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Biomedical subjects

S R Weiss

Publications and source records attributed to S R Weiss.

At least 145 records · Page 8Linked to original sources
PubMed1989

Chronic carbamazepine inhibits the development of local anesthetic seizures kindled by cocaine and lidocaine.

The effects of carbamazepine (CBZ) treatment on local anesthetic-kindled seizures and lethality were evaluated in different stages of the kindling process and under different methods of CBZ administration. Chronic oral CBZ inhibited the development of both lidocaine- and cocaine-induced seizures, but had little effect on the fully developed local anesthetic seizures. Chronic CBZ also decreased the incidence of seizure-related mortality in the cocaine-injected rats. Acute CBZ over a range of doses (15-50 mg/kg) had no effect on completed lidocaine-kindled or acute cocaine-induced seizures. Repeated i.p. injection of CBZ (15 mg/kg) also was without effect on the development of lidocaine- or cocaine-kindled seizures. The differential effects of CBZ depending upon stage of seizure development suggest that distinct mechanisms underlie the development versus maintenance of local anesthetic-kindled seizures. The effectiveness of chronic but not repeated, intermittent injections of CBZ suggests that different biochemical consequences result from the different treatment regimens. The possible utility of chronic CBZ in preventing the development of toxic side effects in human cocaine users is suggested by these data, but remains to be directly evaluated.

Anesthetics↗
PubMed1989

Evidence for a common site of action of lidocaine and carbamazepine in voltage-dependent sodium channels.

The finding that the development of lidocaine-kindled seizures is blocked by carbamazepine suggests an interaction of carbamazepine with local anesthetic mechanisms. To study the site of interaction, the effects of lidocaine, carbamazepine and another anticonvulsant drug, phenytoin on scorpion venom-enhanced specific binding of [3H]batrachotoxinin A 20-alpha-benzoate to the sodium channel gating complex were examined in vitro in a rat brain hippocampus preparation. Lidocaine shifted the concentration inhibition curve of carbamazepine to the right and vice versa. Carbamazepine shifted the concentration inhibition curve of phenytoin to the right and vice versa. The experimentally determined apparent dissociation constants were in a good agreement with the dissociation constants calculated for a one-site model, suggesting that the interaction occurs because lidocaine shares a common binding site with carbamazepine and phenytoin in the voltage-dependent sodium channels.

Animals↗
PubMed1989

Molecular cloning of the gene encoding the putative polymerase of mouse hepatitis coronavirus, strain A59.

Complementary DNA (cDNA) libraries were constructed representing the genome RNA of the coronavirus mouse hepatitis virus, strain A59 (MHV-A59). From these libraries clones were selected to form a linear map across the entire gene A, the putative viral polymerase gene. This gene is approximately 23 kb in length, considerably larger than earlier estimates. Sequence analysis of the 5' terminal region of the genome indicates the presence of the 66-nucleotide leader that is found on all mRNAs. Secondary structure analysis of the 5' terminal region suggests that transcription of leader terminates in the region of nucleotide 66. The sequence of the first 2000 nucleotides is very similar to that reported for the closely related JHM strain of MHV and potentially encodes p28, a basic protein thought to be a component of the viral polymerase (L. Soe, C. K. Shieh, S. Baker, M. F. Chang, and M. M. C. Lai, 1987, J. Virol., 61, 3968-3976). Gene A contains two of the consensus sequences found in intergenic regions. One is adjacent to the 5' leader sequence and the other is upstream from the initiation codon for translation of gene B.

Amino Acid Sequence↗
PubMed1989

Induction of MHC class I antigens on glial cells is dependent on persistent mouse hepatitis virus infection.

H-2 class I antigens, but not class II antigens, were detected on the surface of glial cells persistently infected with mouse hepatitis virus strain A59 (MHV-A59) as late as 90 days post-infection. Uninfected glial cells remained negative for H-2 class I and class II surface antigens. We have previously shown that conditioned media from infected glial cell cultures (supernatants) contain a factor unrelated to infectious virus and capable of inducing H-2 class I antigens on uninfected glial cells. The synthesis of this factor appears to be dependent on production of infectious virus since the H-2 inducing activity could not be detected 3 days following the addition of neutralizing antibodies to the cultures. This suggests that H-2 inducing activity contains an unstable component, the synthesis of which is dependent on continual virus production. Persistent MHV infection and H-2 class I antigen expression may play a role in MHV-induced demyelination.

Animals↗
PubMed1989

Context-dependent cocaine sensitization: differential effect of haloperidol on development versus expression.

