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Biomedical subjects

J W Moore

Publications and source records attributed to J W Moore.

At least 163 records · Page 9Linked to original sources

Dorsolateral pontine tegmentum and the classically conditioned nictitating membrane response: analysis of CR-related single-unit activity.

Previous investigations have suggested that the dorsolateral pontine tegmentum (DLP) may be part of a system essential for classical conditioning of the nictitating membrane response. The present study examined CR-related firing patterns of extracellularly-recorded single units in the DLP. Differential conditioning, using tonal CSs and periocular electrostimulation as the US, was employed so that firing patterns on CR and non-CR trials could be compared. Cells that exhibited CR-related increases in firing (excitatory cells) were found in reticular formation surrounding the motor trigeminal nucleus (zone h), including the supra-trigeminal region, and in a region dorsal and dorsomedial to the brachium conjunctivum. Cells that exhibited CR-related decreases in firing (inhibitory cells) were observed in subcoeruleus/medial parabrachial regions and dorsal nucleus reticularis pontis oralis and caudalis. A third class of cells (temporal cells) exhibited CR-related shifts in the temporal distribution of spikes; these cells were located in various brain stem regions. The firing of many of the excitatory, inhibitory, and temporal cells preceded the behavioral CR by an amount of time sufficient for causal involvement. In light of evidence indicating that the cerebellum is critically involved in conditioning, the present study suggests that two systems, the cerebellum and the DLP, may be in control of CRs. The relationship of the two systems and their possible roles in conditioning are discussed.

Action Potentials↗

Familial isolated aniridia associated with a translocation involving chromosomes 11 and 22 [t(11;22)(p13;q12.2)].

Isolated aniridia segregated as an autosomal dominant trait in a family with 11 affected members spanning five generations. Four of the eight individuals studied had aniridia associated with glaucoma and cataracts. Cytogenetic studies revealed an apparently balanced reciprocal translocation between chromosomes 11 and 22 [t(11;22)(p13;q12.2)], while four unaffected relatives had normal karyotypes. There is no evidence of Wilms tumor or genitourinary abnormalities in any members of the family. Restriction enzyme analysis of the human catalase gene revealed no abnormalities in the individuals with the translocation. A summary of phenotypic abnormalities in 61 cases associated with aniridia is presented, as well as a comparison of breakpoints in 44 cases of 11p deletion. These data indicate that single breaks at 11p13 are associated with isolated aniridia, while deletion of 11p13 results in aniridia combined with Wilms tumor, genitourinary abnormalities, and/or mental retardation.

Abnormalities, Multiple↗

Severe subaortic stenosis associated with congenital rubella syndrome: palliation by percutaneous transcatheter device occlusion of a patent ductus arteriosus.

Congenital rubella syndrome has been associated with several forms of congenital heart disease including left-sided obstructive lesions. This report describes a patient with severe subaortic stenosis, patent ductus arteriosus, and mild pulmonary branch stenosis, a rare condition. Palliation was achieved with percutaneous transcatheter device occlusion of the patent ductus arteriosus.

Aortic Valve Stenosis↗

Simulation of the classically conditioned nictitating membrane response by a neuron-like adaptive element: response topography, neuronal firing, and interstimulus intervals.

A neuron-like adaptive element with computational features suitable for classical conditioning, the Sutton-Barto (S-B) model, was extended to simulate real-time aspects of the conditioned nictitating membrane (NM) response. The aspects of concern were response topography, CR-related neuronal firing, and interstimulus interval (ISI) effects for forward-delay and trace conditioning paradigms. The topography of the NM CR has the following features: response latency after CS onset decreases over trials; response amplitude increases gradually within the ISI and attains its maximum coincidentally with the UR. A similar pattern characterizes the firing of some (but not all) neurons in brain regions demonstrated experimentally to be important for NM conditioning. The variant of the S-B model described in this paper consists of a set of parameters and implementation rules based on 10-ms computational time steps. It differs from the original S-B model in a number of ways. The main difference is the assumption that CS inputs to the adaptive element are not instantaneous but are instead shaped by unspecified coding processes so as to produce outputs that conform with the real-time properties of NM conditioning. The model successfully simulates the aforementioned features of NM response topography. It is also capable of simulating appropriate ISI functions, i.e. with maximum conditioning strength with ISIs of 250 ms, for forward-delay and trace paradigms. The original model's successful treatment of multiple-CS phenomena, such as blocking, conditioned inhibition, and higher-order conditioning, are retained by the present model.

Adaptation, Physiological↗

Serum prolactin levels in women with breast cancer and their relationship to survival.

