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Biomedical subjects

J S Miller

Publications and source records attributed to J S Miller.

At least 163 records · Page 9Linked to original sources
PubMed1986

Some parameters of conditioned immunosuppression: species difference and CS-US delay.

Three experiments were conducted in which an illness-inducing immunosuppressant, cyclophosphamide (an unconditioned stimulus, US) was associated with a previously presented saccharin solution conditioned stimulus (CS). In each experiment, reexposure to the CS produced a conditioned suppression of the plaque-forming-cell response in the experimental groups. Experiment I demonstrated this result with Fisher 344 rats. Experiment II replicated the effect with Balb/c mice. In Experiment III conditioned immunosuppression was demonstrated when mice received CS-US delays as long as 6 hours. No evidence of a delay gradient was present in either the behavioral or the immunologic data. These parallel findings offer no support for the idea of a dissociation between the taste aversion and conditioned immunosuppression processes.

Analysis of Variance↗
PubMed1986

Disruption of neophobia, conditioned odor aversion, and conditioned taste aversion in rats with hippocampal lesions.

Previous studies have implicated the hippocampus in the acquisition of conditioned taste aversions. However, the effect of hippocampal (HPC) lesions on the acquisition of conditioned aversions to the distal olfactory cue has not been investigated. In this study rats with bilateral electrolytic hippocampal lesions were given access to an odor conditioned stimulus (CS) alone or a compound odor-taste CS, followed by an injection of LiCl or saline. The results indicated that HPC lesions attenuated the neophobic response to both CSs, and disrupted conditioned odor and taste aversions, relative to sham-operated controls. Furthermore, the disruption in conditioned odor aversions could not be attributed to attenuation of neophobia in lesioned subjects nor to prolonged neophobia in sham-operated controls. The results are consistent with pharmacological studies in suggesting that the hippocampus is involved in the formation of conditioned odor aversions.

Animals↗
PubMed1985

Microinjection of neurotensin into the ventral tegmental area produces hypothermia: evaluation of dopaminergic mediation.

Neurotensin-producing perikarya and fibers have been identified in the ventral tegmental area of the rat, and recent microinjection studies indicate that neurotensin may function in the ventral tegmental area to regulate body temperature. In this study, the hypothermic response produced by intraventral tegmental injection of neurotensin was shown to be dose-dependent, with a threshold dose between 0.25 and 0.75 micrograms. When fluphenazine, a dopamine receptor antagonist, was microinjected into various forebrain nuclei simultaneous with neurotensin infusion into the ventral tegmental area, it was found to block neurotensin hypothermia. In contrast, injection with fluphenazine into the nucleus accumbens, lateral septum or preoptic area did not alter the hypothermic response. Furthermore, injection with atropine, phentolamine or diphenhydramine into the diagonal band of Broca did not block neurotensin hypothermia. Neurotensin was also injected directly into the preoptic region and shown to produce hypothermia. However, concurrent infusion of fluphenazine with neurotensin into the preoptic region did not attenuate neurotensin hypothermia. These data are consistent with the postulate that neurotensin acts in the ventral tegmental area to enhance dopamine release in the diagonal band of Broca, thereby producing hypothermia. However, neurotensin-induced hypothermia occurring after injection into the preoptic area does not appear to involve dopamine systems.

Animals↗
PubMed1985

A catecholaminergic projection from the ventral tegmental area to the diagonal band of Broca: modulation by neurotensin.

The ventral tegmental area contains a high density of dopaminergic perikarya having ascending projections to a number of limbic forebrain regions. In this study, we use combined retrograde labeling with horseradish peroxidase (HRP) and immunohistochemical staining for tyrosine hydroxylase to examine the catecholaminergic projection from the ventral tegmental area to the diagonal band of Broca. When injection of HRP was restricted to the diagonal band, only neurons in the nucleus linearis, nucleus interfascicularis and ventromedial portion of the nucleus paranigralis were labeled. In contrast, HRP injection into the adjacent nucleus accumbens labeled neurons throughout these nuclei, plus the nucleus parabrachialis pigmentosus, nucleus retroruber and substantia nigra, pars compacta. Approximately 60% of neurons in the ventral tegmental area labeled from the diagonal band contained tyrosine hydroxylase, compared with 79% of the neurons labeled from the nucleus accumbens. Neurotensin is a tridecapeptide found in the ventral tegmental area which has been shown to activate dopamine neurons projecting to the nucleus accumbens. In this study, microinjection of neurotensin into ventral tegmental nuclei which contained neurons retrogradely labeled from the diagonal band significantly elevated the levels of dopamine metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid, in the diagonal band. The results of this study demonstrate that a catecholaminergic projection exists from the ventral tegmental area to the diagonal band of Broca, and that this pathway can be stimulated by intra-ventral tegmental injection with neurotensin.

