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J R Martin

Publications and source records attributed to J R Martin.

At least 127 records · Page 7Linked to original sources
PubMed1990

Role of the herpes simplex virus 1 internal repeat sequences in pathogenicity.

Three independently isolated herpes simplex virus type 1 recombinant viruses containing a deletion of approximately 14 kilobase pairs, representing greater than 95% of the internal repeat DNA sequences, were analyzed for their pathogenicity in mice. The recombinant viruses were found to be avirulent, exhibiting drastically increased LD50 values over wild-type herpes simplex virus 1(F) by intracerebral injection, nonneuroinvasive, unable to spread from the cornea to sensory ganglion, and unable to establish a reactivable latent infection in trigeminal ganglion following either intracerebral inoculation or inoculation of scarified corneas. The potential role of diploid genes in herpes simplex virus pathogenesis in the mouse is discussed.

Animals↗
PubMed1989

Targets of infection in a herpes simplex-reactivation model.

In mice surviving intracerebral inoculation with herpes simplex virus type 2 (HSV-2), recurrent infection was induced using high-dose immunosuppressive treatment. Targets of reactivated infection were identified in serial sections of heads using immunoperoxidase methods to detect viral antigen. Peripheral targets were cranial sensory and autonomic ganglia, peripheral nerves, and many non-neural structures. Central neural tissues included retina, optic nerve and tract, lateral geniculate nucleus and superior colliculus. Brain stem nuclei containing antigen were chiefly those associated with the trigeminal, facial, glossopharyngeal or vagus nerves. A few white matter regions were also positive. This is the first study using antigen methods to show that the central nervous system can be an important target of recurrent HSV infection in an animal model. Patterns of antigen-containing structures suggest that neural connections are important determinants of sites of reactivated infection. Decalcification of bone permits study of antigen distribution in tissues retaining their anatomical relationships.

Animals↗
PubMed1989

Axonal degeneration and regeneration in sensory roots in a genital herpes model.

In a mouse model of genital herpes simplex virus type 2 (HSV-2) infection, roots of the lower spinal cord were examined 5 days to 6 months after inoculation. Using immunoperoxidase methods on paraffin sections, viral antigen was found in sensory ganglia, their proximal roots and distal nerves on days 5 and 6 after infection. In Epon sections, most mice had focal sensory root abnormalities in lower thoracic, lumbar or sacral levels. At days 7 and 10, lesions showed chiefly nerve fiber degeneration, particularly of large myelinated fibers. At 2 weeks, lesions contained relatively large bundles of small unmyelinated fibers with immature axon-Schwann cell relationships. From 3 to 6 weeks, lesions again contained many more small unmyelinated fibers than normal but, in increasing proportions, axons in bundles were isolated from their neighbors by Schwann cell cytoplasm, and Schwann cells having 1:1 relationships with axons showed mesaxon or thin myelin sheath formation. At later times, the proportion of small unmyelinated axons decreased in parallel with increased numbers of small myelinated axons. By 6 months, affected roots showed a relative reduction in large myelinated fibers, increased proportions of small myelinated fibers and Schwann cell nuclei. Numbers of unmyelinated fibers were reduced relative to 3- to 6-week lesions. Axonal degeneration and regeneration appears to be the chief pathological change in sensory roots in this model. If regenerated fibers arise from latently infected neurons, then establishment of latency is not a relatively silent event, but is associated with major long-lasting, morphologically detectable effects.

Animals↗
PubMed1989

Herpes simplex virus type 2 transcripts in trigeminal ganglia during acute and latent infection in mice.

Adult mice were inoculated intracerebrally with herpes simplex virus type 2 (HSV-2), and perfused at days 5, 8, 81, 108, and 130 after infection. Trigeminal ganglia and roots were dissected out and embedded in paraffin. Four 35S-labelled DNA probes that contained immediate-early (ICP-0, ICP-4), delayed-early (thymidine kinase; TK), or late (morphological transforming region; MTR) genes were prepared. In situ hybridization methods or an immunoperoxidase antigen method using HSV-2 antibody were applied to serial sections. During acute infection, use of each of the 4 probes (ICP-0, ICP-4, TK, MTR) gave hybridization signals in a distribution similar to that of antigen. During latent infection, only the ICP-0 probe gave hybridization signals overlying neurons, while in adjacent sections, the other probes (ICP-4, TK, MTR) did not show signals. No antigen was detected during latency. Hybridization signals were also demonstrated in nuclei of neurons during latency using a non-radioactive ICP-0 probe labelled with a steroid hapten. These results suggest that the transcription of the HSV-2 genome is restricted during latency, with transcript localization to nuclei of neurons as has been described in latent HSV-1 infection. Evidence for latent ganglionic infection by in situ hybridization in this model is consistent with that obtained by ganglionic explanation and by reactivations induced by immunosuppression.