Repeated, intermittent administration of psychomotor stimulants has been shown to produce increasing effects (behavioral sensitization) in many species of animals. In a novel two-day sensitization paradigm, rats that received a single high dose of cocaine (40 mg/kg) compared with saline on day 1 showed an increased locomotor response to a challenge dose (10 mg/kg) on day 2. This effect is conditioned or context-dependent; i.e., it is only observed if the rats received cocaine in an environment similar to the test environment. If the cocaine-induced hyperactivity on day 1 is prevented with pharmacological agents such as haloperidol and diazepam, sensitization on day 2 does not occur. Furthermore, although moderate (0.2 mg/kg) and high doses (0.5 mg/kg) of haloperidol (day 1) prevented the development of sensitization to cocaine, they were ineffective when given prior to the day 2 challenge dose in preventing the expression of sensitization. Thus, this type of cocaine sensitization appears to involve conditioning, show stimulus generalization, and offer a possible model for clinical neuroleptic nonresponsiveness once stimulant-induced pathological behavior has been induced.

Animals↗
PubMed1989

Sensitization, kindling, and anticonvulsants in mania.

Cocaine can induce manic syndromes ranging from mild hypomania to severe dysphoric and psychotic mania, in part depending on the number and duration of drug administrations. Repeated cocaine administration in animals results in increased motor (behavioral sensitization) and convulsive (pharmacologic kindling) responses. Study of these progressive syndromes in animals may provide insights into principles underlying the longitudinal evolution of manic syndromes in man, including the increased vulnerability to recurrence following successive episodes. Different phases in the evolution of behavioral sensitization are differentially responsive to neuroleptics while the same principle is evident for different anticonvulsants in kindling. The authors examine whether pharmaco-responsivity may also differ as a function of stage of progression of mania. Antimanic effects of lithium, neuroleptics, and the newer anticonvulsants, such as carbamazepine, valproic acid, and clonazepam, are discussed in this context.

Animals↗
PubMed1988

Intensity difference thresholds after lesions of ectostriatum in pigeons.

Seven pigeons were trained to perform in a psychophysical procedure to determine the smallest difference in luminous intensity (intensity difference threshold) that they could discriminate. When their performance stabilized, lesions were made in the ectostriatum in 4 birds and in the neostriatum in the remaining 3 birds. After surgery, the pigeons with ectostriatum lesions showed markedly elevated thresholds. The neostriatum control cases showed only trivial threshold changes as a consequence of the surgery. A psychophysical scaling analysis showed that the ectostriatum-lesioned pigeons had lost from 50% to 83% of their preoperative capacity to discriminate differences in the intensity of visual stimuli. A multiple-regression analysis based on quantitative reconstructions of the lesions revealed that only damage to the core region of the ectostriatum contributed to the postoperative threshold changes.

Animals↗
PubMed1988

Induction of glial cell MHC antigen expression in neurotropic coronavirus infections. Characterization of the H-2-inducing soluble factor elaborated by infected brain cells.

Neurotropic coronavirus (mouse hepatitis virus strain A59) infection induces major histocompatibility complex class I (H-2) surface antigens on oligodendrocytes and astrocytes, cells that do not normally express detectable MHC antigens on their surface. The induction on MHC antigen expression potentially allows immunocytes to interact with infected glial cells and may play a critical role in the development of virus-induced, immune-mediated demyelination in the central nervous system, a possible model of human multiple sclerosis. In this study, we characterized the soluble factor involved in MHC antigen induction, quantitated induction of MHC antigens, and analyzed the central nervous system cell type involved in the production of the factor. The H-2-inducing factor, most likely produced by astrocytes, was found to be nondialyzable, heat- and trypsin-sensitive, but resistant to treatment at pH 2.0. The m.w. of the factor was estimated as 50 to 100 kDa. Studies on fractionation by ultrafiltration and sucrose density gradient along with antibody-blocking experiments indicate that the factor is not interferon or virus particles.

Animals↗
PubMed1988

Effects of thyroid alterations and carbamazepine on cortical beta-adrenergic receptors in the rat.

The effect of alteration in thyroid status on beta adrenergic receptors in the cortex of the rat was assessed. Normal animals were treated with large doses of thyroxine (T4) and triiodothyronine (T3) and thyroidectomized animals were treated with physiological replacement doses of T4 and T3 in order to assess the possible differential effects of these hormones. In addition, a group of rats was treated with a diet of carbamazepine (an anticonvulsant also used in the treatment of manic-depressive illness), which has been shown to reduce peripheral levels of thyroid hormone in humans. The intended manipulations of the thyroid were achieved by the various treatments with thyroid hormone, and carbamazepine-diet-treated animals had significantly lower plasma T4 levels as compared with controls. No significant alteration in the density or affinity of beta-adrenergic receptors in the cortex was noted with major, short-term alterations in thyroid status or with treatment with carbamazepine. It is concluded that even marked, but relatively short-term, changes in thyroid status do not necessarily affect beta-receptors in the cerebral cortex and that carbamazepine may represent an exception to the general proposition that antidepressant agents decrease the number of beta-receptors.

