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PubMed1992

Spatial frequency mechanisms with short-wavelength-sensitive cone inputs.

We have estimated the minimum number and frequency tuning of spatial mechanisms with Short-Wavelength-Sensitive (SWS)-cone inputs. This was accomplished by isolating SWS cones with intense, long-wavelength (yellow) adaptation, and measuring threshold elevation functions for short-wavelength, spatially localized test stimuli masked by obliquely oriented, short-wavelength, cosine gratings. Peak spatial frequency of the cosine gratings and test stimuli varied from 0.25 to 2.83 cpd in 0.5 octave steps. Results derived in this manner demonstrate that SWS cones input to at least two orientation selective mechanisms with peak spatial frequencies of approx. 0.7 and 1.4 cpd, respectively. The frequency tuning of the isolated-SWS-cone, spatial frequency mechanisms resemble closely the lowest two mechanisms measured with luminance modulation (i.e. normal viewing conditions where all cones contribute to the response).

Contrast Sensitivity↗
PubMed1988

Amphetamine accelerates and attenuates ultradian activity rhythms in preweanling rats.

Developing rats, studied in environmental isolation, display prominent fluctuations in locomotor activity with a periodicity of about 1-3 hr. This ultradian rhythmic pattern is most marked at 2 weeks of age, and appears to be endogenously mediated. (+)Amphetamine (1 mg/kg) was administered to 2 week old rat pups, and their locomotor activity levels were recorded continuously and stored in 5 min intervals using a sensitive computer-interfaced vibrational activity monitor. Activity was recorded for 12 hr after treatment and resulting time-series data were analyzed by harmonic spectral techniques. During the first 6 hr of testing, amphetamine induced a prominent low frequency perturbation in baseline activity levels corresponding to the expected period of acute drug action. During this time, normally prominent ultradian activity rhythms in the range of 8-12 cycles per day (cpd) were diminished in amplitude, even following low frequency smoothing to remove the changes in baseline. Correspondingly, there was also an increase in ultradian rhythm amplitude in amphetamine-treated pups at higher frequencies (32-40 cpd). During the final 6 hr of testing there was a marked suppression of typical ultradian rhythms in amphetamine-treated pups but not in controls. These results suggest that amphetamine treatment both accelerates and attenuates ultradian activity rhythms in developing rats during the acute period of drug action, and produces a prominent diminution in these rhythms during subsequent rebound and recovery periods.

Activity Cycles↗
PubMed1985

The role of platelet-derived growth factor on human pluripotent progenitor (CFU-GEMM) growth in vitro.

The effect of serum on the proliferation of human bone marrow pluripotent progenitor cells (CFU-GEMM), was compared to that of fresh frozen plasma (FFP). Serum significantly increased the number of mixed erythroid-granulocytic-megakaryocytic colonies (CFU-GEMM) and erythrocytic bursts (BFU-E) in this assay system (p less than 0.01 and 0.02, respectively). Two possible explanations for this finding were considered: first the presence of citrate-phosphate-dextrose (CPD) in plasma but not in serum, and second the presence of platelet-derived growth factor (PDGF) in serum but not in plasma. CPD was indeed found to have an inhibitory effect on growth of colonies of all types when added to serum-stimulated cultures. Nevertheless, when heparinized plasma was compared to serum from the same donors, growth of CFU-GEMM and BFU-E was higher in the serum-stimulated cultures (p less than 0.001 and p less than 0.05, respectively). PDGF at concentrations of 120-240 pM was found to enhance the formation of CFU-GEMM and BFU-E by three- and four-fold respectively when added to cultures containing FFP but not when added to cultures containing serum derived from whole blood (WBS). Purified PDGF added at the same concentrations, to cultures containing platelet-poor derived serum (PDS), promoted similar increases in growth of CFU-GEMM and BFU-E but not of granulocytic-macrophage or megakaryocytic colonies. Whether PDGF has a direct action on CFU-GEMM or its growth promoting activity is via an interacting cell population is currently being studied.

Cells, Cultured↗
PubMed1995

Few neocortial and thalamic morphological changes after a neonatal frontal cortical ablation contrast with the effects of a similar lesion in fetal cats.

