Palliative and end-of-life care in the African American community.
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Black or African American↗
Biomedical subjects
T Payne
Publications and source records attributed to T Payne.
Heterologous myb genes distinct from GL1 enhance trichome production when overexpressed in Nicotiana tabacum.
Myb-class transcription factors implicated in cell shape regulation were overexpressed in Arabidopsis thaliana and Nicotiana tabacum in an attempt to assess the extent to which cellular differentiation programs might be shared between these distantly related plants. GLABROUS 1, a myb gene required for trichome development in Arabidopsis, did not alter the trichome phenotype of the tobacco plants in which it was overexpressed. MIXTA, which in Antirrhinum majus is reported to regulate certain aspects of floral papillae development, did not complement the glabrous 1 mutant of Arabidopsis. However, 35S:MIXTA transformants of N. tabacum displayed various developmental abnormalities, most strikingly production of supernumerary trichomes on cotyledons, leaves and stems. In addition, floral papillae were converted to multicellular trichomes. CotMYBA, a myb gene which is expressed in Gossypium hirsutum ovules and has some homology to MIXTA, was also overexpressed in the two species. A similar but distinct syndrome of abnormalities, including the production of cotyledonary trichomes, was observed in 35S:CotMYBA tobacco transformants. However, CotMYBA did not alter trichome production in Arabidopsis. These results suggest that the trichomes of Arabidopsis and Nicotiana are merely analogous structures, and that the myb genes regulating their differentiation are specific and separate.
Amino Acid Sequence↗
Molecular mechanisms of virulence in fungus-host interactions for Aspergillus fumigatus and Candida albicans.
Research on fungi that cause opportunistic infections has increased dramatically during the past few years, largely because these organisms cause significant morbidity and mortality. Most of this research has focused on defining the virulence factors produced by these pathogens, as well as developing methods for the diagnosis of fungal diseases. With regard to studies on the biology of Candida albicans, it is now possible to isolate genes, disrupt their expression, and observe the specific effects of gene disruption on virulence and growth of the organism. Moreover, growth and virulence of this pathogen is also being studied and the effect of environmental factors on gene expression investigated. This subject is especially important in view of the fact that C. albicans can colonize and invade a number of sites in the human body. Thus, its ability to grown in the oral and vaginal tracts, as well as in blood, requires the organism to adapt to a variety of environmental stresses. Here we present observations on the growth, morphogenesis and virulence of the opportunistic fungi C. albicans and Aspergillus fumigatus.
Amino Acid Sequence↗
Different effects of cyclosporin A on bone remodeling in young and adult rats.
Reported effects of cyclosporin A (Sandimmun, CsA) on bone have been both contradictory and controversial. Thus, stimulation of new bone formation as well as increased mineral and matrix resorption have been observed. To investigate the response of basal mineral and matrix turnover to CsA treatment at different stages of skeletal development, comparative experiments were conducted in young growing female rats and in adults. Fifty-six young animals (study A) and 40 adults (study B) received orally either the carrier substance or 5, 15, and 30 mg/kg CsA for 30 days. The following parameters were measured: (a) total skeletal mineral content by dual energy X-ray absorptiometry (DEXA) on days 1 and 30; (b) tibial trabecular volume at day 30; (c) serum osteocalcin at 5-day intervals; (d) urinary deoxypyridinoline (Dpd) excretion (days 1, 15, and 30); and (e) plasma levels of CsA. Results can be summarized as follows: in young rats (study A), total skeletal mineral was not modified by the 5- and 15-mg/kg doses of CsA, whereas 30 mg/kg induced a significant decrease (-15%, p < 0.01). This parameter was not significantly modified in adult animals (study B) subjected to the same doses. The administration of 5 mg/kg CsA did not alter tibial trabecular volume in young rats, but 15 and 30 mg/kg significantly lowered this parameter (-16.3%, p < 0.02, and -42%, p < 0.001, respectively). In adult rats, tibial trabecular volume remained unchanged with the exception of the group receiving 30 mg/kg which exhibited significantly lower values (-28%, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
Absorptiometry, Photon↗
Gastrointestinal hemorrhage and small cell carcinoma.
