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Biomedical subjects

R K Thompson

Publications and source records attributed to R K Thompson.

16 recordsLinked to original sources
PubMed2001

Heterogeneous response of antimitochondrial autoantibodies and bile duct apical staining monoclonal antibodies to pyruvate dehydrogenase complex E2: the molecule versus the mimic.

The 2-oxo-acid dehydrogenase complexes and, in particular, the E2 component of the pyruvate dehydrogenase complex (PDC) are the target of antimitochondrial antibodies (AMA). More than 95% of primary biliary cirrhosis (PBC) patients have detectable levels of autoantibodies to PDC-E2 and in general these react with a region of the molecule that contains the prosthetic group lipoic acid (LA). LA is vital to the function of the enzyme, although there is conflicting evidence as to whether its presence is required for PDC-E2 recognition by AMA. Some, but not all, monoclonal antibodies (mAbs) to PDC-E2 produce an intense staining pattern at the apical surface of bile duct epithelial cells (BEC) in patients with PBC, and it has been argued that the molecule at the apical surface of PBC bile duct cells is a modified form of PDC-E2 or a cross-reactive molecule, acting as a molecular mimic. Herein, we characterize the epitopes recognized by 4 anti-PDC-E2 mAbs that give apical staining patterns (3 mouse and 1 human). In particular, by using a combination of recombinant antigens, competitive inhibition assays, and a unique peptide-on-bead assay, we determined that these apically staining mAbs recognize 3 or 4 distinct epitopes on PDC-E2. More importantly, this suggests that a portion spanning the entire inner lipoyl domain of PDC-E2 can be found at the BEC apical surface. In addition, competition assays with patient sera and a PDC-E2-specific mAb showed significant epitope overlap with only 1 of the 3 mouse mAbs and showed a differential response to the peptide bound to beads. These findings further highlight the heterogeneous response of patient autoantibodies to the inner lipoyl domain of PDC-E2.

Amino Acid Sequence↗
PubMed1998

In vivo activity and pharmacokinetic evaluation of a novel long-acting carbapenem antibiotic, MK-826 (L-749,345).

MK-826 (formerly L-749,345), is a potent 1-beta-methyl carbapenem with a long half-life and broad spectrum of activity. This compound is presently in phase-II clinical trials. Its activity against a number of gram-positive and gram-negative organisms was compared to those of imipenem (IPM) and eight other beta-lactam agents in two in vivo murine infection models. The distribution in tissue and pharmacokinetic properties of MK-826 and ceftriaxone (CTRX) were also evaluated in CD-1 mice following a single intraperitoneal dose (10 mg/kg of body weight). In addition, concentrations in plasma as well as biliary and urinary recovery of MK-826 were compared to that of CTRX in a cannulated rat model. In a localized murine thigh infection model, MK-826 and IPM were superior to a variety of beta-lactam antibiotics in reduction of Staphylococcus aureus CFU compared with results from nontreated controls (eliminating >/=4 log10 CFU). Similar activities of IPM and MK-826 were observed in a gram-positive bacterial murine systemic infection model. While IPM demonstrated greater efficacy than MK-826 against Enterobacter cloacae (50% effective doses [ED50s] of 0.062 and 0.227 mg/kg, respectively) and Pseudomonas aeruginosa (ED50s of 0.142 and 3.0 mg/kg, respectively) systemic infections, MK-826 was 8- to 350-fold more efficacious than IPM against all other gram-negative organisms in this infection model. In mice, MK-826 demonstrated a higher peak concentration in serum (62.8 versus 42.6 microg/ml) and a larger area under the curve (AUC) (150.8 versus 90.0 microg . hr/ml) than CTRX. The concentrations of MK-826 and CTRX in serum declined slowly, with levels of 3.6 and 2.0 microg/ml remaining, respectively, at 6 h posttreatment. The rat pharmacokinetic model showed the average AUC of MK-826 to be greater than that of CTRX (284 versus 142 microg . hr/ml) following a single 10-mg/kg dose. Also, a half-life of MK-826 longer than that of CTRX (3.2 versus 2.3 h) was observed in this species. The total amount of drug excreted in the bile in 8 h was greater for CTRX (55 to 64% of the dose) than for MK-826 (6 to 12.5% of the dose). Urinary recovery was similar for both antibiotics, with 16 to 18% of the dose recovered over an 8-h period. This excellent broad-spectrum in vivo efficacy of MK-826, together with advantageous pharmacokinetics, supports the argument for its further clinical development.

