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Biomedical subjects

C J Douglas

Publications and source records attributed to C J Douglas.

33 records · Page 2Linked to original sources
PubMed1992

Clozapine treatment of psychosis in Parkinson's disease: a report of five consecutive cases.

BACKGROUND: Clozapine has gained acceptance as an antipsychotic in treatment-resistant schizophrenia. Its low propensity to induce extrapyramidal side effects makes clozapine an attractive treatment for patients with Parkinson's disease and dopaminomimetic psychosis. Recent evidence demonstrates that Parkinson's patients are exquisitely sensitive to both the antipsychotic and the potential extrapyramidal effects of clozapine. The uncontrolled studies suggest that low-dose clozapine may be efficacious in this population. The dose range, side effect profiles, and length of treatment varied in these reports. METHOD: We report our experience with five patients with Parkinson's disease and psychosis who were treated with clozapine in an open trial. RESULTS: Three patients were successfully treated with clozapine (25-100 mg/day, mean = 66.7 mg) without worsening their parkinsonism. Adverse effects unrelated to the motor disability required discontinuation of clozapine in the other two patients. At 1- to 2-year follow-up, each patient had required increased dosages of clozapine (75-150 mg/day, mean = 125 mg) for continued management of their psychosis and parkinsonism. The higher dose range was well tolerated. CONCLUSION: These results suggest that clozapine may effectively treat psychosis in Parkinson's disease.

Aged↗
PubMed1991

Exonic sequences are required for elicitor and light activation of a plant defense gene, but promoter sequences are sufficient for tissue specific expression.

The parsley 4CL-1 gene encodes 4-coumarate:CoA ligase, a key enzyme of general phenylpropanoid metabolism. As well as being transcriptionally activated by such stresses as pathogen infection, UV-irradiation, and wounding, expression of 4CL-1 is developmentally regulated. In this paper we present evidence that 4CL-1 cis-acting elements which control stress-induced and developmental expression are physically separated. The ability of a series of 4CL gene constructions to respond to elicitor and light in stably or transiently transformed parsley cells was tested. While inducible expression was observed from all templates in which the 4CL-1 structural gene was fused to the 4CL-1 promoter, fusions of the promoter to the GUS reporter gene were completely unresponsive. The element(s) required for responsiveness appear to be exonic, since 4CL-1 introns and 3' flanking DNA had no effect on inducibility. Furthermore, this unconventional regulatory mode operates in transgenic tobacco plants, where we show that a 4CL-1 promoter fragment specifies correct cell-specific expression when fused to GUS yet is unresponsive to elicitor and light.

Base Sequence↗
PubMed1991

A parsley 4CL-1 promoter fragment specifies complex expression patterns in transgenic tobacco.

The 4CL-1 gene is one of two highly homologous parsley genes encoding 4-coumarate:coenzyme A ligase, a key enzyme of general phenylpropanoid metabolism. Expression of these genes is essential for the biosynthesis of both defense-related and developmentally required phenylpropanoid derivatives. We examined the developmental regulation of the 4CL-1 promoter by analyzing the expression of 4CL-1-beta-glucuronidase fusions in transgenic tobacco plants. A 597-base pair 4CL-1 promoter fragment specified histochemically detectable expression in a complex array of vegetative and floral tissues and cell types. The activity of a series of 5' deleted promoter fragments was analyzed in parsley protoplasts and transgenic tobacco plants. Deletions past -210 base pairs led to a drastic decline in beta-glucuronidase activity in protoplasts and loss of tissue-specific expression in transgenic tobacco. These results were put into the context of potential protein-DNA interactions by in vivo footprint analysis of the 4CL-1 promoter in parsley cells. Loss of promoter activity in parsley protoplasts and transgenic tobacco was correlated with the deletion or disruption of the distal portion of a large (100-base pair) footprinted region within the first 200 base pairs of the 4CL-1 promoter.

Base Composition↗
PubMed1988

Adaptive responses to illness and disability. Healthy denial.