Serum prolactin (HPr) has been measured in 459 patients 1 day before (HPr-1) and in 433 patients 10 days after (HPr-2) treatment. These came from an unselected sequence of 739 patients with operable breast cancer who had been referred to Guy's Hospital over a period of 5 yr. In addition HPr was measured in 100, or more, women at 3, 6 or 12 months after mastectomy. The median levels of either HPr-1 or HPr-2 were higher in pre-menopausal compared with postmenopausal patients (P = 0.03 and 0.06, respectively). Mastectomy was associated with increased serum HPr in both pre- and post-menopausal patients (P less than 0.001 in both cases). Average levels at 3 months, or after, were similar to those found before treatment. Nulliparous women had a higher median amount of HPr-1 than parous which was significant in premenopausal patients (P less than 0.008) whilst HPr-2 levels were not related to parity. Thus the rise in HPr associated with surgery was greater in parous than nulliparous women. Prolactin levels were not related to nodal status or tumour size. However, the amounts of HPR-2 were significantly greater in women with histological grade 3 tumours than those with grade 1 or 2. Standardising for either nodal status, tumour size or histological grade seven situations were found in which HPr-1 or HPr-2 levels were of prognostic significance. Although some of these significant associations could be fortuitous all shared a common feature that the least favourable prognosis was associated with the highest HPr levels.

Adult↗

Antigens expressed on NIH 3T3 cells following transformation with DNA from human pancreatic tumor.

This report documents that the pancreatic adenocarcinoma cell line, HPAF, contains oncogene activity detected by transformation of NIH 3T3 cells through transfection with HPAF DNA. The HPAF transfected NIH 3T3 cells do not contain oncogenes homologous with c-H-ras, c-K-ras, c-N-ras, v-fms, c-myb, c-sis, v-fgr, c-mos, c-myc, c-fos, v-fes, v-src, v-erb A, v-erb B, c-N-myc, v-raf, or v-abl, other than the endogenous mouse genes. The transfectants do express proteins detected by two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis which were not found in nontransfected NIH 3T3 cells. Monoclonal antibodies raised against the transfectants recognize proteins not found in untransfected NIH 3T3 cells that are antigenically identical to proteins found in the HPAF cells. These antigens are also detected on six other human pancreatic adenocarcinoma cell lines but show a much more restricted distribution on lymphoblastoid, melanoma, prostatic carcinoma, and normal skin fibroblast cell lines.

Adenocarcinoma↗

Identification of women at high risk of breast cancer.

Prospective studies of risk factors for breast cancer have been carried out since 1961 on a normal population which now comprises some 15,000 women. Classical (anamnestic) factors such as ages at menarche, menopause, or at first child, post-menopausal weight and high parity are not strong determinants of risk. Measurements of various aspects of endocrine function are more successful in identifying women at risk, as is assessment of mammographic parenchymal patterns but, again, these variables are not effective enough to make an intervention strategy imperative. However, the combination of classical, endocrinological, and radiological factors appears to achieve this aim. A substantial sub-set of women who have a four-fold risk of breast cancer may be identifiable.

Adult↗

Brachium conjuntivum and rubrobulbar tract: brain stem projections of red nucleus essential for the conditioned nictitating membrane response.

The trajectory of the rubrobulbar tract in rabbit to the level of the accessory abducens nucleus is described: orthograde labeling of fibers of the rubrobulbar tract following horseradish peroxidase implants into red nucleus of 8 animals permitted ad hoc analysis of the effects of brain stem lesions on the rabbit's conditioned nictitating membrane response. Twenty-four rabbits, trained to give conditioned NM responses from both eyes, received unilateral lesions of the right pontine brain stem. Six of the 7 cases of post-lesion disruption of ipsilateral conditioned responding involved either ipsilateral brachium conjunctivum or the rubrobulbar tract. This finding, together with a reexamination of data from two related studies from this laboratory strongly support the conclusion that an essential premotor component of the conditioned NM response is a doubly decussating circuit from the interpositus nucleus of the cerebellum to magnocellular red nucleus, via brachium conjunctivum and its decussation, and from red nucleus caudally, via the ventral tegmental bundle and the rubrobulbar tract, to the accessory abducens nucleus, where motoneurons involved in the NM response are located. These findings are consistent with published reports on the essential role of interpositus nucleus of the cerebellum in NM conditioning. The possible role of the supratrigeminal reticular formation in this learned behavior is also discussed.

Abducens Nerve↗

Red nucleus lesions impair acquisition of the classically conditioned nictitating membrane response but not eye-to-eye savings or unconditioned response amplitude.

Following a single electrocoagulating RF lesion aimed at left red nucleus, rabbits received classical conditioning of the nictitating membrane (NM) response. A tone was the conditioned stimulus (CS) and electrostimulation of the eye was the unconditioned stimulus (US). The US was applied to the right eye during the initial phase of training. It was then switched to the left eye to assess transfer of learning and ultimately switched back to the right eye. NM responses were recorded simultaneously from both eyes during each phase of training. Consistent with reports implicating a cerebellar-rubro circuit in this behavior, RN lesions disrupted acquisition of CRs in the eye contralateral to the lesion. Animals with disrupted NM CRs of the right eye resembled controls in showing transfer of conditioning to the left eye. CR-disrupting lesions did not affect UR amplitude.

Animals↗

Adaptation in the input-output relation of the synapse made by the barnacle's photoreceptor.

