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Biomedical subjects

C A Ross

Publications and source records attributed to C A Ross.

At least 19 recordsLinked to original sources
PubMed1992

Cloning and expression of a rat somatostatin receptor enriched in brain.

The tetradecapeptide somatostatin (SRIF) is a hormone release-inhibiting substance that mediates diverse effects in brain and peripheral organs via specific receptors. A cDNA encoding a rat SRIF receptor was identified by use of degenerate oligonucleotide primers and polymerase chain reaction amplification of cDNA prepared from transcripts expressed in rat brain. The complete cDNA encodes a protein of 391 amino acids with seven potential transmembrane domains. Expression of the cDNA product in transfected COS-7 cell lines provides the same high affinity of binding to [125I-Tyr11]SRIF-14 as that of rat cerebral cortex tissues. However, the binding of [125I-Tyr11]SRIF-14 to cloned rat SRIF receptor is not displaced by MK678, a SRIF analog that partially displaces [125I-Tyr11]SRIF-14 binding sites in membranes of rat cerebral cortex. Northern analysis and in situ hybridization indicate that mRNA (4.0 kilobases) for cloned rat SRIF receptor is preferentially expressed in rat brain regions such as cerebral cortex and hippocampus with no detectable expression in most peripheral organs. This pattern contrasts with the exclusive peripheral expression of a recently cloned human SRIF receptor. The cDNA probe of rat receptor detects mRNA from mouse brain but not from human cerebral cortex and cerebellum.

Amino Acid Sequence↗
PubMed1992

Three additional inositol 1,4,5-trisphosphate receptors: molecular cloning and differential localization in brain and peripheral tissues.

Three inositol 1,4,5-trisphosphate receptor (IP3R) cDNAs, designated IP3R-II, -III, and -IV, were cloned from a mouse placenta cDNA library. All three display strong homology in membrane-spanning domains M7 and M8 to the originally cloned cerebellar IP3R-I, with divergences predominantly in cytoplasmic domains. Levels of mRNA for the three additional IP3Rs in general are substantially lower than for IP3R-I, though in the gastrointestinal tract the levels of IP3R-III may be comparable to IP3R-I. Cerebellar Purkinje cells express at least two and possibly three distinct IP3Rs, suggesting heterogeneity of IP3 action within a single cell.

Amino Acid Sequence↗
PubMed1992

Locus coeruleus involvement in Huntington's disease.

Numbers and areas of neuronal profiles from sections of brain stem at specific anatomic levels of the locus coeruleus and the dorsal raphe nucleus were measured in 33 patients with Huntington's disease and in 23 age-matched control subjects. Results from the Huntington's disease cases were correlated with severity of neostriatal atrophy and with systematically collected quantitative clinical data. Among the patients with Huntington's disease, lower locus coeruleus neuronal counts, reduced neuronal areas, and reduced locus coeruleus length (distance between rostral and caudal levels) were associated with features of advanced disease, including severity of neostriatal atrophy, severity of dementia, duration of illness, and severity of motor impairment and activities of daily living impairment. By contrast, there was no evidence of neuronal pathology within the dorsal raphe nucleus in Huntington's disease. Pathologic changes in the locus coeruleus may relate to some of the clinical manifestations of Huntington's disease.

Adult↗
PubMed1992

Identification of the surface components of Trypanosoma evansi.

125I-labelling was used to characterise the surface components of five stocks of Trypanosoma evansi. Two components of 67 and 60.5 kD were labelled in two of the stocks, a single 60.5 kD component in two other stocks and no components in the remaining stock. These differences are probably related to the labelling method and biochemical differences between the stocks.

Animals↗
PubMed1992

Dissociative experiences among psychiatric inpatients.

The Dissociative Experiences Scale was administered to 299 inpatients on an acute care general adult psychiatric ward over a 2-year period. The average score was 14.6, which is significantly higher than the mean for the general population. About one in six inpatients reported very high scores above 50 on the seven most common items in the scale, indicating a high level of dissociative psychopathology. Based on the responses to four items which form a scale factor called Activities of Dissociated States, an estimate is made that 6%-8% of general adult inpatients may have multiple personality disorder. Dissociative psychopathology is common on inpatient units.

Adult↗
PubMed1992

Paranormal experiences in the general population.

The Dissociative Disorders Interview Schedule was administered to a random sample of 502 adults in the general population of Winnipeg, a midwestern Canadian city. Results showed that paranormal/extrasensory experiences were common in the general population. They were linked to a history of childhood trauma and to other dissociative symptom clusters. A factor analysis of the paranormal experiences identified three factors which together accounted for 44.0% of the combined variance of the scores. A model is proposed in which paranormal experiences are conceptualized as an aspect of normal dissociation. Like dissociation in general, paranormal experiences can be triggered by trauma, especially childhood physical or sexual abuse. Such experiences discriminate individuals with childhood trauma histories from those without at high levels of significance.

Acting Out↗
PubMed1991

Neuronal loss in layers V and VI of cerebral cortex in Huntington's disease.

