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J M Horowitz

Publications and source records attributed to J M Horowitz.

At least 91 records · Page 5Linked to original sources

Molecular and biological characterization of the endogenous ecotropic provirus of BALB/c mice.

We have isolated two identical molecular clones of the single, endogenous ecotropic provirus of BALB/c mice. The BALB/c clones are approximately 1/10 as infectious as an exogenous proviral clone derived from AKR mice, p623. Transfection of mouse cells with each BALB/c proviral clone yielded XC-negative, N-tropic, ecotropic virus. Cotransfection of subgenomic fragments of p623 and the BALB/c provirus did not increase infectivity to the level observed for p623; however, a 292-base-pair fragment of the p623 env gene was found to rescue XC-plaque formation. Sequence analysis showed that the XC-negative BALB/c provirus differed from the XC-positive AKR-derived provirus at a single nucleotide at the junction of the gp70 and p15E envelope proteins. Extensive sequence analysis of the BALB/c endogenous provirus showed that it differed from the sequence of the AKR-derived provirus at approximately 0.5% of 4,500 sequenced nucleotides. In addition, the BALB/c long terminal repeat contains a single copy of the enhancer-containing sequences that are repeated twice in p623. The limited variation between the ecotropic proviruses of BALB/c mice and AKR mice suggests that few cycles of reverse transcription separate these viral genomes.

Amino Acid Sequence↗

Severity of emotional distress among sexually abused preschool, school-age, and adolescent children.

Many clinicians do not agree on whether or to what extent sexually abused children suffer emotional harm. An analysis of behavioral problems among 112 preschool, school-age, and adolescent children who had been sexually abused indicated that the preschool and adolescent samples showed relatively few signs of serious disturbance. The school-age group, however, showed a substantial incidence of psychological difficulties. The authors discuss the specific disturbances found among each group, the severity of the disturbances compared with those of normal children and children receiving psychiatric treatment for other reasons, and the implications of the findings for clinical interventions.

Adolescent↗

New directions in scientific computing: impact of advances in microprocessor architecture and system design.

The new generation of microcomputers has brought computing power previously restricted to mainframe and supermini computers within the reach of individual scientific laboratories. Microcomputers can now provide computing speeds rivaling mainframes and computational accuracies exceeding those available in most computer centers. Inexpensive memory makes possible the transfer to microcomputers of software packages developed for mainframes and tested by years of experience. Combinations of high level languages and assembler subroutines permit the efficient design of specialized applications programs. Microprocessor architecture is approaching that of superminis, with coprocessors providing major contributions to computing power. The combined result of these developments is a major and perhaps revolutionary increase in the computing power now available to scientists.

Computers↗

Far-field brainstem responses evoked by vestibular and auditory stimuli exhibit increases in interpeak latency as brain temperature is decreased.

The effect of decreasing brain temperature upon the transmission of neural signals along the brainstem auditory pathway has been well documented in cats and mice. The increase in the absolute and interpeak latencies of components of the brainstem auditory evoked response (BAER) has indicated that a progressive slowing occurs along the pathway as the signals ascend toward higher brainstem areas. Therefore to fully describe BAERs, both peak latencies and temperature are measured, especially in anesthetized preparations when brain temperature can be labile. In comparison to the numerous studies on the auditory system there are few studies that relate far-field responses evoked by angular acceleration to the vestibular system. Moreover the temperature dependence of such responses has apparently not been investigated. In this study we performed experiments designed to examine whether interpeak latencies of the BAER in rats depended upon temperature. This led to experiments designed to examine whether interpeak latencies of responses evoked by an angular acceleration show a dependence on temperature.

Acceleration↗

Impairment of thermogenesis and heat conservation in rats during 3 hours of 3-G exposure.

Heat conservation and production were studied in rats at 3 G and at 1 G. A closed-circuit system that includes a Krogh-type spirometer for the continuous measurement of oxygen consumption was used to determine heat production. At the same time, core temperature (Tc) and tail temperature (Tt) were also measured. During the first 20 min at 3 G, oxygen consumption increased by at most 18% in some of the rats and fell by up to 15% in the remaining rats. However, in all rats at 3 G, there was a fall of Tc during this time. Thus, the initial fall of Tc at 3 G was independent of concurrent changes in the rate of oxygen consumption. Furthermore, the rapid fall in Tc during the initial exposure to hypergravity was not due to reduced heat production (since oxygen consumption was variable and in some rats increased) but to an increase in heat loss. Even after 3 h at 3 G, when heat conservation mechanisms had recovered, the rate of oxygen consumption in rats was not significantly increased relative to the 1 G rate; hence thermogenesis was not activated to rewarm the animal.

