision should replace cone biopsy for frozen-section endocervical evaluation before planned hysterectomy. STUDY DESIGN: This cohort study comprised 31 patients who underwent office deep loop excision with frozen-section analysis followed by hysterectomy and 50 historic controls who underwent cone biopsy with frozen-section analysis followed by hysterectomy. Diagnostic accuracy, margin status, presence of residual disease, morbidity, and cost were compared. RESULTS: Loop excision frozen sections had sensitivity (ectocervical specimen, 96%; deepest endocervical specimen, 93%), specificity (100%, 86%), and positive (100%, 88%) and negative (75%, 92%) predictive values similar to those of frozen cone biopsy (95%, 80%, 98%, and 67%, respectively. No differences in margin status, presence of residual dysplasia, or morbidity were observed. The shorter operating room time for vaginal hysterectomy after loop excision (p < 0.01) resulted in an approximate $2000 savings. CONCLUSION: Office loop excision is a cost-effective option for endocervical evaluation before planned hysterectomy.

Adult↗

Characterization of H. parasuis periplasmic nucleotide pyrophosphatase as a potential target enzyme for inhibition of growth.

The periplasmic nucleotide pyrophosphatase from Haemophilus parasuis was purified 750-fold to electrophoretic homogeneity through salt fractionation and ion-exchange and affinity chromatography. The purified enzyme was monomeric with an apparent M(r) of 70,000 and catalyzed the hydrolysis of the pyrophosphate bond of NAD to yield NMN and AMP as products. The enzyme exhibited negative cooperativity in the hydrolysis of a number of pyridine dinucleotides and structurally-related pyrophosphate compounds as indicated by biphasic double-reciprocal plots and Hill coefficients of 0.5. The kinetic parameters, K(m) and Vm, determined titrimetrically and analyzed through computer programs, were used to compare the relative effectiveness of dinucleotides containing nitrogen bases other than nicotinamide or adenine to that of NAD. Effective substrate-competitive inhibition of the pyrophosphatase was observed with purine and pyrimidine nucleoside diphosphates in the low micromolar concentration range. Although less effective, N1-alkylnicotinamide chlorides also inhibited competitively with respect to the substrate, NAD. In addition to being an effective inhibitor of the purified enzyme, adenosine diphosphate also inhibited growth of H. parasuis at a low micromolar concentration. This inhibition of growth correlates well with inhibition of the periplasmic pyrophosphatase which is supported by the fact that adenosine diphosphate does not effectively inhibit growth when the pyrophosphatase is by-passed by growth on nicotinamide mononucleotide. These observations are all consistent with the periplasmic nucleotide pyrophosphatase being essential for the growth of the organism on NAD and therefore, a very important enzyme with respect to the pathogenesis of the organism. 3-Aminopyridine mononucleotide, which also inhibited growth of H. parasuis at a low micromolar concentration, did not effectively inhibit the purified pyrophosphatase and a different target enzyme needs to be considered to explain growth inhibition by this derivative.

Binding, Competitive↗

The prenatal sonographic appearance of enteric duplication cysts.

Enteric duplication cysts are rare lesions, and relatively few cases have been diagnosed prenatally. We report two cases with a distinctive presentation. One, a duplication of the antrum of the stomach, was adjacent to an extralobar pulmonary sequestration. The other, a duodenal duplication, appeared as a thick-walled right lower quadrant cyst. We observed distinct peristalsis in this cyst, a finding that helped us make a firm diagnosis of enteric duplication.

Adult↗

Purification and characterization of Azotobacter vinelandii glucose-6-phosphate dehydrogenase: dual coenzyme specificity.

Azotobacter vinelandii glucose-6-phosphate dehydrogenase isolated from cell sonicates was purified 81-fold to electrophoretic homogeneity and a specific activity of 73 units/mg protein using ion-exchange and Matrex Dye chromatography. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and molecular exclusion chromatography indicated the enzyme to be a tetramer composed of 52,000 M(r) subunits. The enzyme utilized both NAD and NADP as coenzymes with Km values of 220 and 50 microM, respectively. In addition, the purified enzyme functioned well with the thionicotinamide analogs of NAD and NADP. A sigmoidal response was observed in studies of the effect of glucose 6-phosphate concentration on initial velocities. Evidence in support of one enzyme with dual coenzyme specificity was obtained in purification, thermodenaturation, and inhibitor studies. The enzyme exhibited a pH optimum of 8.5. Coenzyme-competitive inhibition was observed with nine adenosine derivatives with no significant selectivity shown for 2'-phosphoryl derivatives. Ki values for product inhibition by NADH and NADPH were higher than the Km values for the respective oxidized forms of the coenzymes.

Adenine Nucleotides↗

Dexamethasone induction of taxol metabolism in the rat.

