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D A Robinson

Publications and source records attributed to D A Robinson.

At least 37 records · Page 2Linked to original sources

Evidence for the simultaneous expression of two PspAs by a clone of capsular serotype 6B Streptococcus pneumoniae.

Pneumococcal surface protein A (PspA) has been shown to be a serologically variable virulence factor of Streptococcus pneumoniae. In mice, PspA can elicit antibodies capable of protecting them against otherwise fatal infections with encapsulated pneumococci. In previous studies it has been reported that almost all isolates have two apparently unlinked genomic sequences that are highly homologous to the 5' and 3' halves of Rx1 pspA, although out MAbs to PspA have not detected more than one PspA in any given isolate of S. Pneumoniae. Recently, we have identified four isolates from a clone of capsular serotype 6B pneumococci (MC25-28) that simultaneously express two distinct PspAs. Each of the isolates (MC25-28) exhibited the same two Kpn I fragments (each containing a Hind III site) that hybridized with Rx1 pspA. MAbs specific for PspA detected two PspAs characterized by different molecular weights and different serologic patterns of reactivity (PspA type 6 detected by MAbs XiR278 and 2A4, and PspA type 34 detected only by MAb 7D2) in each of the four isolates. In previous studies XiR278 and 2A4 frequently have been observed to react with PspA epitopes of the same strain. Based on molecular weight data both epitopes were always present on the same molecule. Our present findings raise the possibility that pneumococci make a second serologically variable PspA which is generally not detected by currently available MAbs to PspA.

Antigens, Bacterial↗

Synchronous, bilateral mastectomy.

Sixty-four patients (mean age, 51 years) had mastectomies which were synchronous and bilateral. Sixty-one premastectomy biopsies (bilateral, 34 and unilateral, 27) demonstrated the following: invasive carcinoma, 17; noninvasive carcinoma, 24; combination of above, 10; and benign disease, 10. Twenty-two patients had bilateral mastectomy because of bilateral positive biopsy. Twenty-nine patients with unilateral carcinoma on biopsy had bilateral mastectomy. Thirteen patients had bilateral mastectomy despite benign disease only on biopsy (10) or no biopsy (3). Ten unexpected carcinomas (34%) were found in the contralateral breast in the 29 patients with carcinoma diagnosed on unilateral biopsy. The biopsy pathology of these 10 specimens was invasive ductal carcinoma in 1 and multifocal, noninvasive carcinoma (ductal, 3 and lobular, 6) in 9. An unexpected carcinoma may be found in the contralateral breast in a significant number of patients who are selected for bilateral mastectomy, particularly if the selection is on the basis of a noninvasive, lobular histology. Bilateral mastectomy may be appropriate for such patients, particularly when complicated by a strong family history and breasts which are difficult to assess by physical or mammographic examination.

Adult↗

Gain changes of the cat's vestibulo-ocular reflex after flocculus deactivation.

Motor learning can be demonstrated in the vestibulo-ocular reflex (VOR) by changing its gain (eye velocity/head velocity) with goggles and optokinetic (OK) drums. It is known that the flocculus is essential for this plasticity but there is controversy about whether the modifiable synapses mainly responsible are in the flocculus. To investigate this further we utilized the known reciprocal relationship between complex spikes and simple spikes in Purkinje cell discharges. By stimulating climbing fibers from the olive to the flocculus at 7 Hz, the simple spike rate of almost all recorded floccular cells could be driven to zero. This was termed floccular shutdown and it felt to effect a functional, reversible flocculectomy. Sixty single units in the flocculi of four cats were recorded. Stimulation of the climbing fibers at 7 Hz caused the discharge rate to decrease to zero in 95% of these cells. The gain of the horizontal VOR in three cats was driven repeatedly to twice or half its normal value by rotation within a moving OK drum and also by wearing magnifying or fixed-field goggles; this process required 3 days. If, on the 4th day, the cat was exposed to an OK drum rotating in the opposite direction, the gain was driven back to normal in 30 min. If, however, the climbing fibers were stimulated at 7 Hz during these 30 min, the gain did not return--learning was blocked. This verified that loss of floccular activity by this method abolishes VOR gain plasticity. Moreover, when 7 Hz stimulation first began, after 3 days of adaptation, the adapted gain remained at its adapted value, either half or twice normal, even in the face of floccular shutdown. This result appears incompatible with the hypothesis that the modifiable synapses are in the flocculus.