Animals↗

The principal projection pathway between the olfactory bulb and the prepyriform cortex in the cat.

The anatomy and neuroelectric properties of the lateral olfactory tract (LOT) were investigated in the cat. Electron micrographs were obtained from sampled areas across the rostro-caudal projection of the pathway. Fiber diameters were estimated and axon spectra were obtained from three regions corresponding to peduncle, mid-LOT, and caudal-LOT. The mean inside diameter for all measured axons was 1.13 +/- 0.53 microns. The greatest number was found in the peduncle (approximately 600,000 axons). Mid-LOT and caudal-LOT each contained approximately 250,000 axons. Unmyelinated processes were estimated to be more numerous than the myelinated axons. Synaptic structures were also observed in the LOT. Cross-sectional area measurements of the LOT were obtained from tissue prepared for light microscopy. The area decreased from about 0.3 to 0.2 mm2 across the projection from olfactory bulb to cortex. The anatomical data were used to predict the conduction properties of transmission over the LOT. The olfactory bulb mitral cells were stimulated electrically and conduction velocity and temporal dispersion were evaluated in the tract. The strength-duration and stimulus-response curves and the potential profile during stimulation were also obtained. The time constant for LOT axons was 0.3 msec. The stimulus-response curve was sigmoidal in shape for both presynaptic and postsynaptic responses. The relationship between input (the action potentials) and output (cortical postsynaptic potentials) was linear up to 90 times threshold. Action potentials were conducted at 20 m/sec across the pathway over the peduncle and decreased to about 10 m/sec in caudal aspects. The potential profile for action potentials decayed exponentially into the depths of the cortex whereas the synaptic potential was a surface negative dipole field. The axon spectra were convolved with the electrophysiological properties of the LOT to mathematically reconstruct action potentials. The empirically derived mono- and biphasic curves fitted reasonably well with experimentally derived data under various stimulus conditions.

Action Potentials↗

Bone-conducted auditory stimulation in unrestrained, unanesthetized animals.

A new method of eliciting auditory responses using bone-conducted stimuli was developed for use in freely-moving unanesthetized animals. In cats and rats piezoelectric materials were either bolted to or embedded within a dental acrylic skull platform. In order to produce acoustic stimulation, click and pip electrical waveforms were used to drive vibrations in the crystalline material. Responses to the crystal-elicited stimuli were compared with responses to air-coupled stimuli and were found to be virtually identical. Acoustic masking eliminated the response showing there is no significant contribution made to the responses by other sensory modalities.

Acoustic Stimulation↗

Endogenous mouse leukemia viruses.

The earlier demonstration that genes of the mouse greatly influenced the spontaneous incidence of lymphoma was among the more persistent barriers to general acceptance of a viral etiology of this disease. We now can be fairly certain that some of those mouse genes are the DNA life phase of a class of retrovirus known as murine leukemia virus. These MuLV, although related in sequence to each other, are a collection of viruses that show diverse patterns of host range and tissue tropisms. The host-range properties of MuLV serve as means of classifying them into related families known as ecotropic, xenotropic, and amphotropic, and are probably dictated by determinants on gp70. The preferential abilities to replicate in different tissues, on the other hand, may be dictated by the controlling sequences located at the 3' end of the genome, known as U3. MuLV genomes are located at many different sites in the mouse genome. The viral genomes found at those sites can be induced to be expressed with different efficiencies spontaneously in vivo, by chemicals in vitro, or by DNA transfection. Certain MuLV genomes can also interact to increase expression perhaps by recombination or trans complementation. Although the molecular mechanisms that explain these phenomena are not yet clear, the phenomenon of differential expression has important pathological consequences, particularly in the development of lymphoma. The complex process by which endogenous MuLV induce leukemia appears to involve the expression and interaction of multiple MuLV genomes. It seems apparent that expression of an MCF-like gp70 is an invariant aspect of this process, and that observation suggests that this molecule, like the SFFV gp52, may indeed serve to stimulate cell proliferation. The most common means of expressing such a molecule at elevated levels appears to involve recombining it into an ecotropic genome that replicates with high efficiency. Thus, the viral requirements for leukemogenesis may depend on both efficient and perhaps tissue tropic replication as well as on the expression of a particular gp70.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Effect of p-chlorophenylalanine on thermoregulation in unrestrained rats.

