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Biomedical subjects

C A Ross

Publications and source records attributed to C A Ross.

At least 217 records · Page 12Linked to original sources
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↗
PubMed1991

The frequency of multiple personality disorder among psychiatric inpatients.

OBJECTIVE: A 2-year study was undertaken to determine the frequency of multiple personality disorder among general adult psychiatric inpatients. METHOD: All individuals admitted to two 23-bed acute care wards in a teaching hospital in Winnipeg, Man., were screened with the Dissociative Experiences Scale. Individuals with prior diagnoses of multiple personality disorder were excluded. All subjects scoring 20 or higher on the Dissociative Experiences Scale were interviewed with the Dissociative Disorders Interview Schedule. Then subjects with a diagnosis of multiple personality disorder and comparison subjects were interviewed by a clinician who was blind to all research data. RESULTS: A total of 299 subjects completed the Dissociative Experiences Scale and 80 received a structured diagnostic interview. Ten subjects (3.3%) had clinically confirmed multiple personality disorder. CONCLUSIONS: If these results are replicated and accepted, multiple personality disorder will become a serious consideration in the differential diagnosis of many psychiatric patients.

Adult↗
PubMed1991

Dissociative experiences in the general population: a factor analysis.

The 28-item Dissociative Experiences Scale was administered to a stratified cluster sample of 1,055 respondents in the general population of Winnipeg. Dissociative experiences were common in the sample and were not related to socioeconomic status, sex, education, religion, or place of birth, although they declined with age in both sexes. A principal components analysis identified three factors accounting for 47.1 percent of the combined variance of the scores. The first factor, absorption-imaginative involvement, is composed of common, benign experiences, such as missing part of a conversation and being able to ignore pain. The other two factors, activities of dissociated states and depersonalization-derealization, composed of less common experiences such as not recognizing friends or family members and not recognizing one's reflection in a mirror, may be powerful predictors of DSM-III-R dissociative disorders.

Adult↗
PubMed1991

Abuse histories in 102 cases of multiple personality disorder.

The authors interviewed 102 individuals with clinical diagnoses of multiple personality disorder at four centres using the Dissociative Disorders Interview Schedule. The patients reported high rates of childhood trauma: 90.2% had been sexually abused, 82.4% physically abused, and 95.1% subjected to one or both forms of child abuse. Over 50% of subjects reported initial physical and sexual abuse before age five. The average duration of both types of abuse was ten years, and numerous different perpetrators were identified. Subjects were equally likely to be physically abused by their mothers or fathers. Sexual abusers were more often male than female, but a substantial amount of sexual abuse was perpetrated by mothers, female relatives, and other females. Multiple personality disorder appears to be a response to chronic trauma originating during a vulnerable period in childhood.

Adolescent↗
PubMed1991

Epidemiology of multiple personality disorder and dissociation.

A recent survey of a large sample of the general population in the city of Winnipeg, Manitoba, showed that multiple personality disorder related to childhood abuse affects about 1% of the adult population. About 10% of the adult population has had a DSM-III-R dissociative disorder of some kind. Pathologic dissociation appears to be a major form of emotional disturbance in North America, and it appears to be about as common as anxiety, mood, and substance abuse disorders. The dissociative disorders can no longer be considered rare.

Borderline Personality Disorder↗
PubMed1990

Factors that predict scores on the Dissociative Experiences Scale.

Bernstein and Putnam (1986) recently developed the Dissociative Experiences Scale (DES), a reliable and valid measure of dissociative experiences. The purpose of this study was to determine the relationship of the DES to other measures of psychopathology and cognitive functioning. Seventy-six female and 43 male university students were administered the DES, the Hopkins Symptom Checklist (HSCL-90), the Maudsley Obsessional-Compulsive Inventory (MOCI), the Tellegen Absorption Scale (TAS), and the Barnes-Vulcano Rationality Test (BVRT). A standard multiple regression was computed that used the DES as the criterion variable and the HSCL-90, MOCI, TAS, and BVRT as predictor variables. The results showed that 61% of the variance for DES scores could be predicted by three subscales of the HSCL-90 (Phobic Anxiety, Anger-Hostility, Somatization) and the TAS and BVRT. The importance of the relationship between the predictor variables and the DES for understanding dissociative disorders, especially multiple personality disorder, was discussed.