Animals↗
PubMed1988

The relationship between genetic deafness and fear-related behaviors in nervous pointer dogs.

Nervous pointer dogs have been extensively characterized as an animal model for some human pathological anxiety states. During our work with these animals suspicion developed that some of these dogs had a hearing deficit. We decided to systematically evaluate this observation and to study the relation between hearing status and fear-related behaviors in the nervous pointer dogs. Our results revealed that a majority of the nervous dogs in our colony (75%) suffer from bilateral deafness as demonstrated by complete absence of brain stem auditory evoked response. Furthermore, behavioral ratings revealed that hearing and deaf dogs do not differ in their pathological response to the characteristic fear-provoking stimuli (e.g., human interaction) and that both hearing and deaf nervous dogs markedly differ from normal dogs in that respect. The relation between these abnormalities and their implications for research involving breeding of animals for selected traits are further discussed in this report.

Animals↗
PubMed1988

Detection of a murine coronavirus nonstructural protein encoded in a downstream open reading frame.

Mouse hepatitis virus (MHV) gene 5 contains two open reading frames. We have expressed the second open reading frame of this gene (gene 5 ORF 2) in an Escherichia coli expression system. This system utilized a plasmid which contained the promoter and the first 36 codons of the recA gene fused in frame with the MHV gene 5 ORF 2, which is fused in turn to the beta-galactosidase gene. The protein product of this gene fusion was used to raise antibody to gene 5 ORF 2. The specificity of the antibody was verified by immunoprecipitation of the in vitro transcribed and translated protein product of gene 5 ORF 2. The second reading frame of MHV gene 5 was shown to be expressed during the course of infection by immunocytochemistry and radioimmunoprecipitation using the antibody raised against the E. coli fusion protein and by two-dimensional gel electrophoresis.

Genes↗
PubMed1988

Tumor necrosis factor induces expression of MHC class I antigens on mouse astrocytes.

The effect of tumor necrosis factor (TNF) on expression of major histocompatibility complex (MHC) antigens was examined in mouse glial cells in vitro. TNF induced MHC class I, but not class II, antigen expression on the surface of astrocytes but not on oligodendrocytes. Glial cells do not normally express detectable amounts of MHC antigens. Thus TNF may play a role in the immunopathogenesis of neurologic diseases that involve MHC class I-restricted reactions.

Animals↗
PubMed1988

mRNA levels of all three neurofilament proteins decline following nerve transection.

The control of neurofilament (NF) protein gene expression was studied by determining and comparing the levels of mRNA to the heavy (NF-H), mid-sized (NF-M) and light (NF-L) NF protein subunits in rat dorsal root ganglia (DRG) following sciatic nerve transection. mRNA to NF-H (4.5 kb), to NF-M (3.4 kb) and to NF-L (2.5 and 4.0 kb) were identified in Northern blots and quantitated in dot blot analyses, using specific cDNA probes for each NF protein. Following transection and continuing for at least 28 days. The early and co-terminal fall in mRNAs suggests that the 3 NF genes are regulated by common factor(s) and that the function of these factor(s) is influenced by the state of axonal continuity with the target organ.

Animals↗
PubMed1988

The effect of acute treatment with two goitrogens on plasma thyroid hormones, testosterone and testicular morphology in adult male rats.

1. Hypothyroidism was induced in adult male rats by treatment with either iopanoic acid (IOP) or propylthiouracil (PTU). The hypothyroid animals were maintained for a period of 4 weeks. 2. The IOP and PTU treatments produced drastically different thyroid hormone profiles during the treatment period. 3. Serum testosterone levels were not significantly different from controls in either of the goitrogen-treated groups. 4. Testes weights and germ cell populations were not significantly different from controls in either of goitrogen treated groups. 5. Seminiferous tubule morphology showed no significant variation in lumen size or basal lamina structure in either of the treatment groups when compared to the controls.

Animals↗
PubMed1988

Limbic encephalitis after inhalation of a murine coronavirus.

The spread of a neurotropic coronavirus, mouse hepatitis virus strain A59, in the mouse central nervous system was studied after intranasal inoculation. Mouse hepatitis virus strain A59 spread during the 3- to 5-day postinoculation period, through the olfactory pathway into the limbic system. Coronavirus particles were detected in the limbic system by electron microscopy. The combination of temporal propagation through an anatomical-physiological central nervous system pathway and anatomical restriction of viral infection suggests that specific interneuronal transport is important in spread of the virus. This experimental system may represent a model for diseases associated with human coronaviruses (common cold viruses) and/or the human limbic system.

Administration, Intranasal↗