Despite widespread dissemination of primary lung carcinoma by lymphangitic and hematogenous routes, acute gastrointestinal signs and symptoms are rarely presenting symptoms for bronchogenic carcinoma. We present a patient with small cell carcinoma of the lung who came to medical attention because of a lower gastrointestinal hemorrhage. In the absence of radiographically apparent pulmonary disease, the correct diagnosis was suggested by the biopsy specimens of the colon.
Aged↗
An unexpected complication of heated hose humidification.
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Equipment Design↗
Prevention of adjuvant arthritis by cyclosporine in rats.
The effect of cyclosporine A during the development phase of adjuvant arthritis was studied in 40 female rats. Five groups of eight animals each received oral cyclosporine, 2.5, 5, 10, 20, or 30 mg/kg daily for 30 days. Also, eight normal and eight diseased rats served as placebo controls. At the time of inoculation of the adjuvant suspension on day 0, measurement of disease parameters (paw swelling and vertebral density) was started concomitantly with beginning of therapy. On completion of the study, the animals were killed, and after measurement of total skeletal and segmental (hind legs and caudal spine plus two caudal vertebrae) calcium, the two assessed vertebrae and both femoral condyles were removed for histomorphometric evaluation (vertebrae) and for estimation of glycosaminoglycan (GAG) content of cartilage. Blood for osteocalcin determinations also was taken at term from control and untreated arthritic rats and from animals that had received 10 mg/kg cyclosporine. Treatment with 2.5 mg/kg was ineffective, but doses between 5 and 20 mg/kg prevented the development of articular and osseous lesions. The 20 mg/kg dose showed no better effect than 10 mg/kg. This was shown by the absence of inflammation and the presence of normal condylar GAG and total mineral content in the areas screened. Untreated animals showed marked reductions in all of these parameters. The 30 mg/kg dose was effective in blocking the GAG loss, but significant reductions in bone density and trabecular volume were seen. There was a close correlation between GAG and bone density values, suggesting a common causal relationship. Circulating osteocalcin was significantly elevated in the untreated animals with adjuvant arthritis.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
The focally demyelinated rat fimbria: a new in vitro model for the study of acute demyelination in the central nervous system.
We have produced controlled local demyelination in Wistar rat fimbriae by injection of microliter quantities of the detergent lysophosphatidyl choline (LPC) stereotactically. Six to seven days later the hippocampus and fornix was dissected out en bloc and maintained in vitro for electrical evaluation of conduction through the damaged area. The tissue was then fixed for verification of the lesion by light and electron microscopy. All fimbriae showed a normal conducted action potential with a latency of 0.5 to 1.5 ms when the conduction distance was 4-5 mm. LPC-lesioned fimbriae also showed a later wave with a latency of 4-5 ms. This later wave had the same stimulus-response curve as the primary action potential, but was more sensitive to repeated stimulation. We interpret this wave as evidence of conduction into or through a demyelinated region. LPC-lesioned fimbriae also showed histological evidence of demyelination. This preparation provides an in vitro model for the study of acute local demyelination of central nervous system white matter, such as that induced by multiple sclerosis and other focally demyelinating diseases.
Acute Disease↗
Development of an immunization tracking system in a large health maintenance organization. Group Health Cooperative of Puget Sound.
We have successfully developed a mainframe system for tracking all immunizations administered to enrollees in a large HMO. This system will provide comprehensive immunization records on a population of over 350,000 patients. Data required by the National Childhood Vaccine Injury Act of 1986 are locally entered into terminals, and records of immunization are stored in a database. Preliminary results show that data entry times are practical, but that improvement in data quality is needed. This immunization tracking system will be used for research, and as the foundation of an immunization reminder system under development.
Health Maintenance Organizations↗
Pharmacological effects of a new antiarthritic agent, IX 207-887.
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Animals↗
Regression of bone and cartilage loss in adjuvant arthritic rats after treatment with cyclosporin A.
