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Biomedical subjects

K Jackson

Publications and source records attributed to K Jackson.

At least 19 recordsLinked to original sources
PubMed2000

The longitudinal study of phobic disorder in a community sample from early to late adolescence.

PURPOSE: This study explored the development of phobic disorder as young subjects move into late adolescence. The objectives were to determine: the frequency of clinical, subsyndromal and subthreshold phobia in late adolescence; the incident episode and stability of phobic symptoms as adolescents move from early to late adolescence; and the relationship between demographic characteristics in early adolescence and the presence of clinical, subsyndromal and subthreshold phobia in late adolescents.METHODS: The data were taken from a two-stage epidemiological study to determine the frequency of and risk factors for DSM-III major depressive disorders and suicidal behaviors in a community population of adolescents. Data were also collected for the frequency of phobias. Three levels of phobias were defined.RESULTS: The prevalences of clinical, subsyndromal and subthreshold phobias in late adolescence were 0.40%, 1.34%, and 5.74% respectively. The weighted incidence of clinical phobia was 0.28%, of subsyndromal phobia was 0.19% and of subthreshold phobia was 4.63%. Race, sex, and having a subthreshold phobia at the initial interview were significantly associated with subsyndromal phobia in late adolescence. Diagnosis of clinical phobia at initial interview was significant in all the multivariate models. Having a subthreshold phobia at initial interview was significant for subsyndromal phobia in late adolescence.CONCLUSIONS: Data on late adolescence showed a strong trend towards remission of phobic symptoms and disorder. However, those with clinical phobia at baseline had an increased risk of being diagnosed again at late adolescence. The most frequently reported symptoms were simple phobias, suggesting that simple phobias start early, have a higher prevalence, and are more frequent over time than social or agoraphobia. Further longitudinal studies are needed.

Journal Article↗
PubMed2000

Drug-excipient interactions and their affect on absorption.

Excipient(s) are traditionally thought of as inert but they can have a tremendous impact on the ultimate pharmacological availability of a drug substance when added to a formulation. The magnitude of this effect will depend on the characteristics of the drug and on the quantity and properties of the excipients. The aim of this article is to identify the various physicochemical and physiological processes that can be altered by drug-excipient interactions and to explore mechanisms by which they might occur. The regulatory implications of drug-excipient interactions will also be discussed.

Journal Article↗
PubMed2000

Enzymic characteristics of secreted aspartic proteases of Candida albicans.

Candida yeasts are rarely infectious, but frequently cause life-threatening systemic infections in patients immunocompromised by AIDS or by immunosuppressive therapeutics. The secreted aspartic proteases (Saps) are known virulence factors of pernicious Candida species. The most virulent, Candida albicans, possesses at least nine SAP genes, some of which are specifically expressed from cells with morphologies associated with virulence. Only one of these proteases, Sap2, has been previously purified from yeast in sufficient quantities for enzymic studies. The other enzymes are present in low amounts in yeast culture and are difficult to purify. As a consequence, enzyme properties, including the substrate specificities, of all Saps are poorly studied. Therefore, four Saps that are known to be expressed in C. albicans, Sap1, Sap2, Sap3 and Sap6, were produced in Escherichia coli as recombinant zymogens and purified in large quantities. These proenzymes were autoactivated and purified as active proteases. The enzymic properties including the substrate specificities at the P(1) and P(1)' sites were determined using a competitive hydrolysis method employing synthetic substrate mixtures. All four Saps cleave peptide bonds between larger hydrophobic amino acids, but these somewhat broad specificities differ in detail among the four enzymes at both sites. At the P(1) site, Sap1, Sap2 and Sap6 prefer Phe while Sap3 prefers Leu. Positively charged amino acids are also accommodated, especially by Sap2 and Sap3. The specificities at P(1)' are broader than at P(1) for all four enzymes. Sap6 prefers Ala, whereas other Saps prefer Tyr. Acidic side chains are also accommodated at this site. Analysis of substrates with a hydrophobic amino acid in P(1)' reveals that all the Saps possess a unique preference for Ala at this site. The observed differences of residue preferences among Saps may be utilized for the design of specific substrates and inhibitors.