To further understand the neuroanatomical consequences following perinatal brain injury, quantitative morphometric analysis was performed on the brain of cats receiving a unilateral frontal cortical ablation between postnatal days (P) 9 and P 14 and intact control cats. In all cats, the volume of the neocortex and thalamus was measured bilaterally and that of the thalamic ventrobasal complex (VBc) was measured ipsilaterally. In addition, using stereology, the neuronal and glial (presumably) cell packing densities (CPD) and the total number of neurons and glial cells (TCN) were measured in the ipsilateral VBc. The neuronal and glial cell cross-sectional areas (CSA) were also measured in the ipsilateral VBc. The mean ipsilateral and contralateral neocortex volumes were similar between the two animal groups. There was a statistically significant 14% and 13% reduction in mean ipsilateral and contralateral thalamic volumes, respectively for the lesioned animals, while the VBc shrank by 16% relative to intact controls. The mean neuronal and glial CPD were similar between the two groups. The mean neuronal TCN was reduced by 10% in the neonatal-lesioned cats, while the mean glial TCN was reduced by 31% in the same animals, however neither value reached significance. Lastly, the mean CSA of neurons and glial cells showed a tendency to be smaller in the lesioned cats by 8% and 9%, respectively. These results: (a) indicate that the neonatal lesion caused only minor morphological brain alterations and this sharply contrast with the marked changes previously reported in cats with a similar lesion sustained prenatally; (b) suggest that the enhanced behavioral recovery and/or sparing reported for the present cats compared to fetal-lesioned animals is at least partially due to the morphological sparing reported here; (c) together with previous findings in fetal cats, support the hypothesis that the morphological changes after a neonatal neocortical lesion are qualitatively different and may depend on different mechanisms as compared to those occurring after similar damage sustained prenatally.

Animals↗
PubMed1988

Peptide enzymatic microsynthesis, using carboxypeptidase Y as the catalyst: application to stepwise synthesis of Leuenkephalin.

In order to develop the use of carboxypeptidase Y (CPD-Y, EC 3.4.12.1) as a catalyst for radioactive hormonal synthesis, the stepwise synthesis of a pentapeptide, Leu-enkephalin, was studied on a microscale. Each peptide bond was formed by enzymatic catalysis, using microquantities of the precursors (amino acid or peptide esters as acyl-components and amino acid ester or amide as nucleophiles). The high condensation yields obtained suggests that CPD-Y can be a useful tool for preparation of radioactive hormonal peptides.

Carboxypeptidases↗
PubMed1991

The genetic defect in the Chinese hamster ovary cell mutant UV61 permits moderate selective repair of cyclobutane pyrimidine dimers in an expressed gene.

We examined removal of cyclobutane pyrimidine dimers (CPDs) from the dihydrofolate reductase (DHFR) gene in ultraviolet-irradiated Chinese hamster ovary (CHO) UV61 and UV5 cells. The sensitivity of UV61 cells to UV-irradiation is intermediate between that of the parental CHO cells and that of mutants such as UV5 that are highly defective in excision repair. UV61 cells have been characterized as having normal repair of pyrimidine(6-4)pyrimidone photoproducts (6-4 PPs) but no detectable removal of CPDs from the genome overall. We find that the extent of removal of CPDs from the DHFR gene in UV61 cells is intermediate between that of the parental CHO cells and that of the UV5 mutant, and the observed repair appears to be confined to the transcribed strand. We detected no removal of CPDs from the DHFR gene in UV5 cells. Our findings in UV61 cells demonstrate a correlation between survival after UV-irradiation and CPD repair in an expressed gene in a cell line with moderate UV-sensitivity and yet no apparent removal of CPDs from the genome as a whole. We have thus demonstrated that overall repair measurements can be misleading. Our results have implications for the determination of the relative biological importance of the CPD and the 6-4 PP, and they further support the hypothesis that removal of CPDs from transcriptionally active DNA is crucial for UV-resistance.