The authors attempt to understand the nature and sources of "resilience" by a comparison of three individuals who showed unusual courage in the face of death, illness, and congenital disability. Various adaptive traits that enabled them to function effectively and remain optimistic are discussed. The authors specifically consider the role of "healthy" denial and argue that it does not fully explain or account for their singular optimism confronting adversity. The term "resilience" is proposed to describe both the particular cognitive style of "hardiness" and the "ego strength" that characterize such patients. Possible sources and origins of resilience are suggested. Finally, implications for the treatment of such patients are considered.

Adaptation, Psychological↗
PubMed1987

Denial of illness: a reappraisal.

The authors attempt to understand the nature of denial of illness by an examination of two patients with serious and disfiguring physical disorders who postponed medical treatment for over a decade. Both patients subsequently had dramatic negative reactions to the therapeutic efforts of physicians caring for them. Various social, experiential, and characterologic determinants are discussed. In addition, the authors argue that the illness served important organizing functions: it sheltered these patients from the exigencies of everyday life; it allowed them to defeat the physician's efforts to effect a cure; and, finally, the disfigured physical state appeared to correspond to their internalized defective self-image and self-esteem.

Adult↗
PubMed1986

In-vitro effect of itraconazole, ketoconazole and amphotericin B on the phagocytic and candidacidal function of human neutrophils.

Neither itraconazole nor ketoconazole had significant effects on the phagocytosis or killing of Candida albicans blastospores by human neutrophil polymorphonuclear (PMN) leucocytes, whether following simultaneous addition of drug with the blastospores, prior treatment of the PMN cells with drug, or prior treatment of the blastospores with drug. Following simultaneous addition, amphotericin B caused significant impairment of phagocytosis in tests with PMN cells from one of two donors, but had no effect on subsequent killing of ingested blastospores. Prior treatment of PMN cells or blastospores with amphotericin B had no effect on phagocytosis or killing. In tests in which blastospores of an azole-sensitive and an azole-resistant strain of C. albicans were added to PMN cells, fewer than 25% of ingested blastospores of either strain had initiated germ tube formation after 6 h. Addition of ketoconazole had no effect on the proportion of ingested blastospores of either strain which germinated. Ketoconazole had no effect on germ tube elongation of ingested blastospores of the azole-resistant strain, but caused marked inhibition of germ tube elongation of ingested blastospores of the azole-sensitive strain. After 24 h, the azole-resistant strain had produced abundant mycelium and few phagocytic cells remained intact. With the azole-sensitive strain, PMN cells were still evident at 24 h, with ingested germ-tube-forming blastospores, most of which were dead.

Amphotericin B↗
PubMed1985

Identification and genetic analysis of an Agrobacterium tumefaciens chromosomal virulence region.

A genetic analysis of Agrobacterium tumefaciens chromosomal functions required for virulence was undertaken. Large Tn5-containing cosmid clones were isolated from DNA of avirulent A. tumefaciens mutants having chromosomal Tn5 insertions and exhibiting defective attachment to plant cells. The clones from several different mutants each contained overlapping segments of a 30-kilobase A. tumefaciens chromosomal region, which were physically mapped. All chromosomal Tn5 insertions leading to the avirulent, attachment-defective phenotype were localized within an 11-kilobase portion of this chromosomal virulence region. Transposon Tn3::HoHo1 (Tn3 containing lacZ) was used to simultaneously mutagenize and create lac fusions within the virulence region. This analysis demonstrated the presence of two distinct chromosomal virulence loci, which were 1.5 and 5 kilobases long; transposon insertions into these loci led to avirulence and defective attachment. The beta-galactosidase activity associated with various Tn3::HoHo1-created lac fusions indicated that the loci are transcribed in opposite directions, and complementation studies suggested that each locus consists of a single transcriptional unit. A cosmid clone of the chromosomal virulence region containing a lac fusion in the extreme 3' portion of the 5-kilobase locus was used to demonstrate that expression of this region is dependent on the presence of sequences in the 5' portion of the locus, confirming its operon-like nature.

Chromosomes, Bacterial↗
PubMed1985

Role for 2-linked-beta-D-glucan in the virulence of Agrobacterium tumefaciens.