Neuronal loss in the cerebral cortex in Huntington's disease (HD) has not been well documented, nor has its laminar pattern been definitively established. We therefore counted neurons in individual cortical laminae in the dorsal frontal cortex of 5 HD and 5 control autopsy brains. Significant neuronal loss (to 57% of control, P = 0.002) was found in layer VI of HD brains. These cells project principally to the thalamus, the claustrum and other regions of cerebral cortex; thus their loss is unlikely to be the result of retrograde degeneration secondary to striatal pathology. Layer V neurons were also decreased (to 71% of control, P = 0.034). Degeneration of cerebral cortical neurons may be at least partly responsible for some of the non-choreic symptoms of HD, such as dementia, irritability, apathy, and depression.

Autopsy↗
PubMed1991

Inositol 1,4,5-trisphosphate receptors: distinct neuronal and nonneuronal forms derived by alternative splicing differ in phosphorylation.

We have identified two distinct transcripts of inositol 1,4,5-trisphosphate receptor by using the PCR on first-strand cDNAs from various rat tissues. The longer form, corresponding to the previously cloned adult rat brain inositol 1,4,5-trisphosphate receptor, contains a 120-nucleotide insert between the two cAMP-dependent protein kinase phosphorylation consensus sequences. The shorter form (lacking the insert) predominates in fetal brain and peripheral tissues and appears to represent a nonneuronal receptor, whereas the longer form is found in adult brain and appears to be exclusively neuronal. The phosphorylation kinetics by cAMP-dependent protein kinase and the phosphopeptide maps differ for inositol 1,4,5-trisphosphate receptors purified from tissues predominantly expressing different forms of the transcript.

Amino Acid Sequence↗
PubMed1991

Variability of in vitro culture characteristics, including metacyclic trypomastigote production, in different stocks of Trypanosoma congolense.

Six cloned stocks of Trypanosoma congolense, isolated from the same area of Eastern Zambia, were maintained in vitro as insect form cultures producing infective metacyclic trypanosomes. Although the same general culture conditions were applied, different handling regimes were required for optimum growth of each stock. During primary isolation, many differences were found in the culture characteristics of the stocks. The time taken for cytoadherence to occur varied from 14 to 62 days, while the interval between attachment and the appearance of infective metacyclic trypanosomes ranged from 9 to 94 days. There was a 10-fold difference in the numbers of metacyclic forms produced by different stocks. Time in culture appeared to have little effect on the production of metacyclic forms, and it is probable that in vitro characteristics of T. congolense depend on the genetic constitution of individual stocks or clones.

Animals↗
PubMed1991

Trypanosoma congolense: re-expression of a deleted metacyclic variable antigen type in vivo and in vitro.

The expression of variable antigen types (VATs) was determined among dividing populations of T. congolense growing in vivo in rabbit chancres and in vitro on bovine aorta endothelial cell monolayers. Experiments were performed in which a single metacyclic VAT (M-VAT) was deleted from a cultured metacyclic population by neutralisation with a monoclonal antibody and complement. Subsequent expression of the deleted M-VAT and two unrelated M-VATs was determined by an indirect immunofluorescent antibody test. The deleted M-VAT was re-expressed both in vivo and in vitro and the proportions of unrelated M-VATs were not markedly affected by the neutralisation of this single M-VAT. In addition, an overall similarity was observed between M-VAT expression and re-expression in vivo and in vitro.

Animals↗
PubMed1991

Drug-specific F(ab')2 fragment reduces desipramine cardiotoxicity in rats.

Current therapy for cardiotoxicity due to tricyclic antidepressant (TCA) overdose is often ineffective in seriously poisoned patients. We studied the effect of a drug-specific antibody fragment on TCA cardiotoxicity in rats. Animals received anti-TCA F(ab')2 2.0 g/kg i.v. over 10 min starting 15 min after administration of a toxic dose of desipramine (DMI). This anti-TCA F(ab')2 dose was 36.9% of the molar DMI dose in terms of binding sites. Anti-TCA F(ab')2 infusion had no adverse effects and rapidly reduced DMI induced QRS prolongation compared with control F(ab')2 (23 +/- 14 vs 71 +/- 11% QRS prolongation at the end of infusion, P less than 0.001). This beneficial effect lasted for the 45 min duration of the study. Markedly enhanced DMI binding in serum after anti-TCA F(ab')2 was demonstrated by a 48-fold increase in the total DMI concentration over controls and a reduction in the fraction of unbound DMI (44.5 +/- 19.4 vs 0.7 +/- 0.2%). Anti-TCA F(ab')2 reduced the DMI concentration in brain but not in other organs. We conclude that anti-TCA F(ab')2 substantially reduces DMI cardiotoxicity in rats, and does so rapidly enough to be of potential clinical benefit for patients with DMI overdose. Because only a small fraction of the DMI dose was bound by antibody, these data suggest that antibody fragment doses considerably less than equimolar to the DMI dose may be effective in treating DMI cardiotoxicity.

Animals↗
PubMed1991

Paleozoic Foraminifera.