Animals↗
PubMed2006

Production of cis-syn thymine-thymine cyclobutane dimer oligonucleotide in the presence of acetone photosensitizer.

cis-syn Cyclobutane pyrimidine dimer (CPD) oligonucleotide was produced by UV irradiation in the presence of acetone photosensitizer. Acetone could enhance the productivity but evidently induced the photocleavage of oligonucleotide under a long time irradiation. A statistical approach of orthogonal design was applied to optimize the preparation condition for the production of the modified oligonucleotide. Optimal conditions for maximal cis-syn CPD oligonucleotide productivity were determined based on three factors: acetone concentration, initial oligonucleotide concentration, and irradiation time at several different levels. The optimal modified oligonucleotide that this optimization could produce was 32.7%. Through analysis of 20% polyacrylamide gel electrophoresis, it was found that modified oligonucleotide migrated slightly more slowly than the parent oligonucleotide. The photoreactivation of cis-syn thymine-thymine dimer oligonucleotide displayed the selectivity of the substrate specificity of DNA photolyase with high-performance liquid chromatography (HPLC) analysis.

Acetone↗
PubMed2004

Comparison of smoking relapse curves among African-American smokers.

We examined the smoking relapse curves for African-American smokers by level of smoking to characterize nicotine dependence in this population of smokers. This analysis was conducted from data originally collected to study differences in level of smoking among African-Americans at an inner-city health center in Midwest. Relatively little research has been conducted to clarify smoking and quitting patterns among African-American smokers. The median number of cigarettes smoked currently was 7 cigarettes per day (cpd) for light smokers and 20 cpd for the moderate to heavy smokers. The heavier smokers reported smoking at this rate longer than light smokers, 11 and 5 years, respectively. The major finding in this study is that African-American light smokers have abstinence rates very similar to heavier smokers and the median length of their most recent quit attempts were also similar. Therefore, stable light smokers may also need smoking cessation interventions similar to those used for heavier smokers in order to successfully stop smoking.

Adult↗
PubMed2006

Validation of the Dimensions of Tobacco Dependence Scale for adolescents.

The purpose of this study was to refine the Dimensions of Tobacco Dependence Scale (DTDS) - a measure of tobacco dependence for adolescents - by removing poorly discriminating items, testing the measurement structure of the remaining items and examining the predictive utility of the resulting scale in terms of its ability to explain the average number of cigarettes smoked per day (CPD). A total of 1425 current smokers (mean age 16 years) completed the questionnaire. Confirmatory factor analyses of the DTDS items supported a 4-factor model composed of social, emotional, nicotine and sensory related dimensions of tobacco dependence. Predictive utility and incremental validity of the DTDS was evident in the many sizable correlations between the DTDS and CPD as well as measures of self-rated addiction after controlling for scores on several other commonly used measures of nicotine dependence. The results indicate that the DTDS is a reliable and valid measure of tobacco dependence for adolescents that has the potential to enhance our understanding of the complex processes driving the emergence of tobacco dependence and cigarette smoking.

Adolescent↗
PubMed2004

The magnetic resonance imaging-based fetal-pelvic index: a pilot study in the community hospital.

OBJECTIVE: This study was undertaken to assess feasibility of magnetic resonance imaging (MRI) pelvimetry in conjunction with fetal ultrasonography as a technique in evaluating patients with previous cesarean sections for cephalopelvic disproportion (CPD). STUDY DESIGN: Pregnant patients with one previous cesarean section for CPD who planned a trial of labor after cesarean (TOLAC) were recruited to undergo MRI pelvimetry and fetal ultrasonography at 37 to 38 weeks. Entry criteria included no previous successful vaginal deliveries and no contraindications for vaginal delivery in the ongoing pregnancy. A fetal-pelvic index was calculated for each patient but not disclosed to patients or their physicians. The pregnancies were managed routinely. Analysis after delivery was used to ascertain whether this index would have predicted clinical outcome. RESULTS: There were no difficulties in performing the MRI or ultrasound. Sixteen patients completed their pregnancies. Three patients did not labor. The fetal-pelvic index was plotted on a scattergram and compared with the outcome. Three discriminatory zones were identified. Five of 6 patients in the most favorable zone delivered successfully. Two patients in the most unfavorable zone had failed vaginal birth after cesarean section (VBAC) attempts. In the 5 patients in the middle intermediate zone, TOLAC success appeared to depend on fetal presentation and gestational age. CONCLUSION: The use of comparative MRI pelvimetry and fetal ultrasonography is feasible in a community hospital. In this pilot study, it appeared to have potential in enhancing the management of VBAC candidates. This technique may allow sorting of patients before labor into zones that would favor or preclude VBAC attempts.