Phenol-water cell extracts of virulent Agrobacterium tumefaciens A348 and several avirulent mutants with a reduced ability to attach to plant surfaces were examined. A low-molecular-weight 2-linked-beta-D-glucan was identified in the cell wall extracts of the virulent wild-type strain. Analyses of phenol-water extracts and culture filtrates of four mutant strains showed that the mutants did not produce any 2-linked-beta-D-glucan. When these mutants were complemented, the ability to produce the glucan described above was restored. These results suggest that there is a role for 2-linked-beta-D-glucans in the attachment of A. tumefaciens to plant cells. One avirulent, attachment-defective mutant retained its ability to produce the low-molecular-weight glucan. This mutation, however, mapped to a different transcriptional unit than the mutants deficient in the glucan described above. Thus, it appears that 2-linked-beta-D-glucan is only one component that may be necessary for attachment of A. tumefaciens to plant cell surfaces.

Adhesiveness↗
PubMed1985

Homophobia among physicians and nurses: an empirical study.

In a large urban teaching hospital treating many patients with AIDS, 37 medical house officers and 91 registered nurses completed a questionnaire designed to measure attitudes about homosexuality. Mean scores for both physicians and nurses fell in the low-grade homophobic range. No significant differences were found between scores for doctors and nurses, but women respondents were significantly more homophobic than men. Respondents who had a friend or relative who was homosexual were less homophobic than those who did not. Nearly 10 percent of respondents agreed with the statement that homosexuals who contract AIDS are getting what they deserve. The authors consider this to be an alarming statistic and conclude from the findings that homophobia is higher than desirable in this group of health professionals.

Acquired Immunodeficiency Syndrome↗
PubMed1984

Flagella-specific bacteriophages of Agrobacterium tumefaciens: demonstration of virulence of nonmotile mutants.

Bacteriophages GS2 and GS6 for Agrobacterium tumefaciens were shown by electron microscopy to adsorb to flagella. This specificity was confirmed by the finding that phage-resistant mutants were nonmotile. Such mutants retained tumor-inducing virulence and ability to attach to plant cells, indicating that motility was not required for these properties. Both phages had contractile tails and appeared similar in the electron microscope.

Adsorption↗
PubMed1982

Agrobacterium tumefaciens mutants affected in attachment to plant cells.

An analysis of Agrobacterium tumefaciens mutants with Tn5 insertions in chromosomal DNA showed that the chromosome of A. tumefaciens codes for a specific ability of this bacterium to attach to plant cells. This ability is associated with tumorigenesis by A. tumefaciens, the ability of avirulent A. tumefaciens to inhibit tumorigenesis, and the ability to adsorb certain phages. A second class of chromosomal mutations affects tumorigenesis without altering the ability to attach to plant cells. The attachment of A. tumefaciens to plant cells was assayed by mixing radiolabeled bacteria with suspensions of tobacco tissue culture cells or freshly isolated Zinnia leaf mesophyll cells. Under the conditions of this assay, an avirulent Ti plasmid-cured strain attached to the same extent as the same strain containing pTiB6806. Six of eight avirulent mutants with Tn5 insertions in chromosomal DNA showed defective attachment, whereas two retained wild-type attachment ability. In contrast to the strains showing wild-type attachment, the attachment-defective mutants failed to inhibit tumorigenesis when inoculated onto Jerusalem artichoke slices before inoculation of a virulent strain and also showed a loss of sensitivity to two Agrobacterium phages. The loss of phage sensitivity appeared to be due to a loss of ability to adsorb the phages. Staining with Calcofluor indicated that the mutants retained the ability to synthesize cellulose fibrils, which have been implicated in the attachment process. Southern filter hybridizations demonstrated that each mutant contained a single Tn5 insertion, and genetic linkage between the Tn5 insertion in one mutant and the attachment phenotype has also been demonstrated.

Adsorption↗
PubMed1977

Polyamine-stimulated growth of cultured rat urinary bladder epithelial cells.

A technique for isolating and establishing long-term cultures of rat urinary bladder epithelium has been devised. Cells isolated and cultured by this method have been grown for 12 weeks without subculturing. Rat bladder epithelial cells require the addition of putrescine, spermine, and spermidine to attain maximum growth and long-term survival. Monolayer cultures have been subcultured and carried through five passages.

Animals↗