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Biomedical subjects

J M Horowitz

Publications and source records attributed to J M Horowitz.

At least 73 records · Page 4Linked to original sources
PubMed1990

Effects of temperature and acid-base state on hippocampal population spikes in hamsters.

Previous studies have shown that changes in temperature, within the range encountered by hamsters entering hibernation, alter the evoked response of hippocampal pyramidal cells to stimulation of an afferent pathway. The present study was designed to determine whether these alterations are due to changes in the acid-base status of the neural tissue brought about by changes in temperature. Extracellular-evoked responses were recorded from hamster hippocampal slices after Schaffer collateral stimulation. The pH was changed by varying the concentration of CO2 aerating the bathing medium. Buffers contained either 26 or 40 mM bicarbonate ion. The width of the population spike (the synchronous firing of pyramidal cells) was measured as pH was varied between 7.5 and 7.1, with slice temperature set at either 25 or 20 degrees C. There was a significant increase in spike width as temperature was lowered to 20 degrees C, but no significant change in spike width or amplitude as pH or bicarbonate was varied. The effect of temperature (20 degrees C for half-maximal stimulation, and from 20 to 25 degrees C for just maximal stimulation) on spike width and amplitude thus does not appear to be due to pH- or bicarbonate-induced changes.

Acid-Base Equilibrium↗
PubMed1989

Point mutational inactivation of the retinoblastoma antioncogene.

The retinoblastoma (Rb) antioncogene encodes a nuclear phosphoprotein, p105-Rb, that forms protein complexes with the adenovirus E1A and SV40 large T oncoproteins. A novel, aberrant Rb protein detected in J82 bladder carcinoma cells was not able to form a complex with E1A and was less stable than p105-Rb. By means of a rapid method for the detection of mutations in Rb mRNA, this defective Rb protein was observed to result from a single point mutation within a splice acceptor sequence in J82 genomic DNA. This mutation eliminates a single exon and 35 amino acids from its encoded protein product.

Adenovirus Early Proteins↗
PubMed1989

Characteristics of auditory brainstem responses in ground squirrels.

Auditory brainstem responses (ABRs) were characterized at 37 degrees C in ground squirrels (Citellus lateralis) which were implanted with recording screws to record ABRs, and a thermistor to record brain temperature. After two weeks ground squirrels were reanesthetized and tone pips and clicks were delivered through a TDH-49 headphone. Recorded ABRs were found to vary in a predictable manner as a function of stimulus frequency and intensity. At intensities above 50 dB SPL, ABRs could be recorded over the range tested (2-32 kHz). An 8 kHz tone pip was the best frequency for recording ABRs at the lowest stimulus intensities. Latencies decreased as stimulus frequencies increased from 4 kHz to 32 kHz.

Acoustic Stimulation↗
PubMed1989

Auditory brainstem responses in ground squirrels arousing from hibernation.

Auditory brainstem responses (ABRs) were recorded in ground squirrels (Citellus lateralis) arousing from hibernation. Squirrels implanted with recording screws to record ABRs, and a thermistor to record brain temperature, were placed in a cold room at 9 degrees C on a 2L:22D light-dark cycle. Hibernating animals were moved from the cold room and ABRs recorded during arousal. The responses showed a gradual development of all brainstem peaks. At low temperatures there were very long latencies to the peaks. The amplitudes of the peaks increased (with fluctuations) as brain temperature increased. The data indicate that neural generators on the brainstem auditory pathway were all activated early in arousal. These results do not support the hypothesis that successive peaks appear and grow in amplitude only after previous peaks are fully developed.

Acoustic Stimulation↗
PubMed1989

Structure and expression of the murine retinoblastoma gene and characterization of its encoded protein.

