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Biomedical subjects

A Stubbs

Publications and source records attributed to A Stubbs.

13 recordsLinked to original sources
PubMed1998

TCR usage by homocysteine-specific human CTL.

We have recently demonstrated that homocysteine can modify HLA class I Ags and induce homocysteine-specific CTL (Hom-CTL) responses in humans. Here, we have investigated TCR usage by Hom-CTL from five patients with ankylosing spondylitis or reactive arthritis. TCR of HLA-A68-restricted Hom-CTL from two unrelated donors share the same TCR Valpha, Vbeta, and Jbeta gene segments (AV4, BV23, and BJ2S1, respectively) with similar third complementarity determining regions (CDR3) of the beta-chains. Interestingly, the Va and Vbeta gene segments employed by an HLA-B27-restricted Hom-CTL clone are also closely related to AV4 and BV23, indicating strong selection pressure for AV4, BV23, and related gene products in the homocysteine-specific TCR. An arginine or lysine residue frequently appeared at position alpha93 in the CDR3 of the TCR alpha-chains from Hom-CTL restricted by HLA-A68 or -B8. This may suggest a potential salt bridge between the carboxyl group of homocysteine and specific TCR. TCR usage by HLA-B27-restricted Hom-CTL from unrelated individuals appears to be less conserved, although two T cell clones from one individual rearranged the same V gene segments with identical lengths of CDR3. Implications of these data for the molecular mechanisms for homocysteine modification of HLA Ags are also discussed.

Amino Acid Sequence↗
PubMed1998

MT1-MMP and MMP-2 mRNA expression in human ovarian tumors: possible implications for the role of desmoplastic fibroblasts.

Expression of activated MMP-2 (72 kDa type IV collagenase) is highly associated with the malignant phenotype in adenocarcinomas, but predominant expression of the mRNA appears to be in stromal cells. MT1-MMP (membrane type 1-matrix metalloproteinase) is implicated in tumor-epithelial cell surface activation of latent pro-MMP-2, indicating a mechanism for tumor-stromal interaction in invasion. We determined the relative mRNA distribution of these MMPs in human ovarian tumors with a view to analyzing potential variations in the epithelial-mesenchymal interactions dictating ovarian tumor cell spread. In situ hybridization using 35S-labeled riboprobes was used to analyze 33 human ovarian tumors and mouse xenografts of human ovarian (DOV 13, SKOV3) and breast (MCF 7) tumor cell lines known to express MT1-MMP and MMP-2. MMP-2 mRNA was expressed in 31 of 33 and MT1-MMP mRNA was expressed in 29 of 33 tumor cases. MMP-2 mRNA was predominantly expressed in desmoplastic fibroblasts and in the subepithelial stroma. MT1-MMP mRNA showed some colocalization with MMP-2 in stromal cells. Neoplastic epithelial cell labeling for MT1-MMP mRNA was present in borderline and malignant tumors but not in benign tumors, and was invariably less than stromal labeling. Xenografts of DOV 13, SKOV 3, and MCF 7 cells showed some stromal localization of MMP-2 mRNA and weak labeling of DOV 13 cells. There was variable labeling for MT1-MMP mRNA in the neoplastic cells only. The colocalization of MT1-MMP and MMP-2 mRNAs in ovarian carcinoma stroma supports the view that MT1-MMP is closely associated with MMP-2 expression and function. It suggests that either additional mechanisms are involved in regulating MMP-2 activation at the tumor cell surface, or more intriguingly, that desmoplastic fibroblasts may be the primary mediators of extracellular matrix remodeling with respect to this system.

Actins↗
PubMed1997

Prostate cancer; the interface between pathology and basic scientific research.

Current research into prostate cancer increasingly demands greater input from pathologists. There is a requirement for improved morphological assessment, classification and grading of neoplasia. The provision of optimally preserved material and establishment of tissue 'banks' is vital to facilitate molecular biological analysis. Microdissection of archival material can provide a source of relatively pure DNA and mRNA which can 'be further amplified by PCR/RT-PCR. This enables allelic imbalance, point mutations and other genetic abnormalities to be demonstrated. In-situ hybridization for mRNA is feasible on fixed tissues and allows precise localization of gene expression on complex tissues or for labile gene products. Experimental models including transgenic mice and in-vitro co-culture systems require sophisticated morphological analysis. Experts in morphological analysis are essential members of basic scientific and translational research teams.

Animals↗
PubMed1987

Limy 'milky' bile: without apparent gall-bladder obstruction by a gallstone.

Limy bile, characterized by excessive precipitation of calcium carbonate, is an uncommon complication of gallstone disease, and is a condition that seems to follow gall-bladder obstruction. Limy bile was observed at cholecystectomy in a 57 year old woman who presented with biliary colic. At operation a mass of precipitated cohesive crystals, that had coalesced into a whitish paste of calcium carbonate, was observed obstructing the outlet of the gall-bladder. This case report is unique in that calcium carbonate precipitation appears to have preceded gall-bladder obstruction.

Bile↗
PubMed1982

Teaching clinical skills to pre-clinical medical students: integration with basic science learning.