Aspartic Acid Endopeptidases↗
PubMed2000

Noradrenergic lesions differentially alter the expression of two subtypes of low Km cAMP-sensitive phosphodiesterase type 4 (PDE4A and PDE4B) in rat brain.

This study examined the effects of selective, central noradrenergic dennervation with 6-hydroxydopamine (6-OHDA) on the expression of type 4 phosphodiesterases (PDE4). Twenty-one days following i.c.v. injection of 6-OHDA (200 microg) hypothalamus, neostriatum, and cerebellum were dissected. Infusion of 6-OHDA reduced norepinephrine (NE) content in all the brain areas examined (to 17%, 76% and 16% of sham-operated controls in hypothalamus, striatum, and cerebellum, respectively). 6-OHDA injections also reduced dopamine levels in hypothalamus (53%) and neostriatum (68%). Administration of desipramine (20 mg/kg, i.p.) 30 min prior to 6-OHDA injection protected neostriatal and cerebellar noradrenergic neurons NE levels (110-122% of the control levels). Desipramine partially attenuated the 6-OHDA-mediated decrease in NE content of hypothalamus, but had little or no effect on either striatal or hypothalamic dopamine (DA) levels. Western blot analysis using a PDE4A-selective antibody revealed three major bands (109 kDa PDE4A5, 102 kDa PDE4AX and 76 kDa PDE4A1) in hypothalamus and striatum. Infusion of 6-OHDA decreased the expression of PDE4A5 and PDE4AX but not of PDE4A1 in hypothalamus, as determined by quantitative Western blotting. Pretreatment of rats with desipramine attenuated the 6-OHDA-induced down-regulation of PDE4A5 and PDE4AX bands in hypothalamus. The PDE4B selective antibody K118 labels 5 major bands in all the brain regions studied. One hundred kDa PDE4B3, 86 kDa PDE4B2 and a 78 kDa PDE4B band was identified using recombinant proteins. Treatment of rats with 6-OHDA resulted in a 52% decrease in the PDE4B3 and 58% decrease in 78 kDa PDE4B variant in hypothalamus; administration of desipramine attenuated the 6-OHDA-induced down-regulation of both PDE4B variants. Neither 6-OHDA nor desipramine altered striatal PDE4A or PDE4B isozymes. In contrast, cerebellar PDE4B3 variant is up-regulated by 6-OHDA treatment and were partially normalized to control values by desipramine pretreatment. These data demonstrate that PDE4 subtypes are differentially regulated by presynaptic noradrenergic activity and may play an important role in the maintaining homeostasis of noradrenergic signal transduction in rat brain.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2000

Long-term supplementation with melatonin delays reproductive senescence in rats, without an effect on number of primordial follicles.

The primary objective of the present experiment was to determine if lifelong supplementation with melatonin delayed reproductive senescence through decreased loss of ovarian primordial follicles. Holtzman rats were divided into three treatments on Day 10 after pupping (Day 0 = day of pupping). Treatment 1 pups had access to water, whereas Treatment 2 and 3 pups had access to water containing 10 microg/ml melatonin only at night (Treatment 2) or continuously (Treatment 3). Estrous cycles and weights of pups were monitored at selected times during the experiment; ovaries were removed for histology at 75 and 380 days of age. Vaginal opening in Treatment 2 was delayed (P <.01) compared with Treatments 1 and 3, but there was no difference (P > 0.05) among treatments in percentage of normal length estrous cycles from vaginal opening to 75 days of age. There were fewer (P < 0.001) abnormal-length estrous cycles from 180 to 380 days of age in Treatment 2 as compared with Treatments 1 or 3. There was no effect of treatment (P > 0.05) on number of primordial follicles. In conclusion, nighttime, but not continuous supplementation with melatonin, delayed puberty and reproductive senescence without any effect on number of primordial follicles.

Aging↗
PubMed2000

In vivo estrogen bioactivities and in vitro estrogen receptor binding and transcriptional activities of anticoagulant synthetic 17beta-aminoestrogens.

