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Biomedical subjects

C A Ross

Publications and source records attributed to C A Ross.

At least 199 records · Page 11Linked to original sources

Inositol 1,4,5-trisphosphate receptors: immunohistochemical localization to discrete areas of rat central nervous system.

The second messenger inositol 1,4,5-trisphosphate triggers the release of intracellular Ca2+ stores upon binding to the inositol 1,4,5-trisphosphate receptor protein, a calcium channel that has been purified and molecularly cloned. To clarify the roles of inositol 1,4,5-trisphosphate receptor in the central nervous system, we have examined in detail the distribution of inositol 1,4,5-trisphosphate receptors in the rat brain and spinal cord using immunohistochemical methods. Inositol 1,4,5-trisphosphate receptors are present in neuronal cells, fibers and terminals in a wide distribution of areas throughout the central nervous system. These include a number of areas not previously reported, such as the olfactory bulb, thalamic nuclei and dorsal horn of the spinal cord. In addition, we have noted a strikingly high density of inositol 1,4,5-trisphosphate receptors in circumventricular organs and neuroendocrine structures such as the area postrema, choroid plexus, subcommisural organ, pineal gland and pituitary. The distribution of inositol 1,4,5-trisphosphate receptors in discrete structures throughout the central nervous system, including interconnected neuronal systems and neuroendocrine and circumventricular organ structures, presumably reflects the importance of Ca2+ release mediated by the phosphoinositide second messenger system in control of diverse physiological processes.

Animals↗

Correlation between the onset age of Huntington's disease and length of the trinucleotide repeat in IT-15.

Huntington's disease (HD) is an autosomal dominant disorder with a variable age of onset that is influenced by the sex of the affected parent. The recent recognition that HD is caused by an expanded triplet repeat suggests the possibility that the onset age may be predicted by the length of the repeat. This hypothesis was tested by assaying the length of the repeat in 114 individuals who were clinically diagnosed with HD and had a known onset age. Every individual had an expanded allele. The range was from 36 to 82 repeats (mean = 48.4 +/- 9.51) and larger than the normal range (6 to 31). The size of the expanded allele was correlated with the age of onset (r = -0.65 p < .0001). Despite the highly significant correlation, the repeat size explains less than half of the variance in onset age. Furthermore, the age of onset cannot be predicted from the size of the triplet repeat, particularly if the number of repeats is in the smaller end of the expanded range. If the repeat is < or = 50 triplets, the amount of variation in the age of onset explained by the length of the triplet repeat is less than 10%. As an illustration, the onset age of individuals with 39 repeats ranges from 30 to 65 years old. The sex of the affected parent had no effect in our sample beyond the effect of the length of the repeat. Affected offspring of affected fathers had longer repeats and a larger variance in allele size than offspring of affected mothers, perhaps reflecting greater instability in paternal transmission.

Adolescent↗

Correlation of acute cocaine-induced changes in local cerebral blood flow with subjective effects.

The authors administered 48 mg of intravenous cocaine or placebo to eight abstinent cocaine users in a double-blind, crossover design and examined blood flow using single photon emission computed tomography. Cocaine produced significant decreases in frontal cortical and basal ganglia blood flow; these latter correlated negatively with increases in self-ratings of "rush" and "high." The authors conclude that these local effects are compatible with dopaminergic system involvement.

Adult↗

Validity of the Dissociative Experiences Scale in screening for multiple personality disorder: a multicenter study.

OBJECTIVE: The Dissociative Experiences Scale has proved a reliable and valid instrument to measure dissociation in many groups, but its capacity to distinguish patients with multiple personality disorder from patients with other psychiatric disorders has not yet been conclusively tested. METHOD: A discriminant analysis was performed to classify 1,051 subjects as having or not having multiple personality disorder. Another discriminant analysis was performed on a subgroup of 883 subjects more closely representing patients in a typical psychiatric facility in terms of base rates of dissociative disorders. A cutoff score of 30 was also used to classify subjects, and Bayes's theorem, which allows for the calculation of the positive predictive value and the negative predictive value of a screening test, was applied. RESULTS: According to discriminant analysis of the total study group, the scale's sensitivity was 76% and its specificity was also 76%; according to discriminant analysis of the more representative subgroup, the scale's sensitivity was 76% and its specificity was 85%. Use of the cutoff score of 30 produced similar results. Results of the application of Bayes's theorem showed that 17% of the subjects scoring 30 or higher would actually have multiple personality disorder and 99% of those scoring less than 30 would not have multiple personality disorder. CONCLUSIONS: These results indicate that the Dissociative Experiences Scale performs quite well as a screening instrument to identify subjects with multiple personality disorder. In addition, the consistency of responses to scale items across centers indicates that the symptoms reported by patients with multiple personality disorder are highly similar across diverse geographic centers. This consistency supports the reliability and validity of the diagnosis of multiple personality disorder across centers.

