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Biomedical subjects

C A Ross

Publications and source records attributed to C A Ross.

At least 127 records · Page 7Linked to original sources
PubMed1997

Teaching cardiac rhythm strip interpretation within a cross-cultural context: using Nicaraguan nurses as a model.

Critical care nurses have been interpreting rhythm strips in the United States for years, and recently this concept has become a new responsibility for critical care nurses in Nicaragua. The focus of this article is on the unique challenges encountered by a nurse educator when teaching critical care concepts to non-English-speaking critical care nurses. Using Nicaraguan nurses as a model, the author shares experiences of teaching advanced concepts to non-English-speaking nurses. The specific concept taught was rhythm strip interpretation and the potential value in nursing care practice.

Critical Care↗
PubMed1997

Active immunization alters the plasma nicotine concentration in rats.

The ability of active immunization to alter nicotine distribution was studied in rats. Animals were immunized with 6-(carboxymethylureido)-(+/-)-nicotine (CMUNic) linked to keyhole limpet hemocyanin (KLH). Antibody titers determined by ELISA, using CMUNic coupled to albumin as the coating antigen, were greater than 1:10,000. Antibody binding was inhibited by neither of the nicotine metabolites cotinine and nicotine-N-oxide but was inhibited to a greater extent by CMUNic than by nicotine; this suggests the presence of antibodies to the linker structure as well as antibodies to nicotine. Antibody affinity for nicotine measured by soluble radioimmunoassay was 2.4 +/- 1.6 x 10(7) M-1, and binding capacity was 1.3 +/- 0.7 x 10(-6) M, which corresponds to 0.1 +/- 0.05 mg/ml of nicotine-specific IgG per milliliter of serum. One week after their second boost, groups of eight anesthetized rats immunized with either CMUNic-KLH or KLH alone received nicotine 0.03 mg/kg (equivalent to two cigarettes in a human) via the jugular vein over 10 sec. This dosing regimen was shown to mimic the arterio-venous nicotine concentration gradient typical of nicotine delivered by cigarette smoking in humans. Plasma nicotine concentrations at 10 to 40 min were 4 to 6-fold higher in the CMUNic-KLH rats than in controls (P < .001). Nicotine binding in plasma determined by equilibrium dialysis was markedly increased in the CMUNic-KLH group (83.4 +/- 6.8% vs. 16.4 +/- 14.2%), but brain nicotine concentrations at 40 min did not differ (37.9 +/- 4.5 vs. 44.0 +/- 8. 4 ng/g, CMUNic-KLH vs. KLH, P = .1). The amount of nicotine bound to antibody in plasma, estimated from the in vivo data, was 9% of the administered dose. These data demonstrate that active immunization can bind a significant fraction of a clinically relevant nicotine dose in plasma. Observing this effect with antibodies of modest affinity and titer is encouraging, but better immunogens may be needed to alter nicotine distribution to brain and modify nicotine's behavioral effects.

Animals↗
PubMed1996

Lymphocyte apoptosis: mediation by increased type 3 inositol 1,4,5-trisphosphate receptor.

B and T lymphocytes undergoing apoptosis in response to anti-immunoglobulin M antibodies and dexamethasone, respectively, were found to have increased amounts of messenger RNA for the inositol 1,4,5-trisphosphate receptor (IP3R) and increased amounts of IP3R protein. Immunohistochemical analysis revealed that the augmented receptor population was localized to the plasma membrane. Type 3 IP3R (IP3R3) was selectively increased during apoptosis, with no enhancement of type 1 IP3R (IP3R1). Expression of IP3R3 antisense constructs in S49 T cells blocked dexamethasone-induced apoptosis, whereas IP3R3 sense, IP3R1 sense, or IP3R1 antisense control constructs did not block cell death. Thus, the increases in IP3R3 may be causally related to apoptosis.

Amino Acid Sequence↗
PubMed1996

Huntingtin-associated protein (HAP1): discrete neuronal localizations in the brain resemble those of neuronal nitric oxide synthase.