We have isolated a cDNA clone of the murine homologue of the human retinoblastoma (Rb) susceptibility gene. DNA sequence analysis reveals a high degree of conservation with the human Rb sequence, both in the coding and in the noncoding regions. The predicted amino acid sequence of the mouse Rb protein shows 91% identity to that of the human protein. Both proteins were found to contain a peptide sequence reminiscent of a leucine-repeat motif ("leucine-zipper") that is also found in the myc, fos, and jun oncogenes. Synthetic peptide antiserum directed against a portion of the mouse Rb protein detects three proteins of 104-110 kDa in cells that were transiently transfected with a mouse Rb gene expression construct. In the mouse embryo the expression of Rb mRNA was ubiquitous, with maximal expression being observed around 13 days of gestation. In the embryo, the highest level of expression was observed in liver and brain. In contrast, the Rb gene was found to be expressed at a very low level in adult mouse liver with high levels being found in lung, thymus, and spleen. A shorter Rb transcript was detected in mouse testes.

Amino Acid Sequence↗
PubMed1989

Thermoregulation in hypergravity-acclimated rats.

To determine the effect of hypergravity acclimation on thermoregulation, core temperature (Tc), tail temperature (Tt), and O2 consumption (VO2) were measured in control rats (raised at 1 G) and in rats acclimated to 2.1 G. When the animals were exposed to a low ambient temperature of 9 degrees C, concurrently with a hypergravic field of 2.1 G, Tc of rats raised at 1 G fell markedly by approximately 6 degrees C (to 30.8 +/- 0.6 degrees C) while that of the rats raised at 2.1 G remained relatively constant (falling only approximately 1 degree C to 36.4 +/- 0.3 degrees C). Thus prior acclimation to a 2.1-G field enabled rats to maintain Tc when cold exposed in a 2.1-G field. To maintain Tc, thermogenic mechanisms were successfully activated in the 2.1-G-acclimated rats as shown by measurements of VO2. In contrast, VO2 measurements showed that rats reared at 1 G and then cold exposed at 2.1 G did not activate thermogenic mechanisms sufficiently to prevent a fall in Tc. In other experiments, rats acclimated to either 1 or 2.1 G were found to lack the ability to maintain their Tc when exposed to a 5.8-G field or when exposed to prolonged cold exposure at 1 G. Results are interpreted as showing that when placed in a 2.1-G field, rats acclimated to 2.1 G can more closely maintain their Tc near 37 degrees C when cold exposed than can rats acclimated to 1 G. However, this enhanced regulatory ability of 2.1-G-acclimated rats over 1.0-G-acclimated rats is restricted to 2.1-G fields and is not observed in 1.0- and 5.8-G fields.

Adaptation, Physiological↗
PubMed1988

Association between an oncogene and an anti-oncogene: the adenovirus E1A proteins bind to the retinoblastoma gene product.

One of the cellular targets implicated in the process of transformation by the adenovirus E1A proteins is a 105K cellular protein. Previously, this protein had been shown to form stable protein/protein complexes with the E1A polypeptides but its identity was unknown. Here, we demonstrate that it is the product of the retinoblastoma gene. The interaction between E1A and the retinoblastoma gene product is the first demonstration of a physical link between an oncogene and an anti-oncogene.

Adenovirus Early Proteins↗
PubMed1988

Repetitive excitation of bursts of action potentials in the rat hippocampus following single shock stimulation.

1. Post-stimulus time (PST) histograms of rat hippocampal cells were recorded in vivo following single-shock stimulation of the fornix. 2. The PST histograms displayed a series of peaks of decreasing amplitude, similar to damped oscillatory responses previously recorded in cats and rabbits. 3. The effect of increased background activity was investigated by recording histograms with concurrent pulse train stimulation of the contralateral hippocampus. The histograms showed a decreased latency to the onset of the second peak. 4. Damped oscillatory activity seen in the in vivo rat preparation could not be elicited in the in vitro rat slice preparation. Thus species differences cannot account for the absence in slice studies of this type of damped oscillatory activity. 5. We conclude that the level of spontaneous activity is one factor contributing to the genesis of multiple peaks in histograms in the in vivo preparation.

Action Potentials↗
PubMed1988

Core temperature is regulated, although at a lower temperature, in rats exposed to hypergravic fields.

