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Biomedical subjects

B R Moore

Publications and source records attributed to B R Moore.

29 records · Page 2Linked to original sources

A developmentally controlled change in the post-translational modifications on the lysosomal alpha-mannosidase of the cellular slime mould Dictyostelium discoideum.

During the development of the cellular slime mould Dictyostelium discoideum, a second form of a number of lysosomal enzymes begins to accumulate. The second ('late') form of these enzymes differs from the pre-existing ('early') form in post-translational modification. Pulse-chase experiments using [35S]methionine show that the late form of alpha-mannosidase-1 is made by synthesis de novo starting 8 h after the onset of development. These experiments show there is no interconversion between early and late forms in vivo. A one-dimensional peptide map indicated that the early and late forms of alpha-mannosidase have similar amino acid sequences. The two forms have a similar half-life in vivo when measured during the same period of development. Double-labelling studies were performed with 35SO4 and [3H]leucine or 32PO4 and [3H]leucine. and these studies indicated that the oligosaccharides present on the early form of alpha-mannosidase contained more sulphate and phosphate than did those on the late form. The early enzyme had a 10-fold higher 35S/3H ratio and a 4-fold higher 32P/3H ratio. Endocytosis experiments using early and late alpha-mannoside showed that the early form was efficiently taken up by human fibroblasts, whereas the late form was poorly endocytosed. This suggests that the late form lacks the mannose 6-phosphate residue required for efficient uptake.

Chromatography, Affinity↗

Protein modification and its biological role.

The modifications present on a polypeptide play an important role in determining its eventual fate. Modifications, particularly proteolysis, are important in the generation of biological activity. Modifications are used to "target" particular polypeptides to specific cellular locations. Protein modification also plays a role in determining the rate of polypeptide degradation. Cells have developed elaborate systems for the modification of their proteins because these modifications serve important biological functions.

Amino Acid Sequence↗

Changes in the post-translational modification of lysosomal enzymes during development of Dictyostelium.

The form of post-translational modification present on two lysosomal enzymes--acid phosphatase and alpha-mannosidase--changes as part of the developmental program of Dictyostelium discoideum. Prior to 8 h of development, all enzyme molecules are of a single modification type (early form enzyme). Starting at 8 h of development, enzyme molecules with a second type of modification (late-form enzymes) begin to appear in the cell. We separated the early and late forms of these enzymes from each other by chromatography on DEAE-cellulose. We found that the change in protein modification affects the enzymes' in vitro properties. The early and late forms of both of these enzymes differ in thermostability and susceptibility to proteolytic inactivation. We also found that the late form of alpha-mannosidase is preferentially secreted. We suggest that by synthesizing molecules with a second form of modification, the cell confers new characteristics to its lysosomal enzymes.

Acid Phosphatase↗

Dr. Guthrie and Felis domesticus or: tripping over the cat.

The principal reactions described in Guthrie and Horton's classic learning monograph appear to have been caused by the mere presence of the experimenters. Neither escape nor food reinforcement is necessary for the establishment of such responses. They are species-typical "greeting" reactions, readily elicited by the sight of human observers.

Animals↗

The form of the auto-shaped response with food or water reinforcers.

The relation between the form of auto-shaped responses to the lighting of a key and the consummatory responses of pecking grain and drinking water was examined in pigeons. Responses on the key were analyzed by means of high-speed photography, recordings of the force of contact, and judges' ratings of response-form based on film and videotape recordings. The first experiment showed that food-deprived birds presented grain as a reinforcer responded on the key with a grain-pecking movement, while water-deprived birds presented water as a reinforcer responded with drinking-like movements. The second and third experiments showed that the resemblance between auto-shaped and consummatory responses does not require the dominance of the deprivational state appropriate to the reinforcer. Changing the dominant state of deprivation did not immediately change the form of the key response, and in subjects simultaneously deprived of food and water, the form of response depended on the reinforcer. In the fourth and fifth experiments, subjects simultaneously deprived of food and water received one stimulus signalling food and another signalling water in a random series. In most subjects, the response to each stimulus resembled the consummatory response to the particular reinforcer that was signalled by the stimulus. This result demonstrates the role of association between a stimulus and a reinforcer in producing a resemblance of the auto-shaped response to the consummatory response.

Animals↗

Colonic luminal pressure in horses with strangulating and nonstrangulating obstruction of the large colon.

Colonic luminal pressure (median, range) measured during ventral midline celiotomy in 69 horses with strangulating obstruction (SO) of the large colon (SO; > or = 270 degrees large colon volvulus; 27 cm H2O: 2 to 80 cm H2O) was greater (P = .0023) than that measured in 37 horses with nonstrangulating obstruction (NSO) of the large colon (NSO; < or = 180 degrees volvulus or a nonstrangulating displacement; 18 cm H2O; 6 to 46 cm H2O). Sixty-five percent (45 of 69) of horses with SO and all horses with NSO survived. Survival analysis was restricted to 59 horses with large-colon SO that survived to hospital discharge or met the criteria specified for classification as nonsurvivors. Colonic luminal pressure in nonsurvivors (48.5 cm H2O; 34 to 80 cm H2O) was higher (P =.0001) than that measured in survivors (18 cm H2O; 2 to 50 cm H2O) of SO. From response operating characteristic curves, a luminal pressure of 38 cm H2O optimized the distribution of horses with SO into survivor and nonsurvivor groups. Sensitivity, specificity, and positive and negative predictive values for a colonic luminal pressure greater than 38 cm H2O in predicting nonsurvival were 0.89, 0.91, 0.72 and 0.97, respectively. Measurement of colonic luminal pressure may be useful for predicting survival in horses with colonic volvulus.