To test the effect of cyclosporin A (CsA) on arthritis-related bone resorption, we studied 30 female rats with adjuvant-induced arthritis (AIA). The animals were randomly assigned to 5 groups of 6 animals each; they received daily oral doses of 3, 5, 10, or 15 mg/kg CsA or placebo for 10 days. The parameters studied were (a) caliper measurements of hindpaw swelling, (b) radiometric densitometry of caudal vertebrae, (c) quantitative histomorphometry of radiographed vertebrae, and (d) glycosaminoglycan measurements in femoral condyles. A significant dose-dependent regression of articular swelling occurred in rats given 5, 10, and 15 mg/kg CsA, and this was concomitant with improvement in bone density. These results correlated with those of quantitative bone morphometry. Thus, trabecular volume was significantly reduced in AIA rats, but restoration to virtually normal values occurred with CsA doses between 5 and 15 mg/kg. The protective effect of CsA on articular damage was supported by the dose-dependent progressive improvement in total femoral condyle glycosaminoglycan content. The favorable effect of CsA on AIA is likely due to a blockade of T cell activation via an inhibition of production of lymphokines such as interleukin-2 and gamma-interferon. The consequent cessation of the immune reaction would lead to a reduction in the release of cytokines, such as interleukin-1, that are likely to be the mediators of the pathologic bone and cartilage breakdown that is characteristic of arthritic disease.
Animals↗
Inhibition of interleukin-1 release by IX 207-887.
Compound IX 207-887 is a novel antiarthritic agent which inhibits the release of interleukin-1 (IL-1) from human monocytes and mouse peritoneal macrophages in vitro at concentrations which are achieved therapeutically in human rheumatoid arthritis and in animal models of arthritis. In the present studies IL-1 activity in conditioned media, homogenates or lysates was monitored using four independent assay systems. Biologically active IL-1 was determined by, a) the induction of latent metalloproteinase-release from rabbit articular chondrocytes, which is relatively specific for IL-1 and b) by a sensitive thymocyte proliferation assay. Immunoreactive IL-1-beta was assayed by RIA and ELISA. In all test systems IX 207-887 significantly reduced both biologically active and immunoreactive IL-1 in culture media, whereas the levels of IL-1 in homogenates or lysates were either unaffected or only marginally reduced. The release of other monokines tested, such as interleukin-6 and tumour necrosis factor-alpha, and the secretion of lysozyme were only marginally influenced. IX 207-887 neither affected the adherence of human monocytes nor markedly inhibited IL-1 or IL-2-induced thymocyte proliferation. In the chondrocyte test no IL-1 antagonistic activity of IX 207-887 could be observed. All of these data indicate that IX 207-887 has the novel property of being an inhibitor of IL-1 release.
Animals↗
Overcoming multidrug resistance in Chinese hamster ovary cells in vitro by cyclosporin A (Sandimmune) and non-immunosuppressive derivatives.
Cyclosporin A (Sandimmune) increased the in vitro susceptibility of 'parental' and 'multidrug-resistant' (MDR) chinese hamster ovary (CHO) cell lines to three anti-tumour drugs: colchicine, daunomycin, and vincristine. Several immunosuppressive or non-immunosuppressive derivatives of cyclosporin (Cs) were compared for their ability to sensitise both parental and MDR cells to chemotherapeutic agents. Although 5-10-fold increases of sensitivity to anti-tumour drugs could be obtained for cells of the parental line with several Cs-derivatives, the largest 'gains' of sensitivity (chemosensitisation) were obtained for the cells of the MDR line and with only some of the Cs derivatives. The MDR cells employed displayed the typical MDR phenotype. However, we found no correlation between the immunosuppressive activity of Cs derivatives and their capacity to reverse MDR and all four possible combinations of these two activities could indeed be shown among the tested Cs derivatives. This study demonstrates for the first time that some immunosuppressive Cs can be devoid of chemosensitising activity.
Animals↗
Cyclosporine: intrinsic binding energies to interpret structure-activity relationships.
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Cyclosporins↗
Human monocyte or recombinant interleukin 1's are specific for the secretion of a metalloproteinase from chondrocytes.