Huntington disease stems from a mutation of the protein huntingtin and is characterized by selective loss of discrete neuronal populations in the brain. Despite a massive loss of neurons in the corpus striatum, NO-generating neurons are intact. We recently identified a brain-specific protein that associates with huntingtin and is designated huntingtin-associated protein (HAP1). We now describe selective neuronal localizations of HAP1. In situ hybridization studies reveal a resemblance of HAP1 and neuronal nitric oxide synthase (nNOS) mRNA localizations with dramatic enrichment of both in the pedunculopontine nuclei, the accessory olfactory bulb, and the supraoptic nucleus of the hypothalamus. Both nNOS and HAP1 are enriched in subcellular fractions containing synaptic vesicles. Immunocytochemical studies indicate colocalizations of HAP1 and nNOS in some neurons. The possible relationship of HAP1 and nNOS in the brain is reminiscent of the relationship of dystrophin and nNOS in skeletal muscle and suggests a role of NO in Huntington disease, analogous to its postulated role in Duchenne muscular dystrophy.

Animals↗
PubMed1996

Expansion of polyglutamine repeat in huntingtin leads to abnormal protein interactions involving calmodulin.

Huntington's disease (HD) is an inherited neurodegenerative disorder associated with expansion of a CAG repeat in the IT15 gene. The IT15 gene is translated to a protein product termed huntingtin that contains a polyglutamine (polyGln) tract. Recent investigations indicate that the cause of HD is expansion of the polyGln tract. However, the function of huntingtin and how the expanded polyGln tract causes HD is not known. We investigate potential protein-protein interactions of huntingtin using affinity resins. Huntingtin from brain extracts is retained on calmodulin(CAM)-Sepharose in a calcium-dependent fashion. We purify rat huntingtin to apparent homogeneity using a combination of DEAE-cellulose column chromatography, ammonium sulfate precipitation, and preparative SDS/PAGE. Purified rat huntingtin does not interact with CAM directly as revealed by 125I-CAM overlay. Huntingtin forms a large CAM-containing complex of over 1,000 kDa in the presence of calcium, which partially disassociates in the absence of calcium. Furthermore, an increased amount of mutant huntingtin from HD patient brains is retained on CAM-Sepharose compared to normal huntingtin from control patient brains, and the mutant allele is preferentially retained on CAM-Sepharose in the absence of calcium. These results suggest that huntingtin interacts with other proteins including CAM and that the expansion of polyGln alters this interaction.

Animals↗
PubMed1996

Analysis of thirteen trinucleotide repeat loci as candidate genes for schizophrenia and bipolar affective disorder.

A group of diseases are due to abnormal expansions of trinucleotide repeats. These diseases all affect the nervous system. In addition, they manifest the phenomenon of anticipation, in which the disease tends to present at an earlier age or with greater severity in successive generations. Many additional genes with trinucleotide repeats are believed to be expressed in the human brain. As anticipation has been reported in schizophrenia and bipolar affective disorder, we have examined allele distributions of 13 trinucleotide repeat-containing genes, many novel and all expressed in the brain, in genomic DNA from schizophrenic (n = 20-97) and bipolar affective disorder patients (23-30) and controls (n = 43-146). No evidence was obtained to implicate expanded alleles in these 13 genes as causal factors in these diseases.

Base Sequence↗
PubMed1996

Effects of recombinant drug-specific single chain antibody Fv fragment on [3H]-desipramine distribution in rats.

Tricyclic antidepressant overdose can be reversed in rats by drug-specific antibody Fab fragments, but the required Fab dose may itself by toxic. We studied the potential use of a smaller, recombinant desipramine (DMI)-specific single chain Fv fragment (B9-sFv) for this purpose. Anesthetized rats received a tracer (subtoxic) dose of [3H]-DMI followed in 15 min by B9-IgG, B9-Fab, B9-sFv (0.1 mumol of binding sites) or BSA. Each of the active treatments produced a rapid and substantial increase in the serum radiolabel concentration, whereas BSA did not (P < 0.001). The increase in serum radiolabel concentration 1 min after treatment was 13.3-fold with B9-IgG, 10.0-fold with B9-Fab and 7.3-fold with B9-sFv. Serum antibody concentrations were also highest after B9-IgG and lower with B9-Fab or B9-sFv. The 24-hr urinary excretion of radiolabel did not differ among groups, but was extensive even in the BSA group and probably represented the excretion of DMI metabolites. B9-sFv concentrations in urine or buffer at 37 degrees declined by >90% over 24 hr, but this fragment was much more stable in serum, retaining 70% of its activity after 96 hr. These data demonstrate that B9-sFv can alter markedly the distribution of [3H]-DMI in vivo. The rapidity of this effect, and its magnitude in comparison with Fab fragment or IgG, suggest that further study of B9-sFv as a treatment of DMI overdose is warranted.