The approximately 300 million years that make up Paleozoic time saw the evolution of eight of the fifteen recognized suborders of Foraminifera. Of the suborders present in the Paleozoic, seven are morphologically relatively simple, slowly evolving, and continued into Mesozoic and Cenozoic times to become the ancestoral lineages from which evolved several additional post-Paleozoic suborders. In contrast, an eighth Paleozoic suborder, the Fusulinina, was an abundant, ecologically dominant group that evolved from simple to highly specialized forms and had a history of rapid evolution with diverse lineages. Fusulinines became extinct at the end of the Paleozoic. Their early representatives may have given rise to three and eventually four post-Paleozoic suborders. A number of suborders in the Paleozoic have similar, supposedly independent, early evolutionary patterns with the following series of morphological steps: (1) single chambers with or without apertures depending on the amount of wall cement; (2) groups of chambers that appear to be buds or aggregations of individuals rather than true chambers; (3) a proloculus followed by a tubular second chamber that is first erect and gradually evolves into enrolled free-living individuals; (4) development of constrictions in the tubular chamber; and finally (5) evolution of true chambers. These morphological steps, which are basic organizational steps with evolutionary significance, appear in lineages with quite different test compositions and, therefore, are considered only distantly related in the present classification.

Animals↗
PubMed1991

Localization of an endoplasmic reticulum calcium ATPase mRNA in rat brain by in situ hybridization.

SERCA-2 is an endoplasmic reticulum Ca2+ ATPase present in brain [Gunteski-Hamblin A.-M. et al. (1988) J. biol. Chem. 263, 15032-15040]. We sought to map the distribution of this pump in the rat brain and investigate its relationship to Ca2+ uptake by brain endoplasmic reticulum. Using in situ hybridization and Northern blots with antisense oligonucleotide probes, we found that SERCA-2 is concentrated most densely in the cerebellum, especially in Purkinje cells, and in the hippocampus, with heavy labeling also in cortex, thalamus, pontine nuclei and the mitral cell layer of the olfactory bulb. 45Ca2+ uptake displayed a similar pattern with heaviest accumulation in cerebellum, hippocampus, cortex, thalamus and olfactory bulb. In corpus striatum and substantia nigra, relative 45Ca2+ accumulation was greater than SERCA-2 mRNA. Thus, SERCA-2 appears to be involved in Ca2+ uptake into endoplasmic reticulum in brain for release by inositol 1,4,5-trisphosphate and other agents.

Animals↗
PubMed1991

Delirium: phenomenologic and etiologic subtypes.

While all delirious patients have clouding of consciousness (alteration of attention) and cognitive dysfunction, the level of alertness of different patients may range from stuporous to hyperalert. We, therefore, developed an analog scale to rate the alertness of delirious patients, and a separate scale to rate the severity of their clouding of consciousness. Based on these scales, patients were categorized overall as relatively "activated" (relatively alert despite clouding of consciousness), or "somnolent" (relatively stuporous along with clouding of consciousness). Cognitive function was estimated using the Mini-Mental Status Exam. Separate ratings were made of hallucinations, delusions, illusions, and agitated behavior. Activated and somnolent patients had similar ages, overall severity of delirium, and Mini-Mental Status Exam scores. Activated patients, however, were more likely to have hallucinations, delusions, and illusions than somnolent patients, and were more likely to have agitated behavior. Patients with hepatic encephalopathy were more likely to have somnolent delirium, while patients with alcohol withdrawal appeared more likely to have activated delirium. These data indicate that phenomenologic subtypes of delirium can be defined on the basis of level of alertness. These subtypes are validated in part by their differing associations with symptoms unrelated to alertness. These subtypes may have different pathophysiology, and thus, potentially different treatments.

Aged↗
PubMed1991

CNS arousal systems: possible role in delirium.

Delirium is often considered a global and nonspecific alteration in cerebral function. However, the recent clinical evidence for heterogeneity within the syndrome of delirium suggests that different systems of the brain may be important in different kinds of delirium. Some forms of delirium, such as anticholinergic toxicity and hepatic encephalopathy, may be caused by drugs or toxins acting on specific brain neurochemical systems. The neurophysiological bases of the control of normal arousal and attention are still relatively poorly understood. However, the recent appreciation of the existence of neurotransmitter-specific projections from the hypothalamus and brain stem directly to the cerebral cortex has spurred new research. Some of these projections may be important in particular kinds of delirium; for instance, evidence from a number of different lines of research implicates GABA systems in the brain as being important in the delirium of hepatic encephalopathy. Cholinergic neurons in the basal forebrain and pons innervate the cerebral cortex. Both of these neurons, but particularly the pontine group, may be important in the delirium of anticholinergic toxicity. Thus, more research on the physiology of these systems in normal sleep and arousal, as well as in pathophysiological states, is indicated. Little is known about changes in these systems with aging. The well-known degeneration in cholinergic systems in Alzheimer's disease, and the sensitivity of individuals with Alzheimer's disease to anticholinergic toxicity, suggest a role of central cholinergic systems in anticholinergic delirium in demented patients. Further research into the involvement of the other systems in aging and delirium apparently would be fruitful.

Aged↗