A study was made of synaptic transmission between the four median photoreceptors of the giant barnacle (Balanus nubilus) and their post-synaptic cells (I-cells). Simultaneous intracellular recordings were made from the presynaptic terminal region of a photoreceptor and from the soma of an I-cell. The photoreceptor's membrane potential provided feed-back to bath electrodes that passed current into the receptors' axons, permitting the voltage to be controlled at the point of arborization of their presynaptic terminals. Simultaneous recordings from a second photoreceptor showed that its voltage tracked the first. Step depolarizations of the receptors from their dark resting potential (about -60 mV) caused hyperpolarizations of the I-cell that reached a peak, then decayed to a plateau value. The amplitude of the I-cell's response grew with presynaptic depolarizations, saturating at presynaptic values 10-20 mV depolarized from dark rest. Step hyperpolarizations of the receptors from dark rest evoked depolarizations of the I-cell consisting of an initial peak, which varied greatly in amplitude and wave form from preparation to preparation, followed by a plateau. The presence of this post-synaptic response indicates that transmitter is released continuously from the receptors at their dark resting potential. An input-output relation of the synapse was obtained by presenting step depolarizations from a holding potential of -80 mV, where steady-state transmitter release is shut off. The relation is sigmoidal; in the exponentially rising phase of the curve, a 5-11 mV presynaptic change produces a 10-fold change in post-synaptic response. When the presynaptic holding potential was set at values ranging from -80 to -40 mV, the relation between the I-cell's response and the absolute potential to which the receptor was stepped shifted along the presynaptic voltage axis. The slopes of the input-output relations were roughly parallel or increased as the photoreceptors were held more depolarized. This observation limits the possible mechanisms of the shift.

Action Potentials↗

Comparison of the neovascular effects of stimulated macrophages and neutrophils in autologous rabbit corneas.

The ability of peritoneal exudate macrophages and neutrophils to induce neovascularization was tested in autologous rabbit corneas. Macrophages and neutrophils elicited by proteose peptone or glycogen and macrophages activated by C parvum were purified, pelleted, and implanted 1-2 mm from the corneal limbus. Neovascular responses were evaluated by daily slit-lamp observations and terminal whole-mount and histologic examinations of colloidal carbon-perfused vessels. Pellets of elicited macrophages (5 X 10(5) - 6 X 10(6) cells, 92-98% macrophages) or activated macrophages (2 X 10(6) cells, 87-97% macrophages) induced neovascularization by 4 days in 72-82% of cases. In contrast, pellets of neutrophils (1 X 10(5) - 8 X 10(6) cells, 92-98% neutrophils) did not induce neovascularization in any case. Histologic examinations at 4-24 hours revealed diapedesis and substantial infiltration of peripheral blood neutrophils in response to implants of either macrophages or neutrophils. Infiltration was diminished by 48 hours and negligible at later times. The finding that neovascular responses were not evoked by implantation of neutrophils or by the accompanying infiltration of neutrophils indicates that neutrophils do not initiate neovascularization in this model. Under similar test conditions, neovascular responses were initiated by implantation of either elicited or activated macrophages.

Adjuvants, Immunologic↗

Trace conditioning of the nictitating membrane response in decorticate rabbits.

Rabbits with substantial neocortical lesions were given trace conditioning of the nictitating membrane response over a range of interstimulus intervals (ISIs). Unlike hippocampal lesioned animals, which show deficits in such conditioning, the decorticates were not impaired and they gave greater numbers of conditioned responses at longer ISIs than did sham-operated controls. These results suggest that a neocortical-entorhinal input to the hippocampus may not be crucial for trace conditioning.

Animals↗

Serum oestradiol-17 beta and prolactin concentrations during the luteal phase in women with benign breast disease.

Serum profiles of both oestradiol and prolactin were measured during the luteal phase in normal women, in women with cyclical breast pain and in women with recently biopsied benign breast disease. The results suggest that, in women with benign breast disease, the concentration of both hormones may be increased, when compared to the normal controls, during the evening in the latter part of the luteal phase.

Adult↗

Compensation for resistance in series with excitable membranes.

Extracellular resistance in series (Rs) with excitable membranes can give rise to significant voltage errors that distort the current records in voltage-clamped membranes. Electrical methods for measurement of and compensation for such resistances are described and evaluated. Measurement of Rs by the conventional voltage jump in response to a current step is accurate but the measurement of sine-wave admittance under voltage-clamp conditions is better, having about a fivefold improvement in resolution (+/- 0.1 omega cm2) over the conventional method. Conventional feedback of the membrane current signal to correct the Rs error signal leads to instability of the voltage clamp when approximately two-thirds of the error is corrected. We describe an active electronic bridge circuit that subtracts membrane capacitance from the total membrane current and allows full, yet stable, compensation for the voltage error due to ionic currents. Furthermore, this method provides not only fast and accurate control of the membrane potential in response to a command step, but also fast recovery following an abrupt change in the membrane conductance. Marked changes in the kinetics and amplitude of ionic currents resulting from full compensation for Rs are shown for several typical potential patterns.

Animals↗