Analysis of Variance↗
PubMed1996

A controlled trial of idebenone in Huntington's disease.

One hundred patients with clinically diagnosed Huntington's disease (HD) were randomized to either idebenone, an antioxidant and enhancer of oxidative metabolism, or placebo, in a 1-year, double-blind, parallel-group study aimed at slowing the rate of progression of the disease. Ninety-one patients completed the study. There were no significant differences between groups on the primary outcome measures of the Huntington's Disease Activities of Daily Living Scale (ADL-an index of functional status) and the Quantified Neurologic Examination (QNE). Sample size calculations based on progression of the ADL and QNE in this study group revealed that a larger study group is necessary to detect any differences less than an almost complete halting of the disease. This argues for multicenter efforts for future therapeutic trials in HD.

Activities of Daily Living↗
PubMed1996

cDNA cloning and characterization of an atrophin-1 (DRPLA disease gene)-related protein.

Dentatorubral and pallidoluylsian atrophy (DRPLA) is a progressive neurological disorder characterized by neuronal degeneration, especially in the cerebellar dentate nucleus. DRPLA is caused by an unstable expansion of a CAG trinucleotide repeat coding for glutamine in a gene of unknown function, termed atrophin-1, located on chromosome 12. To gain additional understanding of atrophin-1, we have isolated a second member of the atrophin-1 gene family by screening rat cDNA libraries. The 1006-amino-acid product of this gene, which we have termed rat atrophin related protein(rARP), does not contain a glutamine repeat, but it does contain two regions of alternating acidic and basic amino residues similar to those found in atrophin-1. rARP is widely expressed as both a 7.4- and a 9.4-kb message, with enrichment in cerebellum and testis. Like atrophin-1, the rARP in vitro translation product migrates more slowly on SDS-polyacrylamide gel electrophoresis than predicted by molecular weight. We conclude that, at least in the rat, polyglutamine is not an essential feature of the atrophin family of genes.

Amino Acid Sequence↗
PubMed1996

Trypanosomosis research at the Centre for Tropical Veterinary Medicine (CTVM) 1970 to 1995.

This review covers aspects of research work carried out on animal trypanosomes at the Centre for Tropical Veterinary Medicine (CTVM) during the last 25 years. The review covers work on antigenic variation, tissue culture, drug resistance, immunology, biochemistry and pathology of Trypanosoma brucei, T. congolense, T. gambiense and T. evansi. It is not intended as an exhaustive review of the subject but focuses on certain aspects of these areas which are presented in relation to work carried out within the broader scientific community.

Animals↗
PubMed1996

Psychosis and genes with trinucleotide repeat polymorphism.

Abnormal expansion of genes with trinucleotide repeat (TNR) polymorphism has been found in a number of neuropsychiatric disorders. These disorders and the major psychoses, schizophrenia and bipolar affective disorder, appear to share an interesting phenomenon: genetic anticipation. Because TNR expansion correlates with anticipation, these unstable DNA sites are considered important candidate loci for the major psychoses. We investigated genes with TNR polymorphisms, including B1, B33, B37, and the N-cadherin gene, in unrelated Caucasian North American and Italian schizophrenics (n = 53 to 74), and matched controls. Also, unrelated Caucasian North American patients with bipolar I affective disorder were screened for the B33 and N-cadherin genes (n = 49 and 63, respectively). No unusually long alleles that would suggest abnormal expansion of the TNR were observed for any of these genes. Also, no statistically significant results were found in tests for genetic association between any of these genes and schizophrenia. For B37, a trend toward a difference in allele counts between schizophrenics and controls was observed. However, no clear evidence for a role of these TNR-containing genes in schizophrenia or bipolar affective disorders was found.

