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Biomedical subjects

S Lane

Publications and source records attributed to S Lane.

At least 19 recordsLinked to original sources
PubMed2000

Quality of care and temperament determine changes in cortisol concentrations over the day for young children in childcare.

The current study investigated whether patterns of cortisol production in preschool-aged children in group care were influenced by characteristics such as group size, adult:child ratio, separation from family/parents, and quality of attention and stimulation from the childcare provider. Data were obtained from preschoolers attending home-based childcare. Cortisol levels were sampled at home and at childcare. Parents and teachers assessed the child's temperament (CBQ, TBQ). At childcare, the children were observed using the Observational Ratings of the Caregiving Environment (ORCE). Childcare characteristics were independent of family or child characteristics. In home-based childcare, children's cortisol patterns over the day correlated significantly with the amount of attention and stimulation provided by the childcare provider. Using a median split on the quality index measure of focused attention/stimulation, children in settings that were above the median exhibited no change in cortisol from home to childcare, while those in settings below the median exhibited a reversal of the typical pattern of cortisol production from morning to afternoon. At home these children exhibited the expected decrease in cortisol from morning to afternoon. Patterns of cortisol production at childcare were also correlated with child temperament with larger increases from morning to afternoon for more emotionally negative children and those with less self-control. Finally, cortisol production in home-based childcare was compared to data from children in center-based childcare and children not enrolled in full-day childcare.

Attention↗
PubMed1999

The High-Resolution FTIR Far-Infrared Spectrum of Formamide.

The far-infrared spectrum of formamide (HCONH2) has been recorded at high resolution and over 9000 vibration-rotation lines assigned. Molecular parameters from the rovibrational analyses of the unperturbed 12(1)0 out-of-plane vibration band have been obtained for the ground state and the excited state. An analysis of the complicated resonance system between the 9(1)0, 11(1)0, and 12(2)0 bands has also been carried out. The mid-infrared spectrum of formamide has been recorded at low resolution and assignments for the fundamental, combination, and overtone bands in this region are given. The Large Amplitude Motion (LAM) of the out-of-plane mode has been reanalyzed using the new parameter set. Copyright 1999 Academic Press.

Journal Article↗
PubMed1998

Ipsapirone neuroendocrine challenge: relationship to aggression as measured in the human laboratory.

Thirty-one human subjects were administered a neuroendocrine challenge with the 5-HT1a agonist ipsapirone after completing six sessions of a laboratory measure of aggression, the Point Subtraction Aggression Paradigm (PSAP), in order to determine if a laboratory measure of aggression was related to serotonin function. Subjects who showed more aggressive responding on the PSAP (n = 11) had a significantly blunted temperature response to ipsapirone compared to those with less aggressive responding (n = 20). There was no difference between the two groups on the cortisol response to ipsapirone. This study supports a relationship between serotonin function and aggression as measured in the human laboratory, similar to the well-documented association between self-reported aggression and serotonin.

Adult↗
PubMed1998

The importance of the 4'-hydroxyl hydrogen for the anti-trypanosomal and antiviral properties of (+)-5'-noraristeromycin and two 7-deaza analogues.

(+)-5'-Noraristeromycin (1) has shown significant antiviral activity while its 7-deaza analogue 2 is an antitrypanosomal candidate. To determine the relevance of the 4'-hydroxyl hydrogen in these activities, a derivative of 1 (that is, 3) where the C-4' hydroxyl hydrogen has been replaced by a methyl group has been prepared beginning with palladium (0) mediated coupling of the sodium salt of N6-benzoyladenine (9) and (1S,4R)-4-methoxy-2-cyclopenten-1-yl acetate (5). The synthesis of compound 5 is described from (1S,4R)-1-[(tert-butyldimethylsilyl)oxy]-4-hydroxycyclopent-2-ene (6) in three steps. Analogous preparations of the 7-deaza and 8-aza-7-deaza derivatives of 3 related to 2 (that is, 4 and 12) are also reported. The new derivatives (3, 4, and 12) failed to show improved antiviral activity. Compound 12 was the only derivative with some anti-trypanosomal activity, giving 40% inhibition of growth at 100 microM against bloodstream forms of a Typanosoma brucei brucei isolate in a standard in vitro screen. This study indicated that the C-4'-hydroxyl hydrogen plays a role in the medicinal properties of 1 and 2.