Adaptation, Physiological↗

The natural history of asymptomatic carotid artery disease.

PURPOSE: The purpose of this article is to determine the natural history of carotid artery disease among asymptomatic patients with cervical bruits or other risk factors for stroke and to study the value of duplex ultrasonography in predicting future neurologic events. METHODS: Two hundred forty-two asymptomatic, unoperated patients, referred for evaluation of asymptomatic carotid artery disease, were followed prospectively with duplex ultrasonography. RESULTS: Fifteen ischemic strokes (6.2%) and 20 transient ischemic attacks (TIA) (8.3%) occurred in 34 patients during a mean follow-up of 27.4 months. Annual stroke, TIA, and combined event rates were 2.7%, 3.6%, and 6.2%, respectively. Although patients with 80% to 99% lesions had a 20.6% annual event rate, most events occurred contralateral to these lesions; the vessel-specific annual event rate for 80% to 99% disease was 5.1%. Only one of 15 strokes occurred ipsilateral to an 80% to 99% stenosis. Echolucent plaques were associated with TIA and stroke (5.7% annual vessel event rate vs 2.4% for echogenic plaques, p = 0.03). Disease progression was highly correlated with TIA and stroke (p < 0.0001), but it usually occurred in association with rather than before ischemic events, thus proving more useful in explaining pathogenesis than in predicting future events. There was no association between aspirin use and TIA, but patients taking aspirin had a threefold higher annual stroke rate (1.6% vs 4.8%, p = 0.027). CONCLUSIONS: This study, while confirming significant risk for asymptomatic patients with critical stenosis or echolucent plaque, demonstrates the importance of contralateral disease and the absence of orderly progression from minimal disease through high-grade stenosis to symptomatic cerebral ischemia. TIA and stroke commonly occur in association with abrupt, unpredictable, quantum changes in carotid artery disease.

Adult↗

Visually induced cross-axis postsaccadic eye drift.

1. It has been previously shown that, if a visual pattern is transiently moved just after every saccade, it is possible to induce horizontal, postsaccadic, ocular drift after horizontal saccades that persists in the dark. In this study we show that horizontal ocular drift can also be created after vertical saccades. Five human subjects viewed binocularly the interior of a full-field hemisphere filled with a random-dot pattern. They were encouraged to make frequent vertical saccades. During training, eye movements were recorded by the electrooculogram. A computer detected the end of every saccade and immediately moved the pattern to the left after up saccades and right after down saccades. The motion was exponential, its amplitude was 25% of the vertical component of the antecedent saccade, its time constant was 50 ms. Before and after 2-3 h of training, movements of both eyes were measured by the eye-coil/magnetic-field method while subjects were instructed to make vertical saccades in the dark, in the presence of the movable adapting pattern, and between stationary targets for calibration. 2. After training (approximately 20,000 saccades) all subjects developed a zero-latency, exponential ocular drift to the left after up saccades and to the right after down saccades. The amplitude of the horizontal drift, expressed as a percentage of the vertical component of the preceding saccade, was 2.7% in the dark. This rose to 10.2% in the presence of the movable adapting stimulus. The latter rise is not due to visual following systems but to a zero-latency increase in initial drift velocity. 3. The horizontal drifts were usually unequal between the two eyes, indicating the presence of disconjugate movements. We measured intrasaccadic disconjugate horizontal movements of all subjects. In agreement with studies by others of saccades in the light, we measured a divergence during up saccades (1.3 degrees) and a convergence for down (0.4 degrees), but in this case for spontaneous saccades in the dark. After training, these values increased for saccades in the dark but decreased in the light in the presence of the adapting stimulus. These changes were largely idiosyncratic and statistically significant in only a few subjects. 4. The cross-axis postsaccadic drifts were separated into their conjugate and disconjugate components. The disconjugate components were small and idiosyncratic, and the means were small for saccades in the dark. The only consistent trend was in the presence of the adapting stimulus where up saccades were often followed by convergence.(ABSTRACT TRUNCATED AT 400 WORDS)

Adaptation, Physiological↗

A neural network model of the vestibulo-ocular reflex using a local synaptic learning rule.