Bipolar Disorder↗
PubMed1996

Alteration to one of three adenosine transporters is associated with resistance to cymelarsan in Trypanosoma evansi.

Continuous exposure of Trypanosoma evansi bloodstream forms to Cymelarsan in vitro resulted in the induction of resistance to the drug over a period of 4.5 months. Induction of resistance to Cymelarsan was accompanied by increased resistance to both Arsobal and Berenil, but Cymelarsan-resistant trypanosomes remained sensitive to Suramin and Antrycide. Since resistance to arsenical drugs in trypanosomes has been linked to changes in adenosine uptake, the adenosine metabolism in drug-sensitive and drug-resistant clones was measured. The initial rate of [3H]-adenosine uptake was much higher in sensitive trypanosomes than in drug-resistant parasites, but the amount of radiolabel accumulated by each population was similar. Both adenine and inosine inhibited incorporation of [3H]-adenosine in each population, but in quite different ways. Adenine inhibited more than 80% of adenosine incorporation in drug-sensitive trypanosomes but suppressed less than half of this process in the resistant population. In contrast, inosine inhibited only 10-15% of adenosine incorporation in the sensitive parasites but was inhibitory to a much greater extent in resistant trypanosomes. Lysis of drug-sensitive trypanosomes by 1 microM Cymelarsan was inhibited by adenosine, adenine and Berenil but not by inosine. Furthermore, in drug-sensitive trypanosomes, adenosine uptake could be reduced in three stages by the sequential addition of inosine, Berenil and adenine, whereas in drug-resistant parasites a reduction in adenosine uptake was caused only by the addition of inosine and adenine. These observations provide evidence that the acquisition of resistance to Cymelarsan is accompanied by the loss of one of three adenosine transporters in T. evansi. In drug-sensitive trypanosomes, this transporter mediates the entry of adenine and also of Cymelarsan and Berenil into the parasites.

Adenosine↗
PubMed1996

DRPLA gene (atrophin-1) sequence and mRNA expression in human brain.

Dentatorubral pallidoluysian atrophy (DRPLA, Smith's disease) is one of five disorders currently known to result from expansion of a CAG trinucleotide repeat encoding glutamine. The reported full length cDNA sequence encodes a serine repeat and a region of alternating acidic and basic amino acids, as well as the glutamine repeat. We now report the nucleic acid and deduced amino acid sequences of the open reading frame of this gene, obtained from a series of independently isolated and sequenced cDNA clones. Eight nucleotide differences from the originally published sequence result in a change of 34 amino acids, most prominently in the region of alternating acidic and basic residues. Northern analysis and in situ hybridization indicate that atrophin-1 mRNA is expressed in multiple brain regions. The level of mRNA expression as determined by in situ hybridization in a DRPLA-diseased brain is indistinguishable from the level observed in a matched control brain. These results indicate that the correlation between atrophin-1 expression and regions of pathology in DRPLA is at best partial, and that the expanded allele does not cause a major loss of mRNA expression. The pathology of the disorder may therefore arise from the altered structure and function of the abnormal protein.

Amino Acid Sequence↗
PubMed1996

Trypanocidal resistance in Trypanosoma evansi in vitro: effects of verapamil, cyproheptidine, desipramine and chlorpromazine alone and in combination with trypanocides.

A study was conducted in vitro to assess the ability of calcium antagonists to reverse trypanocidal resistance in Trypanosoma evansi. Susceptibility patterns of sensitive and resistant parasites were evaluated against calcium antagonists of several chemical classes (verapamil, cyproheptidine, desipramine and chlopromazine), alone and in combination with suramin, diminazene aceturate or melarsen oxide cyteamine. The putative resistance modulators were intrinsically antitrypanosomal, but were unable to reverse resistance to any of the trypanocides tested. It was thus concluded that resistance to these trypanocides in T. evansi may differ from drug resistance mechanisms occurring in cancer cells, malaria or in South American trypanosomosis, where calcium antagonists have successfully reversed resistance.

Animals↗
PubMed1996

Serum prostate-specific antigen and digital rectal examination for early detection of prostate cancer in a national community-based program. The Prostate Cancer Education Council.