Adult↗
PubMed2004

Blockage of RNA polymerase II at a cyclobutane pyrimidine dimer and 6-4 photoproduct.

The blockage of transcription elongation by RNA polymerase II (pol II) at a DNA damage site on the transcribed strand triggers a transcription-coupled DNA repair (TCR), which rapidly removes DNA damage on the transcribed strand of the expressed gene and allows the resumption of transcription. To analyze the effect of UV-induced DNA damage on transcription elongation, an in vitro transcription elongation system using pol II and oligo(dC)-tailed templates containing a cyclobutane pyrimidine dimer (CPD) or 6-4 photoproduct (6-4PP) at a specific site was employed. The results showed that pol II incorporated nucleotides opposite the CPD and 6-4PP and then stalled. Pol II formed a stable ternary complex consisting of pol II, the DNA damage template, and the nascent transcript. Furthermore, atomic force microscopy imaging revealed that pol II stalled at the damaged region. These findings may provide the basis for analysis of the initiation step of TCR.

DNA↗
PubMed2005

Relative sparing of primary auditory cortex in Williams Syndrome.

Williams Syndrome (WS) is a neurodevelopment disorder associated with a hemizygous deletion on chromosome 7. WS is characterized with mental retardation, severe visual-spatial deficits, relative language preservation, and excellent facial recognition. Distinctive auditory features include musical ability, heightened sound sensitivity, and specific patterns of auditory evoked potentials. These features have led to the hypothesis that the dorsal forebrain is more affected than the ventral. Previously, we reported primary visual area 17 abnormalities in rostral striate cortex, a region contributing to the dorsal visual pathway. Based on the dorsal-ventral hypothesis, and language and auditory findings, we predicted a more normal histometric picture in auditory area 41. We used an optical dissector method to measure neurons in layers II-VI of area 41 in right and left hemispheres of the same 3 WS and 3 control brains used in the area 17 study. There was a hemisphere by diagnosis interaction in cell packing density (CPD) in layer IV and in cell size in layer III between WS and control brains. Post hoc analysis disclosed in control brains, but not WS, a layer IV left > right asymmetry in CPD, and a layer III left < right asymmetry in cell size. WS brains showed more large neurons bilaterally in layer II and in left layer VI. Histometric alterations in area 41 were less widespread than rostral visual cortex. Also, there was less asymmetry in the WS brain. We interpret layers II and VI differences as reflecting increased limbic connectivity in primary auditory cortex of WS.

Adult↗
PubMed2005

Telomerase-immortalized human fibroblasts retain UV-induced mutagenesis and p53-mediated DNA damage responses.

Immortalized cells frequently have disruptions of p53 activity and lack p53-dependent nucleotide excision repair (NER). We hypothesized that telomerase immortalization would not alter p53-mediated ultraviolet light (UV)-induced DNA damage responses. DNA repair proficient primary diploid human fibroblasts (GM00024) were immortalized by transduction with a telomerase expressing retrovirus. Empty retrovirus transduced cells senesced after a few doublings. Telomerase transduced GM00024 cells (tGM24) were cultured continuously for 6 months (>60 doublings). Colony forming ability after UV irradiation was dose-dependent between 0 and 20J/m2 UVC (LD50=5.6J/m2). p53 accumulation was UV dose- and time-dependent as was induction of p48(XPE/DDB2), p21(CIP1/WAF1), and phosphorylation on p53-S15. UV dose-dependent apoptosis was measured by nuclear condensation. UV exposure induced UV-damaged DNA binding as monitored by electrophoretic mobility shift assays using UV irradiated radiolabeled DNA probe was inhibited by p53-specific siRNA transfection. p53-Specific siRNA transfection also prevented UV induction of p48 and improved UV survival measured by colony forming ability. Strand-specific NER of cyclobutane pyrimidine dimers (CPD) within DHFR was identical in tGM24 and GM00024 cells. CPD removal from the transcribed strand was nearly complete in 6h and from the non-transcribed strand was 73% complete in 24h. UV-induced HPRT mutagenesis in tGM24 was indistinguishable from primary human fibroblasts. These wide-ranging findings indicate that the UV-induced DNA damage response remains intact in telomerase-immortalized cells. Furthermore, telomerase immortalization provides permanent cell lines for testing the immediate impact on NER and mutagenesis of selective genetic manipulation without propagation to establish mutant lines.