Animals↗
PubMed1989

Mechanism of pressor response to posterior hypothalamic injection of neuropeptide Y.

Unilateral microinjection of neuropeptide Y (NPY) into the posterior hypothalamic nucleus was previously found to evoke an increase in mean arterial pressure (MAP) in urethan-anesthetized rats. In this study, the mechanism by which this increase occurs was examined. Pretreatment of rats with 2.0 mg/kg (iv) of phenoxybenzamine, or 7.5 mg/kg (iv) of pentolinium, resulted in a significant reduction in the peak MAP evoked by microinjection of NPY (2.35 nmol) into the posterior hypothalamic nucleus. Administration of the vasopressin V1-receptor antagonist [d(CH2)5Tyr(Me)]AVP (10 micrograms/kg iv) before microinjection of NPY failed to attenuate the increase in MAP. Similar results were obtained with respect to the effect of these three antagonists on the increase in MAP evoked by injection of the cholinergic muscarinic agonist carbachol (5.48 nmol) into the posterior hypothalamic nucleus. Furthermore, microinjection of NPY or carbachol elicited a significant elevation of renal sympathetic nerve activity and an increase in resistance of the hindquarter vascular bed. However, NPY elicited a decrease and carbachol an increase in the resistance of the mesenteric bed, whereas NPY elicited an increase and carbachol a decrease in the resistance of the renal bed. These results suggest that NPY elicits an increase in MAP via centrally mediated sympathetic excitation. Furthermore, NPY and carbachol differentially affect sympathetic outflow to peripheral vascular beds after microinjection into the posterior hypothalamic nucleus.

Animals↗
PubMed1989

Biophysical analyses of sequential bands of enamel related to ruffle-ended and smooth-ended maturation ameloblasts.

During amelogenesis in the rat incisor, modulating ruffle-ended (RA) and smooth-ended (SA) ameloblasts are distributed as bands in the enamel organ of the maturation zone. This distribution of the two cell types has been shown to be precisely correlated with a banding of the underlying enamel, as shown by staining and other cyclical indicators (Takano et al., 1982a,b). Several biophysical approaches have been taken here to characterize the enamel bands sequentially and to determine whether the appearance of such bands is attributable to differences in inorganic composition possibly related to RA and SA. Sprague-Dawley rats were decapitated under ether anesthesia, lower incisors were dissected from surrounding alveolar bone, and enamel organs were wiped from the teeth with moistened gauze. Analyses were performed on either the surface of intact enamel or on individual strips of enamel dissected from the tooth surface, by use of the translucent bands that appear during drying as reference marks for the positions of the overlying cell type. X-ray diffraction (XRD), infrared spectroscopy (IR), x-ray photoelectron spectroscopy (XPS), and wave-length-dispersive electron probe x-ray micro-analysis (WDS) all failed to detect significant differences between analysis areas; data were characteristic of enamel apatite having typical XRD maxima (hkl = 002, 211, 112, 300), IR absorption bands (PO4(3-) and CO3(2-], XPS Ca and P binding energies (Ca2p = 350.5, 346.9 eV; P2p = 133.7, 132.7 eV), and WDS Ca/P molar ratios (1.33-1.49).(ABSTRACT TRUNCATED AT 250 WORDS)

Ameloblasts↗
PubMed1989

Protective HLA-DR phenotypes in rheumatoid arthritis.

In a study of HLA-DR phenotypes in patients with rheumatoid arthritis (RA) and controls from the Saskatoon area and in Newfoundland, we found that certain phenotypes occurred more frequently in the patients than in healthy controls in both populations ("increased risk phenotypes"). The reverse was also true: certain phenotypes were reduced or excluded from patients with RA compared with controls. Three increased risk phenotypes with twice the expected frequencies or more were HLA-DR1,DR4; DR4 and DR4,DR5. Four "protective" phenotypes with half or less the expected frequencies were HLA-DR1, DR5; DR2; DR2,DR3 and DR3,DR7. We speculate that at least for the DR3,DR7 phenotype, the protective effect may be due to a hybrid DQw2 molecule.