Estrogenic activities of the two 17beta-aminoestrogen (AE) derivatives, prolame and butolame, were studied upon coagulation, serum luteinizing hormone (LH) and uterine weight, including endometrial morphology in castrated female rats. We have also investigated the ability of these two compounds, as well as another AE pentolame, to activate transcription through the estrogen receptor alpha (ERalpha) and the estrogen receptor beta (ERbeta). Administration of prolame and butolame to castrated animals increased significantly (P < 0.01) the mean clotting time when compared with that obtained in the group of control animals. Butolame was a more potent anticoagulant than prolame (P < 0.01), as judged by their corresponding IC(50) (5.4 +/- 0.65 and 66.6 +/- 2.57 micro;g/animal, respectively). In contrast, estradiol significantly shortened blood clotting times (P < 0.005). Both prolame and butolame caused a significant inhibition of serum LH levels (EC(50) 8.10 +/- 0.79 and 17 +/- 64 microg/animal, respectively), and restored castration-induced reduction in uterine weight of ovariectomized rats (EC(50) 4.14 +/- 1.57 and 17.0 +/- 1.78 microg/animal, respectively). In terms of the effects of prolame, butolame and pentolame in transient transfection assays, all the three AE activated ER dependent reporter gene expression, however, only at high concentrations. Prolame had the highest activity followed by butolame and pentolame. Induction of transcription by these compounds was preferentially mediated through the ERalpha, especially in the case of pentolame where little, if any, activation occurred through the ERbeta. None of the compounds showed antagonistic activities through either ER subtype. The overall data suggest that modifications in the structure and length of the amino-alcohol side-chain at C-17 might have an impact on the affinity and estrogenic intrinsic properties of AE at the level of diverse target tissues.

Amino Alcohols↗
PubMed2000

Effects of repeated antidepressant treatment of type 4A phosphodiesterase (PDE4A) in rat brain.

In a previous study, an up-regulation of rolipram-sensitive, low-Km, cyclic AMP phosphodiesterase (PDE4) subtype PDE4A in rat cerebral cortex following repeated treatment of desipramine was observed. To determine whether this effect is shared by antidepressants from different pharmacological classes, PDE4A expression was examined using immunoblot analyses following repeated treatment with the norepinephrine re-uptake inhibitor desipramine, the monoamine oxidase inhibitor phenelzine, the atypical antidepressant trazodone, and the serotonin reuptake inhibitor fluoxetine. Desipramine, phenelzine, and fluoxetine all increased the intensities of the PDE4A bands in hippocampal preparations; trazodone did not. In preparations of cerebral cortex, the intensities of the PDE4A bands were increased following desipramine treatment, not changed following phenelzine or fluoxetine treatment, and decreased following trazodone treatment. It appears that repeated treatment with antidepressant drugs from different pharmacological classes produces similar effects on the expressions of PDE4A variants in hippocampus. This effect is not correlated with the changes in beta-adrenergic receptor densities, suggesting these antidepressants may at some point alter intracellular signal transduction pathways in a similar manner.

Animals↗
PubMed2000

Collaboration in disability policies--collaboration between stakeholders of disability policies in the South and in the North.

Four studies have been recently undertaken at the Centre for International Child Health on the collaboration between the stakeholders of disability policies, in Southern and Northern countries. Informed by the literature, the authors have explored the roles disabled people's organizations, non-governmental organizations, government and professionals play in the design, provision and evaluation of services for disabled people. They also highlight the different forms participation can take and their most relevant features. The main factors influencing collaboration processes are then classified in three different categories: social factors, ideology-related factors and project-related factors. They are subsequently analysed. The first group encompasses the societal framework in which collaboration may take place, while the identity of the stakeholders is reflected in the ideology-related factors. The nature of the activities undertaken by stakeholders is characterized by the third group of factors. In the conclusion it is suggested that stakeholders, and especially disabled people's counterparts, should increase their awareness of the social model of disability, adopt participatory practices and promote participation at higher levels. However, they should acknowledge that it implies more trust between partners and an alteration of their structures.

Community Networks↗
PubMed2000

Evaluation of the kaiser physical activity survey in women.