Adult↗
PubMed1990

Trypanosoma congolense: an in vitro assay to distinguish drug-resistant from drug-sensitive populations.

An in vitro assay to distinguish drug-resistant from drug-sensitive populations of Trypanosoma congolense has been developed. The incorporation of radiolabelled hypoxanthine by procyclic trypanosomes in vitro was measured after 48 h exposure to different concentrations of trypanocides. In the presence of either isometamidium chloride (Samorin) or diminazene aceturate (Berenil), the ability of procyclics of a drug-sensitive stock (TREU 1627) to incorporate hypoxanthine at 28 degrees C was impaired to a much greater extent than that of procyclics of a drug-resistant stock (TREU 1467), when compared with control organisms grown in the absence of drugs. Serum from a rabbit given 1 mg/kg Samorin also inhibited incorporation of radiolabel in TREU 1627 procyclics more severely than in TREU 1467 procyclics, although the difference between stocks was not substantial. When used with cultured blood-stream forms maintained at 35 degrees C, the assay could distinguish the stocks in the presence of Samorin, but no difference was detected between the populations in their incorporation of hypoxanthine after exposure to Berenil.

Amidines↗
PubMed1990

Stability of metacyclic variable antigen types (M-VATs) during the early stages of infection with Trypanosoma congolense.

Expression of nine metacyclic variable antigen types (M-VATs) of Trypanosoma congolense in chancres from infected rabbits was determined using monoclonal antibodies raised against metacyclic forms of trypanosomes. Trypanosomes present in chancres 7-9 days post infection expressed M-VATs present in metacyclic populations of the parasites. The majority of M-VATs expressed showed little proportional change from those observed on metacyclic trypanosomes during this period although expression of one M-VAT increased, and another decreased. Although trypanosomes in chancres continued to express M-VATs, other VATs, not present in the M-VAT repertoire were also expressed and neutralization tests showed that new VATs appeared by 7 days after infection. In infected sheep neutralizing antibodies against M-VATs were detected by day 14 in lymph from efferent lymphatics draining lymph nodes in the region of chancres. Neutralizing antibodies directed against metacyclics were also present in the serum by day 14 and were still detectable for up to 35 days post infection. Hence, it is likely that in the vertebrate host the trypanosomes multiplying in the skin at the site of tsetse bit express all M-VATs characteristic of that particular serodeme, enabling the host to develop immunity to all antigen types present in the M-VAT repertoire.

Animals↗
PubMed1990

Messenger molecules in the cerebellum.

As data accumulate, the mammalian brain reveals its complex and subtle synaptic mechanisms. In the simplest system, a neurotransmitter binds to the receptor portion of a molecular complex incorporating an ion channel and thus alters the membrane potential, leading to excitatory or inhibitory effects. In more complex systems, receptors are coupled to second messenger systems to generate signals of longer duration and to modulate more diverse molecular mechanisms. The cerebellar cortex has a relatively simple wiring diagram with the primary neurotransmitter of most inhibitory and excitatory synapses well established. The second messenger signalling systems are more complex and those of the cerebellar output, the Purkinje cells, are the best characterized. More recently, molecules that might act as neuromodulators, carrying messages between neurons and between neurons and glial cells, have been identified, such as endothelin and nitric oxide. The classic neurotransmitters and novel neuromodulators, together with second messenger-activated trophic factors, can interact in complex ways; in this review Christopher Ross, David Bredt and Solomon Snyder discuss how studies of cerebellar circuitry and biochemistry are revealing such interrelations.

Adenosine↗
PubMed1990

Characterization of Trypanosoma congolense serodemes in stocks isolated from Chipata District, Zambia.