Arthritis, Rheumatoid↗
PubMed1989

Pharmacological profile of moclobemide, a short-acting and reversible inhibitor of monoamine oxidase type A.

The novel antidepressant moclobemide is a reversible inhibitor of monoamine oxidase (MAO), preferentially of type A. Moclomide was active in three animal models considered predictive for antidepressant activity: 1) it prevented dose-dependently akinesia and blepharospasm induced in mice and rats by Ro 4-1284, a short-acting amine releasing agent. Prevention of akinesia by moclobemide also depended upon the dose of Ro 4-1284. For comparison also, effects of cimoxatone, harmaline, tranylcypromine and clorgyline are presented: 2) in cats, it selectively and dose-dependently suppressed rapid eye movement sleep without disturbing the sleep-wakefulness cycle; and 3) in the behavioral despair test in mice, it decreased the immobility score to a similar degree as amitriptyline or imipramine. In addition, moclobemide potentiated 5-hydroxytryptophan-induced stereotypies in rats with a potency similar to cimoxatone and with a duration of action of less than 24 hr. Moclobemide had almost no effect on the spontaneous behavior in mice, rats, cats and monkeys. Only in higher doses, marginal sedation and slight impairment in motor performance were seen. Moclobemide did not prevent pilcarpine-induced salivation in mice, demonstrating the absence of anticholinergic activity. Blood pressure and heart rate of freely moving, spontaneously hypertensive rats were only slightly decreased for less than 3 hr. Moclobemide moderately potentiated the pressor effect of p.o. tyramine in rats. In conclusion, the reversible MAO inhibitor moclobemide is active in animal models sensitive to all major drugs used in the treatment of depression. In contrast to imipramine-like antidepressants, it lacks anticholinergic activity and it differs from classic MAO inhibitors by potentiating only weakly the pressor effect of p.o. tyramine.

2H-Benzo(a)quinolizin-2-ol, 2-Ethyl-1,3,4,6,7,11b-↗
PubMed1988

Herpes-simplex-related antigen in human demyelinative disease and encephalitis.

Using immunohistochemical methods optimized to detect herpes simplex virus type 2 (HSV-2) antigen, paraffin sections from human central nervous system tissues from 31 cases pathologically diagnosed as multiple sclerosis (MS), 34 cases of other neurological diseases, 4 adult cases of HSV encephalitis, and mouse brains infected with various HSV strains were examined. Two distinct patterns of immunoreactivity with HSV antisera were seen. In typical acute human and experimental encephalitis, antigen was readily detected using high dilutions of antisera to both HSV types -1 and -2, and was found nonselectively in both neurons and glia. Lesions were destructive, with necrosis of all neural cell types, and inflammation was a mixture of polymorphonuclear and mononuclear cells. By contrast, immunoreactivity in lesions in each of three MS cases and in one case of brain stem encephalitis was found only with HSV-2 antisera, and relatively high antiserum concentrations were required to detect it. Reactivity appeared to be largely restricted to glial cell nuclei within and near lesions that were selectively demyelinated. Only mononuclear inflammation was present. These experiments suggest that HSV-related antigen may be found in a broader spectrum of human CNS lesions than has previously been recognized, and that HSV or a related agent may be associated with a selective infection of glial cells and with CNS demyelination.

Adult↗
PubMed1988

Remyelination of central nervous system lesions in experimental genital herpes simplex virus infection.

To study spinal cord remyelination in a model of genital herpes simplex virus type 2 (HSV-2) infection, adult female mice were inoculated by a vaginal route. At intervals up to 6 months after infection, cord tissues were removed and examined by light and electron microscopy and by immunohistochemical methods. As a consequence of acute infection, 60% of mice developed multifocal central nervous system (CNS) demyelinative lesions in the lower thoracic, lumbar, or upper sacral cord. These lesions, already present 10 days after infection, contained naked axons and mononuclear cells, including macrophages. At 2 weeks, while active myelin breakdown was still ongoing, numerous Schwann cells were present in lesions and surrounded denuded axons. At 3 weeks, the earliest remyelination was seen, and was carried out by Schwann cells and to a lesser extent by oligodendrocytes. Remyelination was extensive by 6-10 weeks and was apparently completed after 3 months. Immunocytochemical studies using antisera to myelin proteins showed relatively distinct zones of central and peripheral remyelination in some lesions, whereas remyelination was of mixed type in others. Thus the remyelinative response following experimental HSV-2-induced CNS demyelination begins promptly, proceeds briskly and goes to completion. With a natural route of inoculation and a relatively avirulent strain of this human pathogen, we have produced a model of CNS white matter injury and repair in a high proportion of infected mice that may be useful in understanding mechanisms of human demyelinative disease.