This study examined the effect of dexamethasone (DEX), 100 mg/kg/day for 3 days, on [3H]taxol metabolism in liver microsomes and hepatocytes of male and female Sprague-Dawley rats. In control rats, two isomeric monohydroxylated metabolites, M1 and M2, were formed. The formation of both metabolites was 2-3 times greater in the male than in the female animals. After DEX treatment, M1 increased 2.6-fold in the male animals and 6.5-fold in the female animals. This was accompanied by similar increases in hepatic cytochrome P4503A protein and testosterone 6 beta-hydroxylation. Three additional metabolites (U1, U2, and U3) were formed in the DEX-treated animals only. Isolation of these metabolites from rat hepatocyte incubates by reversed-phase HPLC permitted structure identification of U2 and U3, using tandem MS. The mass spectrum of U3 was consistent with deacetylation of taxol, whereas the mass spectrum of U2 was consistent with deacetylation of the monohydroxylated taxol metabolite M2. A comparison of HPLC and MS data for U3 with those of standard 10-deacetyltaxol suggested that the site of deacetylation might be the 4-position of the taxane ring. Preliminary observations indicate that the deacetylation is caused by a DEX-inducible cytochrome P450.

Animals↗

Purification and characterization of Clostridium difficile glutamate dehydrogenase.

Recombinant Clostridium difficile glutamate dehydrogenase (L-glutamate:NAD oxidoreductase, EC 1.4.1.2) was purified 177-fold to electrophoretic homogeneity with a 62% recovery through a four-step procedure involving gel filtration and ion-exchange and dye affinity chromatography. The approximate molecular weights of the native enzyme by gel filtration and subunits by sodium dodecyl sulfate-polyacrylamide gel electrophoresis were consistent with a hexameric structure for the purified enzyme. The enzyme-catalyzed glutamate oxidation was an NAD-dependent sequential process in which NADP could not be substituted as coenzyme. Several dinucleotide analogs of NAD structurally altered in either the pyridine or the purine moiety were observed to function as coenzymes when substituted for NAD. Nicotinamide mononucleotide did not serve as a coenzyme for glutamate oxidation. Product inhibition by NADH was competitive with respect to NAD. In deadend inhibition studies, adenosine diphosphoribose was shown to be an effective coenzyme-competitive inhibitor.

Chromatography, Affinity↗

Preparation and characterization of the NAD vinylogue, 3-pyridylacryloamide adenine dinucleotide.

The vinylogue of NAD, 3-pyridylacryloamide adenine dinucleotide, was prepared from NAD and 3-pyridylacryloamide through the snake venom NADase-catalyzed transglycosidation reaction. The analog, purified by ion-exchange chromatography, was obtained in a 55% yield. The cyanide adduct and reduced form of the analog exhibited absorbance maxima at 358 nm and 378 nm, respectively, with extinction coefficients in each case being 2.3-times higher than those reported for the corresponding NAD derivatives. 3-Pyridylacryloamide adenine dinucleotide served as a coenzyme with bovine liver glutamic dehydrogenase and to a lesser extent with malate and lactate dehydrogenases. The analog was not reduced in reactions catalyzed by yeast and horse liver alcohol dehydrogenases, sheep liver sorbitol dehydrogenase, and rabbit muscle glycerophosphate dehydrogenase. Substitution of the pyridylacryloamide analogs for NAD and NADH in the assay of substrates for glutamic dehydrogenase was demonstrated.

Coenzymes↗

Nonpolar interactions in the modification of an essential sulfhydryl of sorbitol dehydrogenase by N-alkylmaleimides.

A series of N-alkylmaleimides varying in chainlength from N-methyl- to N-octylmaleimide inclusive was shown to effectively inactivate sheep liver sorbitol dehydrogenase at pH 7.5 and 25 degrees C. The apparent second-order rate constants for inactivation increased with increasing chainlength of the N-alkylmaleimide used. Positive chainlength effects were also indicated by the Kd values for the N-ethyl and N-heptyl derivatives obtained from studies of the saturation kinetics observed for inactivation of the enzyme at high concentrations of these maleimides. The complete inactivation of sorbitol dehydrogenase was demonstrated to occur through the selective covalent modification of one cysteine residue per subunit of enzyme. The stoichiometry of enzyme inactivation was supported on the one hand by fluorescence titration with fluorescein mercuric acetate of the native and the inactivated enzyme, and, on the other hand, by the simultaneous inactivation of the enzyme with selective modification of one sulfhydryl per subunit by N-[p-(2-benzoxazolyl)phenyl]maleimide. Protection of the enzyme from N-alkylmaleimide inactivation was observed with the binding of NADH, whereas both NAD and sorbitol were ineffective as protecting ligands. Diazotized 3-aminopyridine adenine dinucleotide, in contrast to previous studies of this reagent with yeast alcohol dehydrogenase and rabbit muscle glycerophosphate dehydrogenase, did not function as a site-labeling reagent for sorbitol dehydrogenase.

Animals↗