Adenosine↗
PubMed1997

Mechanical stretch induces vascular permeability factor in human mesangial cells: mechanisms of signal transduction.

Hemodynamic abnormalities have been implicated in the pathogenesis of the increased glomerular permeability to protein of diabetic and other glomerulopathies. Vascular permeability factor (VPF) is one of the most powerful promoters of vascular permeability. We studied the effect of stretch on VPF production by human mesangial cells and the intracellular signaling pathways involved. The application of mechanical stretch (elongation 10%) for 6 h induced a 2.4-fold increase over control in the VPF mRNA level (P < 0.05). There was a corresponding 3-fold increase in VPF protein level by 12 h (P < 0. 001), returning to the baseline by 24 h. Stretch-induced VPF secretion was partially prevented both by the protein kinase C (PKC) inhibitor H7 (50 microM: 72% inhibition, P < 0.05) and by pretreatment with phorbol ester (phorbol-12-myristate-13 acetate 10(-)7 M: 77% inhibition, P < 0.05). A variety of protein tyrosine kinase (PTK) inhibitors, genistein (20 microg/ml), herbimycin A (3.4 microM), and a specific pp60(src) peptide inhibitor (21 microM) also significantly reduced, but did not entirely prevent, stretch-induced VPF protein secretion (respectively 63%, 80%, and 75% inhibition; P < 0.05 for all). The combination of both PKC and PTK inhibition completely abolished the VPF response to mechanical stretch (100% inhibition, P < 0.05). Stretch induces VPF gene expression and protein secretion in human mesangial cells via PKC- and PTK-dependent mechanisms.

Capillary Permeability↗
PubMed1997

B-Myb function can be markedly enhanced by cyclin A-dependent kinase and protein truncation.

Transcription of the B-Myb gene is cell cycle regulated by an E2F-dependent mechanism and its product, B-Myb, is itself a transcription factor required for S-phase entry. Previously, we have shown that B-Myb is specifically phosphorylated during S-phase and that similar modification to a less electrophoretically mobile form could be induced by baculovirus-expressed cyclin A/Cdk2 kinase. We report here that cyclin A-mediated phosphorylation of B-Myb is associated with a marked increase in transactivation function in U-2 OS cells. In contrast to previous studies, transactivation of the luciferase reporter was dependent upon Myb binding sites located upstream of the promoter. Enhancement of B-Myb activation function was also obtained by truncation of the C-terminus just downstream of a domain conserved in evolution. Potentiation of B-Myb activity by phosphorylation was not simply a consequence of overcoming the negative effect of the C-terminus, however, as the truncated protein was to a lesser extent also activated by cyclin A/Cdk2. Whereas wild-type B-Myb transactivation activity could not be potentiated by cyclin A/Cdk2 in NIH3T3 cells, the truncated protein was hyperactive. Finally, we showed that B-Myb synergises with cyclin A to promote U-2 OS cells into S-phase.

3T3 Cells↗
PubMed1997

Synthesis and anti-trypanosomal activity of various 8-aza-7-deaza-5'noraristeromycin derivatives.