Apoptosis↗
PubMed2005

Short stature--an independent risk factor for Cesarean delivery.

OBJECTIVE: The present study was aimed to investigate pregnancy outcome of patients with short stature (height<155 cm), and specifically to elucidate if patients with short stature are at an increased risk for Cesarean section (CS) even after controlling for labor dystocia. METHODS: A population-based study comparing pregnancy outcome of patients with and without short stature, was performed. Deliveries occurred during the years 1988-2002, in a tertiary medical center. Stratified analyses, using the Mantel-Haenszel technique, and a multiple logistic regression model were performed to control for confounders. RESULTS: During the study period, 159,210 deliveries occurred. Of these, 5822 (3.65%) were of patients with short stature. Patients with short stature had statistically significant higher rates of CS compared with patients>or=155 cm (21.3% versus 11.9%, odds ratio (OR)=2.0; 95% confidence interval (CI): 1.9-2.1; P<0.001). Furthermore, there patients had higher rated of previous deliveries by CS (17.5% versus 10.3%, OR=1.8; 95% CI: 1.7-2.0; P<0.001), intrauterine growth restriction (IUGR, 3.2% versus 1.9%, OR=1.7; 95% CI: 1.4-1.9; P<0.001), premature rupture of membranes (PROM, 7.1% versus 5.6%, OR=1.3; 95% CI: 1.2-1.4; P<0.001), failed induction (0.7% versus 0.4%, OR=2.0; 95% CI: 1.5-2.8; P<0.001), labor dystocia (6.1% versus 3.5%, OR=1.8; 95% CI: 1.6-2.0; P<0.001), mal-presentations (7.6% versus 6.1%, OR=1.3; 95% CI: 1.1-1.4; P<0.001), and cephalopelvic disproportion (CPD, 0.9% versus 0.3%, OR=2.6; 95% CI: 1.9-3.4; P<0.001). No significant differences were noted between the groups regarding perinatal complications such as low birth-weight, meconium-stained amniotic fluid, perinatal mortality, and low Apgar scores at 5 min. Controlling for possible confounders such as previous CS, IUGR, PROM, failed induction, labor dystocia, mal-presentations and CPD, using the Mantel-Haenszel technique, did not change the significant association between short stature and CS. Moreover, a multiple logistic regression model was constructed with CS as the outcome variable, controlling for all these confounders. The model found short stature to be an independent risk factor for CS (OR=1.7; 95% CI: 1.6-1.9; P<0.001). CONCLUSION: Short stature is an independent risk factor for Cesarean delivery. Further studies investigating the actual indication for CS should be performed in order to make an informed recommendation regarding the preferred mode of delivery in short parturient women.

Adult↗
PubMed2005

Population pharmacokinetic modeling for enterohepatic recirculation in Rhesus monkey.