p-Chlorophenylalanine (PCPA), a serotonin depletor, was used to investigate thermoregulation of unrestrained unanesthetized rats exposed to warm (approximately 32 degrees C) and cold (approximately 3 degrees C) environments. PCPA (300 mg/kg, ip) was administered approximately 48-96 h prior to the experimental trials. After 60 min of warm exposure, PCPA-treated rats had a significantly smaller increase in mean tail temperature (3.05 degrees C) and a greater increase in mean core temperature (1.47 degrees C) than did the control rats (6.13 and 1.20 degrees C, respectively) as measured via chronically implanted thermistors. A noninvasive method, infrared photography, was also used to monitor skin temperatures following heat exposure. Changes were qualitatively similar to those seen with thermistors, although differences between control and PCPA-treated groups were not statistically significant. During cold exposure, thermistor measurements indicated that the decrease in mean core temperature of the PCPA-treated rats (0.62 degrees C) did significantly differ from that of the controls (1.11 degrees C), whereas tail temperatures did not. These data confirm other studies implicating serotonin in the thermoregulation of rats. In particular, these results show that in a warm environment, PCPA may alter, albeit subtly, peripheral vasodilation in unrestrained rats.

Animals↗

Hypergravic fields and parallel controllers for thermoregulation.

To test the proposal that mammals have parallel neurocontrollers for temperature regulation, Long-Evans hooded male rats were exposed to cold while in a 3-G field. When exposed to cold, these rats consumed 35% less oxygen/min at 3 G than they did when exposed to cold at 1 G. However, rats acclimated for 6 wk to 5 degrees C consumed oxygen at the same rate during cold exposure at 3 G as at 1 G. Because cold-acclimated rats generate heat primarily by nonshivering thermogenesis while rats acclimated to room temperature rely to a greater extent on shivering, the 35% decrease in oxygen consumption of cold-exposed room-temperature rats in 3-G fields may reflect an inactivation of shivering. These oxygen consumption measurements, together with measurements of core and tail temperatures of rats in 3-G fields, are consistent with the proposal that neurocontrollers for thermoregulation are arranged in parallel and can be uncoupled by hypergravic fields.

Acclimatization↗

Structure and expression of endogenous ecotropic murine leukemia viruses in RF/J mice.

High leukemic mouse strains possess proviral genomes that are more inducible for virus expression by halogenated pyrimidines than the proviral genomes harbored by low leukemic mice. We investigated the induction and arrangement of ecotropic proviruses in RF mice, a strain of mouse that develops a moderate incidence of leukemia late in life. We found that RF mice, unlike either high or low leukemic inbred strains, carried both a gene for high efficiency virus induction (Rjv-1) and a gene for low efficiency virus induction (Rjv-2). Virus induction from mice that contained Rjf-2 alone was observed only in crosses with two other strains that carried ecotropic proviruses, i.e., DBA/2 and C57BL/6, and not in crosses performed with mice that lacked ecotropic proviruses, i.e., 129, SWR, and NFS. Inheritance of the Rjv-1 gene frequently resulted in viremia when a virus-suppressive gene(s) of RF (most likely Fv-1) was not present in the same individual. Rjv-1 and Rjv-2 virus induction genes co-segregated with ecotropic proviruses integrated in different cellular DNA sequences. Rjv-2, the less inducible ecotropic provirus in RF mice, is located in cellular DNA sequences very similar to those found adjacent to the ecotropic provirus of BALB/c. These results document a second system of virus interaction or complementation and demonstrate that ecotropic proviruses of different phenotypes can be found within an individual mouse strain.

Animals↗

A locus that enhances the induction of endogenous ecotropic murine leukemia viruses is distinct from genome-length ecotropic proviruses.

The segregation of genes that enhance the induction of ecotropic murine leukemia viruses (In loci) has been compared with the segregation of ecotropic-specific nucleotide sequences in 12 low-leukemic mouse strains and 18 recombinant inbred strains. Endogenous ecotropic viruses of these strains are of genome length and structurally similar to AKR ecotropic proviruses. Low-leukemic strains of related pedigree contain ecotropic proviruses at common integration sites. Loci previously identified which enhance induction of ecotropic viruses (In genes) were correlated with the inheritance of ecotropic viral sequences in inbred low-leukemic mouse strains and in CXB recombinant inbred mouse strains. However, four BXH recombinant inbred strains were observed to possess an In gene(s) yet lack the probed envelope gene region for the corresponding endogenous ecotropic virus. These observations indicate that at least one gene that enhances ecotropic virus expression in vitro is encoded by DNA sequences outside ecotropic proviruses or by subgenomic viral sequences.

AKR murine leukemia virus↗

Localization and characterization of adrenergic receptors on frog skin melanophores.