1. In rats acclimated to 23 degrees C (RT rats) or 5 degrees C (CA rats), core temperature (Tc), tail temperature (Tt) and oxygen consumption (VO2) were measured during exposure to a hypergravic field. 2. Rats were exposed for 5.5 h to a 3 g field while ambient temperature (Ta) was varied. For the first 2 h, Ta was 25 degrees C; then Ta was raised to 34 degrees C for 1.5 h. During this period of warm exposure, Tc increased 4 degrees C in both RT and CA rats. Finally, Ta was returned to 25 degrees C for 2 h, and Tc decreased toward the levels measured prior to warm exposure. 3. In a second experiment at 3 g, RT and CA rats were exposed to cold (12 degrees C) after two hours at 25 degrees C. During the one hour cold exposure, Tc fell 1.5 degrees C in RT and 0.5 degree C in CA rats. After cold exposure, when ambient temperature was again 25 degrees C, Tc of RT and CA rats returned toward the levels measured prior to the thermal disturbance. 4. Rats appear to regulate their temperature, albeit at a lower level, in a 3 g field.

Acclimatization↗
PubMed1987

Nucleotide conservation of endogenous ecotropic murine leukemia proviruses in inbred mice: implications for viral origin and dispersal.

Nucleotide sequence analysis of the ecotropic murine leukemia proviruses of AKR, BALB/c, and C57BL/6 mice indicated that these viral genomes differ from each other in less than 0.5% of their sequenced nucleotides, whereas they differ from the laboratory Moloney, Friend, or RadLV viruses or a partial ecotropic provirus found in wild mice by 8-22% of their sequenced nucleotides. The limited variation of endogenous ecotropic proviruses found in these common mouse strains indicates that few cycles of virus replication separated the introduction of the ecotropic endogenous retroviruses into the germlines of the progenitors of these now divergent mouse strains, and is consistent with the hypothesis that these common inbred strains were derived from a pool of very few mice, at least one of which was infected with an ecotropic murine leukemia virus. Ecotropic germline proviruses now found in common inbred mice most likely derive from germline reintegrations of the viral progeny of that initial single infection.

Animals↗
PubMed1987

A simulation of the effects of temperature on hippocampal neurons.

We have developed a model to predict the effects of temperature on the electrical activity of a hippocampal pyramidal cell. Four populations of membrane channels in the pyramidal cell were simulated. Equations for current through these ion channels are similar to those first developed by Hodgkin and Huxley for Na+ and K+ channels in the squid axon and more recently extended by Traub to include not only these channel types but, in addition, Ca2+ and Ca2+ mediated K+ channels in hippocampal cells. Voltage- and/or concentration-dependent rate functions are used to describe the kinetic behavior of each population of channels. A temperature-dependent term is included for each rate function to simulate the effect of changing temperature on neural activity. Model simulations correspond to experimental data over a range of temperature from 40 degrees C to 35 degrees C.

Action Potentials↗
PubMed1987

Thermal dependence of neural activity in the hamster hippocampal slice preparation.

1. Neural activity was recorded in an in vitro hamster hippocampal slice preparation while the temperature of the Ringer's solution bathing in the slice was controlled at selected levels. 2. The amplitude of the population spike (action potentials from a group of pyramidal cells) was measured as bath temperature was lowered from 35 degrees C to temperatures where a response could not be evoked. 3. Plots of population spike amplitude versus temperature have bell-shaped curves. The population spikes increased in amplitude as temperature was lowered from 35 degrees C, reached a peak amplitude between 25 and 20 degrees C, and then decreased until a response could not be evoked when temperature was further lowered. 4. These in vitro results obtained in the slice preparation are related to in vivo hippocampal studies. Results are interpreted as consistent with the proposal reviewed here that neural activity in the hippocampus plays a role at specific stages of entrance into and arousal from hibernation.

Acclimatization↗
PubMed1987

Deletions of a DNA sequence in retinoblastomas and mesenchymal tumors: organization of the sequence and its encoded protein.