Animals↗
PubMed1985

E1a regions of the human adenoviruses and of the highly oncogenic simian adenovirus 7 are closely related.

Simian adenovirus 7 (SA7) is a highly oncogenic virus, capable of causing tumors in hamsters upon the direct injection of viral DNA. We determined the transcriptional organization of the transforming region and compared it with that of the human adenoviruses. This analysis demonstrated that there are two independently promoted transcription units similar to the E1a and E1b regions of the human adenoviruses. The nucleotide sequence of the SA7 E1a region demonstrated considerable homology with the human adenoviruses, both in the sequences that regulate E1a expression and in the encoded polypeptides. The amino acid homology was reflected in the ability of SA7 to complement the growth of human adenoviruses mutant in the E1a region. Furthermore, we found two regions of amino acid homology unique to SA7 and the highly oncogenic human adenovirus 12.

Adenoviridae↗
PubMed1985

Individual adenovirus type 5 early region 1A gene products elicit distinct alterations of cellular morphology and gene expression.

Adenovirus early region 1A (E1A), which gives rise to three overlapping transcripts, was inserted into a murine leukemia virus-derived vector, and recombinant viruses were used to prepare permanent cell lines of NIH 3T3 cells containing DNA copies of the individual 13S, 12S, and 9S mRNAs. Integrated proviral copies of the recombinant genomes were rescued as bacterial plasmids from each of the cell lines, and the DNA sequence of E1A was demonstrated to be a precise copy of the individual transcripts. The DNA copies were shown to be expressed as part of the full-length retroviral transcript by S1 nuclease analysis, and the synthesis of their encoded polypeptides was demonstrated by immunoprecipitation. Those cell lines expressing the polypeptide encoded by the 13S transcript were shown to contain that function required for regulating the accumulation of mRNAs from adenovirus early genes by their ability to complement the adenovirus type 5 E1A deletion mutant dl312. Cell lines expressing polypeptides encoded by the 13S, 12S, and 9S transcripts showed characteristic alterations in morphology. Two-dimensional gel electrophoresis of total cellular protein derived from the three cell lines demonstrated that each E1A gene product elicits specific alterations in the patterns of proteins expressed. Studies of the expression of two specific genes, those encoding fibronectin and collagen type 1, indicated that the observed alteration in levels of the two proteins results from a reduction in RNA levels induced by E1A functions.

Adenoviruses, Human↗
PubMed1985

Sensitization to repeated enkephalin administration into the ventral tegmental area of the rat. I. Behavioral characterization.

Acute injection with the enkephalin analog, D-Ala2-Met5-enkephalinamide (DALA), into the ventral tegmental area (VTA) of the rat will elicit behavioral hyperactivity. In this study it was found that daily intra-VTA injection with DALA results in a progressively enhanced motor response. The augmented behavioral response was dose-related, occurring at a threshold dose between 0.3 and 1.0 microgram of DALA per side. It consisted of a significant increase in locomotion and bursting, and a decrease in the occurrence of sleep/still. The augmented motor response did not result from decreased elimination of microinjected DALA from the VTA. Naloxone blocked the development of an enhanced motor response, as did substitution with the putative kappa opioid agonist, dynorphin. However, the sensitization to DALA was retained when the delta opioid agonist, D-Ala2-D-Leu5-enkephalin, was substituted for DALA and partial sensitization occurred when the mu opioid agonist, morphine, was substituted for DALA. Conditioning to the behavioral apparatus was not found to play a role in the sensitization to DALA. These data demonstrate that daily exposure of neurons in the VTA to enkephalin analogs results in a semipermanent alteration in the response of these neurons to subsequent injections with enkephalin analogs.

Animals↗
PubMed1984

Substance P modulation of dopamine in the nucleus accumbens.