Animals↗
PubMed1997

Language-naive chimpanzees (Pan troglodytes) judge relations between relations in a conceptual matching-to-sample task.

Three chimpanzees with a history of conditional and numeric token training spontaneously matched relations between relations under conditions of nondifferential reinforcement. Heretofore, this conceptual ability was demonstrated only in language-trained chimpanzees. The performance levels of the language-naive animals in this study, however, were equivalent to those of a 4th animal--Sarah--whose history included language training and analogical problem solving. There was no evidence that associative factors mediated successful performance in any of the animals. Prior claims of a profound disparity between language-trained and language-naive chimpanzees apparently can be attributed to prior experience with arbitrary tokens consistently associated with abstract relations and not language per se.

Animals↗
PubMed1991

Acute traumatic midbrain hemorrhage: experimental and clinical observations with CT.

Traumatic brain stem hemorrhage (TBH) after blunt head impact is an uncommon injury and has historically been associated with high mortality. Retrospective clinical review identified 64 patients with TBH admitted during a 5-year period. Complete imaging and clinical records for 45 of these patients demonstrated that TBH could be categorized into three groups. The most frequent site of hemorrhage, in 31 (69%) of 45 patients (group 1), was the midline rostral anterior brain stem, posterior to the interpeduncular cistern, and this injury was associated with a 71% survival rate. This pattern was also associated with a predominantly anterior site of head and/or face impact. Eight (18%) patients (group 2) had miscellaneous foci of acute brain stem hemorrhage with seven (88%) surviving. Six (13%) patients (group 3) had brain stem hemorrhage associated with transtentorial herniation and brain stem compression, with 100% mortality. Experimental findings in a canine model and clinical results indicate that the anterior rostral midbrain is a common site of TBH and appears to arise from sudden craniocaudal displacement of the brain at impact. Survival is unexpected high with this location of traumatic midbrain hemorrhage.

Acute Disease↗
PubMed1990

Infant chimpanzees spontaneously perceive both concrete and abstract same/different relations.

We used a familiarization-novelty procedure to determine whether 4 infant chimpanzees spontaneously perceive the sameness of and the difference between both concrete objects and relations between objects. In Experiment 1, a single object was presented on the Familiarization Trial 1 and the animal's looking time recorded. On the Test Trial 2, an object was presented that was either identical to or different from that shown on Trial 1. Looking times on Test Trial 2 were less when the same item had been presented on the preceding familiarization trial. Novel items on Trial 2 were attended to longer, indicating that the infant chimpanzees perceived concrete objects were either the same or different. In Experiment 2, a single pair of objects was presented on the Familiarization Trial 1, and handling time was measured. The objects in a pair were either the same or different (e.g., AA vs. CD). On the Test Trial 2, a new object pair (e.g., BB vs. EF) was presented that instantiated either the relation shown on Trial 1 or the alternative relation. Handling time on Trial 2 was influenced by the relation instantiated on Trial 1. Handling times on Test Trial 2 were less when the identical relation had been presented on the preceding familiarization trial. Novel relations on Trial 2 were attended to relatively longer. This result indicates that infant chimpanzees perceive similarities and differences between abstract relations as well as between concrete objects. That is to say, they perceived relations between relations in Experiment 2. Despite this ability to perceive both concrete and abstract "same/different" relations, the same chimpanzees subsequently failed to use the latter knowledge in a matching-to-sample task in Experiment 3. Although they successfully matched single objects, they were unable to match object pairs instantiating the same relation (e.g., if AA then match BB; if CD then match EF). These results contradict claims that failure to learn an instrumental discrimination involving abstract relations reflects an inability to detect such relations. In every species there may be a disparity between the ability to perceive spontaneously a property of the world and the ability to use the concept instrumentally.

Aging↗
PubMed1989

von Hippel-Lindau syndrome presenting as pancreatic endocrine insufficiency: a case report.

The visceral manifestations of von Hippel-Lindau syndrome rarely are clinically significant until late in the disease process. Pancreatic endocrine insufficiency in the syndrome is extremely uncommon. We report a case of a 32-year-old woman with von Hippel-Lindau syndrome whose initial diagnosis came to light because of a clinical presentation with complications related to pancreatic endocrine insufficiency.