A recent observation that (+)-7-deaza-5'-noraristeromycin (1), as an L-like analogue of aristeromycin, possessed meaningful anti-trypanosomal properties has prompted a search of other 7-deazapurines with similar or improved anti-trypanosomal responses. In that direction a series of pyrazolo[3,4-d]pyrimidines (that is, 8-aza-7-deaza-5'-noraristeromycin derivatives, 2-11) related to 1 have been prepared. These derivatives were evaluated against bloodstream forms of Trypanosoma brucei brucei and Trypanosoma brucei rhodesiense grown in vitro. Of these compounds, the parent L-like derivative 2 was less potent (IC50 40-70 microM) than 1 (IC50 0.165-5.3 microM) whereas the D-like analogue 3 was inactive, which is the same trend observed previously with 7-deaza-5'-noraristeromycin. Interestingly, some moderate activity (IC50 12.2-16.8 microM) was seen in the D-like 4'-methyl derivative 7 while its L-like partner was inactive.

Adenosine↗
PubMed1997

Association of cancer prevention-related nutrition knowledge, beliefs, and attitudes to cancer prevention dietary behavior.

OBJECTIVE: To examine the relationship of cancer prevention-related nutrition knowledge, beliefs, and attitudes to cancer prevention dietary behavior. SUBJECTS/SETTING: Noninstitutionalized US adults aged 18 years and older. METHODS: Data collected in the 1992 National Health Interview Survey Cancer Epidemiology Supplement were analyzed. The supplement included questions to ascertain knowledge, beliefs, and attitudes and a food frequency questionnaire to ascertain nutrient intake. STATISTICS: Multivariate linear regression modeling was conducted to assess the hypothesized relationships. RESULTS: After adjustment for relevant covariates (age, sex, education, total energy, perceived barriers to eating a more healthful diet), knowledge and belief constructs were predictive of dietary behavior. Specifically, fat, fiber, and fruit and vegetable intakes more closely approximated dietary recommendations for persons with more cancer-prevention knowledge. The strength of the associations between these constructs and dietary behavior varied in some cases according to level of education and perceived barriers to eating a healthful diet. Of the perceived barriers to eating a healthful diet, perceived ease of eating a healthful diet was most strongly and consistently predictive of intake. CONCLUSIONS: Research findings challenge dietetics practitioners to design diet- and health-promotion programs and activities that not only educate the public about the importance of diet to health, but also address barriers to dietary change.

Adult↗
PubMed1997

Polyamine derivatives as inhibitors of trypanothione reductase and assessment of their trypanocidal activities.

Trypanothione reductase (TR) occurs exclusively in trypanosomes and leishmania, which are the etiological agents of many diseases. TR plays a vital role in the antioxidant defenses of these parasites and inhibitors of TR have potential as antitrypanosomal agents. We describe the syntheses of several spermine and spermidine derivatives and the inhibiting effects of these compounds on T. cruzi TR. All of the inhibiting compounds displayed competitive inhibition of TR-mediated reduction of trypanothione disulfide. The three most effective compounds studied were N4,N8-bis(3-phenylpropyl)spermine (12), N4,N8-bis(2-naphthylmethyl)spermine (14), and N1,N8-bis(2-naphthylmethyl)spermidine (21), with Ki values of 3.5, 5.5 and 9.5 microM, respectively. Compounds 12, 14, and 21 were found to be potent trypanocides in vitro with IC50 values ranging from 0.19 to 0.83 microM against four T. brucei ssp. strains. However, these compounds did not prolong the lives of mice infected with trypanosomes. This work indicates that certain polyamine derivatives which target a unique pathway in Trypanosomatidae have potential as antitrypanosomal agents.

Animals↗
PubMed1997

Using a performance improvement team to reinvent a mandatory education program.