Rats were implanted with bilateral injection cannulae in the nucleus accumbens. While microinjection of substance P (1.0-10.0 micrograms/side) did not alter locomotor or rearing behavior, it did potentiate the motor stimulant effects of intra-accumbens injection with dopamine. Further, substance P injection into the nucleus accumbens significantly elevated the levels of dopamine metabolites in that nucleus. Both the behavioral and neurochemical dose-response curves were biphasic, with 3.0 micrograms of substance P producing a maximal response. These data suggest an interaction between substance P and dopamine in the nucleus accumbens.

Animals↗
PubMed1984

Neurotensin neurons in the ventral tegmental area project to the medial nucleus accumbens.

A high density of neurotensin-containing neuronal perikarya are found in the ventral tegmental area, and some of these neurons also contain dopamine. In this study, we used retrograde transport of horseradish peroxidase (HRP) coupled with immunohistochemical staining for neurotensin to determine whether ventral tegmental neurotensin neurons project to known dopamine terminal areas of the limbic forebrain. It was found that HRP injection into the medial nucleus accumbens and diagonal band of Broca resulted in neurons in the ventral and medial ventral tegmental area containing both HRP granules and neurotensin immunoreactivity.

Animals↗
PubMed1984

Conditioned place preference with morphine: the effect of extinction training on the reinforcing CR.

Rats were injected with either morphine (5 mg/kg) or saline in association with one set of distinct environmental stimuli, and injected with saline in association with a different set of stimuli. After four conditioning trials, animals were given a 15-minute free-choice test to determine which stimulus environment was preferred. Animals displayed CPP as a significant increase in duration spent within the morphine-associated environment, but did not display any change in number of entries into that environment. In contrast, when extinction training was given following CPP, animals displayed a significant decrease in duration spent per entry into the morphine-associated environment, but did not display any change in total duration spent in that environment. These results suggest that assessment of the reinforcing conditioned response (CR) in the CPP model may require measurement of both duration spent in and number of entries into the drug-associated environment.

Animals↗
PubMed1984

Opiate receptor supersensitivity produced by chronic naloxone treatment: dissociation of morphine-induced antinociception and conditioned taste aversion.

In three separate experiments, rats were used to assess the effects of chronic administration of naloxone on specific binding of 3H-naloxone in various regions of the central nervous system (CNS) and on the efficacy of morphine to produce antinociception and a conditioned taste aversion. Chronic naloxone treatment increased opiate binding in medulla-pons, midbrain, hypothalamus, hippocampus, striatum, and prefrontal cortex, but not in either spinal cord or cerebellum. In those CNS regions exhibiting increased opiate binding, the duration of increased binding following termination of the naloxone treatment differed between regions. In conjunction with the increase in opiate binding, the efficacy of morphine to produce antinociception was potentiated, while the efficacy to produce a conditioned taste aversion was unchanged. Moreover, the administration of naloxone during behavioral testing blocked completely the antinociceptive effect, but not the aversive effect, of morphine. These results indicate that morphine-induced antinociception and conditioned taste aversion may be dissociated neuropharmacologically.

Animals↗
PubMed1984

Structure and arrangement of the beta-tubulin genes of Leishmania tropica.

We studied the organization and arrangement of the genes encoding beta-tubulin in the protozoan parasite Leishmania tropica and examined the structure and orientation of the beta-tubulin mRNA relative to the gene. There were found to be eight to nine beta-tubulin genes arranged in an array of direct tandem repeat units with a length of 3.8 kilobase pairs, and they were extremely homologous, if not identical, in sequence. These repeat units did not contain the alpha-tubulin genes. The transcribed sequences within the beta-tubulin genes were localized, and the orientation of the major alpha-tubulin mRNA was mapped on the gene by S1 nuclease analysis.

Animals↗
PubMed1983

Methods utilizing cell-free protein-synthesizing systems for the identification of recombinant DNA molecules.

Herein we outline three methods that, when coupled with cell-free protein synthesis, permit the identification of recombinant DNA molecules encoding specific polypeptides. RNAs enriched by fractionation on methylmercury hydroxide agarose gels are used to prepare sequence-specific probes. Recombinant DNA clones thus identified are further characterized as to their encoded polypeptides by either hybrid selection or hybrid arrest of translation.

Actins↗