Adult↗
PubMed1988

Brain stem hemorrhage: historical perspective.

Brain stem hemorrhage was first recorded in 1812. Its origin has been the subject of much study and experimentation. We review the studies that stress mechanical forces because dynamic axial distortion of the brain stem is a major factor in the physiology and pathology of the central nervous system.

Brain Stem↗
PubMed1988

Dynamic axial brain stem distortion as a mechanism in the production of brain stem hemorrhages: role of the carotid arteries.

Dynamic axial distortion of the brain stem has long been recognized as occurring in the presence of supratentorial mass lesions. Although brain stem hemorrhages occur under these circumstances, the pathophysiology of these hemorrhages is still a matter of controversy. In the present study, the role of the carotid arteries in tethering the brain stem was evaluated during dynamic axial distortion of the neuraxis of the dog. Brain stem hemorrhages occurred in 32 of 48 dogs in which the carotid arteries were left intact (67%) and in only 9 of 46 animals in which the carotid arteries were sectioned (20%). The difference between the two groups is statistically significant (chi 2 = 19.3; P less than 0.001). In this study, we can eliminate intracranial pressure as the primary cause of the lesions because a single variable is present in one series and absent in the other, whereas intracranial pressure and its duration are kept constant. It is concluded that the tethering effect of the carotid arteries is a significant factor in the production of brain stem hemorrhages in the dog by dynamic axial distortion of the brain stem. A selective review of the literature on production of brain stem lesions is provided to support these findings.

Animals↗
PubMed1988

Spontaneous transfer of matching by infant chimpanzees (Pan troglodytes).

Four infant chimpanzees learned a matching-to-sample task when only two training stimuli were used. They then spontaneously transferred the matching concept to novel items, including three-dimensional objects and fabric swatches, without any experimenter-provided differential feedback. These results support the view that the matching concept is broadly construed by chimpanzees from the beginning and does not depend upon explicit training.

Animals↗
PubMed1983

Day-case cataract surgery.

The results of 501 day-case cataract extractions are presented. This is a safe way to manage an operation for which there will be an increased demand. Only 13% of these patients stated that they would have preferred to stay in hospital after surgery.

Aged↗
PubMed1980

Day-case cataract surgery.

This is a report of prospective trial to compare day-case and inpatient surgery for senile cataract. In this district, cataract extraction is usually delayed until bilateral surgery is warranted. Both eyes are then operated upon a week or so apart. Such patients are ideal for comparing the results of day-case and in-patient management, since if one eye is done by each method, there is a perfect match for age, sex, general medical health, and domestic circumstances. During a period of 27 months, 138 patients aged 50 years or over were included in this trial. Five more patients were dropped from the trial and 78 other cataract operations were performed outside the trial for various reasons. For those included in the trial, the eye with the worse vision was operated upon first and patients were randomly allocated to have this eye managed as a day-case or an inpatient. All these operations were performed by the same surgeon (D.B.). Details of events during the 48 hours after surgery were kept (M.J.T.) separate from the hospital records used for follow-up (R.M.I.) and refraction (R.K.T.), which were therefore done without knowledge of how each eye had been managed. Visual acuity and intraocular pressure were recorded 2 to 3 months and one year after operation for those in the trial. Visual acuity alone was recorded at 2 to 3 months for those not in the trial. It is concluded that provided the patients are carefully selected, the advantages of day-case surgery outweigh the disadvantages both for patient management and considerations of economy.

Aged↗
PubMed1977

Memory for lists of sounds by the bottle-nosed dolphin: convergence of memory processes with humans?

After listening to a list of as many as six discriminably different 2-second sounds, a bottle-nosed dolphin classified a subsequent probe sound as either "old" (from the list) or "new." The probability of recognizing an old probe was close to 1.0 if it matched the most recent sound in the list and decreased sigmoidally for successively earlier list sounds. Memory span was estimated to be at least four sounds. Overall probabilities of correctly classifying old and new probes corresponded closely, as if recognition decisions were made according to an optimum maximum likelihood criterion. The data bore many similarities to data obtained from humans tested on probe recognition tasks.

Animals↗