Animals↗
PubMed1988

Ro 15-4513: partial inverse agonism at the BZR and interaction with ethanol.

The imidazobenzodiazepinone derivative Ro 15-4513 has the activity profile of a partial inverse (low efficacy) agonist at the benzodiazepine receptor (BZR). It reverses central nervous depressant effects of diazepam, and, in part, of phenobarbitone and ethanol in mice, rats and cats in behavioural, electrophysiological, and neurochemical paradigms. The interaction of Ro 15-4513 with barbiturates and ethanol is due to its inverse agonistic (negative allosteric modulatory) property at the BZR, as it was reversed by the selective BZR blocker flumazenil (Ro 15-1788). In the present experiment situations, other BZR partial inverse agonists in subconvulsant or overt convulsant doses were less effective against ethanol effects than Ro 15-4513. Possible mechanisms for this differential activity of BZR inverse agonists are discussed.

Animals↗
PubMed1988

Pneumoconiosis in iron ore surface mining in Labrador.

A cross-sectional survey of the work force at an iron ore surface mine and beneficiation plant in Labrador identified cases with a radiologic diagnosis compatible with simple pneumoconiosis by the International Labour Organization (ILO) classification (1980). Their distribution by ILO categories 1, 2, and 3, after excluding those with confounding diagnoses for pneumoconiosis, was 30, 10, and 2 cases, respectively. ILO category was related to age, duration of current employment, and cumulative respirable dust and quartz levels, as well as to decrement in ventilatory function.

Adult↗
PubMed1988

Blood pressure increases after injection of neuropeptide Y into posterior hypothalamic nucleus.

Unilateral microinjection of neuropeptide Y (NPY; 0.235-2.35 nmol) into the posterior hypothalamic nucleus was found to evoke a concentration-dependent increase in mean arterial pressure (MAP) of Urethane-anesthetized rats. Concentration-dependent pressor responses were also elicited by unilateral administration of histamine (0.543-17.9 nmol) into the posterior hypothalamic nucleus. Administration of 30 nmol of the histamine H1-receptor antagonist, chlorpheniramine, but not 43.5 nmol of the histamine H2-receptor antagonist, cimetidine, into the posterior hypothalamic nucleus 10 min before 5.43 nmol histamine administration, significantly attenuated the histamine-induced pressor response. These concentrations of chlorpheniramine or cimetidine did not affect the increase in MAP, which could be evoked by the administration of 5.48 nmol of the cholinergic muscarinic agonist carbachol into the posterior hypothalamic nucleus. The carbachol-induced increase in MAP was, however, completely blocked by administration of 12 nmol of the cholinergic muscarinic antagonist atropine into the posterior hypothalamic nucleus 10 min before carbachol administration. This concentration of atropine did not affect the histamine-induced pressor response. Administration of atropine or chlorpheniramine into the posterior hypothalamic nucleus 10 min before 2.35 nmol NPY significantly attenuated the pressor response evoked by NPY. Cimetidine, on the other hand, was unable to significantly affect the increase in MAP evoked by NPY. These results demonstrate that NPY administered into the posterior hypothalamic nucleus can elicit a pressor response, and that this pressor response might involve local histaminergic and cholinergic neuronal pathways.

Animals↗
PubMed1987

Further evidence that a single dose of an opiate can increase dopamine receptor sensitivity in mice.

Previous findings in our laboratory indicated that a single administration of morphine or levorphanol to mice could induce the development of supersensitive dopamine receptors. To further study this phenomenon, the ability of haloperidol to inhibit dopamine agonist-induced climbing was determined in mice 3 h following morphine (10 mg/kg i.p.) or levorphanol (2.0 mg/kg i.p.) pretreatment. The dose of haloperidol required to inhibit climbing behavior induced by 2.4 mg/kg (i.p.) of apomorphine or (-) N-n-propylnorapomorphine was increased significantly in the opiate-pretreated mice. Morphine pretreatment did not significantly affect the apparent pA2 of apomorphinehaloperidol for climbing behavior suggesting that the affinity of the dopamine receptor was not altered. This observation was supported by a lack of difference in the Kd of haloperidol binding sites between saline- and morphine-pretreated mice. There was, however, a significant increase in the Bmax in the morphine-pretreated animals. This increase was blocked when 5 mEq/kg of lithium (i.p.) or 5 mg/kg naloxone (i.p., administered twice) was administered concurrently with the morphine. Concurrent lithium or naloxone administration also attenuated the morphine-induced increase in dose of haloperidol required to inhibit dopamine agonist-induced climbing behavior. These results suggest that a single administration of an opiate can cause the development of dopamine receptor supersensitivity which is due to an increase in dopamine receptor density.