Six stocks of Trypanosoma congolense were cloned from 17 stocks isolated from Eastern Zambia and used to initiate insect-form in vitro cultures producing metacyclic trypanosomes. Serological assays were then developed using these in vitro-derived metacyclics as a reference collection of antigens. Monoclonal antibodies recognized 8 metacyclic variable antigen types (M-VATs) of one stock, T. congolense TREU 1885, representing 70-80% of that stock's M-VAT repertoire, and in an indirect fluorescent antibody test (IFAT) there were no cross-reactions between them and the metacyclic trypanosomes of the other 5 stocks. Cross-protection assays between the 6 stocks in mice showed that the stocks cultured in vitro were serologically distinct. In order to facilitate serological typing for serodeme characterization, an IFAT was developed using formalin-fixed metacyclic trypanosomes to identify VAT specific immune responses using 21 day post-infection antisera. The cultured stocks reacted only with their homologous antisera thus confirming the results obtained in the cross-protection assays. No cross-reactions were observed with the 6 cloned stocks and antisera against the 11 stocks of T. congolense isolated in the same area at the same time suggesting that these stocks were different from the reference collection of cultured metacyclics. Hence, at least 7 serodemes of T. congolense have been identified from the 17 stocks isolated.

Animals↗
PubMed1990

Endothelin in brain: receptors, mitogenesis, and biosynthesis in glial cells.

We have explored the cellular loci of endothelin (ET) actions and formation in the brain, using cerebellar mutant mice as well as primary and continuous cell cultures. A glial role is favored by several observations: (i) mutant mice lacking neuronal Purkinje cells display normal ET receptor binding and enhanced stimulation by ET of inositolphospholipid turnover; (ii) in weaver mice lacking neuronal granule cells, ET stimulation of inositolphospholipid turnover is not significantly diminished; (iii) C6 glioma cells and primary cultures of cerebellar astroglia exhibit substantial ET receptor binding and ET-induced stimulation of inositolphospholipid turnover; (iv) ET promotes mitogenesis of C6 glioma cells and primary cerebellar astroglia; and (v) primary cultures of cerebellar astroglia contain ET mRNA. ET also appears to have a neuronal role, since it stimulates inositolphospholipid turnover in primary cultures of cerebellar granule cells, and ET binding declines in granule cell-deficient mice. Thus, ET can be produced by glia and act upon both glia and neurons in a paracrine fashion.

Animals↗
PubMed1990

The inositol 1,4,5,-trisphosphate receptor in cerebellar Purkinje cells: quantitative immunogold labeling reveals concentration in an ER subcompartment.

The Ca2+ mobilization effect of inositol 1,4,5-trisphosphate, the second messenger generated via receptor-stimulated hydrolysis of phosphatidylinositol 4,5-bisphosphate, is mediated by binding to intracellular receptors, which are expressed in high concentration in cerebellar Purkinje cells. Partially conflicting previous reports localized the receptor to various subcellular structures: elements of ER, both rough and smooth-surfaced, the nuclear envelope, and even the plasma membrane. We have now reinvestigated the problem quantitatively by using cryosections of rat cerebellar tissue immunolabeled with polyclonal monospecific antibodies against the inositol 1,4,5-trisphosphate receptor. By immunofluorescence the receptor was detected only in Purkinje cells, whereas the other cells of the cerebellar cortex remained negative. In immunogold-decorated ultrathin cryosections of the Purkinje cell body, the receptor was concentrated in cisternal stacks (piles of up to 12 parallel cisternae separated by regularly spaced bridges, located both in the deep cytoplasm and beneath the plasma membrane; average density, greater than 5 particles/micron of membrane profile); in cisternal singlets and doublets adjacent to the plasma membrane (average density, approximately 2.5 particles/micron); and in other apparently smooth-surfaced vesicular and tubular profiles. Additional smooth-surfaced elements were unlabeled. Perinuclear and rough-surfaced ER cisternae were labeled much less by themselves (approximately 0.5 particles/micron, two- to threefold the background), but were often in direct membrane continuity with heavily labeled, smooth-surfaced tubules and cisternal stacks. Finally, mitochondria, Golgi cisternae, multivesicular bodies, and the plasma membrane were unlabeled. In dendrites, approximately half of the nonmitochondrial, membrane-bound structures (cisternae, tubules, and vesicles), as well as small cisternal stacks, were labeled. Dendritic spines always contained immunolabeled cisternae and vesicles. The dendritic plasma membrane, of both shaft and spines, was consistently unlabeled. These results identify a large, smooth-surfaced ER subcompartment that appears equipped to play a key role in the control of Ca2+ homeostasis: in particular, in the generation of [Ca2+]i transients triggered by activation of specific receptors, such as the quisqualate-preferring trans(+/-)-1-amino-1,3-cyclopentamedicarboxylic acid glutamatergic receptors, which are largely expressed by Purkinje cells.

Animals↗