Animals↗

Heparin: a review of its pharmacology and therapeutic use in horses.

Heparin is used clinically in horses to treat hemostatic abnormalities associated with severe gastrointestinal disease, septicemia, and endotoxemia. The primary anticoagulant effect of heparin is through the suppression of thrombin-dependent amplification of the coagulation cascade, and inhibition of thrombin-mediated conversion of fibrinogen to fibrin. Heparin may be of benefit in preventing the complications associated with hypercoagulable states such as jugular vein thrombosis, laminitis, and organ failure. Heparin may also be beneficial in the prevention of intraabdominal adhesions after gastrointestinal surgery, and in amelioration of hemodynamic abnormalities associated with endotoxic shock. Because a sequential rise in serum heparin concentration occurs during a uniform dosage regimen, a decreasing dosage regimen is recommended. The initial dose recommended is 150 U heparin/kg body weight subcutaneously, followed by 125 U heparin/kg body weight subcutaneously, every 12 hours for six doses. The dose should be decreased to 100 U heparin/kg body weight subcutaneously, every 12 hours, after the seventh dose. Anemia, hemorrhage, thrombocytopenia, and painful swelling at injection sites are complications of heparin administration in horses.

Animals↗

Hyperlipemia in 9 miniature horses and miniature donkeys.

The medical records from 9 consecutive miniature horses (n = 5) and miniature donkeys (n = 4) with hyperlipemia (serum triglyceride concentration > 500 mg/dL) were reviewed. In all cases, hyperlipemia was a secondary complication of a primary systemic disease including septicemia, colitis, parasitism, esophageal obstruction, gastric impaction and rupture, fecalith, and pituitary adenoma. Therapy consisted of specific treatment for the primary disease, supportive care, and nutritional support. The mean time for resolution of hyperlipemia in cases requiring nutritional support (n = 6) was 7 days, and the duration of nutritional support in surviving patients was 11.7 days. Seven of 9 patients survived. The primary disease resulted in death in 2 patients. Enteral feeding with commercially prepared low residue diets and treatment of the primary disease was successful in reversing hyperlipemia in 5 of 6 surviving patients that required nutritional support. Parenteral administration of a glucose-based (non-lipid) solution was successful in resolving hyperlipemia in 1 patient.

Animals↗

Necrotizing enterocolitis in horses: a retrospective study.

The clinical and clinicopathologic characteristics of fatal necrotizing enterocolitis were examined in 16 horses (age 4 months to 12 years). At initial presentation, 8 of 16 horses were pyrexic (median temperature, 38.4 degrees C; range, 33.8 to 40.6 degrees C); all 16 were tachycardic (median heart rate, 93 bpm, range, 66 to 138 bpm); 13 of 16 were tachypneic (median heart rate, 36 bpm, range, 16 to 80 bpm), dehydrated, and had discolored mucous membranes. All horses that were pyrexic were also tachycardic and tachypneic. PCV was high (> 45%) in 14 horses. Six horses were leukopenic (< 5,000 cells/microL); 12 were neutropenic (< 2,300 cells/microL), and 14 had > 100 band neutrophils/microL. Twelve horses were acidemic (pH < 7.37; range, 6.88 to 7.33) and the venous bicarbonate concentration was low (< 23 mEq/L) in 14 horses. Median anion gap in 16 horses was 31.5 mEq/L (> 15 mEq/L in 15 horses). Eleven of 16 horses were hyponatremic (< 137 mEq/L), 1 horse was hypernatremic (> 143 mEq/L), 3 were hypokalemic (< 3.2 mEq/L), 6 were hyperkalemic (> 4.5 mEq/L), and 14 were hypochloremic (< 98 mEq/L). Serum creatinine concentrations were high (> 1.4 mg/dL) in 15 horses. Abdominal fluid was examined in 12 horses 4 had total protein concentrations > 2.5 g/dL and 6 had nucleated cell counts > 5,000/ microL and < 10,000/microL; none had > 10,000/microL. Eight of 12 samples revealed a nondegenerate neutrophilia (> 50%). Abdominal fluid collected from 4 horses immediately before death was normal in 2 horses and indicative of suppurative inflammation in 2. All 8 horses tested had low or nonexistent serum immunofluorescent antibody titers to Ehrlichia risticii. Four of 16 horses had Salmonella spp isolated from feces or tissues. All 16 horses either died (5 of 16; 31%) or were euthanized because of a grave prognosis. Median time to death was 45.5 hours (range, 7 to 113 hours) from the time of admission. Death was preceded by severe abdominal pain in 14 horses. Fatal necrotizing enterocolitis of horses is characterized by a brief course, profound dehydration, electrolyte derangements, acid-base abnormalities, and terminally, severe abdominal pain. Abdominal fluid analysis was frequently not indicative of the severity of disease.

Acid-Base Equilibrium↗