Animals↗
PubMed1987

Virus spread and initial pathological changes in the nervous system in genital herpes simplex virus type 2 infection in mice. A correlative immunohistochemical, light and electron microscopic study.

Mice were infected by the vaginal route with the MS strain of herpes simplex virus type 2 (HSV-2). Serial vaginal cultures were used to confirm infection and to select mice for this study. Two mice were killed by perfusion on days 2-6 post infection (p.i.) and lumbar and sacral cord with cauda were fixed and embedded for electron microscopy. Semithin Epon-sections were stained for viral antigen using a rabbit anti-HSV-2 antiserum and the Avidin-Biotin (ABC) method. Thin sections from antigen-positive blocks were examined by electron microscopy, and the number and types of infected cells detected by these two methods were compared. A good correlation was found between detection of infected cells by these methods. Infected cells included neurons of dorsal root ganglia and spinal cord, satellite cells of dorsal root ganglia, non-myelinating Schwann cells, astrocytes, oligodendrocytes and arachnoidal cells. Infected cells were first detected in the cauda on day 3 p.i. and in the spinal cord on day 5 p.i. The temporal and spatial distribution of infected cells was consistent with neural spread to and within the CNS. The pathological lesions showed a good correlation with the distribution and number of infected cells and are probably due to a direct virus effect. The similar sensitivity of the Epon-ABC method to electron microscopy in detecting infected cells indicates that this method may have useful applications in both experimental and diagnostic work.

Animals↗
PubMed1987

Inflammatory sensory polyradiculopathy and reactivated peripheral nervous system infection in a genital herpes model.

To study effects of herpesvirus reactivation on the nervous system, mice with latent genital herpes simplex virus type 2 (HSV-2) infections were immunosuppressed. Reactivated infection was detected by virus isolation or by antigen screening in histological sections of spines that contained cords, roots, and dorsal root ganglia. In ganglia, viral antigen was restricted to 2 distinct groups at T9-L2, and L6-S2 levels. In some ganglia, antigen was found in up to 4% of non-contiguous neurons, in their axons, and in endoneurial and satellite cells. Nerve roots distal to ganglia contained a few antigen-positive endoneurial cells and axons, but convincing antigen was not seen in proximal roots. Rare foci of anterior horn cells in the lower cord were the only central sites found to contain antigen. Comparison of antigen-containing ganglionic neuron counts to vaginal culture data indicate that peripheral virus shedding may depend on the number of neurons with reactivated infection. In non-immunosuppressed, latently infected mice, virus recovery was restricted to ganglionic explants from lower thoracic and lumbosacral regions; these ganglia contained no infectious virus in homogenates and no detectable antigen. These mice had an inflammatory polyradiculopathy in a similar distribution to virus found in latent and reactivated infection. The data show that genital HSV-2 infection can result in more extensive ganglionic latency and peripheral nervous system disease than has previously been recognized. Immunosuppression leads to reactivation and widespread, anatomically restricted antigen expression in many ganglia, consistent with the innervation of the genitourinary tract. Decalcified spine preparations provide a sensitive and simple way to detect virus reactivations and disease in these neural tissues.

Animals↗
PubMed1987

Drinking by portacaval shunted rats to regulatory challenges.

Male rats received an experimental portacaval shunt (PCS) which diverted all of the hepatic-portal blood from the liver into the vena cava. Several months postsurgery, the regulation of fluid balance was evaluated in PCS and sham operated rats. PCS and Sham groups exhibited increased drinking in response to water deprivation and to an osmotic load, however, in both situations the PCS rats drank more than their surgical controls. Despite this difference in intake (adjusted for differences in body weight), the initial bout parameters of the PCS group following osmotic challenge were not appreciably different from those of the Sham group. The reduction of plasma volume with polyethylene glycol treatment elicited drinking in both PCS and Sham groups, with the former group consuming more fluid than the latter after polyethylene glycol but not after vehicle treatment. The results indicate that even after portacaval anastomosis rats were capable of increasing drinking in response to regulatory challenges and that the greater spontaneous fluid intake of PCS rats relative to controls which has often been observed persists during such compensatory responses.

Animals↗