Clinical skills are usually learned by pre-clinical students in a manner divorced from their basic science foundations. The value of previously learned basic sciences thus fails to be re-enforced. A clinical skills course was developed for an experimental curriculum of medical students in their first year. It was organized and taught by a team of basic and clinical scientists and emphasized the basic pathophysiological principles underlying clinical skills. Sessions were supported by related basic science audiovisual resources and a series of clinical problems with questions obliging the student to reason through basic-science mechanisms. Over the span of the course, students' interest shifted dramatically from a focus on proficiency in motor skills to an understanding of basic pathophysiological mechanisms underlying observed phenomena. Compared to conventional curriculum students, those in the experimental curriculum failed to show a diminution in perceived value of basic sciences in their future career and, on cumulative, cognitive examinations, scored equally in basic science, but significantly higher in clinical science subjects. A clinical skills course integrating both teachers and concepts from basic, as well as clinical sciences can improve student attitudes toward basic sciences.

Clinical Competence↗
PubMed1978

Localization of vasodilator dopamine receptors in the canine hindlimb.

1 Vascular responses to local injection of dopamine and isoprenaline have been compared in the blood-perfused gracilis muscle and hind paw pads of dogs anaesthetized with chloralose. 2 In the paw pads, dopamine (0.5 to 5.0 microgram) caused a transient vasoconstriction followed by dose-dependent vasodilatation. alpha-Adrenoceptor blockade converted this response to pure vasodilatation, which was attenuated or abolished by the dopamine-receptor antagonist, haloperidol (1 to 2 mg i.a.). In the gracilis, dopamine produced only vasoconstriction. Following alpha-adrenoceptor blockade this was abolished, but only a very small dilator response was revealed. 3 Isoprenaline (0.05 to 0.5 microgram) caused dose-dependent dilatation in both beds, which was attenuated by propranolol (0.1 mg/kg i.v.). 4 Glyceryl trinitrate (0.2 to 5.0 microgram) was used to assess vascular reactivity. When responses to isoprenaline and dopamine were compared with those to glyceryl trinitrate, both beds had approximately equal reactivity to isoprenaline. In contrast the paw pads were 10 fold more responsive to dopamine than was the gracilis. 5 We conclude that the vessels of the paw pads play an important part in the femoral dilator response to dopamine.

Animals↗
PubMed1970

Conditioned reinforcement and discrimination performance.

Pigeons were trained in a three-key chamber to peck one side key in the presence of a vertical line on the center key and to peck the other side key in the presence of a horizontal line. Correct choice responses were reinforced with food according to fixed- and variable-ratio, fixed-interval, and differential-reinforcement-of-long-latency schedules of reinforcement. For each schedule, the birds performed under each of two conditions: (1) each correct choice response produced a brief presentation of stimuli intermittently paired with food, then the next trial; (2) each correct choice response produced an intertrial interval only. For all schedules except one long latency schedule, response rates were higher under the condition of brief stimulus presentation than under the comparable control condition. Presentation of brief magazine stimuli increased choice accuracy. The amount of change in accuracy was correlated with the rate of food presentation. Performance under the schedules with highest food reinforcement rates showed no enhancement; performance under the schedules with the lowest reinforcement rates showed the greatest enhancement.

Journal Article↗
PubMed1969

Contiguity of briefly presented stimuli with food reinforcement.

Pigeons performed on second-order schedules of reinforcement consisting of four fixed-interval components. Only the terminal component ended with food. Performance was studied both when a brief stimulus followed the completion of each of the first three fixed intervals (brief-stimulus schedule) and when the stimulus was omitted (tandem schedule). Variations in the temporal contiguity of the last presentation of the stimulus and the presentation of food indicated that the shorter the delay, the greater was the enhancement of rate of responding in comparison with tandem performance. A positively accelerated pattern of responding within fixed-interval components was a function of the contiguity of the brief stimulus and reinforcement; this pattern was absent for all tandem-schedule performance.

Journal Article↗
PubMed1968

The discrimination of stimulus duration by pigeons.

Pigeons were trained to discriminate the duration of a stimulus. One response in a psychophysical choice situation was reinforced, given the immediately prior presentation of a stimulus duration in one class of durations called short durations, and the other response was reinforced given the immediately prior presentation of a stimulus duration in a second class called long durations. Durations of equal logarithmic difference from the cutoff, whether in the short or long class, yielded equal accuracy. Accuracy was a function not only of the properties of the stimuli to be discriminated, but also of the experimental contingencies used. Accuracy was greater in variable-ratio than in fixed-ratio schedules of reinforcement of the discriminative responses, and was lower at the beginning than later in individual fixed ratios. Proportion of short or long responses (response bias) was affected by sequential dependencies among long and short durations and was effectively controlled through the use of asymmetric reinforcement and fixed-ratio contingencies.

Animals↗
PubMed1967

Stimulus control of temporally spaced responding in second-order schedules.

Second-order schedules consisting of sequences of component differential-reinforcement-of-low-rate schedules were used to investigate two different methods of introducing exteroceptive stimuli. When different exteroceptive stimuli were associated with each component (chained schedule), periods of pausing and lower response rates developed in the early components compared to the early components of the same sequence in the presence of a single exteroceptive stimulus (tandem schedule). When a brief stimulus change occurred at the completion of each component, response rates were higher in the early components compared to the tandem schedule. Changes in response rates in the early components were directly related to changes in reinforcement frequency in the terminal components produced by the two methods of presenting the exteroceptive stimuli.

Animals↗