PURPOSE: The Kaiser Physical Activity Survey (KPAS) was evaluated for test-retest reliability and comparison with direct and indirect measures of physical activity (PA) in 50 women (ages 20-60 yr) with a broad range of physical activity (PA) habits. METHODS: The KPAS, an adaptation of the Baecke usual physical activity survey, was designed specifically to assess activity in women. It provides four summary activity indexes: housework/caregiving, active living habits, sports, and occupation. Summary indexes were compared against direct (Caltrac accelerometer and PA records) and indirect (cardiorespiratory fitness (VO2 peak) and percent body fat) criterion measures of PA. Participants kept detailed PA records for two, 7-d periods, separated by 1 month. Caltrac accelerometers were worn concurrently with the PA records. RESULTS: Intraclass correlations for 1-month test-retest reliability were high for all KPAS indexes (r = 0.79 to 0.91, P < 0.01). Age-adjusted Spearman rho correlations between the KPAS sports/exercise and active living habits indexes were of moderate magnitude for VO2 peak (r = 0.34 to 0.76, P < 0.01) and percent body fat (r = -.30 to -0.59, P < 0.05). KPAS caregiving and occupation indexes were related to Caltrac kcal x d(-1) (r = 0.30 to 0.44, P < 0.05). Correlations between similar activities from the KPAS and PA records ranged from r = 0.03 to 0.64. Daily, habitual activities from the KPAS and PA records had the highest correlations (r > 0.28). Correlations among infrequent activities were lower (r < 0.05). CONCLUSION: The KPAS demonstrated good reliability and was reasonably accurate in detecting regular housework/caregiving, occupation, sports/exercise, and active leisure activities among women with a broad range of physical activity habits.

Activities of Daily Living↗
PubMed2000

Classification of small type B/C follicles as primordial follicles in mature rats.

In the present study, follicles were classified according to the morphology of their granulosa cells. Type B follicles contained only flattened granulosa cells; type B/C follicles had a mixture of flattened and cuboidal granulosa cells in a single layer, and type C follicles had a single layer of cuboidal granulosa cells. The primary objectives of the study were to determine whether 5-bromo-2-deoxyuridine incorporation into type B/C follicles was a marker for initiation of growth and how long type B/C follicles could remain at the same stage before transformation to type C follicles. Female Holtzman rats received bromo-deoxyuridine for 7 days. After the infusion (day minipumps were removed = day 0), rats were ovariectomized on days 0 (n = 9), 30 (n = 8), 90 (n = 8) and 150 (n = 9). The numbers of type B, B/C and C follicles within one ovary were determined using modified fractionator counting. Analysis over all times demonstrated that there were more (P < 0.0001) type B/C (941 +/- 61 per ovary) than type C (140 +/- 18 per ovary) or type B (159 +/- 19 per ovary) follicles. The numbers of type B and type C follicles did not differ from each other at any time. Only one of 34 rats evaluated had bromo-deoxyuridine-labelled type B follicles. On day 150, 57% of the bromo-deoxyuridine-labelled type B/C follicles remained from day 0. It is concluded that (1) DNA synthesis in granulosa cells of type B/C follicles is not a reliable indicator of impending growth; and (2) type B and type B/C follicles are both components of the pool of primordial follicles.

Analysis of Variance↗
PubMed1999

Mutations in a new Arabidopsis cyclophilin disrupt its interaction with protein phosphatase 2A.

The heterotrimeric protein phosphatase 2A (PP2A) is a component of multiple signaling pathways in eukaryotes. Disruption of PP2A activity in Arabidopsis is known to alter auxin transport and growth response pathways. We demonstrated that the regulatory subunit A of an Arabidopsis PP2A interacts with a novel cyclophilin, ROC7. The gene for this cyclophilin encodes a protein that contains a unique 30-amino acid extension at the N-terminus, which distinguishes the gene product from all previously identified Arabidopsis cyclophilins. Altered forms of ROC7 cyclophilin with mutations in the conserved DENFKL domain did not bind to PP2A. Unlike protein phosphatase 2B, PP2A activity in Arabidopsis extracts was not affected by the presence of the cyclophilin-binding molecule cyclosporin. The ROC7 transcript was expressed to high levels in all tissues tested. Expression of an ROC7 antisense transcript gave rise to increased root growth. These results indicate that cyclophilin may have a role in regulating PP2A activity, by a mechanism that differs from that employed for cyclophilin regulation of PP2B.