OBJECTIVES: This study analyzed methods of prostate cancer early detection in community settings throughout the United States against standards and findings of earlier studies conducted at academic medical centers. METHODS: The study was conducted at 148 clinical centers during Prostate Cancer Awareness Week in September 1993 and continued through June 1994. A total of 31,953 eligible subjects were tested by both digital rectal examination (DRE) and prostate-specific antigen (PSA). PSA was tested with the Abbott IMx PSA assay and reported by Roche Biomedical, Inc. RESULTS: The study confirmed that elevated PSA levels (greater than 4.0 ng/mL) aid in the detection of organ-confined prostate cancer when used in conjunction with the DRE. Reflecting more conservative biopsy decision-making practices, study results nonetheless are comparable to earlier reports. Among 1307 subjects who underwent biopsy, 322 cancers were detected. The cancer detection rate was 3.6% for PSA, 3.0% for DRE, and 4.7% if either test result was positive. The positive predictive value (PPV) for elevated PSA levels (greater than 4.0 ng/mL) was 3l.6%, significantly better (P < 0.0001) than the PPV for abnormal DRE results (25.5%). Nearly 90% (88.9%) of staged cancers were diagnosed as localized. Elevated PSA levels detected more localized cancers (76 of 105 [72.4%]) than the DRE (72 of 105 [68.6%]). Of localized tumors, 33 (31.4%) were missed by DRE and detected solely by PSA, and 29 (27.6%) were missed by PSA and detected solely by DRE. The combined use of the two methods detected 33 additional localized tumors. CONCLUSIONS: Community practice throughout the United States demonstrates that PSA and DRE are consistently effective and efficient in the early detection of prostate cancer.

Aged↗
PubMed1996

Age- and race-specific reference ranges for prostate-specific antigen from a large community-based study.

OBJECTIVES: To analyze the relationship of age and race to prostate-specific antigen (PSA) levels among participants in a community-based study. METHODS: A total of 77,700 records of men aged 40 to 79 years were analyzed from a longitudinal study of PSA conducted during Prostate Cancer Awareness Week 1993 and 1994. Records from 1994 were not included for men who were tested in 1993. All cases of prostate cancer were excluded. Records with outlier PSA values greater than 20 ng/mL were eliminated from the analysis (n = 190; 24%). RESULTS: Mean PSA values (ng/mL) of 10-year age groups differed significantly (P < 0.0001) between each group (ages 40-49, 0.83; 50-59, 1.23; 60-69, 1.83; 70-79, 2.31). In each successively older age group, PSA variance increased significantly (P = 0.0001). Standard deviations (SD) by age group were: 40-49, 0.79; 50-59, 1.33; 60-69, 1.94; and 70-79, 2.35. Significant differences in mean PSA by race were found. Pairwise differences in mean PSA were found between whites and blacks, whites and Latinos, blacks and Asians, and Asians and Latinos (P < 0.0001). No statistically significant differences in PSA variance between racial groups were found. Age-within-race analysis resulted in consistent statistical significance when comparing variance among age cohorts in each race. CONCLUSIONS: Age-specific PSA reference ranges are a result of the increasing mean PSA and increasing PSA variance in successively older cohorts of men. Mean PSA values differ significantly by race, but differences in PSA variance do not. The clinical significance of race-specific PSA reference ranges has yet to be determined.

Adult↗
PubMed1996

Schizophrenia, the heteromodal association neocortex and development: potential for a neurogenetic approach.

The heteromodal association neocortex is believed to be a major site of involvement in schizophrenia. This system includes the prefrontal cortex and portions of the superior temporal and inferior parietal cortices, which are linked in cognitive networks observing complex executive functions. The heteromodal cortex is highly elaborated in humans and is believed to continue to develop past birth. The neuropathology of schizophrenia is likely to be heterogeneous and appears to involve developmental abnormalities, with a prominent genetic component. However, the genes involved in the development of the neocortex, and particularly the heteromodal cortex, are not well understood. A candidate-gene approach to schizophrenia using techniques of differential expression might now be feasible and could illuminate the basic neurobiology of the heteromodal cortical network.

Cerebral Cortex↗