The functional location of adrenergic binding sites was studied in frog skin melanophores by injecting norepinephrine (NE) outside and inside a melanophore. In 49 groups of cells (75% of the fields tested) iontophoretic injection of NE outside the cell caused melanosome aggregation in the target cell and/or in the field. In six cells in which a resting membrane potential was measured before and after intracellular injection (10-90 nA), NE elicited no change in melanosome configuration. Once the receptors were localized, the effect of temperature on these receptors was determined by measuring the reflectance of skins (an indication of melanosome aggregation or dispersion) in two populations of frogs treated with NE, Rana pipiens pipiens (with dominant alpha-receptors) and Rana berlandieri forreri (with dominant beta-receptors). NE (0.1 mM) caused melanosome aggregation in the former and dispersion in the latter tested at 12, 22, and 40 degrees C. The iontophoretic and reflectance results suggest that the binding site of the adrenergic receptor is located on the outer surface of the plasma membrane of melanophores and that alpha- and beta-receptors evoke aggregation and dispersion, respectively, within the temperature range of these experiments.

Animals↗

Oscillatory neural networks in the rabbit hippocampus.

A model is described to account for damped oscillatory activity of two interacting neural populations, pyramidal cells and interneurons. This network in the hippocampus is treated as a lumped system with time delays between elements. The physiological mechanism underlying the oscillatory activity appears to involve neural population interaction and cannot be described in terms of a network composed of but two neurons, a single pyramidal cell and a single interneuron. An unusual aspect of the model is the explicit incorporation of an ongoing background input to raise the mean level of activity of the pyrammidal cell population. This model has evolved from a series of studies previously performed on cats. To test the model experiments were performed on rabbits. The data showing oscillatory activity following fornix stimulation in the rabbit indicate that the model can be applied not only to the cat but also to the rabbit. In additions, for commissural stimulation oscillatory potentials of neural populations and individual pyramidal cells were evoked as predicted by the model.

Animals↗

Effects of gravitational profiles on the rat's thermoregulatory response to cold.

Unrestrained rats were subjected to a 1-h period of cold exposure during centrifugation to characterize their ability to regulate core temperature (Tc) and to determine if this regulation was dependent on the amplitude of the hypergravic field before the cold exposure. Tc was measured in unrestrained rats by the use of a thermistor implanted adjacent to the carotid artery. One hour of cold exposure applied over the last hour of either a 1-, 4-, 7-, 13-, 19-. 25-, or 37-h period at 3 G evoked a decrease in Tc of about 3 degrees C. This fall in Tc was significantly greater than changes in Tc in cold-exposed rats at 1 G. No significant differences were found between the measured decreases in Tc observed for the 1-h cold exposures during the first 37 h at 3 G. However, when rats were subjected concurrently to cold and acceleration after 8 days at 3 G, they exhibited a smaller fall in Tc, suggesting a partial recovery of the acceleration-induced impairment of temperature regulation. In another series of experiments, the gravitational field profile was changed in amplitude in three different ways during the 3-h period preceding the 1-h cold exposure at 3 G. Despite the different gravitation field profiles before cold, the magnitude of the fall in Tc over the 1-h period of cold exposure was the same of all cases. These results suggest that the thermoregulatory impairment has a rapid onset, it a manifestation of an ongoing effect of hypergravity, and is not dependent on the prior G profile. The inability of rats to maintain Tc when cold exposed may be transient as indicated by the partial recovery of regulation by the 8th day.

Animals↗

The response of single melanophores to extracellular and intracellular iontophoretic injection of melanocyte-stimulating hormone.

The purpose of this study was to determine if MSH, a peptide hormone, injected within a frog skin melanophore could elicit a physiological response, melanosome dispersion. Multibarreled electrodes were used to iontophoretically inject alpha-MSH inside frog skin melanophores of Rana pipiens pipiens. In 46 cells, intracellular MSH was ineffective in producing melanosome dispersion as viewed through the microscope. Because the frog skin is a complex of closely spaced cells, at times the microelectrode may have impaled cells other than melanophores. Therefore, in order to verify that the electrode was in a melanophore and not some other cell type, cAMP, shown to produce melanosome dispersion, was iontophoretically injected to 17 cells, causing the melanosomes to disperse. In these 17 cells, prior injection of MSH caused no dispersion. The response was monitored by observing the target cell with surrounding cells serving as a control. As an additional control to determine if adequate amounts of MSH were released, the electrode was withdrawn from the cell and placed near a group of melanophores, and in all cases the cells close to the electrode tip showed melanosome dispersion after MSH injection. The results of this study remain consistent with the view that MSH receptors in frog skin melanophores are located on the external surface of the plasma membrane, and MSH injected into the cytoplasm of the cell has no short term effect.

Animals↗