Amino Acid Sequence↗
PubMed1999

Type IV collagen and laminin regulate glomerular mesangial cell susceptibility to apoptosis via beta(1) integrin-mediated survival signals.

Postinflammatory scarring is characterized by changes in extracellular matrix (ECM) composition and progressive loss of normal resident cells. In glomerular inflammation there is now evidence that unscheduled apoptosis (programmed cell death) of mesangial and other resident cells may mediate progression to irreversible glomerulosclerosis. In the current study we examined the hypothesis that ECM components may differ in their capacity to support mesangial cell survival by suppression of apoptosis. Using a well-established in vitro model of mesangial cell apoptosis, we found that collagen IV and laminin, components of normal mesangial ECM, protected rat mesangial cells from apoptosis induced by serum starvation and DNA damage, by a beta(1) integrin-mediated, but arg-gly-asp (RGD)-independent mechanism. In contrast, collagen I, fibronectin, and osteonectin/SPARC, which are overexpressed in diseased glomeruli, failed to promote rat mesangial cell survival. However, the survival-promoting effect of collagen IV and laminin was not associated with changes in cellular levels of apoptosis regulatory proteins of the Bcl-2 family. These experiments demonstrate that glomerular mesangial cell survival is dependent on interactions with ECM and provide insights into potential mechanisms by which resident cell loss may occur during acute inflammation and postinflammatory scarring of the kidney and other organs.

Animals↗
PubMed1999

The RCN1-encoded A subunit of protein phosphatase 2A increases phosphatase activity in vivo.

Protein phosphatase 2A (PP2A), a heterotrimeric serine/threonine-specific protein phosphatase, comprises a catalytic C subunit and two distinct regulatory subunits, A and B. The RCN1 gene encodes one of three A regulatory subunits in Arabidopsis thaliana. A T-DNA insertion mutation at this locus impairs root curling, seedling organ elongation and apical hypocotyl hook formation. We have used in vivo and in vitro assays to gauge the impact of the rcn1 mutation on PP2A activity in seedlings. PP2A activity is decreased in extracts from rcn1 mutant seedlings, and this decrease is not due to a reduction in catalytic subunit expression. Roots of mutant seedlings exhibit increased sensitivity to the phosphatase inhibitors okadaic acid and cantharidin in organ elongation assays. Shoots of dark-grown, but not light-grown seedlings also show increased inhibitor sensitivity. Furthermore, cantharidin treatment of wild-type seedlings mimics the rcn1 defect in root curling, root waving and hypocotyl hook formation assays. In roots of wild-type seedlings, RCN1 mRNA is expressed at high levels in root tips, and accumulates to lower levels in the pericycle and lateral root primordia. In shoots, RCN1 is expressed in the apical hook and the basal, rapidly elongating cells in etiolated hypocotyls, and in the shoot meristem and leaf primordia of light-grown seedlings. Our results show that the wild-type RCN1-encoded A subunit functions as a positive regulator of the PP2A holoenzyme, increasing activity towards substrates involved in organ elongation and differential cell elongation responses such as root curling.

Arabidopsis↗
PubMed1999

Treatment of Parkinson hypophonia with percutaneous collagen augmentation.

OBJECTIVES: It has been estimated that more than 70% of patients with Parkinson disease experience voice and speech disorders characterized by weak and breathy phonation, and dysarthria. This study reports on the efficacy of treating Parkinson patients who have glottal insufficiency. STUDY DESIGN AND METHODS: Thirty-five patients underwent collagen augmentation of the vocal folds for hypophonia associated with Parkinson disease, using a new technique of percutaneous injection with fiberoptic guidance. Patient response to the collagen augmentation was determined by telephone survey. RESULTS AND CONCLUSIONS: The procedure required minimal patient participation and was safely performed on all the patients who were studied. Results of the survey indicated that 75% of patient responses demonstrated satisfaction with the technique, compared with 16% of patient ratings reflecting dissatisfaction. These results were moderately correlated with the duration of improvement of the dysphonia. Results of this preliminary evaluation demonstrate that voice deficits in Parkinson disease are amenable to vocal fold augmentation. Because this procedure requires minimal patient participation and can be safely performed in an office setting, it may also be useful in other severely debilitating neuromotor diseases that result in glottal insufficiency and hypophonia.

Aged↗