Macrophage products induce production of proteases that contribute to cartilage degradation in various joint diseases. In these studies we stimulated rabbit chondrocytes with various cytokines in vitro in order to determine which were responsible for changes in the release of prostaglandin, plasminogen activator, and a metalloproteinase. The metalloproteinase assayed in these studies is a latent enzyme whose activity can rapidly be measured with fluorogenic casein. Conditioned media from stimulated human peripheral blood mononuclear cells; purified human monocyte IL 1, pI 7,6, and 5; and recombinant human IL 1, beta or alpha forms, all changed the secretory pattern of rabbit articular chondrocytes in a similar manner: production and secretion of a latent metalloproteinase(s) and prostaglandin E were stimulated in a concentration-dependent fashion, whereas the activity of plasminogen activator was strongly reduced. Antibodies against human monocyte IL 1 blocked the active principle in various mononuclear cell-conditioned media, suggesting that uncharacterized factors present in these supernatants do not affect the metalloproteinase response. When added to confluent chondrocytes, phorbol myristate acetate, concanavalin A, IL 2, lipopolysaccharide, indomethacin, and prostaglandin E2, which interfere with lymphocyte proliferation assays for IL 1, failed to influence chondrocyte metalloproteinase secretion. Recombinant human IFN-alpha or IFN-gamma in the presence or absence of IL 1 had no effect on rabbit chondrocytes, whereas recombinant human tumor necrosis factor decreased plasminogen activator but had no effect on prostaglandin or metalloproteinase production. These results support the concept that IL 1 specifically induces chondrocytes to produce metalloproteinases, and hence may play an important role in destructive joint diseases.
Animals↗
Immunologic response to early and routine DTP immunization in infants.
The effect of early immunization, prior to discharge from the newborn nursery, on subsequent immunity as determined by enzyme-linked immunosorbent assay (ELISA) immunoglobulin (Ig) M and IgG antibody titers to filamentous hemagglutinin and lymphocytosis-promoting toxin (LPT) of Bordetella pertussis and by standard pertussis agglutinin titers was investigated. Eighteen infants received routine diphtheria-tetanus-pertussis (DTP) immunization at 2, 4, and 6 months of age; 17 other infants received routine immunization and an additional DTP immunization in the newborn nursery. Antibody was determined on samples of cord blood and whole blood obtained at 4, 6, and 9 months of age. IgM anti-filamentus hemagglutinin was significantly higher at 4 and 6 months of age in the group that received early immunization (P less than .05). There was no significant difference in IgM anti-LPT, IgG anti-filamentus hemagglutinin, IgG anti-LPT, or pertussis agglutinin antibodies. Six control infants had high cord IgG anti-LPT titers. These six infants had significantly lower antibody titers to LPT at 6 and 9 months of age when compared with control with control infants with lower cord titers. Thirteen infants in the early immunization group with lower cord IgG anti-LPT titers achieved significantly lower titers at 9 months of age than the 12 comparable infants in the control group.
Bacterial Toxins↗
Educational priorities in the newborn nursery.
The newborn nursery provides an ideal setting for introducing basic concepts in primary care. The incorporation of the new born (low risk) nursery as a component of a division of ambulatory and community pediatrics presents an opportunity to address many of these issues and provides a focus for mother-child and family-institution bonding. In the University of California, Irvine, Medical Center nursery, management plans of residents and medical students are reviewed by a multidisciplinary team. The team considers the many physiologic adjustment a newborn infant must undergo to adapt successfully to its environment and discusses the impact of psychosocial stress, economic conditions, citizenship status, and environmental concerns on the ability of the parents to provide a supportive environment for their infant. Supervision of direct patient care and administrative responsibility for medical decisions in the nursery are the duties of the child health associate assigned to the nursery and his supervising physician.
Education, Medical↗
Phagocytosis stimulates the release of a slow reacting substance in cultured macrophages.
1 A slow-reacting substance (SRS) was released from non-elicited mouse peritoneal macrophages during phagocytosis of zymosan particles, whereas no detectable SRS was produced by resting cells. 2 The macrophage SRS induced a delayed and slow contraction of the guinea-pig ileum but not of the chick rectum. 3 The myotonic activity was antagonized by low concentrations of FPL 55712 (sodium 7-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)-2-hydroxypropoxy]-4-oxo-8-propyl-4H-1 -benzopyran-2 carboxylate) but was not affected by mepyramine or hyoscine, and was not associated with tachyphylaxis. 4 SRS release was increased by indomethacin and was abolished by the lipoxygenase and cyclooxygenase inhibitor, BW755C (3-amino-1-[m-(trifluoromethyl)-phenyl]-2-pyrazoline). 5 Addition of exogenous arachidonic acid or cysteine enhanced SRS production.
Animals↗