BACKGROUND: To improve employee attendance at Annual Review Day, the day when all mandatory hospitalwide education requirements are presented. The Finley Hospital (Dubuque, Iowa) initiated a performance improvement team in March 1993. Data collected previous to 1993 indicated that the compliance goal of 90% was being met only with difficulty. PERFORMANCE IMPROVEMENT TEAM: Data indicated three main areas where improvements could be made-communication, enforcement, and curriculum. Recommendations of task forces, with team members as leaders, were implemented. Decisions were made to change Annual Review Day to a full-day format to include all mandatory education, make outcomes competency based, and maintain cost-effectiveness. TRIAL RUN AND EVALUATION: The one-year trial run began in 1994 with gradual changes in the program from a lecture and video format to an interactive game format. For example, at one point a crossword puzzle with information on infection control and bloodborne pathogens was added. The Jeopardy Game format, used to teach the principles of emergency preparedness, was added in June 1994. Full implementation of the curriculum, communication, and enforcement recommendations have resulted in 100% compliance. MAINTAINING THE GAIN: The performance improvement team has continued to monitor results and submit quarterly reports to the quality management department. All participants must complete and pass a competency-based test on the information covered; all 760 participants have passed. The curriculum task force continues to meet on a yearly basis to evaluate the ever-evolving format, analyze attendee evaluations, and consider annual changes to the format.

Accreditation↗
PubMed1997

The orofacial cancer patient's support from the general practitioner, hospital teams, family, and friends.

BACKGROUND: After the diagnosis of cancer, about a third of patients have adjustment disorders. Of recently diagnosed patients, 5 to 15% experience serious psychological disturbances, but their distress is often undetected and untreated. Little attention has been directed to the patients' sources of support and their adequacy. METHODS: This study assessed a defined group (n = 49) of cancer patients' ratings of the support they received from general practitioners, hospital teams, family, and friends. Additional information was collected on the patients' interest in receiving further hospital services and their psychological morbidity (i.e., anxiety and depression). RESULTS: The results show wide variation in patients' perceptions of the helpfulness of the primary and secondary care teams, raising concern about the levels of help and support available to some cancer patients. CONCLUSIONS: Although this sample rated the help received from the hospital very highly, those patients who requested more information from the hospital sector showed little evidence of having had their general anxiety "buffered" by involvement of family members.

Adjustment Disorders↗
PubMed1997

Synthesis and antitrypanosomal activities of a series of 7-deaza-5'-noraristeromycin derivatives with variations in the cyclopentyl ring substituents.

Previous work in our laboratories has suggested that (+)-5'-nor-7-deazaaristeromycin (compound 1) may represent a prototype structure for a series of compounds with significant antitrypanosomal activities. To test this possibility, a series of derivatives of compound 1 with changes in the cyclopentyl substituents (compounds 3 to 10) have been studied. Although some growth activity was obtained with the L-like compound 5, related compounds 3 and 7 had little or no activity below 100 microM. D-like compounds 4 and 6 showed some activity at or below 100 microM, but the most interesting finding was that both the D- and L-like compounds having a methyl substituent on the 4' position were most active.

Adenosine↗
PubMed1996

Pseudoaneurysm causing partial obliteration of the left atrium: case report and review.

We describe a case of left ventricular pseudoaneurysm with subepicardial dissection onto the left atrial wall, mimicking a smooth left atrial mass, causing partial obliteration of the left atrial cavity. This patient presented with a transient ischemic attack, most likely resulting from a thromboembolic episode to the brain. Emergent surgery was successfully performed and the patient is doing well at 1-year follow-up, with no signs of left atrial compression by transthoracic echocardiography.

Aged↗
PubMed1996

Biochemical adaptations in the mesolimbic dopamine system in response to repeated stress.