Vertebrates use the vestibulo-ocular reflex to maintain clear vision during head movements. This reflex requires eye-velocity commands from the semicircular canals to be integrated (mathematically) to produce eye-position commands for the extraocular muscles. This is accomplished by a neural network in the caudal pons. A model of this network is proposed using positive feedback via lateral inhibition. The model has been adapted to a learning network. We have developed a synaptic learning rule using only local information to make the model more physiological.

Algorithms↗

Safety and efficacy of fire ant venom in the diagnosis of fire ant allergy.

Thirty-three adult patients who had had systemic allergic reactions to fire ant stings and 33 insect-nonallergic control subjects were skin tested with single lots of Solenopsis invicta (Sol i) fire ant venom (IFAV) and two commercially available imported fire ant whole body extracts (IFA WBEs). All three extracts were analyzed for protein concentration. Sol i II and Sol i III concentrations were each assayed by means of two ELISAs with complementary monoclonal antibodies, one species specific and one cross-reactive. Radioallergosorbent test (RAST) to IFAV and both IFA WBEs was performed on sera from all study subjects. Both IFA WBEs contained high concentrations of fire ant body proteins. Sol i II and III concentrations each varied twofold between the two IFA WBE preparations. Patients were generally more reactive to IFAV than IFA WBE by skin testing and RAST. IFAV RAST appeared to be a more sensitive assay than IFA WBE RAST. No adverse reactions occurred to skin testing with IFAV, but intradermal testing with higher concentrations of IFA WBE caused delayed large local reactions in 16 of 30 (53%) control subjects. These reactions were attributed to the large amounts of extraneous body proteins in IFA WBE. These results (1) demonstrate that skin testing with IFAV is safe, (2) indicate that IFAV is more potent than IFA WBE, and (3) suggest that IFAV may be the superior reagent for diagnosis of fire ant allergy.

Adult↗

Context-specific adaptation of the gain of the vestibulo-ocular reflex in humans.

Previous experiments show that altered visual feedback can change VOR gain. Such changes also presumably occur when eyeglasses are donned and doffed, or when bifocals are worn. In these cases, a nonvisual cue accompanies the required gain adjustment (frames on/off for eyeglasses, looking up/down for bifocals). We set out to show that a subject can establish two VOR gains, and to determine if one of the associated nonvisual cues alone is sufficient to subsequently determine which gain to employ. Each of three subjects sat in a rotating chair inside an OKN drum during 2 hours of sinusoidal rotation at 0.2 Hz, 30 degrees/s peak. For 10 minutes the chair and drum counterrotated , driving VOR gain toward 1.7, while subjects looked up 20 degrees. Chair and drum were then coupled for 10 minutes, driving gain toward zero, during which subjects looked down 20 degrees. This sequence was repeated for 2 hours. Immediately thereafter, VOR gains were measured while subjects looked alternately up and down, using 20 degrees to 40 degrees step rotations. A fixation target, presented before and after each step, provided accurate gain determination by measuring the size of the re-fixation saccade. Results show a consistent reduced VOR gain looking downward (average 6%) and increased gain looking upward (average 6%) and increased gain looking upward (average 8%). We conclude that humans can adjust their VOR gain dependent on a situational context; we speculate that this context can take many forms.

Adaptation, Ocular↗

Failure of the oculomotor neural integrator from a discrete midline lesion between the abducens nuclei in the monkey.

Recent anatomical studies indicate that axons of neurons in the vestibular nuclei, projecting to the contralateral abducens nuclei, cross the midline at the abducens level. These axons then give off collaterals to the contralateral vestibular and prepositus nuclei that may be important for the neural integrator that converts eye-velocity to eye-position signals. We disrupted a subset of these commissural projections by making a small midline lesion between the abducens nuclei in a monkey. The vestibulo-ocular reflex and saccades were still present post-lesion, indicating that premotor drive was intact, but the lesion produced severe post-saccadic drift, indicating failure of the neural integrator. We conclude that commissural projections crossing at the abducens level may be important for oculomotor integration.