Retinoblastoma is a childhood tumor that can arise because of mutant alleles acquired as somatic or germinal mutations. The mutant allele can be carried in the germ line. The mutations creating these alleles act by inactivating copies of a recessive oncogene located within band q14 of chromosome 13 and termed the RB1 locus. We have reported isolation of a cDNA fragment that recognizes chromosomal sequences possessing many of the attributes of the retinoblastoma gene associated with the RB1 locus. We now report that this segment is additionally the target of somatic mutations in mesenchymal tumors among patients having no apparent predisposition to retinoblastoma and no previous evidence of retinoblastoma. These tumors provide additional evidence that the cloned sequences are representative of a gene that is a frequent target of inactivation during tumorigenesis. Sequence analysis of this cDNA provides little insight into its normal functional role.

Amino Acid Sequence↗
PubMed1987

Germ line integration of a murine leukemia provirus into a retroviruslike sequence.

Nucleotide sequence analysis of the cellular sequences flanking the integrated ecotropic (mouse-infectious) murine leukemia provirus of BALB/c mice indicated that the murine leukemia provirus is integrated in opposing transcriptional orientation within a solo long terminal repeat (LTR) of the VL30 family of endogenous retrovirus-related sequences. To quantify the effect of this integration event on the ability of the ecotropic provirus to be expressed, we constructed recombinant molecules that carried the chloramphenicol acetyltransferase (cat) gene and various viral LTRs and determined the CAT activity induced by these constructs after transfection of NIH 3T3 cells. Our results indicate that the BALB/c ecotropic LTR is about 10-fold more active than the VL30 LTR. The presence of the VL30 LTR did not affect the transcriptional activity of the ecotropic LTR in the context of the integration event. Our results also indicate that the LTRs of the BALB/c provirus are less transcriptionally active than are the proviral LTRs of AKR murine leukemia virus and the Harvey murine sarcoma virus.

Animals↗
PubMed1985

Norepinephrine depolarizes sartorius but hyperpolarizes soleus muscles in vitro.

Having previously found that in vivo administration of norepinephrine (NE) depolarizes the membrane of hamster sartorius muscle cells, the present study evaluated NE effects in vitro where alterations in blood flow were eliminated. Muscles were submerged in a temperature-controlled chamber, held at their resting length, and impaled with glass microelectrodes. Norepinephrine addition (maximum concentration of 10-20 microM at the muscle surface) induced significant depolarization in sartorius muscle cells and significant hyperpolarization in soleus muscle cells (P less than 0.05). Ascorbic acid (final concentration 15-25 microM), the vehicle for NE, evoked no significant alteration in resting membrane potentials of either muscle. Isoproterenol, a beta-adrenoceptor agonist, elicited responses similar to those of NE; phenylephrine, an alpha-adrenoceptor agonist, had no significant effect. The data suggest that the NE response is mediated through the beta-adrenergic pathway and that in the hamster, both hyperpolarization and depolarization can be observed under the same experimental conditions, depending on the muscle in question.

Adrenergic Agonists↗
PubMed1985

Temperature effects on evoked potentials of hippocampal slices from euthermic chipmunks, hamsters and rats.

1. Neural activity was recorded in hippocampal slices from euthermic chipmunks, hamsters and rats. 2. While recording the evoked potentials, the temperature of the Ringer's solution bathing the slice was varied by controlling the temperature of an outer chamber jacketing the recording chamber. 3. The temperature just below that at which a population spike could be evoked, Tt, was 10.4 +/- 0.3 degrees C (mean +/- SEM) for chipmunk slices, 14.1 +/- 0.4 degrees C for rat slices and 14.8 +/- 0.4 degrees C for hamster slices. Tt was significantly lower in the chipmunk slices (P<0.01) than in the rat and hamster slices. 4. Data were interpreted as consistent with the hypothesis that chipmunk hippocampal neurons are intrinsically cold resistant.

Animals↗