We have demonstrated previously that chronic administration of morphine, cocaine, or ethanol produces some common biochemical adaptations in the ventral tegmental area (VTA) and nucleus accumbens (NAc), components of the mesolimbic dopamine system implicated in the reinforcing and locomotor activating properties of these drugs of abuse. Because this neural pathway is also regulated by stress, and because stress has been shown to influence an animal's behavioral responses to drugs of abuse, it was of interest to determine whether repeated exposure to stress results in similar biochemical adaptations. By use of immunoblot analysis, we show here that a course of chronic "unpredictable" stress, like chronic drug exposure, increased levels of immunoreactivity of tyrosine hydroxylase and glial fibrillary acidic protein and decreased levels of immunoreactivity of neurofilament proteins in the VTA. Chronic unpredictable stress also increased levels of cyclic AMP-dependent protein kinase activity and decreased levels of immunoreactivity of the G protein subunit, Gi alpha, in the NAc. These effects required long-term exposure to stress and were in most cases not seen in the substantia nigra and caudate-putamen, components of the nigrostriatal dopamine system studied for comparison. The biochemical effects of chronic stress in the VTA and NAc differed among three strains of rat studied. Fischer 344 rats were the most responsive in that they exhibited all of the aforementioned adaptations, whereas Lewis rats were the least responsive in that they exhibited none of these adaptations; Sprague-Dawley rats exhibited an intermediate number of responses. Taken together, the results of the present study demonstrate that chronic exposure to stress results in biochemical adaptations in the mesolimbic dopamine system that resemble the chronic actions of several drugs of abuse. These adaptations could contribute to the convergent behavioral effects induced by treatments that are mediated via the VTA-NAc pathway.

Adaptation, Physiological↗
PubMed1996

Koilocytosis; an indication for conservative management.

The management of women with mild dyskaryosis continues to be the subject of debate. The management of cases with such smears could be improved if additional morphological features were found to be indicative of low/high grade cervical intraepithelial neoplasia (CIN). Our own experience in the routine audit of the diagnostic accuracy of cervical smears had suggested that cases of dyskaryosis with koilcytosis were associated with low risk of CINIII. Two hundred and forty-four cervical smears reported as showing evidence of warty virus infection were reviewed and their subsequent histories noted. Of these smears, 173 demonstrated clear evidence of koilocytosis. Irrespective of the initial grade of dyskaryosis, only 28 cases (16.2%) had underlying CIN or had progressed to CIN over a minimum follow-up period of 21 months. Only two cases (1.2%) showed evidence of CINIII. Koilcytosis is associated with a low risk of CIN and an especially low risk of CINIII. The management of women with koilocytic smears should be modified accordingly.

Colposcopy↗
PubMed1996

Antitrypanosomal activity of purine nucleosides can be enhanced by their conversion to O-acetylated derivatives.

Fifteen purine nucleosides and their O-acetylated ester derivatives were examined for in vitro antitrypanosomal activity against the LAB 110 EATRO isolate of Trypanosoma brucei brucei and two clinical isolates of Trypanosoma brucei rhodesiense. Initial comparisons of activity were made for the LAB 110 EATRO isolate. Three nucleoside analogs exhibited no significant activity (50% inhibitory concentrations [IC50s] of > 100 microM), whether they were O acetylated or unacetylated; three nucleosides showed almost equal activity (IC50s of < 5 microM) for the parent compound and the O-acetylated derivative; nine nucleosides showed significantly improved activity (> or = 3-fold) upon O acetylation; of these nine analogs, six displayed activity at least 10-fold greater than that of their parent nucleosides. The most significant results were those for four apparently inactive compounds which, upon O acetylation, displayed IC50s of < or = 25 microM. When the series of compounds was tested against T. brucei rhodesiense isolates (KETRI 243 and KETRI 269), their antitrypanosomal effects were comparable to those observed for the EATRO 110 strain. Thus, our studies of purine nucleosides have determined that O acetylation consistently improved their in vitro antitrypanosomal activity. This observed phenomenon was independent of their cellular enzyme targets (i.e., S-adenosylmethionine, polyamine, or purine salvage pathways). On the basis of our results, the routine preparation of O-acetylated purine nucleosides for in vitro screening of antitrypanosomal activity is recommended, since O acetylation transformed several inactive nucleosides into compounds with significant activity, presumably by improving uptake characteristics. O-acetylated purine nucleosides may offer in vivo therapeutic advantages compared with their parent nucleosides, and this possibility should be considered in future evaluations of this structural class of trypanocides.

Acetylation↗