Abducens Nerve↗

A learning network model of the neural integrator of the oculomotor system.

Certain premotor neurons of the oculomotor system fire at a rate proportional to desired eye velocity. Their output is integrated by a network of neurons to supply an eye position command to the motoneurons of the extraocular muscles. This network, known as the neural integrator, is calibrated during infancy and then maintained through development and trauma with remarkable precision. We have modeled this system with a self-organizing neural network that learns to integrate vestibular velocity commands to generate appropriate eye movements. It learns by using current eye movement on any given trial to calculate the amount of retinal image slip and this is used as the error signal. The synaptic weights are then changed using a straight-forward algorithm that is independent of the network configuration and does not necessitate backwards propagation of information. Minimization of the error in this fashion causes the network to develop multiple positive feedback loops that enable it to integrate a push-pull signal without integrating the background rate on which it rides. The network is also capable of recovering from various lesions and of generating more complicated signals to simulate induced post-saccadic drift and compensation for eye muscle mechanics.

Algorithms↗

Benefits of a multidisciplinary pulmonary rehabilitation program. Improvements are independent of lung function.

We evaluated the conditions of 33 patients who completed an outpatient pulmonary rehabilitation program to determine what types of improvements occurred, and whether these changes were related to the baseline degree of ventilatory impairment, to determine whether rehabilitation was beneficial to patients, regardless of the degree of underlying lung dysfunction. Endurance measurements, including sustained submaximal performance on a cycle ergometer and the 12-minute walk distance (1,349 +/- 625 feet to 1,700 +/- 670 feet) increased significantly (p less than 0.01), as did multiple educational and subjective parameters. Maximal exercise performance on a graded cycle test improved very little, with a decline in the ventilatory equivalent for oxygen consumption (VE/VO2) being the only significant change (48.2 +/- 28.3 L/ml to 36.6 +/- 8.7 L/ml). Of the observed changes, only one endurance measurement, the sustained submaximal exercise performance, correlated with FEV1 (r = 0.5, p less than 0.01), but only if it was expressed as an absolute number (liters) and not as percent predicted. Lung function did not correlate with changes in the 12-minute walk distance, in maximal exercise performance on the cycle ergometer or with changes in educational and subjective parameters. We conclude that because the magnitude of change in both physiologic and psychologic parameters was not directly related to lung function, the benefits of rehabilitation can extend to all patients with chronic lung disease, regardless of the severity of preexisting pulmonary dysfunction.

Aged↗

Distributed parallel processing in the vertical vestibulo-ocular reflex: learning networks compared to tensor theory.

The vestibulo-ocular reflex (VOR) is capable of producing compensatory eye movements in three dimensions. It utilizes the head rotational velocity signals from the semicircular canals to control the contractions of the extraocular muscles. Since canal and muscle coordinate frames are not orthogonal and differ from one another, a sensorimotor transformation must be produced by the VOR neural network. Tensor theory has been used to construct a linear transformation that can model the three-dimensional behavior of the VOR. But tensor theory does not take the distributed, redundant nature of the VOR neural network into account. It suggests that the neurons subserving the VOR, such as vestibular nucleus neurons, should have specific sensitivity-vectors. Actual data, however, are not in accord. Data from the cat show that the sensitivity-vectors of vestibular nucleus neurons, rather than aligning with any specific vectors, are dispersed widely. As an alternative to tensor theory, we modeled the vertical VOR as a three-layered neural network programmed using the back-propagation learning algorithm. Units in mature networks had divergent sensitivity-vectors which resembled those of actual vestibular nucleus neurons in the cat. This similarity suggests that the VOR sensorimotor transformation may be represented redundantly rather than uniquely. The results demonstrate how vestibular nucleus neurons can encode the VOR sensorimotor transformation in a distributed manner.

Animals↗