Adult↗

Psychiatric health care costs of multiple personality disorder.

The lifetime psychiatric health care costs of 15 women with multiple personality disorder (MPD) who were admitted to the senior author's inpatient service over a four-year period were tabulated. A calculation of the projected costs of treatment based on costs incurred since diagnosis was made, and this was compared to prediagnosis baseline costs projected forwards for ten years. The result of the calculation was a saving of $84,899.44 per patient over ten years due to the diagnosis and psychotherapeutic treatment of MPD. If the length of time in the health care system prior to diagnosis was reduced from the average of 98.77 months experienced by these 15 women to 12 months, the savings would be over $250,000.00 per case. Because the potential savings from the diagnosis and treatment of MPD appear to be so large, replication of the study with a longer followup is required.

Adult↗

A comparison of in vitro assay systems for the measurement of drug sensitivity of Trypanosoma evansi.

Two in vitro assay systems were investigated for their effectiveness in detecting the sensitivity of Trypanosoma evansi stocks to the trypanocide suramin. These assay systems measured 1) incorporation of radiolabelled nucleic acid precursor, hypoxanthine; and 2) pyruvate production. They were compared with the direct counting method in which numbers of motile trypanosomes were estimated using a Neubauer haemocytometer chamber. Three stocks of T. evansi were tested-2 suramin sensitive stocks from Indonesia, TREU 1840 and TREU 1981, and a suramin resistant stock from the Sudan, TREU 2136. Each assay system distinguished between the suramin sensitive and resistant stocks. However, inhibition compared to untreated control cultures was less when assessed from pyruvate concentration in culture supernatants than by direct counting. The length of incubation with drug before addition of radio-label was the most important variable in the hypoxanthine incorporation assay. A pre-incubation time of 16 hours with the drug before adding the label for the further 8 hours of the assay was found to be the most sensitive. Under these conditions, the IC50 values (drug concentrations causing 50% inhibition) were similar to those obtained from direct counts. Pre-incubation of parasites with drug before adding the label resulted in a decrease of the IC50. These results suggest that the discrepancy between the levels of pyruvate production and relative growth at inhibitory concentrations of the drug are due to metabolism by the parasites during the initial stages of the assay, before the drug has began to inhibit cell growth.

Animals↗

Anticipation in bipolar affective disorder.

Anticipation refers to the increase in disease severity or decrease in age at onset in succeeding generations. This phenomenon, formerly ascribed to observation biases, correlates with the expansion of trinucleotide repeat sequences (TNRs) in some disorders. If present in bipolar affective disorder (BPAD), anticipation could provide clues to its genetic etiology. We compared age at onset and disease severity between two generations of 34 unilineal families ascertained for a genetic linkage study of BPAD. Life-table analyses showed a significant decrease in survival to first mania or depression from the first to the second generation (P < .001). Intergenerational pairwise comparisons showed both a significantly earlier age at onset (P < .001) and a significantly increased disease severity (P < .001) in the second generation. This difference was significant under each of four data-sampling schemes which excluded probands in the second generation. The second generation experienced onset 8.9-13.5 years earlier and illness 1.8-3.4 times more severe than did the first generation. In additional analyses, drug abuse, deaths of affected individuals prior to interview, decreased fertility, censoring of age at onset, and the cohort effect did not affect our results. We conclude that genetic anticipation occurs in this sample of unilineal BPAD families. These findings may implicate genes with expanding TNRs in the genetic etiology of BPAD.

Adult↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