Enterohepatic recirculation (EHR) occurs via biliary excretion and intestinal reabsorption of a drug. Drug recycling through EHR can lead to a change in pharmacokinetic (PK) properties, such as reduced clearance (CL), extended half-life (T(1/2)) and increased plasma exposure (AUC). As a result, EHR may prolong the pharmacological effect of drugs. In the present study, the compound (Cpd A) was found to exhibit EHR in Rhesus monkeys associated with a reduction in CL (from 3.8 to 0.33 Lh(-1), IV; from 2.3 to 0.4 Lh(-1), PO), and an increase in T(1/2) (from 0.9 to 18 h, IV) and in AUC (from 1.5 to 17.4 microg h/mL, IV; from 2.8 to 16.3 microg h/mL, PO), by comparing the PK in the monkeys via the interruption of EHR (bile-duct cannulation) with that in the intact monkeys. A population four-compartment model was constructed based on recirculation loops incorporating all possible inputs (bile secretion, a lag-time model for gall bladder emptying, routes and amounts of a single dose administration) to fully evaluate the EHR of Cpd A. The plasma concentrations versus time profiles predicted from the model had a good fit to the values observed in the subjects and were further simulated with 90% confidence interval to demonstrate its utility. Thus, the model could be applied as a useful tool to evaluate the drugs or compounds that undergo EHR in different species.

Animals↗
PubMed2003

Effect of intraocular lens implantation on visual acuity, contrast sensitivity, and depth of focus.

PURPOSE: To determine the role of spherical and irregular aberrations in the optics of the natural eye and after intraocular lens (IOL) implantation in terms of visual acuity, contrast sensitivity, and depth of focus. SETTING: Laboratory of Experimental Ophthalmology, University of Groningen, Groningen, The Netherlands. METHODS: Visual acuity and defocus-specific contrast sensitivity in 11 pseudophakic patients (IOL group) and 27 age-matched phakic subjects were compared. The results were obtained psychophysically. Spherical and irregular aberrations were subsequently estimated by comparing the measured myopic shift (optimum focus of contrast sensitivity at 4 cycles per degree [cpd] compared to that at 16 cpd) and depth of focus with those of theoretical eye models with varying amounts of irregular and spherical aberrations. RESULTS: The best corrected visual acuity and best corrected contrast sensitivity in the IOL group did not significantly differ from that in the phakic group. The depth of focus was larger in the IOL group at a pupil diameter of 6.0 mm (P<.05). Comparison with theoretical eye models suggested a higher amount of spherical aberration in the IOL group; irregular aberration was almost the same in both groups. CONCLUSIONS: There was a higher amount of spherical aberration in the IOL group, related to a larger depth of focus, without loss of contrast sensitivity at optimum focus or loss of visual acuity. This might contribute to better quality of vision in pseudophakic subjects than in presbyopic phakic subjects.

Contrast Sensitivity↗
PubMed2004

Laser in situ keratomileusis for myopia and the contrast sensitivity function.

PURPOSE: To characterize the clinical effects of laser in situ keratomileusis (LASIK) on the cornea and visual performance by the contrast sensitivity function (CSF). SETTING: Clinique d'Ophtalmologie IRIS, Laval, Quebec, Canada. METHODS: Thirty-four patients aged 18 to 50 years volunteered for this prospective study. All patients had bilateral LASIK to correct myopia between -1.00 and -6.75 diopters (D) and refractive astigmatism less than 2.50 D. The mean spherical equivalent (SE) refractive error in the 68 eyes was -3.93 D +/- 1.67 (SD). A Hansatome microkeratome (Bausch & Lomb) and a Technolas 217C excimer laser (Bausch & Lomb) driven by the PlanoScan program were used. The monocular CSF for spatial frequencies of 3, 6, 12, and 18 cycles per degree (cpd) for both day and night vision simulations were made with a CSV-1000E system (Vector Vision) before and 1 month and up to 9 months after LASIK. All patients wore their best spectacle correction for the baseline CSF. RESULTS: The group (n = 68) averaged preoperative and postoperative CSFs did not differ at 1 month (analysis of variance [ANOVA], P>.05). In a subgroup of 11 eyes that had corneal microstriae, however, there was a significant reduction in the photopic and mesopic CSF at 6, 12, and 18 cpd (ANOVA, P<.05) despite normal Snellen visual acuities. The CSF normalized in 6 to 9 months as the microstriae became less visible. CONCLUSIONS: Subtle central corneal microstriae after LASIK can reduce the baseline CSF at medium to high spatial frequencies even with 20/20 visual acuity. The CSF normalizes as the microstriae fade over time.

Adolescent↗